Toxic Effects Research Articles

In Vitro Evaluation of Anti-Parasitic Activities of Quinolone-Coumarin Hybrids Derived from Fluoroquinolones and Novobiocin Against Toxoplasma gondii.

Toxoplasmosis is caused by the parasite Toxoplasma gondii (T. gondii). In immunocompetent individuals, the infection is often asymptomatic; however, in expectant mothers and those with immune system deficiencies, complications may arise. Consequently, there is a need for new drugs that cause minimal damage to host cells. The purpose of this study was to investigate the in vitro antiparasitic efficacy of quinolone-coumarin hybrids QC1-QC12, derived from quinolone antibacterials and novobiocin, against T. gondii. The derivatives were compared with novobiocin and ciprofloxacin during testing, with pyrimethamine used as a positive control. We conducted the MTT assay to examine the anti-toxoplasmic effects of the test compounds and novobiocin. Evaluation included the infection and proliferation indices, as well as the size and number of plaques, based on the viability of both healthy and infected cells. The in vitro assays revealed that QC1, QC3, QC6, and novobiocin, with selectivity indices (SIs) of 7.27, 13.43, and 8.23, respectively, had the least toxic effect on healthy cells and the highest effect on infected cells compared to pyrimethamine (SI = 3.05). Compared to pyrimethamine, QC1, QC3, QC6, and novobiocin Without having a significant effect on cell viability, demonstrated a significant effect on reducing in both infection index and proliferation index, in addition to reducing the quantity and dimensions of plaques ( P < 0.05). Based on our results, QC1, QC3, QC6, and novobiocin due to their significant therapeutic effects could be considered as potential new leads in the development of novel anti-Toxoplasma agents.

Improved Treatment Outcome Following the Use of a Wound Dressings in Cutaneous Leishmaniasis Lesions

Leishmaniasis, caused by Leishmania parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development of better alternatives. Bacterial NanoCellulose (BNC), a biocompatible nanomaterial, has unique properties regarding wound healing. In a previous study, we showed that use of topical BNC + systemic MA significantly increased the cure rate of CL patients, compared to treatment with MA alone. Herein, we performed a study comparing the combination of a wound dressing (BNC or placebo) plus systemic MA versus systemic MA alone, in CL caused by Leishmania braziliensis. We show that patients treated with the combination treatment (BNC or placebo) + MA showed improved cure rates and decreased need for rescue treatment, although differences compared to controls (systemic MA alone) were not significant. However, the overall time-to-cure was significantly lower in groups treated with the combination treatment (BNC+ systemic MA or placebo + systemic MA) in comparison to controls (MA alone), indicating that the use of a wound dressing improves CL treatment outcome. Assessment of the immune response in peripheral blood showed an overall downmodulation in the inflammatory landscape and a significant decrease in the production of IL-1a (p &lt; 0.05) in patients treated with topical BNC + systemic MA. Our results show that the application of wound dressings to CL lesions can improve chemotherapy outcome in CL caused by L. braziliensis.

Kinetically Inert Platinum (II) Complexes for Improving Anticancer Therapy: Recent Developments and Road Ahead.

The search for better chemotherapeutic drugs to alleviate the deficiencies of existing platinum (Pt) drugs has picked up the pace in the millennium. There has been a disparate effort to design better and safer Pt drugs to deal with the problems of deactivation, Pt resistance and toxic side effects of clinical Pt drugs. In this review, we have discussed the potential of kinetically inert Pt complexes as an emerging class of next-generation Pt drugs. The introduction gives an overview about the development, use, mechanism of action and side-effects of clinical Pt drugs as well as the various approaches to improve some of their pharmacological properties. We then describe the impact of kinetic lability on the pharmacology of functional Pt drugs including deactivation, antitumor efficacy, toxicity and resistance. Following a brief overview of numerous pharmacological advantages that a non-functional kinetically inert Pt complex can offer; we discussed structurally different classes of kinetically inert Pt (II) complexes highlighting their unique pharmacological features.

