Potential Toxicity Risk Research Articles

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport.

The nose-to-brain drug-delivery system has emerged as a promising strategy to overcome the challenges associated with conventional drug administration for central nervous system disorders. This emerging field is driven by the anatomical advantages of the nasal route, enabling the direct transport of drugs from the nasal cavity to the brain, thereby circumventing the blood-brain barrier. This review highlights the significance of the anatomical features of the nasal cavity, emphasizing its high permeability and rich blood supply that facilitate rapid drug absorption and onset of action, rendering it a promising domain for neurological therapeutics. Exploring recent developments and innovations in different nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, micelles, nanoemulsions, nanosuspensions, carbon nanotubes, mesoporous silica nanoparticles, and nanogels unveils their diverse functions in improving drug-delivery efficiency and targeting specificity within this system. To minimize the potential risk of nanoparticle-induced toxicity in the nasal mucosa, this article also delves into the latest advancements in the formulation strategies commonly involving surface modifications, incorporating cutting-edge materials, the adjustment of particle properties, and the development of novel formulations to improve drug stability, release kinetics, and targeting specificity. These approaches aim to enhance drug absorption while minimizing adverse effects. These strategies hold the potential to catalyze the advancement of safer and more efficient nose-to-brain drug-delivery systems, consequently revolutionizing treatments for neurological disorders. This review provides a valuable resource for researchers, clinicians, and pharmaceutical-industry professionals seeking to advance the development of effective and safe therapies for central nervous system disorders.

Dimethyl phthalate induced cardiovascular developmental toxicity in zebrafish embryos by regulating MAPK and calcium signaling pathways

Dimethyl phthalate (DMP), the lowest-molecular-weight phthalate ester (PAE), is one of the most commonly detected persistent organic pollutants in the environment, but its toxic effects, especially cardiovascular developmental toxicity, are largely unknown. In this study, zebrafish embryos were exposed to sublethal concentrations of DMP from 4 to 96 hpf. Our results showed that DMP treatment induced yolk retention, pericardial edema, and swim bladder deficiency, as well as increased SV-BA distance and decreased heart rate, stroke volume, ventricular axis shortening rate and ejection fraction. In addition, oxidative stress and apoptosis were found to be highly involved in this process. The results of transcriptome sequencing and mRNA expression of related genes indicated that MAPK and calcium signaling pathways were perturbed by DMP. These findings have the potential to provide new insights into the potential developmental toxicity and cardiovascular disease risk of DMP.

An Assessment of Metal Pollution in the Surface Sediments of an East Antarctic Lake

ABSTRACT This study discusses the metal concentrations and sedimentological data from Lake L55, a dried, land-locked lake from Schirmacher Oasis, East Antarctica. Toxic metals in sediments are a major threat to the environment. Twenty-five surface sediment samples were analyzed for the presence of fifteen metals. The sedimentological data indicates that the sediments are predominantly sandy with low concentrations of silt and clay. The chemical weathering index for the sediments reflects low degree of weathering. Negligible concentrations of organic content were present in the sediments owing to the cold and dry conditions of the study area. The environmental pollution indices indicate elevated concentrations of Ba, Zn, As and Pb in the sediments. Barium could be supplied by the weathering of the quartzofeldspathic catchment rocks, while Zn, As and Pb could be supplied from the fuel burning for power generation and logistical activities, paint residue, and battery waste. The sediment quality guidelines were calculated for the sediments, and they indicate that the sediments have a 21% risk of being toxic. The pollution load index, potential ecological risk index (PERI) and toxic risk index (TRI) values suggest low toxic risk in the sediments of the lake.

Phthalate Biomarkers Composition in Relation to Fatty Liver: Evidence from Epidemiologic and in vivo studies

