Toxic Effects Research Articles

Hormone Receptor Positive Breast Cancer in Young Women: A Review.

The global incidence of hormone-positive breast cancer (HR+ BC) in young women is rising, though the underlying reasons remain unclear. HR+ disease in younger women appears to represent a distinct clinical entity compared to that in older women, exhibiting distinct clinicopathological characteristics, outcomes and responses to treatment. Despite these differences, there is a paucity of large-volume data focusing on young women with HR+ in contemporary literature. Hormone receptor positive breast cancer in young women is associated with poorer prognoses compared to older women. Additionally, early age onset breast cancer presents unique challenges, including concerns related to fertility, the toxic effects of therapeutic agents, and specific surgical considerations. The purpose of this review is to report the existing literature on HR+ disease in young women.

Evaluation of the Cytotoxicity Effects of Bacteriophage VbɸPA-1 on the Virulent Pseudomonas aeruginosa, A375 Human Skin Melanoma Epithelial, and HFSF PI3 Human Skin Fibroblast Cells

Background: Gram-negative bacteria are the most common infectious bacteria and are life-threatening in burn patients. Phage therapy studies can help the hospital community eliminate these bacterial pathogens. Objectives: This study aimed to evaluate the effects of the isolated bacteriophages from hospital wastewater against Gram-negative pathogenic bacteria and investigate their cytotoxicity on two human skin cell lines. Methods: The bacterial strains were isolated from burn wound infections. Bacteriophages were isolated from the hospital wastewater treatment plant in Isfahan, Iran. Transmission electron microscopy, spot tests, and restriction enzyme digestion were considered for phage identification. Finally, the lactate dehydrogenase (LDH) and tetrazolium-based MTT assays were used to realize the cytotoxicity impacts of the isolated phages. The statistical analysis of cell viability was performed using a two-way analysis of variance (ANOVA). Results: The results showed that among the isolated strains, P. aeruginosa strain NEG_RA1300 (GenBank accession number: MW845642) was sensitive to the isolated phage VbɸPA-1. The TEM results showed a possible viral taxonomy of VbɸPA-1 based on its morphology, which belonged to the Myoviridae (T4-like phages). The MTT and LDH experiments showed no cytotoxicity of VbɸPA-1 on two tested cell lines. Conclusions: Based on the results, the inhibitory effect of isolated phage on P. aeruginosa isolated from burn wounds with no toxic effect on cell lines was very significant. This phage can also be an acceptable selection against burn wound infections.

Oxidative stress and cytotoxicity of co-formulants of glyphosate-based herbicides in HMWB cells

Abstract Background Glyphosate-based herbicides (GBHs) are widely used worldwide because of their effectiveness and low cost. However, there is a growing concern regarding the potential health risks associated with glyphosate exposure. Glyphosate is always marketed in formulations containing ingredients other than the active substance. These co-formulants may have toxic effects on humans and animals. Although several studies have assessed the health risks related to glyphosate, the toxicological effects of the co-formulants must be analysed in more detail to ensure the health and safety of pesticide users and the general population. This study aimed to characterize and compare the cytotoxic effects of co-formulants with those of the active substance and GBH formulations. Methods Human mononuclear white blood (HMWB) cells were exposed to varying concentrations (0.1 µM, 1µM, 10 µM, 100 µM, 1 mM, 10 mM) of glyphosate, three GBHs (Fozat 480, Roundup, and Glyfos), and two co-formulants for 4- and 20-hours. Cytotoxicity was assessed using the CCK-8 assay, and oxidative stress levels in HMWB cells were evaluated using the superoxide dismutase (SOD) assay. Cell viability and SOD activity were analysed using a spectrophotometer at 460 nm absorbance. Results Glyphosate alone did not significantly affect the cell viability. However, notable cytotoxic effects were observed in response to GBHs and adjuvants at concentrations as low as 100 µM. Furthermore, the Oxidative stress levels in cells treated with GBHs or adjuvants were significantly higher than those treated with glyphosate alone. Conclusions These findings suggest that the cytotoxic effects of GBHs are likely attributed to the adjuvants present in the formulations, which promote oxidative stress. Further studies are necessary to evaluate the health risks associated with using glyphosate-based herbicides, and co-formulants should be considered when assessing their safety. Key messages • The safety of GBHs cannot be solely attributed to glyphosate itself but also to the other components in the formulation. • Toxicity evaluation should take into account not only glyphosate but also the co-formulants present in these herbicides when assessing their safety.