Ameliorative Effect of Teucrium polium Extract against Nicotine Induced Liver Toxicity in Swiss Albino Mice

Background: Nicotine can be consumed in many forms, the most common of which is smoking tobacco. Tobacco smoking is a global problem that negatively affects human health. Natural plants are vital antioxidants that may antagonize the toxic effects of smoking. We designed the present study to assess the protective potential of Teucrium polium extract (TPE) on nicotine-induced liver toxicity in male mice. Methods: Twenty-four animals were allocated into four equal groups and daily treated for 21 constitutive days. Control group one received distilled water, group two orally received 100 mg/kg TPE, group three received subcutaneous injections of 2.5 mg/kg nicotine and group four received 100 mg/kg TPE orally then 2.5 mg/kg nicotine subcutaneously after one hour. Result: Nicotine exposure significantly elevated liver enzymes; alanine transaminase (ALT) and aspartate transaminase (AST). The levels of malondialdehyde (MDA) and nitric oxide (NO) were also elevated along with a reduction in glutathione reduced content (GSH), superoxide dismutase (SOD) and catalase (CAT) activity. Treatment with TPE considerably ameliorated the serum levels of liver enzymes, lowered MDA and NO levels, as well as elevated the antioxidant defense system. Also, TPE improved the histological structure and modulated apoptosis caused by nicotine. The current study proved the effectiveness of TPE as a natural antioxidant for the alleviation of nicotine-induced hepatic biochemical and histopathological alterations through attenuating oxidative stress, improving antioxidant systems and abrogating apoptosis.

Phytotoxicity and Residual Effect of Some Herbicides on three Egyptian Rice Cultivars (Oryza sativa L.)

The current study was carried out at the experimental farm of Rice Research Department, Sakha Agricultural Research Station and Central Agricultural Pesticide Laboratory, ARC, Egypt during the summer season of 2021 and 2022 to study the sensitivity of three Egyptian rice cultivars against four common herbicides and its effect on physiological and agronomic characteristics of rice as well as herbicide residues in rice seeds. The field study was laid out in split plot design with three replications. Three rice cultivars (Giza 177, Giza 179 and Sakha 108) were randomly distributed in main plots, while weed control treatments included four herbicides at recommended doses (penoxsulam 2.5% OD, bispyribac-sodium 2% SL, cyhalofop-butyl 10% EC and fenoxaprop-p-ethyl 7.5% EW) as compared to hand weeding were devoted in sub plots. The obtained results revealed that Sakha 108 as Japonica rice cultivar was resistant against tested herbicides and recorded the highest values of rice dry weight, chlorophyll content, number of panicles m-2, panicle weight and grain yield, while scored the lowest values of total phenols. On the other hand, Giza 177 as short duration Japonica rice cultivar showed the higher sensitivity against tested herbicides and achieved the lowest values of abovementioned agronomic traits and chlorophyll content. Cyhalofop-butyl as ACCase herbicide was safer on studied rice cultivars and recorded the highest values of studied agronomic characteristics for rice as well as chlorophyll content, while recorded the lowest values of total phenols during the study. On the other hand, bispyribac-sodium 2% SL resulted in more toxic effect for rice cultivars and recorded the lowest values of studied agronomic traits for rice. fenoxaprop-p-ethyl 7.5% EW achieved the lowest chlorophyll content and highest values of total phenols during the study. Giza 179 as Indica-Japonica rice cultivar appeared high sensitivity when sprayed with bispyribac-sodium and fenoxaprop-ethyl but made recovery after 12 days from herbicidal application and recorded the highest chlorophyll content, dry weight, panicles m-2 and grain yield with no significant differences between Sakha 108 rice cultivar during the study. In respect of herbicide residues in rice seeds, all tested herbicides didn’t have residues in rice seeds at 100 days after treatment. It means that tested herbicides didn’t have any residues in rice seeds.

Histidine-Rich Glycoprotein Modulates the Toxic Effects of High-Dose Polyphosphate in Mice.