Phthalates, classified as environmental endocrine disruptors, pose potential toxicity risks to human health. Metabolic dysfunction-associated fatty liver disease is one of the most widespread liver diseases globally. Compared to studies focusing on metabolic disorders in relation to pollutants exposure, the impact of individual factors such as fatty liver on the in vivo metabolism of pollutants is always overlooked. Therefore, this study measured concentrations and composition of phthalate monoesters (mPAEs) in human urine samples, particularly those from fatty liver patients. Furthermore, we induced fatty liver in male Wistar rats by formulating a high-fat diet for twelve weeks. After administering a single dose of DEHP at 500 mg/kg bw through gavage, we compared the levels of di-2-ethylhexyl phthalate (DEHP), its metabolites (mDEHPs) and three hepatic metabolic enzymes, namely cytochrome P450 enzymes (CYP450), UDP glucuronosyltransferase 1 (UGT1), and carboxylesterase 1 (CarE1), between the normal and fatty liver rat groups. Compared to healthy individuals (n = 75), fatty liver patients (n = 104) exhibited significantly lower urinary concentrations of ∑mPAEs (median: 106 vs. 166 ng/mL), but with a higher proportion of mono-2-ethylhexyl phthalate in ∑mDEHPs (25.7 % vs. 9.9 %) (p < 0.05). In the animal experiment, we found that fatty liver in rats prolonged the elimination half-life of DEHP (24.61 h vs. 18.89 h) and increased the contents of CYP450, CarE1, and UGT1, implying the common but differentiated metabolism of DEHP as excess lipid accumulation in liver cells. This study provides valuable information on how to distinguish populations in biomonitoring studies across a diverse population and in assigning exposure classifications of phthalates or similar chemicals in epidemiologic studies.

Developments and Trends of Nanotechnology Application in Sepsis: A Comprehensive Review Based on Knowledge Visualization Analysis.

Sepsis, a common life-threatening clinical condition, continues to have high morbidity and mortality rates, despite advancements in management. In response, significant research efforts have been directed toward developing effective strategies. Within this scope, nanotechnology has emerged as a particularly promising field, attracting significant interest for its potential to enhance disease diagnosis and treatment. While several reviews have highlighted the use of nanoparticles in sepsis, comprehensive studies that summarize and analyze the hotspots and research trends are lacking. To identify and further promote the development of nanotechnology in sepsis, a bibliometric analysis was conducted on the relevant literature, assessing research trends and hotspots in the application of nanomaterials for sepsis. Next, a comprehensive review of the subjectively recognized research hotspots in sepsis, including nanotechnology-enhanced biosensors and nanoscale imaging for sepsis diagnostics, and nanoplatforms designed for antimicrobial, immunomodulatory, and detoxification strategies in sepsis therapy, is elucidated, while the potential side effects and toxicity risks of these nanomaterials were discussed. Particular attention is given to biomimetic nanoparticles, which mimic the biological functions of source cells like erythrocytes, immune cells, and platelets to evade immune responses and effectively deliver therapeutic agents, demonstrating substantial translational potential. Finally, current challenges and future perspectives of nanotechnology applications in sepsis with a view to maximizing their great potential in the research of translational medicine are also discussed.

Molecular insights into the interaction between myoglobin and Imidacloprid: Multi-spectral experiments and computational simulations

Imidacloprid (IMI) belongs to the neonicotinoid insecticides, specifically the imidazole chemical group, which exhibits a high level of contact, digestive, and systemic effects on the central nervous system of insects. In this study, we investigated the impact of IMI on the conformation and structural stability of myoglobin (Mb) protein using spectroscopic techniques combined with molecular docking and simulation approaches. Additionally, we examined the thermal stability of the resulting complex. The UV–Visible results demonstrated the interaction between IMI and Mb protein. The intrinsic fluorescence of Mb was effectively quenched by IMI, indicating successful binding and the formation of a stable complex. Thermodynamic analysis revealed that the spontaneous bonding process was primarily governed by van der Waals forces and hydrogen bonds. FT-IR analysis indicated that IMI induced conformational changes in Mb, providing further evidence of its potential toxicity and structural damage to Mb. Furthermore, the interaction significantly enhanced the thermal stability of Mb compared to Mb alone. Molecular docking revealed the preferred binding site of IMI within the Mb structure. Molecular dynamics (MD) simulation results further supported the findings by demonstrating a decrease in compactness and an increase in the stability of the Mb-IMI complex. These findings offer valuable insights into the potential toxicity risks of IMI to human health and shed light on the binding mechanism between IMI and Mb. The results of this study serve as a useful model for gaining a deeper understanding of the effects of these pesticides on proteins and body health.