Supramolecular Self-Assembled Hydrogel for Antiviral Therapy through Glycyrrhizic Acid-Enhanced Zinc Absorption and Intracellular Accumulation.

Respiratory syncytial virus (RSV) is a common pathogen that causes respiratory infections in infants and children worldwide, significantly impacting hospitalization rates in this age group. Zinc ions are considered to have broad-spectrum antiviral potential against RNA viruses, including RSV. However, poor organism absorption and low intracellular accumulation of zinc require repeated high-dose supplementation, which may lead to unnecessary toxic side effects. In this research, a Zn2+-mediated glycyrrhizinic acid (GA)-based hydrogel (ZnGA Gel) was introduced and potentially developed to be a clinically available drug candidate for RSV therapy. ZnGA Gel was fabricated based on the cooperation of two potential RSV inhibiting molecules (Zn2+ and GA), where Zn2+ promoted self-assembly of GA and reduced its gel concentration and GA promoted zinc absorption and distribution in lung tissue in vivo. The facile construction of supramolecular hydrogel by the self-assembled coordination complex made it an injectable, temperature-sensitive, and pH-responsive controlled-release drug delivery for Zn2+. Most importantly, GA was observed to enhance organism absorption and intracellular accumulation of Zn2+ and was identified as a zinc ionophore for the first time. GA can colonize on the cell membrane and disturb cell membrane potential, resulting in an enhanced cell membrane permeability. In the presence of GA, more than 4.7-fold increasing Zn2+ concentrations materialized in the intracellular cytoplasm, compared to Zn2+ alone administration. This intracellular Zn2+ accumulation directly boosted the antiviral activities through improved inhibition of RSV replication-associated proteins and significantly inhibited RSV replication. Oral administration of ZnGA Gel on the RSV-infected mice model achieved an ideal therapeutic effect by effectively lowering viral load in the lungs, alleviating lung injury symptoms, and reducing inflammatory cell infiltration at pathological sites. The mechanism involved the inhibition of RSV replication-related proteins, aligning with our in vitro results. Additionally, ZnGA Gel had demonstrated biocompatibility, and reasonable supplementation of zinc was acceptable and effective for infants and children in clinical practice. Hence, the ZnGA Gel developed by us holds promise as an effective anti-RSV medicine in the future.

Evaluation of Toxicity of Feed Additive for Highly Productive Animals

The study of new feed additives requires toxicological research to assess their safety for further use. This research presents the results of an acute toxicity study of the feed additive "Bodrivin," developed for highly productive animals of dairy, meat-dairy, and meat breeds. The aim is to prevent stress of various etiologies, enhance the nutritional value of the diet, especially during periods of energy deficiency, and consequently improve productivity and profitability in production. Non-linear laboratory rats were used for the experiment. The first experimental group received a single oral dose of the feed additive via syringe and atraumatic needle with a bulbous end at a dosage of 2000 mg/kg. After obtaining the results of the experiment over a 14-day period, a similar experiment was conducted on the second experimental group. At the conclusion of the experiment, no signs indicating toxic effects of the studied feed additive were observed in the animals, and the body weight of the experimental animals remained unchanged in both the first and second series of the experiment. The acute toxicity study of the feed additive "Bodrivin" indicated that the evaluated feed additive belongs to Class V of danger according to GOST 32644-2014.

Future of Uremic Toxin Management

During the progression of chronic kidney disease (CKD), the retention of uremic toxins plays a key role in the development of uremic syndrome. Knowledge about the nature and biological impact of uremic toxins has grown exponentially over the past decades. However, the science on reducing the concentration and effects of uremic toxins has not advanced in parallel. Additionally, the focus has remained for too long on dialysis strategies, which only benefit the small fraction of people with CKD who suffer from advanced kidney disease, whereas uremic toxicity effects are only partially prevented. This article reviews recent research on alternative methods to counteract uremic toxicity, emphasizing options that are also beneficial in the earlier stages of CKD, with a focus on both established methods and approaches which are still under investigation or at the experimental stage. We will consequently discuss the preservation of kidney function, the prevention of cardiovascular damage, gastro-intestinal interventions, including diet and biotics, and pharmacologic interventions. In the final part, we also review alternative options for extracorporeal uremic toxin removal. The future will reveal which of these options are valid for further development and evidence-based assessment, hopefully leading to a more sustainable treatment model for CKD than the current one.