Polyphosphate (polyP), a procoagulant released from platelets, activates coagulation via the contact system and modulates cardiomyocyte viability. High-dose intravenous polyP is lethal in mice, presumably because of thrombosis. Previously, we showed that HRG (histidine-rich glycoprotein) binds polyP and attenuates its procoagulant effects. In this study, we investigated the mechanisms responsible for the lethality of intravenous polyP in mice and the impact of HRG on this process. The survival of wild-type or HRG-deficient mice given intravenous synthetic or platelet-derived polyP in doses up to 50 mg/kg or saline was compared. To determine the contribution of thrombosis, the effect of FXII (factor XII) knockdown or enoxaparin on polyP-induced fibrin deposition in the lungs was examined. To assess cardiotoxicity, the ECG was continuously monitored, the levels of troponin I and the myocardial band of creatine kinase were quantified, and the viability of a cultured murine cardiomyocyte cell line exposed to polyP in the absence or presence of HRG was determined. In HRG-deficient mice, polyP was lethal at 30 mg/kg, whereas it was lethal in wild-type mice at 50 mg/kg. Although FXII knockdown or enoxaparin administration attenuated polyP-induced fibrin deposition in the lungs, neither affected mortality. PolyP induced dose-dependent ECG abnormalities, including heart block and ST-segment changes, and increased the levels of troponin and myocardial band of creatine kinase, effects that were more pronounced in HRG-deficient mice than in wild-type mice and were attenuated when HRG-deficient mice were given supplemental HRG. Consistent with its cardiotoxicity, polyP reduced the viability of cultured cardiomyocytes in a dose-dependent manner, an effect attenuated with supplemental HRG. High-dose intravenous polyP is cardiotoxic in mice, and HRG modulates this effect.

Development of Recombinant High-Density Lipoprotein Platform with Innate Adipose Tissue-Targeting Abilities for Regional Fat Reduction.

As an escalating public health issue, obesity and overweight conditions are predispositions to various diseases and are exacerbated by concurrent chronic inflammation. Nonetheless, extant antiobesity pharmaceuticals (quercetin, capsaicin, catecholamine, etc.) manifest constrained efficacy alongside systemic toxic effects. Effective therapeutic approaches that selectively target adipose tissue, thereby enhancing local energy expenditure, surmounting the limitations of prevailing antiobesity modalities are highly expected. In this context, we developed a temperature-sensitive hydrogel loaded with recombinant high-density lipoprotein (rHDL) to achieve targeted delivery of resveratrol, an adipose browning activator, to adipose tissue. rHDL exhibits self-regulation on fat cell metabolism and demonstrates natural targeting toward scavenger receptor class B type I (SR-BI), which is highly expressed by fat cells, thereby achieving a synergistic effect for the treatment of obesity. Additionally, the dispersion of rHDL@Res in temperature-sensitive hydrogels, coupled with the regulation of their degradation and drug release rate, facilitated sustainable drug release at local adipose tissues over an extended period. Following 24 days' treatment regimen, obese mice exhibited improved metabolic status, resulting in a reduction of 68.2% of their inguinal white adipose tissue (ingWAT). Specifically, rHDL@Res/gel facilitated the conversion of fatty acids to phospholipids (PA, PC), expediting fat mobilization, mitigating triglyceride accumulation, and therefore facilitating adipose tissue reduction. Furthermore, rHDL@Res/gel demonstrated efficacy in attenuating obesity-induced inflammation and fostering angiogenesis in ingWAT. Collectively, this engineered local fat reduction platform demonstrated heightened effectiveness and safety through simultaneously targeting adipocytes, promoting WAT browning, regulating lipid metabolism, and controlling inflammation, showing promise for adipose-targeted therapy.

DNMT1-targeting remodeling global DNA hypomethylation for enhanced tumor suppression and circumvented toxicity in oral squamous cell carcinoma

