Toxic Levels Research Articles

Treatment of produced water from the Permian Basin: Chemical and toxicological characterization of the effluent from a pilot-scale low-temperature distillation system

Thermal distillation presents a promising solution to achieve the beneficial reuse of hypersaline-produced water (PW). This study evaluated the performance of a novel pilot-scale low-temperature thermal distillation system treating PW from the Permian Basin and studied the suitability of the effluent for surface discharge applications. The robustness of the system was evaluated by monitoring over 16 key parameters during continuous operation. Water quality was assessed using a targeted chemical scheme and whole effluent toxicity (WET) tests with model organisms from four trophic levels. The system showed a robust performance during the operation and effectively reduced salinity (>99%), major ions (95–99%), heavy metals (60–100%), ammonia (93%), and organics (43–60%) in feed PW. The WET assessment showed adverse effects on the organisms across multiple trophic levels, involving algae, invertebrates, fish, and bacteria. Comprehensive chemical characterization identified 14 constituents listed as priority pollutants in the distillate, including volatile and semi-volatile organic compounds, metals, and nitrogenous compounds. This study identified 5 constituents at potentially toxic levels for the organisms tested, providing insight into additional polishing steps that may be coupled with distillation to achieve non-toxic effluents suitable for discharge. This study serves as a critical resource for future risk-based research, informs risk assessment efforts, and guides the development of treatment strategies for the beneficial reuse of hypersaline PW.

Trace element distribution, sources, toxicity risk characteristics associated with lacustrine groundwater discharge in boreal lakes: Implications for the eco-environmental security in the Yellow River Basin, China

Although the pollution of trace elements has been extensively studied, there is still a lack of comprehensive understanding regarding accumulation of these elements in lake ecosystems within the Yellow River basin, specifically the effects of lacustrine groundwater discharge (LGD) on trace elements. This study investigated the distribution, sources, and toxicity risks associated with 20 target trace elements (i.e., Li, Sc, Ti, V, Mn, Cr, Co, Ni, Cu, Zn, Rb, Y, Mo, Sb, Ba, W, Tl, Pb, U and Sr) in lake water (LW), groundwater (GW), and river water (RW) influenced by the LGD process in lake Ulansuhai and lake Daihai. The natural source is the primary contributor of trace elements in both LW and GW within the two lake basins, while industrial discharge plays a secondary role. The average LGD fluxes in lake Ulansuhai and Daihai basins were 6.39 × 105 m3/d and 1.07 × 105 m3/d, respectively. Additionally, the trace element fluxes from LGD in lake Ulansuhai (mean of 106,659.37 g/d) exceeded those observed in lake Daihai (mean of 3236.57 g/d). The overall toxicity risk was found to be higher in lake Ulansuhai (LW (17.36) > RW (16.81) > GW (12.76)) compared to lake Daihai (GW (10.43) > LW (9.10) > RW (4.63)). As well as the toxicity levels of trace elements in lake Ulansuhai were elevated compared to Daihai, which can be attributed to the influenced of ion compositions and water nutrients. Among them, Ca2+, Mg2+, and SO42+ were identified as key ions impacting the toxicity of trace elements in lake Ulansuhai. These findings provide crucial insights for targeted monitoring and mitigation of trace element pollution in the Yellow River basin’s lake ecosystems.

Evaluating the behavior and environmental risks of carbamazepine and its metabolites in soil aquifer treatment: Insights from deconjugation dynamics and toxicity assessment

The presence of pharmaceuticals in the environment has been a growing concern. Recent studies highlight the ecological risks of pharmaceuticals, but most risk assessments focus on the parent drug, neglecting metabolites. This study examines the behavior and environmental risks of carbamazepine (CBZ) and its metabolites in soil aquifer treatment (SAT) for wastewater reclamation. Findings indicate that CBZ metabolites' total concentration exceeds that of CBZ. Notably, carbamazepine-N-glucuronide (CBZ-N-Glu) concentration decreased from 48.12 ng/L to undetectable levels during SAT, while CBZ concentration increased from 64.87 to 95 ng/L, suggesting possible deconjugation of CBZ-N-Glu. Batch and column experiments confirmed the hypothesis, showing a gradual disappearance of CBZ-Glu and a corresponding rise in CBZ concentration when CBZ-N-Glu was spiked into a recirculated SAT system. Quantitative structure-activity relationships (QSAR) analysis revealed that CBZ exhibits higher acute and chronic toxicity, with metabolites showing varying levels of developmental toxicity. The study also evaluates the persistence, mobility, and toxicity (PMT) characteristics of CBZ and its metabolites, highlighting CBZ-N-Glu's particularly adverse PMT characteristics compared to CBZ. In summary, the residual pharmaceuticals in the reclaimed water process should be evaluated systematically, considering both the parent compounds and their metabolites.