Toxic effects of microplastic and nanoplastic on the reproduction of teleost fish in aquatic environments.

Microplastics and nanoplastics are widely present in aquatic environments and attract significant scholarly attention due to their toxicity, persistence, and ability to cross biological barriers, which pose substantial risks to various fish species. Microplastics and nanoplastics can enter fish through their digestive tract, gills and skin, causing oxidative damage to the body and adversely affecting their reproductive system. Given that fish constitute a crucial source of high-quality protein for humans, it is necessary to study the impact of microplastics on fish reproduction in order to assess the impact of pollutants on ecology, biodiversity conservation, environmental sustainability, and endocrine disruption. This review explores the reproductive consequences of microplastics and nanoplastics in fish, examining aspects such as fecundity, abnormal offspring, circadian rhythm, gonad index, spermatocyte development, oocyte development, sperm quality, ovarian development, and changes at the molecular and cellular level. These investigations hold significant importance in environmental toxicology.

Phytochemical Analysis, Total Phenolic Content, Hemolytic and Anti-hemolytic Activities of Centaurea iberica (Asteraceae)

Several plants contain chemical substances that have various biological activities, but they also probably cause harmful effects on cellular membranes. This work deals with the Centaurea iberica (Iberian starthistle) plant. The objective of this study is to identify the main chemical groups in the methanolic extract 80% of the plant, determine its total phenolic content, evaluate its toxic effect on human erythrocytes, and also assess its activity in the protection of normal and glucose-6-phosphate dehydrogenase (G6PD) enzyme-deficient human erythrocytes membranes against oxidative hemolysis. Phytochemical analysis revealed that C. iberica extract contains several bioactive compounds. The results also showed that the plant extract contained good level of total phenolic compounds. The extract exhibited a low hemolytic effect. It also showed excellent activity in the protection of normal and G6PD-deficient human erythrocytes against oxidative hemolysis. KEYWORDS Erythrocytes, G6PD, Iberian starthistle, methanolic extract, toxic effect, oxidative hemolysis

Sensing of endogenous retroviruses-derived RNA by ZBP1 triggers PANoptosis in DNA damage and contributes to toxic side effects of chemotherapy

Excessive DNA damage triggers various types of programmed cell death (PCD), yet the regulatory mechanism of DNA damage-induced cell death is not fully understood. Here, we report that PANoptosis, a coordinated PCD pathway, including pyroptosis, apoptosis and necroptosis, is activated by DNA damage. The Z-DNA binding protein 1 (ZBP1) is the apical sensor of PANoptosis and essential for PANoptosome assembly in response to DNA damage. We find endogenous retroviruses (ERVs) are activated by DNA damage and act as ligands for ZBP1 to trigger PANoptosis. By using ZBP1 knock-out and knock-in mice disrupting ZBP1 nucleic acid-binding activity, we demonstrate that ZBP1-mediated PANoptosis contributes to the toxic effects of chemotherapeutic drugs, which is dependent on ZBP1 nucleic acid-binding activity. We found that ZBP1 expression is downregulated in tumor tissue. Furthermore, in colorectal cancer patients, dsRNA is induced by chemotherapy and sensed by ZBP1 in normal colonic tissues, suggesting ZBP1-mediated PANoptosis is activated by chemotherapy in normal tissues. Our findings indicate that ZBP1-mediated PANoptosis is activated by DNA damage and contributes to the toxic side effects of DNA-damage-based chemotherapy. These data suggest that ZBP1 could be a promising therapeutic target to alleviate chemotherapy-related side effects.