Investigation on recrystallization of cryoprotectant solutions during warming under alternating electric fields

In the field of cryopreservation, recrystallization during rewarming is a significant factor leading to cryo-injury, causing ice crystal-induced mechanical injury to biological samples. Currently, methods, such as adding ice recrystallization inhibiting agents and increasing warming rates, have been adopted to reduce recrystallization injury. These methods also greatly increase the potential toxicity risk and engineering difficulty of cryopreservation. Accumulating research has progressively demonstrated that application of an electromagnetic field during cryopreservation can influence the preservation efficacy. However, the mechanism of action of the electric field has remained a subject of ongoing debate. We observed the recrystallization phenomenon of cryoprotectant solutions under a polarized light microscope and discovered promising experimental results. The electric field strength did not exhibit a discernible impact on the ice crystal size, while electric field frequency exerted a more significant impact. We found that at specific frequencies, the ice crystal size and growing rate were significantly affected during annealing. Compared to no electric field, an alternating electric field with a voltage of 10 V and a frequency of 5 × 104 Hz increased the recrystallization areas of a 15% (w/v) propylene glycol solution by 57%. And an alternating electric field with a voltage of 3 V and a frequency of 5 × 108 Hz decreased the recrystallization area of a 0.9% (w/v) NaCl aqueous solution by 9.9%. Different types of cryoprotectants exhibit varying responses to alternating electric fields frequency. These findings prompt us to reevaluate the role and mechanism of alternating electric fields in the cryopreservation of biological materials.

Safety of blood reinfusion drains after local infiltration analgesia in total joint replacement

BackgroundLocal infiltration analgesia (LIA) is frequently administered to patient undergoing joint replacement surgical procedures. The aim of the present research was to verify the safety of collected shed blood to be reinfused postoperatively, by measuring levobupivacaine levels in drainage blood in patients undergoing LIA during knee replacement surgery.Patients and Methods24 patients who underwent total knee arthroplasty (TKA) and 12 scheduled for total hip arthroplasty (THA) who received intraoperative LIA were considered. Blood samples were collected from shed blood which was present in drainage 2 and 5 hours after surgery and serum was analysed by liquid chromatography-tandem mass spectrometry.ResultsAt 2 hours postoperatively, the median levobupivacaine serum concentration in the collected shed blood was 1.2 mg/L (SD: 4.2) for TKA and 17.13 mg/L (SD: 24.4) for THA. At 5 hours, levobupivacaine concentration was 1.84 mg/L (SD: 2.2) for TKA and 17.5 mg/L (SD: 25.2) for THA. Higher values of average serum levobupivacaine concentration were reported in drains collected from patients who had undergone THA compared to TKA (p<0.001). BMI significantly influenced levels of serum drug, that resulted to be higher in patients with BMI<25 (p= 0.01).ConclusionLevobupivacaine from collected shed blood that would have been returned to the patient, was below toxicity level at 2 and 5 hours after LIA during total joint replacement. The average serum levobupivacaine concentration was found to be higher in drains taken from THA patients than TKA patients. Patients with lower BMI demonstrated the highest levels of levobupivacaine in shed blood and a lower blood volume needed for central nervous system toxicity. Therefore, in patients with a lower BMI undergoing THA, anaesthetic dosage should be reduced or autotransfusion should be avoided to prevent potential risks of toxicity.

Spatial Distribution, Ecological Risk Assessment, and Source Identification of Metals in Sediments of the Krka River Estuary (Croatia)

To evaluate the level of contamination and predict the potential toxicity risk, selected metal concentrations (Cd, Pb, Cr, Mn, Co, Ni, Cu, Zn, and As) were determined in 40 surface sediment samples from the stratified karstic Krka River estuary (Croatia). In addition, diffusive gradients in thin films (DGT) probes were deployed in situ to understand the mobilization mechanisms and bioavailability of metals in the sediment. The results show significant spatial differences between the upper and lower estuary, with the latter being more affected by anthropogenic pollution. The pollution assessment using the enrichment factor (EF), the geoaccumulation index (Igeo), and the pollution load index (PLI) showed a strong enrichment of metals in the lower part of the estuary, especially of Mn, Cu, Zn, Pb, and As. The statistical analysis (PCA) revealed the former ferromanganese factory and the port as major sources of pollution in the area. Nickel, Co, and Cr, although slightly elevated, may be attributed to the natural origin. The metal mobility in the estuarine sediment was primarily governed by early diagenetic processes (aerobic organic matter mineralization, Fe and Mn oxyhydroxide reduction), which caused the release of metals from the sediment into the pore water and subsequently into the overlying water column.