BackgroundThe faithful maintenance of DNA methylation homeostasis indispensably requires DNA methyltransferase 1 (DNMT1) in cancer progression. We previously identified DNMT1 as a potential candidate target for oral squamous cell carcinoma (OSCC). However, how the DNMT1- associated global DNA methylation is exploited to regulate OSCC remains unclear.MethodsThe shRNA-specific DNMT1 knockdown was employed to target DNMT1 on oral cancer cells in vitro, as was the use of DNMT1 inhibitors. A xenografted OSCC mouse model was established to determine the effect on tumor suppression. High-throughput microarrays of DNA methylation, bulk and single-cell RNA sequencing analysis, multiplex immunohistochemistry, functional sphere formation and protein immunoblotting were utilized to explore the molecular mechanism involved. Analysis of human samples revealed associations between DNMT1 expression, global DNA methylation and collaborative molecular signaling with oral malignant transformation.ResultsWe investigated DNMT1 expression boosted steadily during oral malignant transformation in human samples, and its inhibition considerably minimized the tumorigenicity in vitro and in a xenografted OSCC model. DNMT1 overexpression was accompanied by the accumulation of cancer-specific DNA hypomethylation during oral carcinogenesis; conversely, DNMT1 knockdown caused atypically extensive genome-wide DNA hypomethylation in cancer cells and xenografted tumors. This novel DNMT1-remodeled DNA hypomethylation pattern hampered the dual activation of PI3K-AKT and CDK2-Rb and inactivated GSK3β collaboratively. When treating OSCC mice, targeting DNMT1 achieved greater anticancer efficacy than the PI3K inhibitor, and reduced the toxicity of blood glucose changes caused by the PI3K inhibitor or combination of PI3K and CDK inhibitors as well as adverse insulin feedback.ConclusionsTargeting DNMT1 remodels a novel global DNA hypomethylation pattern to facilitate anticancer efficacy and minimize potential toxic effects via balanced signaling synergia. Our study suggests DNMT1 is a crucial gatekeeper regarding OSCC destiny and treatment outcome.

Oropharyngeal Cancer Staging Health Record Extraction Using Artificial Intelligence

Accurate, timely, and cost-effective methods for staging oropharyngeal cancers are crucial for patient prognosis and treatment decisions, but staging documentation is often inaccurate or incomplete. With the emergence of artificial intelligence in medicine, data abstraction may be associated with reduced costs but increased efficiency and accuracy of cancer staging. To evaluate an algorithm using an artificial intelligence engine capable of extracting essential information from medical records of patients with oropharyngeal cancer and assigning tumor, nodal, and metastatic stages according to American Joint Committee on Cancer eighth edition guidelines. This retrospective diagnostic study was conducted among a convenience sample of 806 patients with oropharyngeal squamous cell carcinoma. Medical records of patients with staged oropharyngeal squamous cell carcinomas who presented to a single tertiary care center between January 1, 2010, and August 1, 2020, were reviewed. A ground truth cancer stage dataset and comprehensive staging rule book consisting of 135 rules encompassing p16 status, tumor, and nodal and metastatic stage were developed. Subsequently, 4 distinct models were trained: model T (entity relationship extraction) for anatomical location and invasion state, model S (numerical extraction) for lesion size, model M (sequential classification) for metastasis detection, and a p16 model for p16 status. For validation, results were compared against ground truth established by expert reviewers, and accuracy was reported. Data were analyzed from March to November 2023. The accuracy of algorithm cancer stages was compared with ground truth. Among 806 patients with oropharyngeal cancer (mean [SD] age, 63.6 [10.6] years; 651 males [80.8%]), 421 patients (52.2%) were positive for human papillomavirus. The artificial intelligence engine achieved accuracies of 55.9% (95% CI, 52.5%-59.3%) for tumor, 56.0% (95% CI, 52.5%-59.4%) for nodal, and 87.6% (95% CI, 85.1%-89.7%) for metastatic stages and 92.1% (95% CI, 88.5%-94.6%) for p16 status. Differentiation between localized (stages 1-2) and advanced (stages 3-4) cancers achieved 80.7% (95% CI, 77.8%-83.2%) accuracy. This study found that tumor and nodal staging accuracies were fair to good and excellent for metastatic stage and p16 status, with clinical relevance in assigning optimal treatment and reducing toxic effect exposures. Further model refinement and external validation with electronic health records at different institutions are necessary to improve algorithm accuracy and clinical applicability.