MoS2 coupled with ball milling co-modified sludge biochar to efficiently activate peroxymonosulfate for neonicotinoids degradation: Dominant roles of SO4•-, 1O2 and surface-bound radicals

An efficient catalyst of molybdenum disulfide (MoS2) coupled with ball milling modified sludge biochar (BMSBC) was prepared to efficiently activate peroxymonosulfate (PMS) for neonicotinoids elimination. As expected, 95.1% of imidacloprid (IMI) was degraded by PMS/BMSBC system within 60 min and it was accompanied by the outstanding mineralization rate of 71.9%. The superior pore structures, rich defects, oxygen-containing functional groups and grafted MoS2 on BMSBC offered excellent activation performance for PMS. The influencing factor experiments demonstrated that PMS/BMSBC system performed high anti-interference to wide pH range and background constituents (e.g., inorganic ions and humic acid). Quenching experiments and electron paramagnetic resonance analysis revealed that SO4•−, 1O2, and surface-bound radicals played critical roles in IMI degradation. Electron donors on biochar activated PMS, producing surface radicals. The lone pair electrons within the Lewis basic site of C=O on BMSBC enhanced PMS decomposition by facilitating the cleavage of the -O-O- bond in PMS to release 1O2. The activation process of PMS by MoS2 accelerated the oxidation of Mo (IV) to Mo (VI) to generate SO4•−. Based on the transformed products (TPs), four degradation pathways of IMI in PMS/BMSBC system were suggested, and all TPs toxicity levels were lower than that of IMI by ECOSAR analysis. Additionally, BMSBC exhibited outstanding sustainable catalytic activity towards PMS activation with the well accepted degradation rate of 71.3% for IMI even after five reuse cycles. PMS/BMSBC system also exhibited satisfactory degradation rates (>71.8%) for IMI in various real waters (e.g., sewage effluent and livestock wastewater). Furthermore, PMS/BMSBC system also offered a favorable broad-spectrum elimination performance for other typical neonicotinoids (e.g., thiamethoxam, clothianidin, thiacloprid) with the degradation rates over 98%. This study has developed a desirable neonicotinoids purification technology in view of its high degradation/mineralization rate, outstanding detoxification performance, satisfied anti-interference to ambient conditions and sustainable sludge management.

Biomedical Perspectives of Citronellal: Biological Activities, Toxicological Profile and Molecular Mechanisms.

Citronellal (CIT) also known as rhodinal, is a naturally occurring monoterpenoid aldehyde distinctly found in the distilled oils of Cymbopogon species. It is traditionally used in air freshener, cleaner, floor polishing, deodorants, deodorizer, fragrance component, moisturizing hand/body lotion, perfumes, and adhesives due to its lemon characteristic fragrance and therapeutic benefits. This study aimed to summarize the pharmacological activities and underlying mechanisms of CIT against different diseases, as well as its toxicological profile. The data was collected from various reliable and authentic literatures by searching different academic search engines, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. The findings imply that CIT possesses several pharmacological effects in various preclinical and pharmacological experimental systems. The results indicated that CIT demonstrated antioxidant, anti-inflammatory, antibacterial, antifungal, anthelminthic, and anticancer effects with beneficial effects in neurological and cardiovascular diseases. Our findings also indicated the toxic level of the phytochemical. In conclusion, it has been proposed that CIT has the capability to serve as a hopeful therapeutic agent, so further extensive clinical research is necessary to develop it as a reliable drug.