Developmental iron exposure induces locomotor alterations in Drosophila: Exploring potential association with oxidative stress

Prenatal iron (Fe) exposure has been associated with learning and cognitive impairments, which may be linked to oxidative stress resulting from elevated Fe levels and harm to the vulnerable brain. Drosophila melanogaster has contributed to our understanding of molecular mechanisms involved in neurological conditions. This study aims to explore Fe toxicity during D. melanogaster development, assessing oxidative stress and investigating behaviors in flies that are related to neurological conditions in humans. To achieve this goal, flies were exposed to Fe during the developmental period, and biochemical and behavioral analyses were conducted. The results indicated that 20 mM Fe decreased fly hatching by 50 %. At 15 mM, Fe exposure increased lipid peroxidation, and GSH levels decreased starting from 5 mM of Fe. Superoxide Dismutase activity was enhanced at 15 mM, while Glutathione S-Transferase activity was inhibited from 5 mM. Although chronic Fe exposure did not alter acetylcholinesterase (AChE) activity, flies exhibited reduced locomotion, increased grooming, and antisocial behavior from 5 mM of Fe. This research highlights potential Fe toxicity risks during development and underscores the utility of D. melanogaster in unraveling neurological disorders, emphasizing its relevance for future research.

Mechanisms of oxidative response during biodegradation of malathion by S. oneidensis MR-1

Malathion, an extensively used organophosphorus pesticide, poses a high potential risk of toxicity to humans and the environment. Shewanella (S.) oneidensis MR-1 has been proposed as a strain with excellent bioremediation capabilities, capable of efficiently removing a wide range of hard-to-degrade pollutants. However, the physiological and biochemical response of S. oneidensis MR-1 to malathion is unknown. Therefore, this study aimed to examine how S. oneidensis MR-1 responds physiologically and biochemically to malathion while also investigating the biodegradation properties of the pesticide. The results showed that the 7-day degradation rates of S. oneidensis MR-1 were 84.1, 91.6, and 94.0% at malathion concentrations of 10, 20, and 30 mg/L, respectively. As the concentration of malathion increased, superoxide dismutase and catalase activities were inhibited, leading to a significant rise in malondialdehyde content. This outcome can be attributed to the excessive production of reactive oxygen species (ROS) triggered by malathion stress. In addition, ROS production stimulates the secretion of soluble polysaccharides, which alleviates oxidative stress caused by malathion. Malathion-induced oxidative damage further exacerbated the changes in the cellular properties of S. oneidensis MR-1. During the initial stages of degradation, the cell density and total intracellular protein increased significantly with increasing malathion exposure. This can be attributed to the remarkable resistance of S. oneidensis MR-1 to malathion. Based on scanning electron microscopy observations, continuous exposure to contaminants led to a reduction in biomass and protein content, resulting in reduced cell activity and ultimately leading to cell rupture. In addition, this was accompanied by a decrease in Na+/K+- ATPase and Ca2+/Mg2+-ATPase levels, suggesting that malathion-mediated oxidative stress interfered with energy metabolism in S. oneidensis MR-1. The findings of this study provide new insights into the environmental risks associated with organophosphorus pesticides, specifically malathion, and their potential for bioremediation.Graphical

Can Microplastics Accumulate Toxic dye in Water? An adsorption-desorption Study under Different Experimental Conditions.

The adsorption/desorption of Rhodamine B (RhB) on Polystyrene (PS), polypropylene (PP), and polyvinyl chloride (PVC) microplastics (MPs) was investigated in this study. The results showed that RhB adsorption on the selected MPs was fast. The adsorption coefficients (Kd) of RhB were 2036 ± 129, 1557 ± 91, and 63 ± 8.5L kg- 1 for PS, PP, and PVC, respectively. RhB adsorption on PS and PP increased with increasing temperature and decreasing ionic strength, whereas RhB adsorption on PVC showed a completely opposite trend. The binding strength of RhB on the three types of MPs was weak as demonstrated by the high total desorption percentage, which ranged from 79.59 ~ 89.39%. This study shows that PP and PS MPs can accumulate RhB in the aquatic environment and their potential combined toxic risks should be taken seriously.