Decline of a national icon: Derogatory representations of the Romanian peasant in recent television programs

Intellectuals and artists have been crafting an image of the Romanian peasant as the building block of the nation since the second half of the 19th century. The process went hand in hand with the modernization of the elites, and the peasant was thus mainly ‘discovered’ within the cultural framework of Romanticism, as the ‘eternal autochthon’ (Mihăilescu,2017, p.173), creator of the specific Kultur of the Romanian people. However, dramatic social transformations such as the difficult transition period of the ʹ90s have shifted the focus from a complimentary representation of the peasant as the national foundation – and all the positive characteristics of his/her habitus in terms of material, spiritual and aesthetic values– to a rather alienated and anachronistic figure coming across as a burden that has to be carried into modernity by the enlightened social strata. This paper uses visual analysis, grounded in Barthesian semiotics, to explore the changes in modes of representation of the peasant in popular media from the depository of national values to a marginal lower class, striving to keep up with the urban lifestyle. Various portrayals of peasants in TV series and sketches, movies and memes point to the degradation of the peasant figure in the public imagination. Images of poverty, bad taste and a lack of hygiene seem to pollute the bodies, garments and home environments of the rural characters, with a toxic effect on their language and behaviour as well. Although there have always been derogatory images of the peasants in the discourse of the elites (Mihăilescu also coined the term ‘domestic primitive’ for the representation associated with the historical tendency to portray the peasants as a backward population incapable of progress), in recent times this tendency has prevailed, especially with the rural-themed successful TV series Las Fierbinți, for mainly ideological reasons which will be discussed. Thus, apart from deconstructing a national myth, I argue that the representation of contemporary peasants and their degenerating habitus also contributes to the polarization in the Romanian society.

A combination of microbial electrolysis cells and bioaugmentation can effectively treat synthetic wastewater containing polycyclic aromatic hydrocarbon

ABSTRACT The anaerobic biodegradation of polycyclic aromatic hydrocarbons (PAHs) is challenging due to its toxic effect on the microbes. Microbial electrolysis cells (MECs), with their excellent characteristics of anodic and cathodic biofilms, can be a viable way to enhance the biodegradation of PAHs. This work assessed different cathode materials (carbon brush and nickel foam) combined with bioaugmentation on typical PAHs-naphthalene biodegradation and analyzed the inhibition amendment mechanism of microbial biofilms in MECs. Compared with the control, the degradation efficiency of naphthalene with the nickel foam cathode, supplied with bioaugmentation dosage, realized a maximum removal rate of 94.5 ± 3.2%. The highest daily recovered methane yield (227 ± 2 mL/gCOD) was also found in the nickel foam cathode supplied with bioaugmentation. Moreover, the microbial analysis demonstrated the significant switch of predominant PAH-degrading microorganisms from Pseudomonas in Control to norank_f_Prolixibacteraceae in MECs. Furthermore, hydrogentrophic methanogenesis prevailed in MEC reactors, which is responsible for methane production. This study proved that MEC combined with bioaugmentation could effectively alleviate the inhibition of PAH, with the nickel foam cathode obtaining the fastest recovery rate in terms of methane yield.

Effects of Salicylic Acid Seed Priming on Germination of Lentil (Lens culinaris Medik.) Exposed to Salt Stress

Lentil (Lens culinaris Medik.) is an essential crop globally, particularly in Türkiye, West Asia, Southern Europe, India, and Africa. Lentil is a valuable food source, rich in proteins, carbohydrates, minerals, and vitamins. However, lentil production faces challenges due to salinity stress, which hampers water uptake and causes toxic effects on plants. The study aimed to investigate the effects of salicylic acid (SA) seed priming and varying salt (NaCl) concentrations on the germination and development of lentil seeds. The research was conducted in the Field Crops Biotechnology Laboratory, University of Dicle, Faculty of Agriculture, Türkiye. In the research, control, two salt (NaCl), four salicylic acid (SA) doses and their combinations were used on Lens culinaris variety called İlke. Germination percentage, energy, rate index, mean germination time, peak value, and vigor index were calculated. The results demonstrated that SA had a significant impact on improving lentil germination under salt stress conditions. Specifically, lower concentrations of NaCl combined with SA showed positive effects on germination and growth parameters compared to higher NaCl concentrations. The highest germination percentage, energy, and rate index values were in the control and 0.25 SA dose treatment. Salicylic acid doses under 50 NaCl concentration exhibited higher germination percentage, energy, and rate index values than under 100 NaCl. Increasing SA and salt doses negatively affected lentil seed germination. This finding is significant for lentil cultivation in salt-affected areas, offering a potential strategy to improve crop resilience and yield in challenging environmental conditions.