Leveraging new approach methodologies: ecotoxicological modelling of endocrine disrupting chemicals to Danio rerio through machine learning and toxicity studies

New approach methodologies (NAMs) offer information tailored to the intended application while reducing the use of animals. NAMs aim to develop quantitative structure-activity relationship (QSAR) and quantitive-Read-Across structure-activity relationship (q-RASAR) models to predict and categorize the acute toxicity of known and unknown endocrine-disrupting chemicals (EDCs) against zebrafish. EDCs are a diverse group of toxic substances that disrupt the endocrine system of humans and animals. The q-RASAR model was constructed and verified using validation metrics (R 2 = 0.886 and Q 2 = 0.814) which found to be more reliable model compare to QSAR model. The substructure fingerprint was well-fitted for the classification model and it was validated using 10-fold average accuracy (Q = 86.88%), specificity (Sp = 88.89%), Matthew’s correlation curve (MCC = 0.621) and receiver operating characteristics (ROC = 0.828). The dataset of unknown substances revealed that phenolphthalein (Php) exhibited a significant level of toxicity based on q-RASAR model. The docking and simulation study indicated that the computationally derived important features successfully bound to the target zebrafish sex hormone binding globulin (zfSHBG). The experimental LC50 value of 0.790 mg L−1 was very close to the predicted value of 0.763 mg L−1, which provides high confidence to the developed model.

3D X-ray Tomography Analysis of Mg–Si–Zn Alloys for Biomedical Applications: Elucidating the Morphology of the MgZn Phase

Temporary metal implants, made from materials like titanium (Ti) or stainless steel, can cause metabolic issues, raise toxicity levels within the body, and negatively impact the patient’s long-term health. This necessitates a subsequent operation to extract these implants once the healing process is complete or when they are outgrown by the patient. In contrast, medical devices fabricated from absorbable alloys have the advantage of being biodegradable, allowing them to be naturally absorbed by the body once they have fulfilled their role in facilitating tissue healing. Among the various absorbable alloy systems studied, magnesium (Mg) alloys stand out due to their biocompatibility, mechanical properties, and corrosion behavior. The existing literature on absorbable Mg alloys highlights the effectiveness of silicon (Si) and zinc (Zn) additions in improving mechanical properties and controlling corrosion susceptibility; however, there is a lack of comprehensive quantitative morphological analysis of the intermetallic phases within these alloy systems. The quantification of the complex morphology of intermetallic particles is a challenging task and has significant implications for the micromechanical properties of the alloys. This study, therefore, aims to introduce a robust set of morphometric parameters for evaluating the morphology of intermetallic phases within two as-cast Mg alloys with Si and Zn additions. X-ray Computed Tomography (XCT) was used to capture the 3D tomographic data of the alloys, and a novel pair of morphological parameters (ratio of convex hull to particle volume and convex hull sphericity) was applied to the 3D tomographic data to assess the MgZn phase formed in the two alloys. In addition to the impact of composition, the effect of solidification rate on the morphological parameters was also studied. Furthermore, Scanning Electron Microscopy (SEM) and Energy-Dispersive Spectroscopy (EDS) were employed to gather detailed 2D microstructural and compositional information on the intermetallics. The comprehensive characterization reveals that the morphological complexity and size distribution of the MgZn phase are influenced by both compositional changes and the solidification rate. However, the change in MgZn intermetallic particle morphology with size was found to follow a predictable trend, which was relatively agnostic of the chosen casting conditions.

Assessing the risk of consuming fish from Kanyakumari (Tamil Nadu), India: An evaluative study on bioaccumulated heavy metals in different fish species using inductively coupled plasma mass spectrometry

Environmental pollutants which are developing an alarming situation in the contemporary world captured attention in the present research. When it comes to food safety and security concerns it becomes an important field to be studied rigorously as food contributes majorly to human and animal health. The pollution of aquatic ecosystems by heavy metals (HMs) ultimately results in adverse effect on the food chain, which is covered in the current study. Fish is considered to be one of the main components of a balanced diet plate due to its high-quality protein, which sets it apart from other dietary sources. On the other hand, it is also susceptible to the absorption and bioaccumulation of HMs at toxic levels. In our study, we have considered three different species (Nemipterus japonicus, Oreochromis mossambicus, and Lates calcarifer) of fish collected from Kanyakumari, Tamil Nadu (India). Three organs namely liver, gill, and muscle were taken into consideration for the HM profiling using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The Arsenic (As), Cadmium (Cd), Chromium (Cr), Mercury (Hg) and Lead (Pb) were found to be in varied concentrations ranging from 0.1 to 1.13, 0.89–1.45, 9.95–30.66, 0.14–1.62, and 24.69–189.5 µg/kg respectively, in the studied organs of fish. Carcinogenic and noncarcinogenic risk assessments were also done indicating a notable level of Pb and Cr in selected fish species. The Hazard Index (HI) for Oreochromis mossambicus was >1 for adults and children, indicating future possibility of probable health hazards on daily consumption of these fish. In Oreochromis mossambicus, the cancer risk (CR) values for Cr and As were significantly high, particularly for children, indicating a possible occurrence of acute health risk as it exceeded the threshold of 1 × 10−3 and suggesting a significant concern. Though consumption of fish on daily basis in such significant quantity is practically impossible both for adult and children, rendering these species safe.