Adsorptive Removal of Dyes: A Comparison of Graphene Oxide to Granular Activated Carbon and Zeolite NaY

Synthetic carbon-based compounds are a prevalent wastewater contaminant that can adversely impact water resources due to their potential carcinogenic and toxic effects on aquatic biota and human health. This research investigates the versatility of graphene oxide (GO) as an alternative to commonly used adsorbents (zeolite NaY (NaY) and granular activated carbon (GAC)) for removal of synthetic cationic dyes. Rhodamine B (RhB) and methylene blue (MB), were selected as the target contaminants to represent cationic synthetic dyes with differing molecular sizes and structural compositions. Batch experiments using GO, NaY, and GAC as adsorbents were used to assess both physicochemical interactions between adsorbent surfaces and contaminants, and removal efficiency. GO demonstrated the highest removal efficiency for both target contaminants—at 99% and 86%, respectively—while the lowest removal efficiency was observed for NaY. Langmuir, Freundlich, Temkin, and BET isotherm models were used to describe the adsorption isotherms. Overall, GO demonstrated a more robust and higher removal efficiency of cationic dyes compared with GAC and NaY, indicating the potential of graphene oxide for the removal of complex structured organic contaminants in wastewater treatment.

Design, Synthesis, and Evaluation of Doxifluridine Derivatives as Nitroreductase-Responsive Anticancer Prodrugs

Antimetabolite antitumor drugs interfere with nucleic acid and DNA synthesis, causing cancer cell death. However, they also affect rapidly dividing normal cells and cause serious side effects. Doxifluridine (5′-deoxy-5-fluorouridine [5′-DFUR]), a 5-fluorouracil (5-FU) prodrug converted to 5-FU by thymidine phosphorylase (TP), exerts antitumor effects. Since TP is distributed in tumor and normal tissues, 5′-DFUR features side effects. Here we designed a series of novel 5′-DFUR derivatives based on high nitroreductase (NTR) levels in the hypoxic microenvironment of tumor tissues by introducing nitro-containing moieties into the 5′-DFUR structure. These derivatives exert their antitumor effects by producing 5-FU under the dual action of TP and NTR in the tumor microenvironment. The derivatives were synthesized and their stability, release, and cytotoxicity evaluated in vitro and antitumor activity evaluated in vivo. Compound 2c, featuring nitrofuran fragments, was stable in phosphate-buffered saline and plasma at different pH values and reduced rapidly in the presence of NTR. The in vitro cytotoxicity evaluation indicated that compound 2c showed excellent selectivity in the MCF-7 and HT29 cell lines. Moreover, it exhibited antitumor effects comparable to those of 5′-DFUR in vivo without significant toxic side effects. These results suggest that compound 2c is a promising antitumor prodrug.

Synergistic Anti-Tumor Effects of Newcastle Disease Virus and Doxorubicin: Evidence from A Murine Breast Cancer Model

BackgroundDespite the recent advances in the diagnosis and treatment of breast cancer, triple-negative breast cancer (TNBC) remains a clinical challenge due to its aggressive nature and resistance to conventional therapies. Virotherapy has emerged as a promising cancer treatment strategy, leveraging the ability of viruses to specifically target and replicate in cancerous cells. This study evaluated the oncolytic potential of a combined therapeutic strategy, utilizing Newcastle disease virus (NDV) and Doxorubicin hydrochloride (Dox) both in vitro and in vivo. MethodsThe in vitro experiments involved exposing human and mouse TNBC cell lines (MDA-MB-231 and 4T1, respectively) to NDV and Dox, individually or in combination. Cell viability assays and flow cytometry analyses were conducted to assess the synergistic effects of NDV and Dox on regulating breast cancer cell behavior in vitro. Furthermore, the immune-stimulating potential of NDV was investigated by examining its effects on dendritic cell (DC) maturation using flow cytometry and T cell proliferation. The in vitro anti-tumor effects of NDV were examined in both parental and tamoxifen-resistant cancer cells to assess its efficacy against chemoresistance. Animal models of breast cancer were treated with NDV in combination with Dox. The body weight changes, tumor volume, and survival rates of the mice were monitored throughout the study. Histopathological analyses were conducted to evaluate the potential toxic effects of the treatments. ResultsBased on the MTT results, NDV at optimal concentrations synergized the effect of Dox to reduce the viability of both MDA-MB231 and 4T1 cell lines (Isobologram combination index of less than 1). Additionally, individual treatment with NDV was able to significantly reduce the viability of patient-derived breast cancer cells, compared to the untreated control (P < 0.05) without affecting the cells of normal adjacent tissue. Furthermore, a combination of NDV and Dox significantly enhanced the percentage of early and late apoptotic cells in MDA-MB-231 (P < 0.0001) and late apoptotic cells in 4T1 (P < 0.0001), in comparison with individual treatment with these agents. Flow cytometry results showed that, compared to wild type MDA-MB-231 cells, NDV-infected MDA-MB-231 cells were better inducers of T cell proliferation and DC maturation as evidenced by increased proliferation index (P < 0.05) and elevated expression of CD1a, CD83, and CD86 (P < 0.0001), respectively. Moreover, co-treatment of both wild-type and (tamoxifen) TAM-resistant MCF-7/TAMR-1 cells with TAM and NDV significantly reduce the viability of the cancer cells (P < 0.0001). In tumor-bearing mice locally engrafted with 4T1 cells, combined treatment of NDV and Dox exhibited a marked reduction in median tumor volume compared to the control group, validating our in vitro findings on their synergistic anti-tumor effects. These findings suggest that combining NDV with Dox can effectively inhibit tumor progression and has the potential to reduce the dose, and consequently the toxic side-effects, of Dox in breast cancer therapy.