Gastrointestinal Incomplete Degradation Exacerbates Neurotoxic Effects of PLA Microplastics via Oligomer Nanoplastics Formation.

Biodegradable plastics, hailed for their environmental friendliness, may pose unforeseen risks as they undergo gastrointestinal degradation, forming oligomer nanoplastics. Despite this, the influence of gastrointestinal degradation on the potential human toxicity of biodegradable plastics remains poorly understood. To this end, the impact of the murine in vivo digestive system is investigated on the biotransformation, biodistribution, and toxicity of PLA polymer and PLA oligomer MPs. Through a 28-day repeated oral gavage study in mice, it is revealed that PLA polymer and oligomer microplastics undergo incomplete and complete degradation, respectively, in the gastrointestinal tract. Incompletely degraded PLA polymer microplastics transform into oligomer nanoplastics, heightening bioavailability and toxicity, thereby exacerbating overall toxic effects. Conversely, complete degradation of PLA oligomer microplastics reduces bioavailability and mitigates toxicity, offering a potential avenue for toxicity reduction. Additionally, the study illuminates shared targets and toxicity mechanisms in Parkinson's disease-like neurotoxicity induced by both PLA polymer and PLA oligomer microplastics. This involves the upregulation of MICU3 in midbrains, leading to neuronal mitochondrial calcium overload. Notably, neurotoxicity is mitigated by inhibiting mitochondrial calcium influx with MCU-i4 or facilitating mitochondrial calcium efflux with DBcAMP in mice. These findings enhance the understanding of the toxicological implications of biodegradable microplastics on human health.

Metabolic Composition of Methanolic Extract of the Balkan Endemic Species Micromeria frivaldszkyana (Degen) Velen and Its Anti-Inflammatory Effect on Male Wistar Rats

Extracts from medicinal plants are widely used in the treatment and prevention of different diseases. Micromeria frivaldszkyana is a Balkan endemic species with reported antioxidant and antimicrobial characteristics; however, its phytochemical composition is not well defined. Here, we examined the metabolome of M. frivaldszkyana by chromatography–mass spectrometry (GC-MS), ultra-performance liquid chromatography–mass spectrometry (UPLC-MS-MS), and inductively coupled plasma mass spectrometry (ICP-MS). Amino acids, organic acids, sugars, and sugar alcohols were the primary metabolites with the highest levels in the plant extract. Detailed analysis of the sugar content identified high levels of sucrose, glucose, mannose, and fructose. Lipids are primary plant metabolites, and the analysis revealed triacylglycerols as the most abundant lipid group. Potassium (K), magnesium (Mg), zinc (Zn), and calcium (Ca) were the elements with the highest content. The results showed linarin, 3-caffeoil-quinic acid, and rosmarinic acid, as well as a number of polyphenols, as the most abundant secondary metabolites. Among the flavonoids and polyphenols with a high presence were eupatorin, kaempferol, and apigenin—compounds widely known for their bioactive properties. Further, the acute toxicity and potential anti-inflammatory activity of the methanolic extract were evaluated in Wistar rats. No toxic effects were registered after a single oral application of the extract in doses of between 200 and 5000 mg/kg bw. A fourteen-day pre-treatment with methanolic extract of M. frivaldszkyana in doses of 250, 400, and 500 mg/kg bw induced anti-inflammatory activity in the 1st, 2nd, and 3rd hours after carrageenan injection in a model of rat paw edema. This effect was also present in the 4th hour only in the group treated with a dose of 500 mg/kg. In conclusion, M. frivaldszkyana extract is particularly rich in linarin, rosmarinic acid, and flavonoids (eupatorin, kaempferol, and apigenin). Its methanolic extract induced no toxicity in male Wistar rats after oral application in doses of up to 5000 mg/kg bw. Additionally, treatment with the methanolic extract for 14 days revealed anti-inflammatory potential in a model of rat paw edema on the 1st, 2nd, and 3rd hours after the carrageenan injection. These results show the anti-inflammatory potential of the plant, which might be considered for further exploration and eventual application as a phytotherapeutic agent.