P719 Vitamin and micronutrient excess in patients with Crohn’s disease under oral ambulatory exclusive enteral nutrition

Abstract Background Exclusive enteral nutrition (EEN) is recommended for preoperative nutritional optimization (PNO) in adult Crohn's disease (CD) patients. However, during ambulatory oral EEN, a lack of routine monitoring for vitamins may occur, with a potential risk of hypervitaminosis-related toxicity, which remains unexplored. This study aims to assess the serum levels of vitamins and micronutrients in CD patients undergoing EEN and to examine its potential impact. Methods Complicated phenotype CD patients followed at a University Tertiary Hospital who were started on oral EEN June 2021 - June 2023 were prospectively included. EEN composition was determined and modified by an IBD nutritionist according to patients’ nutritional status and needs and laboratory values. Compliance was monitored daily, both for in- and outpatients. Patients’ weight and serum values (albumin, C-reactive protein [CRP], iron, folic acid, and vitamins B1, B6, B12, A, D, E and K) were monitored weekly. Results Nine patients (median age 29 years, 55.6% female) received a median of 24 (IQR 14.5-25.0) days of EEN, for PNO of symptomatic stricturing (7, 77.8%) or abdominal penetrating disease (2, 22.2%). All patients were discharged while on EEN, which was maintained until elective surgery (4, 44.4%) or the planned start of advanced medical therapy (5, 55.6%), with EEN successfully avoiding emergent surgeries. Patients were started on a combination of hypercaloric-hyperproteic and hypercaloric-normoproteic ready-to-drink concentrated polymeric formulas, providing 30 kcal/kg/d and 1.2-1.5g/kg/d of protein. EEN daily volume ranged from 1000 to 1400mL. Compliance was 100%, requiring flavour adjustments for tolerance. Table 1 illustrates changes over time in patients' weight and serum levels of interest. Resolution of anaemia and hypoalbuminemia was achieved, while weight was maintained . Hypervitaminosis cases were remarkably detected: 5 (55.6%) for vitamin B1, 4 (44.4%) for A, 2 (22.2%) for E, and 3 (33.3%) for K, with increasing trends over time. However, no symptoms related to hypervitaminosis were reported. Conclusion Our study on PNO EEN in CD uncovered a gap in routine monitoring for essential vitamins during EEN. While achieving significant clinical improvement, our findings revealed subtle and asymptomatic cases of hypervitaminosis in short-term EEN courses. These results underscore that vitamin monitoring is advisable during EEN, especially in prolonged EEN protocols due to possible hypervitaminosis-related toxicity.

Temporal change of potential toxic element contamination, ecological and toxicological risk in holocene in Southern Black Sea coasts (Türkiye)

This study was carried out to evaluate the temporal variation of the potential toxic element concentration and ecological risk level during the Holocene along the Southern Black Sea coasts. Ecological and ecotoxicological indices such as enrichment factor (EF), modified ecological risk index (mRI), modified potential ecological risk index (mPER) and toxic risk index (TRI) were used in the study. Anthropogenic effects were determined to be more dominant in the western and middle parts of the Southern Black Sea Region. As, Cu, Pb, Zn, Cd, Hg, Ni enrichments were observed in the last 200 – 300 years and the potential risk index values related to them increased. Source of enrichment detected in the cores was found to be related to the volcanic activities that occurred in different geological periods. It was determined that the increases in PTE concentration observed specifically in the middle parts of the cores coincided with the dates of the volcanic activities observed in Anatolia.

Mandatory fortification of rice in the public distribution system in India: An ethics perspective.

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

Molecular interaction between cypermethrin and myoglobin: Spectroscopy and molecular dynamics simulation analysis

Pesticides are essential agricultural chemicals to kill harmful organisms that have been utilized a lot in recent years, but their excessive use has become a great menace to mankind's health. In this study, the effect of cypermethrin (CYP) on myoglobin (Mb) was determined to evaluate the toxicity of insecticides at the protein level using molecular modeling, steady-state fluorescence, ultraviolet–visible (UV–Vis), and FTIR. The Fluorescence spectroscopy displayed that the Mb fluorescence quenched by CYP was the outcome of CYP-Mb composite production. Effective quenching constants (Kq) parameters at three different temperatures were calculated using the modified Stern-Volmer equation to be 1.81 × 1012, 5.16 × 1012, and 6.69 × 1012 M−1S−1, respectively. According to calculations, the enthalpy variation (ΔH°) and entropy alteration (ΔS°) were 168.11 kJ mol−1 and 610.51 J.mol−1K−1, respectively, showing that hydrophobic bonds were the main intermolecular power stabilizing the complex. FTIR spectroscopy demonstrated that CYP could alter Mb's global and local conformation, showing its potential toxicity and the structural harm it could inflict. The findings provided important information about the potential toxicity risk of CYP to human health.