Enhancing the Phytoremediation of Heavy Metals by Plant Growth Promoting Rhizobacteria (PGPR) Consortium: A Narrative Review.

Heavy metal pollution has become a significant concern as the world continues to industrialize, urbanize, and modernize. Heavy metal pollutants impede the growth and metabolism of plants. The bioaccumulation of heavy metals in plants may create chlorophyll antagonism, oxidative stress, underdeveloped plant growth, and reduced photosynthetic system. Finding practical solutions to protect the environment and plants from the toxic effects of heavy metals is essential for long-term sustainable development. The direct use of suitable living plants for eliminating and degrading metal pollutants from ecosystems is known as phytoremediation. Phytoremediation is a novel and promising way to remove toxic heavy metals. Plant growth-promoting rhizobacteria (PGPR) can colonize plant roots and help promote their growth. Numerous variables, such as plant biomass yield, resistance to metal toxicity, and heavy metal solubility in the soil, affect the rate of phytoremediation. Phytoremediation using the PGPR consortium can speed up the process and increase the rate of heavy metal detoxification. The PGPR consortium has significantly increased the biological accumulation of various nutrients and heavy metals. This review sheds light on the mechanisms that allow plants to uptake and sequester toxic heavy metals to improve soil detoxification. The present review aids the understanding of eco-physiological mechanisms that drive plant-microbe interactions in the heavy metal-stressed environment.

Phytoconstituents, Antioxidant Activity and Cytotoxicity of Puya chilensis Mol. Extracts in Colon Cell Lines

Puya chilensis Mol. is a plant of the Bromeliaceae family, which has been traditionally used for medicinal applications in various digestive disorders. In this study, the phytoconstituents of six extracts of stems and flowers of P. chilensis were evaluated: phenols, flavonoids and total anthraquinones, as well as their antioxidant capacity and cytotoxicity in colon cancer cell lines HT-29. The data demonstrate that the ethyl acetate extract of P. chilensis flowers is cytotoxic in HT-29 cell lines (IC50 = 41.70 µg/mL) without causing toxic effects on healthy colon cells (IC50 &gt; 100 µg/mL); also, this extract concentrated the highest amount of phenols (4.63 μg GAE/g d.e.), flavonoids (31.5 μg QE/g d.e.) and anthraquinones (12.60 μg EE/g d.e.) among all the extracts tested, which also correlated with its highlighted antioxidant capacity (DPPH∙IC50 = 4.15 mg/mL and FRAP 26.52 mM TEAC) over the other extracts. About thirty-five compounds were identified in this extract−the fatty acid esters present have been shown to have therapeutic effects on several types of cancer and could explain its antiproliferative activity.