Anticancer Mechanism of Astragalus Polysaccharide and Its Application in Cancer Immunotherapy

Astragalus polysaccharide (APS) derived from A. membranaceus plays a crucial role in traditional Chinese medicine. These polysaccharides have shown antitumor effects and are considered safe. Thus, they have become increasingly important in cancer immunotherapy. APS can limit the spread of cancer by influencing immune cells, promoting cell death, triggering cancer cell autophagy, and impacting the tumor microenvironment. When used in combination with other therapies, APS can enhance treatment outcomes and reduce toxicity and side effects. APS combined with immune checkpoint inhibitors, relay cellular immunotherapy, and cancer vaccines have broadened the application of cancer immunotherapy and enhanced treatment effectiveness. By summarizing the research on APS in cancer immunotherapy over the past two decades, this review elaborates on the anticancer mechanism of APS and its use in cancer immunotherapy and clinical trials. Considering the multiple roles of APS, this review emphasizes the importance of using APS as an adjunct to cancer immunotherapy and compares other polysaccharides with APS. This discussion provides insights into the specific mechanism of action of APS, reveals the molecular targets of APS for developing effective clinical strategies, and highlights the wide application of APS in clinical cancer therapy in the future.

A novel nano-drug delivery system of glycyrrhetinic acid-mediated intracellular breakable brucine for enhanced anti-hepatitis B efficacy.

Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3'-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63mg/mL. The rats injected with d-GalN (450mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.

Microwave assisted black phosphorus-based core-shell composites with synergistic antibacterial and osteogenic ability for bone tissue repair

In clinics, repairing bone tissue with methicillin-resistant Staphylococcus aureus (MRSA) infections and bone defects remains a remarkable challenge. This study designs new core-shell composites of PMP/PVA (Fe3O4@APNs based on magnesium phosphate cement/Fe3O4@APNs-VAN-PLGA microspheres-agarose hydrogel). With Fe3O4@APNs (Phytic acid dodecasodium exfoliated BPNs (APNs) modified with Fe3O4) as an enhanced microwave (MW) sensitizer, the PMP/PVA system exhibits outstanding MW thermal performance. Under MW irradiation, the PMP/PVA exerts dual antibacterial activity through the MW thermal effect (MTE, quickly increased to 68.7 ± 2.4 °C in 5 min at 2.45 GHz, 10 W/cm2) and MW-triggered chemotherapy (CTH, in vitro: 99.98 ± 0.02 % (MRSA), 99.43 ± 0.73 % (E. coli); in vivo: 99.98 ± 0.02 %), which possesses antibacterial ability in vitro and anti-infective effects in vivo with low toxicity and side effects. In addition, PMP/PVA possesses biodegradability with Ca2+, Mg2+, and PO43− released, which not only facilitates the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSC) in vitro but also promotes new bone formation for bone defect sites with chronic osteomyelitis in vivo (the implantations were gradually replaced with a large area of new bone without apparent cortical reactions). Therefore, PMP/PVA with dual antibacterial activity, osteogenic performance, and low toxicity ability can potentially repair bone tissue with MRSA infections and refractory bone defects. The proposed system is promising for bone tissue repair of chronic osteomyelitis with bone defects.