Curcumin-Dichloroacetate Hybrid Molecule as an Antitumor Oral Drug against Multidrug-Resistant Advanced Bladder Cancers.

Tumor cells produce excessive reactive oxygen species (ROS) but cannot detoxify ROS if they are due to an external agent. An agent that produces toxic levels of ROS, specifically in tumor cells, could be an effective anticancer drug. CMC-2 is a molecular hybrid of the bioactive polyphenol curcumin conjugated to dichloroacetate (DCA) via a glycine bridge. The CMC-2 was tested for its cytotoxic antitumor activities and killed both naïve and multidrug-resistant (MDR) bladder cancer (BCa) cells with equal potency (<1.0 µM); CMC-2 was about 10-15 folds more potent than curcumin or DCA. Growth of human BCa xenograft in mice was reduced by >50% by oral gavage of 50 mg/kg of CMC-2 without recognizable systemic toxicity. Doses that used curcumin or DCA showed minimum antitumor effects. In vitro, the toxicity of CMC-2 in both naïve and MDR cells depended on increased intracellular ROS in tumor cells but not in normal cells at comparable doses. Increased ROS caused the permeabilization of mitochondria and induced apoptosis. Further, adding N-Acetyl cysteine (NAC), a hydroxyl radical scavenger, abolished excessive ROS production and CMC-2's cytotoxicity. The lack of systemic toxicity, equal potency against chemotherapy -naïve and resistant tumors, and oral bioavailability establish the potential of CMC-2 as a potent drug against bladder cancers.

Phytochemical Analysis, Antioxidant Properties, Anti-nutrient Contents and Antimicrobial Study of Aqueous Extract of Morinda lucinda, Solanum erianthun, and Dryopteris expansa

The emergence of antibiotic-resistant microorganisms poses a significant challenge in clinical practice by complicating treatment options for infections. Exploring natural products as alternative drugs presents a promising approach to addressing these issues. Medicinal plants, acknowledged by the World Health Organization (WHO) as a preferred and safest source of various medicines, have gained considerable attention. Therefore, this study was conducted to investigate the phytochemical constituents, antioxidant properties, anti-nutrient content, and antimicrobial activities of Morinda lucinda, Solanum erianthun, and Dryopteris expansa The phytochemical analysis indicates that while flavonoids, saponins, and reducing sugars are common across the studied plants, Morinda lucida and Dryopteris expansa exhibit higher levels of saponins and the present of alkaloids, suggesting potential unique medicinal properties. The antimicrobial study revealed that the aqueous leaf extract of Morinda lucida made Streptococcus pyogenes and Staphylococcus aureus susceptible to its effects, while Dryopteris expansa made only Streptococcus pyogenes susceptible and the aqueous leaf extract of Solanum erianthum made the fungal species Penicillium chrysogenum susceptible to its action. All the studied plants demonstrated very strong antioxidant activity. The anti-nutrient analysis showed that Morinda lucida had the lowest cyanide content at 5.50 mg/100 g, while Solanum erianthum had the highest cyanide content at 6.89 mg/100 g. Dryopteris expansa exhibited the lowest levels of oxalates and phytates, with values of 0.28 mg and 0.20%, respectively. The results of this study demonstrate that each of these plants possesses significant potential as antimicrobial agents and antioxidants, with low toxicity levels. Consequently, they hold promise for medicinal applications and drug development.

Mitophagy in acute central nervous system injuries: regulatory mechanisms and therapeutic potentials.

Acute central nervous system injuries, including ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, and spinal cord injury, are a major global health challenge. Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities. Mitochondria are susceptible to damage after acute central nervous system injury, and this leads to the release of toxic levels of reactive oxygen species, which induce cell death. Mitophagy, a selective form of autophagy, is crucial in eliminating redundant or damaged mitochondria during these events. Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries. In this review, we provide a comprehensive overview of the process, classification, and related mechanisms of mitophagy. We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy. In the final section of this review, we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

Application of Nanotechnology and Phytochemicals in Anticancer Therapy.