Exploring pisciculture potentiality in Samdihi OCP: A comparative study on trace elements, potentially toxic metals and basic nutritive components of two edible cultured fish species of Samdihi OCP, Paschim Bardhaman, West Bengal, India

Opencast coal mining results into formation of huge pit like void locally called khadan which eventually being filled with water serves as a reservoir of aquatic resources. Present study intends to explore the pisciculture potentiality in one abandoned Samdihi opencast coal pit using two economically important edible fish species, viz. Cirrhinus mrigala (mrigal) and Oreochromis niloticus (tilapia). Analysis of trace elements of fish samples were done by using energy-dispersive X-Ray fluorescence spectrometry, dominant potentially toxic metals of water and fish samples were done using atomic absorption spectroscopy, and basic nutritional evaluation through AOAC FAM (2012) and Lowry et al. (1951) protocols. The comparative analysis of trace elements, viz., sodium and potassium revealed that the fish from culture pond had slightly elevated concentrations compared to opencast coal pit bred fish and they ranged between 1116.54±1.54 and 3791.01±1.35 mg/kg and 5321.96±1.11 and 6797.96±2.78 mg/kg for sodium and potassium respectively. On the other hand, the comparative values of calcium and chloride revealed similar trends, where the opencast coal pit bred fish had higher concentrations (6658.46±2.03 to 9767.91±1.10 mg/kg for calcium and 3266.55±1.08 to 4238.54±1.71 mg/kg for chloride respectively) than fish from culture pond. Analysis of potentially toxic metals viz., cadmium, arsenic, lead and nickel of fish from opencast coal pit and culture pond revealed values within the standard FSSAI limit, where, cadmium concentration in mrigal and tilapia from opencast coal pit were much lower (0.25±0.02 and 0.24±0.02 mg/kg respectively) than fish from culture pond and similar trends were followed by arsenic, lead and nickel. The comparative study on nutritive components of fish from opencast coal pit and culture pond revealed that the total protein content, total carbohydrate and total fat content were within 77.20±0.25 and 85.82±0.40 mg/g, 1.75±0.02 to 4.14±0.15% and 14.42±0.34 and 18.51±0.42 mg/g respectively, where in most of the cases the opencast coal pit bred fish were found having a little higher values. Results revealed that there is no significant difference in comparing the macronutrients like sodium, calcium, potassium and chloride in fish from opencast coal pit and culture pond. Whereas, average values of potentially toxic metals (cadmium, arsenic, lead and nickel) concentration in opencast coal pit and culture pond were within the safe limits as per FSSAI, as well as lower values of target hazard quotient (THQ&lt;1) predicting no potential risk of metal toxicity for human. Also, both the opencast coal pit and control pond bred fish maintained a good status in respect to protein, carbohydrate and fat content. In terms of estimated daily intake, estimated fish nutritional index, basic nutritional profiling and macronutrients study, the fish cultured in opencast coal pit showed relatively higher values than that of fish from culture pond. Thus, the current investigation features the intense potential of sustainable pisciculture in Samdihi abandoned opencast coal pit directing the sustainable development of socio-economy of local community along with environmental resource reclamation.

Assessment of possible potential toxicity risks in albino mice exposed to amine coated silver nanoparticles

Nanoparticles have a wide range of physiochemical properties that can harm many organs, tissues, enzymatic and hormonal activities. Throughout the world, silver nanoparticles (AgNPs) are frequently used in consumer products. The aim of the current study was to synthesize the AgNPs and to investigate their impact on hormones, antioxidant enzymatic activities, and histopathology of the liver of albino mice. The precursor salt silver nitrate and the reducing and capping agent triethylamine were used to synthesize silver nanoparticles. SEM analysis indicated particles ranged between 10–20 nm. The EDX analysis indicated distinct peaks, which illuminated the crystalline, spherical, and face-centred cubic structure of the silver particles being analyzed. Further, the albino model showed that increasing the concentration of AgNPs increased the level of plasma cortisol, T3 and T4. Catalase (CAT), Superoxide Dismutase (SOD), and Glutathione S-Transferase (GST) activities increased at 5 mg/kg but decreased dramatically at 50 mg/kg, whereas Glutathione (GSH) activities and lipid peroxidation (LPO) levels increased with increasing AgNPs concentration. Furthermore, AgNPs caused neutrophilic and lymphocytic infiltration, central vein damage, and hemorrhage in albino mouse liver at low concentrations (5 mg/kg). High concentrations of AgNPs (50 mg/kg) caused the formation of pknotic nuclei, pyknosis, apoptosis, and vacuolation. The study concluded that AgNPs have dose-dependent toxicity that alters stress hormones, T3 and T4, antioxidant enzymatic activities, and produces some histopathological alterations.