Toxicity of Bt Protein on Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae) Fed With Corn Leaves in Paraguay

The fall armyworm Spodoptera frugiperda is the most destructive pest in corn cultivation in Paraguay with yield losses of 20 to 70%. The adoption of genetically modified crops (GMO) is a valid technique for managing this pest. The objective of this investigation was to evaluate the toxicity among Bt events used locally; determining mortality and important biological parameters. The S. frugiperda population previously collected from the field was raised under laboratory conditions fed with leaves from events MIR162TM (Vip3A19), VT3ProTM (Cry1A105, Cry2Ab2, Cry3Bb), PowerCoreTM (Cry1A105, Cry1F, Cry2Ab2) and a treatment with non-maize. Bt BR106TM. The mortality of 120 larvae was evaluated for each treatment and the viability until the adult stage of those larvae that managed to survive the different treatments was observed. A high toxicity effect was verified with 100% mortality of neonatal larvae fed with the MIR162TM (Vip3A19) event; as for the other events, 86% and 61% VT3ProTM (Cry1A105, Cry2Ab2, Cry3Bb), and PowerCoreTM (Cry1A105, Cry1F, Cry2Ab2) respectively; with 13% mortality for the non-Bt control variety BR106TM. The oviposition period, viability and number of eggs laid in adults surviving the PowerCoreTM (Cry1A105, Cry1F, Cry2Ab2) and VT3ProTM (Cry1A105, Cry2Ab2, Cry3Bb) events were reduced, affecting the fecundity of the surviving insect population.

Modeling Absorption Dynamics of Differently Shaped Gold Glioblastoma and Colon Cells Based on Refractive Index Distribution in Holotomographic Imaging.

Herein, it is demonstrated that the toxic effect of gold nanoparticles (Au NPs) on three different cancer cell lines (U-118 and LN-299 glioblastoma and HCT-116 colon) depends on their absorption dynamics by cells, related to the shapes of the NPs. This hypothesis is confirmed by showing that i) based on refractive index (RI) values, typical for cell components and gold nanoparticles, it is possible to show the absorption dynamics and accumulation locations of the latter ones inside and outside of the cells. Moreover, ii) the saturation of the accumulated Au NPs volume in the cells depends on the nanoparticle shape and is reached in the shortest time for star-shaped Au NPs (AuS NPs) and in the longest time for spherical Au NPs (AuSph NPs) and on the cancer cells, where the longest and the shortest saturation are noticed for HCT-116 and LN-229 cells, respectively. A physical model of Au NPs absorption dynamics is proposed, where the diameter and shape of the Au NPs are used as parameters. The obtained theoretical data are consistent with experimental data in 85-98%.

Application of the Drosophila melanogaster Research Model to Evaluate the Toxicity Levels between Lead and Copper

Applications of the Drosophila melanogaster (D.m.) research model have an important means both for genetic investigations and for the study of metal toxicity, because D.m. has physiological mechanisms comparable to those in human organisms. In this research, the toxic effect of lead (Pb2+) and copper (Cu2+) on four D.m. genotypes—the wild genotype (Oregon-R, used as control) and three mutant genotypes (white, brown, and white-vestigial)—was compared. Five replicates were made to observe the development progress of monitorized genotypes exposed to five different concentrations 0, 0.50, 0.75, 1.00, and 2.00 mM of copper (CuSO4) and lead Pb(C2H3O2)2. Proliferation rates of larvae, pupae, and adults depend on genetic factors, metals used (copper or lead), and their concentrations. The white-vestigial mutant genotype showed the greatest sensitivity at IC50 concentration (inhibition of proliferation of more than 50% compared with the control sample) at doses of 1.00 mM for Cu2+ and 2.00 mM for Pb2+. In contrast, the control genotype (Oregon-R) showed only an inhibition IC50 concentration of 2.00 mM for Cu2+. The white-vestigial mutant genotype showed the greatest sensitivity at IC50 concentration (inhibition of proliferation of more than 50% compared with the control sample) at doses of 1.00 mM for Cu2+ and 2.00 mM for Pb2+. In contrast, the control genotype (Oregon-R) showed an inhibition at the IC50 concentration of 2.00 mM for Cu2+. The results conclude that (i) the dose influences the prolificacy rate in a directly proportional way, (ii) the comparative analyses between Cu2+ and Pb2+ revealed a more acute effect of Cu2+, and (iii) differentiated prolificacy values according to genotypes were recorded. Those reflect the importance of using D.m. as a research model in the comparative studies of the interactions between genetic factors and metal toxicity. Also, this study provides significant information on non-toxic maximum doses for organisms.