Cancer is well recognized as a leading cause of mortality. Although surgery tends to be the primary treatment option for many solid cancers, cancer surgery is still a risk factor for metastatic diseases and recurrence. For this reason, a variety of medications has been adopted for the postsurgical care of patients with cancer. However, conventional medicines have shown major challenges such as drug resistance, a high level of drug toxicity, and different drug responses, due to tumor heterogeneity. Nanotechnology-based therapeutic formulations could effectively overcome the challenges faced by conventional treatment methods. In particular, the combined use of nanomedicine with natural phytochemicals can enhance tumor targeting and increase the efficacy of anticancer agents with better solubility and bioavailability and reduced side effects. However, there is limited evidence in relation to the application of phytochemicals in cancer treatment, particularly focusing on nanotechnology. Therefore, in this review, first, we introduce the drug carriers used in advanced nanotechnology and their strengths and limitations. Second, we provide an update on well-studied nanotechnology-based anticancer therapies related to the carcinogenesis process, including signaling pathways related to transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), Wnt, poly(ADP-ribose) polymerase (PARP), Notch, and Hedgehog (HH). Third, we introduce approved nanomedicines currently available for anticancer therapy. Fourth, we discuss the potential roles of natural phytochemicals as anticancer drugs. Fifth, we also discuss the synergistic effect of nanocarriers and phytochemicals in anticancer therapy.

Determination of the occurrence of and exposure to bisphenol A and its analogues in carbonated beverages and canned tuna using liquid chromatography − tandem mass spectrometry

Bisphenol A (BPA), a known endocrine disruptor, is commonly used in food containers and packaging. Recently, alternatives such as bisphenol AF (BPAF), bisphenol B (BPB), and bisphenol E (BPE) have been introduced to replace BPA. However, these substitutes have been reported to exhibit toxicity levels similar to BPA. In this study, we developed and validated a method for the analysis of trace bisphenols (BPA, BPAF, BPB, and BPE) in food using immunoaffinity column (IAC) clean-up. The method demonstrated satisfactory accuracy and precision. We applied this validated method to analyze 56 carbonated beverage samples and 30 canned tuna samples. In the carbonated beverages, average concentrations of BPA and BPAF were 0.4 and 0.2 μg kg−1, respectively. In canned tuna, BPA and BPAF were found at average concentrations of 22.2 and 0.7 μg kg−1, respectively, while BPB and BPE were not detected in any samples. Estimated exposure levels ranged from 0.13 to 0.18 ng kg bw−1 day−1 in the general population and from 205.2 to 232.0 ng kg bw−1 day−1 among consumers. The commercial IAC-based analytical method used in this study can contribute to the safety management of BPA, BPAF, BPB, and BPE.

Доклиническая оценка безопасности нового лекарственного препарата для собак и кошек Supramil® эмульсия

This article presents the results of a toxicological evaluation of a new drug for veterinary use, Supramil® emulsion based on R-praziquantel and milbemycin oxime. The drug is intended for the treatment of intestinal nematodes and cestodes, mixed infestations in cats and dogs, as well as for the prevention of dirofilariasis. A single intragastric administration of the drug in doses of a toxic level for rats and mice did not cause toxicosis or death in laboratory animals, on the basis of which the average lethal dose (LD50) for the drug Supramil® emulsion could not be determined. As a result of the assessment of subchronic oral toxicity, it was established that the tested doses of the drug when administered daily to white outbred rats for 14 days are ineffective. An assessment of the ability of the drug, when introduced into the body, to cause a state of hypersensitivity did not reveal an allergenic effect. Thus, the results of this study allow us to conclude that the Supramil® emulsion does not have toxic or allergenic properties and is well tolerated by laboratory animals.