Long-acting dolutegravir formulations prevent neurodevelopmental impairments in a mouse model.

The World Health Organization has recommended dolutegravir (DTG) as a preferred first-line treatment for treatment naive and experienced people living with human immunodeficiency virus type one (PLWHIV). Based on these recommendations 15 million PLWHIV worldwide are expected to be treated with DTG regimens on or before 2025. This includes pregnant women. Current widespread use of DTG is linked to the drug's high potency, barrier to resistance, and cost-effectiveness. Despite such benefits, potential risks of DTG-linked fetal neurodevelopmental toxicity remain a concern. To this end, novel formulation strategies are urgently needed in order to maximize DTG's therapeutic potentials while limiting adverse events. In regard to potential maternal fetal toxicities, we hypothesized that injectable long-acting nanoformulated DTG (NDTG) could provide improved safety by reducing drug fetal exposures compared to orally administered native drug. To test this notion, we treated pregnant C3H/HeJ mice with daily oral native DTG at a human equivalent dosage (5mg/kg; n = 6) or vehicle (control; n = 8). These were compared against pregnant mice injected with intramuscular (IM) NDTG formulations given at 45 (n = 3) or 25 (n = 4) mg/kg at one or two doses, respectively. Treatment began at gestation day (GD) 0.5. Magnetic resonance imaging scanning of live dams at GD 17.5 was performed to obtain T1 maps of the embryo brain to assess T1 relaxation times of drug-induced oxidative stress. Significantly lower T1 values were noted in daily oral native DTG-treated mice, whereas comparative T1 values were noted between control and NDTG-treated mice. This data reflected prevention of DTG-induced oxidative stress when delivered as NDTG. Proteomic profiling of embryo brain tissues harvested at GD 17.5 demonstrated reductions in oxidative stress, mitochondrial impairments, and amelioration of impaired neurogenesis and synaptogenesis in NDTG-treated mice. Pharmacokinetic (PK) tests determined that both daily oral native DTG and parenteral NDTG achieved clinically equivalent therapeutic plasma DTG levels in dams (4,000-6,500ng/mL). Importantly, NDTG led to five-fold lower DTG concentrations in embryo brain tissues compared to daily oral administration. Altogether, our preliminary work suggests that long-acting drug delivery can limit DTG-linked neurodevelopmental deficits.

Evaluation of a Microphysiological Human Placental Barrier Model for Studying Placental Drug Transfer

Understanding drug transport across the placental barrier is important for assessing the potential fetal drug toxicity and birth defect risks. Current in vivo and in vitro models have structural and functional limitations in evaluating placental drug transfer and toxicity. Microphysiological systems (MPSs) offer more accurate and relevant physiological models of human tissues and organs on a miniature scale for drug development and toxicology testing. MPSs for the placental barrier have been recently explored to study placental drug transfer. We utilized a multilayered hydrogel membrane-based microphysiological model composed of human placental epithelial and endothelial cells to replicate the key structure and function of the human placental barrier. A macroscale human placental barrier model was created using a transwell to compare the results with the microphysiological model. Placental barrier models were characterized by assessing monolayer formation, intercellular junctions, barrier permeability, and their structural integrity. Three small molecule drugs (glyburide, rifaximin, and caffeine) that are prescribed or taken during pregnancy were studied for their placental transfer. The results showed that all three drugs crossed the placental barrier, with transfer rates in the order: glyburide (molecular weight, MW = 494Da) < rifaximin (MW = 785.9Da) < caffeine (MW = 194.19Da). Using non-compartmental analysis, we estimated human pharmacokinetic characteristics based on in vitro data from both MPS and transwell models. While further research is needed, our findings suggest that MPS holds potential as an in vitro tool for studying placental drug transfer and predicting fetal exposure, offering insights into pharmacokinetics.