Interplay of toxic metal levels and endoplasmic reticulum stress gene profile in type 2 diabetes mellitus

The increasing global prevalence of type 2 diabetes mellitus (T2DM) necessitates investigating its complex etiology. This study aimed to explore the relationship between exposure to toxic metals, expression of endoplasmic reticulum stress response (ERSR) genes, and various biochemical parameters, including glycated hemoglobin (HbA1c), insulin resistance (HOMA-IR)/sensitivity (QUICKI), lipid profile, and estimated glomerular filtration rate (eGFR) in T2DM patients. T2DM patients and control subjects were matched for age, gender, and lifestyle factors. Biochemical parameters, toxic metal levels, and ERSR gene expression were analyzed using inductively coupled plasma mass spectrometry (ICPMS) and quantitative reverse transcription PCR (qRT-PCR), respectively. T2DM patients exhibit dysregulated lipid profiles and significantly higher fasting blood sugar (FBS), HbA1c, and insulin levels (all p < 0.0001). The insulin sensitivity was lower in T2DM patients (0.32 ± 0.09) than in the control group (0.35 ± 0.02, p = 0.02). Insulin resistance was significantly higher in the T2DM group (5.38 ± 3.15) than in the control group (1.98 ± 0.86, p = 0.0001). Nickel (4.75 ± 2.45 ppb, p < 0.0001) and arsenic (1.85 ± 1.78 ppb, p < 0.0001) levels were significantly elevated in T2DM patients. There was significant upregulation of ER stress genes: GRP78, CHOP, IRE1, ATF4, ATF6, and XBP1 (all p < 0.0001), while PERK was significantly down regulated (0.68-fold, p < 0.0001). Nickel levels were positively correlated with HOMA-IR (r = 0.49, p < 0.0001) and HbA1c (r = 0.35, p = 0.002). Arsenic levels were correlated with insulin (r = 0.34, p < 0.0001), insulin resistance (r = 0.51,p < 0.0001), HbA1c (r = 0.53, p < 0.0001), Arsenic levels (β = 0.37, p < 0.001), XBP1 (β = 0.36, p < 0.0001) independently associated with HbA1c.This study has revealed a significant association between arsenic exposure and the upregulation of XBP1 at the onset of T2DM. The overexpression of XBP1 and high levels of arsenic were independently associated with HbA1c and insulin resistance.

Polyfluoroalkyl-Substances Detection in Junk Food Packing Materials Using Various Analytical Methods: A Review.

Per- and polyfluoroalkyl substances (PFAS) are unseen, dangerous organic compounds that can cause major health disorders. PFASs have been categorized as persistent, bioaccumulative, and toxic (PBT). This review provides knowledge about the PFASs present in junk food packaging materials, which can migrate into the food. Different types of samples were analyzed using the analytical methods. The most preferred method of extraction is ultrasonic-assisted extraction (UAE). It summarizes the analytical approaches of PFASs. The results of numerous studies show that perfluorooctanoic acid is the most often detected compound with high concentrations. The European Food Safety Authority (EFSA) announced that the tolerable weekly intake (TWI) of PFASs is 4.4 ng/kg. The US Environmental Protection Agency (EPA) has announced the limit for perfluorobutane sulfonic acid due to its toxicity level. These compounds have potential effects on both people's health and the biosphere. PFAS usage has to stop in the industries for a better future.

Medicinal Plants as Effective Antiviral Agents and Their Potential Benefits

This paper explores a diverse field of medicinal plants as potential antiviral agents, and delves into utilization of plant medicine for combating viral infections, emphasizing recent surge in research on natural products from plants as antiviral agents. Specific plant-derived compounds, like phyllanthin and iscador, have been proven to exhibit antiviral properties with great potential for pharmaceutical development. Mechanisms of antiviral action by phytochemicals that are present in medicinal plants, including direct viral inhibition, degradation of viral capsid, and immunomodulation were identified, and a combination therapy of medicinal plants with conventional antiviral drugs were explored. Efficacy of medicinal plants as antiviral agents was critically assessed and revealed that the complexity and variability of herbal formulations, and safety concerns regarding toxicity levels, pose challenges in drug development. However, research on medicinal plants is often hindered by limited understanding of phytochemical mechanisms, the complexity and variability of herbal formulations, and safety concerns regarding toxicity and interactions with other medications. The way forward in harnessing full potential of medicinal plants as antiviral agents underscores the need for further research into developing models that seek to enhance the selectivity of plant extracts in order to minimize toxicity levels.

Evaluation of Hydrazide-hydrazone and 4-thiazolidinone Derivatives of Etodolac as Potential Anticancer Agents in Leukemia Cells

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used for their anti-inflammatory and analgesic properties, have also been found to prevent cancer. (±)(R,S) Etodolac is an NSAID that belongs to the class of cyclooxygenase-2 inhibitors. Various derivatives of etodolac are synthesized to boost its anti-proliferative action and lessen its potential negative effects. In our earlier studies, some novel derivatives of etodolac exhibited stronger cytotoxic effects on prostate cell lines and had similar effects on leukemia cells in pre-screening experiments. Objective: Using the K562 leukemia cell line as a model, we sought to investigate the anti-cancer properties of a hydrazide-hydrozone derivative (SGK-205) and a 4-thiazolidinone derivative of etodolac (SGK-216). Materials and Methods: In the current investigation, SGK-205 and SGK-216 compounds were administered to K562 cells for 24 and 48 hours at concentrations of 10, 25, 50, 75 and 100 μM. Cell viability was assessed using the MTT test, and apoptosis by Annexin V-PI staining and mitochondrial membrane potential assays, together with mRNA expressions of apoptotic proteins. The levels of the proteins, HER2 and COX2, were also examined to evaluate COX2 inhibitory capacity. Results: In K562 cells, there was a definite dose-dependent response to SGK-205 and SGK-216 compounds. Results from MTT viability tests, together with mitochondrial membrane potential measurements and Annexin V-PI staining, revealed that SGK-216 and SGK-205 significantly outperformed etodolac in terms of their apoptotic and anti-proliferative activities. The concentration range of 10-20 M for both chemicals was sufficient to start biological responses. Apoptosis was also investigated through the expressions of pro- and anti-apoptotic proteins. Additionally, gene expression research demonstrated SGK-205 to be a beneficial substitute to etodolac in lowering COX-2 and human epidermal growth factor receptor-2 (HER2) expression. Conclusion: Our data indicated both derivatives to have higher anti-proliferative and apoptotic effects compared to etodolac. An overall assessment highlighting apoptotic induction potential, acceptable toxicity levels, a consistent dose-response relationship, and COX2 inhibitory actions, in particular, indicated SGK-205 as a viable novel therapeutic.

Histology of skin, gill, liver, and kidney of tilapia Oreochromis niloticus exposed by azo dyes acid red 88.

Abstract Coloring is one of the main process in textile production. Using azo dyes type are the first pick of textile industries. Therefore, the disposal of dye waste containing high levels of azo can increase the toxicity level also impact the fish. Acid Red 88 is an azo type dye which provides a red color as the basic color for coloring textile products. Acid Red 88 are left behind as much as 60% of textile waste. the textile factories wastewater in Indonesia contains an average of 750 mg/L suspended solids. The aim of this study was to determine the effect of azo dye Acid Red 88 exposure to tilapia by the histology of its skin, gills, liver and kidneys. The method used was experimental method with 4 different exposure concentrations of Acid Red 88 P0 (0 mg/L), P1 (75 mg/L), P2 (150 mg/L), P3 (225 mg/L), and P4 (300 mg/L). The damage is identified on the histology of the organs and then measured using a scoring method. The results showed that several damages were found such as epithelial erosion, edema, hyperplasia, telangectasis, hemorage, fatty degeneration, congestion and necrosis.

Rapid Vacuolar Sorting of the Borate Transporter BOR1 Requires the Adaptor Protein Complex AP-4 in Arabidopsis.

Plants maintain nutrient homeostasis by controlling the activities and abundance of nutrient transporters. In Arabidopsis thaliana, the borate (B) transporter BOR1 plays a role in the efficient translocation of B under low-B conditions. BOR1 undergoes polyubiquitination in the presence of sufficient B and is then transported to the vacuole via multivesicular bodies (MVBs) to prevent B accumulation in tissues at a toxic level. A previous study indicated that BOR1 physically interacts with µ subunits of adaptor protein complexes AP-3 and AP-4, both involved in vacuolar sorting pathways. In this study, we investigated the roles of AP-3 and AP-4 subunits in BOR1 trafficking in Arabidopsis. The lack of AP-3 subunits did not affect either vacuolar sorting or polar localization of BOR1-GFP, whereas the absence of AP-4 subunits resulted in a delay in high-B-induced vacuolar sorting without affecting polar localization. Super-resolution microscopy revealed a rapid sorting of BOR1-GFP into AP-4-positive spots in the trans-Golgi network (TGN) upon high-B supply. These results indicate that AP-4 is involved in sequestration of ubiquitinated BOR1 into a TGN-specific subdomain "vacuolar-trafficking zone," and is required for efficient sorting to MVB and vacuole. Our findings elucidate the rapid vacuolar sorting process facilitated by AP-4 in plant nutrient transporters.