Monitoring of urinary nickel and chromium in metal industries workers in Alborz, Iran

Heavy metal contamination from occupational sources is a cause for concern due to its potential accumulation in the environment and the body of living organisms, which leads to long-term toxic effects. There is limited evidence on the concentration of heavy metals in the body fluids of welding workers. This study aimed to measure the concentration of nickel (Ni) and chromium (Cr) as two main toxic heavy metals in the urine samples of welders and determine the potential relationship of various environmental factors on their concentration levels. This study was conducted in Iran in 2022–2023. Eighty-five urine samples were collected from the studied welding workers. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to measure the concentration of Ni and Cr. Data related to socio-demographic characteristics (education level, income, work experience, age, and body mass index (BMI)), lifestyle profile (consumption of seafood and canned food, smoking, physical activity), type of ventilation and preventive devices at work, and suffering from underlying diseases (cardiovascular and high blood pressure) were collected using valid questionnaires. Ni and Cr were present in 100% of urine samples with mean concentrations of (1.09 ± 0.294) and (11.45 ± 16.751) µg/g creatinine, respectively. A significant correlation was observed between the mean concentration of Ni and Cr with the level of education, income, work experience, age, consumption of seafood and canned food, smoking, type of ventilation and preventive devices, and underlying diseases (p-value < 0.05). Also, there was no significant difference between Ni concentration and physical activity and Cr concentration with BMI. Lifestyle determinants and not using preventive devices are important predictors of urinary heavy metals in welding workers. Therefore, more research is required to determine the adverse effects of long-term exposure to these heavy metals.

An integrated proteomics and metabolomics analysis of methylglyoxal-induced neurotoxicity in a human neuroblastoma cell line

This study aimed to highlight the molecular and biochemical changes induced by methylglyoxal (MGO) exposure in SH-SY5Y human neuroblastoma cells, and to explore how these changes contribute to its neurotoxicity, utilizing an integrated proteomics and metabolomics approach. Using label-free quantitative nanoLC-MS/MS proteomics and targeted LC-TQ-MS/MS-based metabolomics, the results revealed that MGO exposure, particularly at cytotoxic levels, significantly altered the proteome and metabolome of SH-SY5Y cells. Analysis of proteomics data showed significant alterations in cellular functions including protein synthesis, cellular structural integrity, mitochondrial function, and oxidative stress responses. Analysis of metabolomics and integration of metabolomics and proteomics data highlighted significant changes in key metabolic pathways including arginine biosynthesis, glutathione metabolism, cysteine and methionine metabolism, and the tricarboxylic acid cycle. These results suggest that MGO exposure induced both toxic effects and adaptive responses in cells. MGO exposure led to increased endoplasmic reticulum stress, disruptions in cellular adhesion and extracellular matrix integrity, mitochondrial dysfunction, and amino acid metabolism disruption, contributing to cellular toxicity. Conversely, cells exhibited adaptive responses by upregulating protein synthesis, activating the Nrf2 pathway, and reprogramming metabolism to counteract dicarbonyl stress and maintain energy levels. Furthermore, a set of key proteins and metabolites associated with these changes were shown to exhibit a significant concentration-dependent decrease or increase in their expression levels with increasing MGO concentrations, suggesting their potential as biomarkers for MGO exposure. Taken together, these findings provide insight into the molecular mechanisms underlying MGO-induced neurotoxicity and potential targets for therapeutic intervention.

The diagnostic value of cytokines in chronic glomerulonephritis in children

In modern clinical practice of pediatricians, the problem of timely adequate treatment of chronic glomerulonephritis (CGN) in children is of particular relevance, due to both the high prevalence of the disease and the severity of its course, the complexity of therapy and the ambiguity of the prognosis. Lesions of the urinary system in children are not only common, but also tend to grow, and often at an early age. Deterioration of the environmental background, toxic and allergic effects of drugs lead to damage primarily to the kidneys, which are the eliminating organ. The aim of the study was to study urocytokines to assess the immune response in children with HCG, depending on the association with cytomegalovirus infection. The study included 100 children aged 4-7 years, permanently residing in the Bukhara region of the Republic of Uzbekistan. At the time of the study, the patients were undergoing routine treatment in the Department of Pediatric Nephrology of the Bukhara Regional Children’s Multidisciplinary Medical Center. All children underwent general clinical (general blood test with leukoformula, general urine analysis, biochemical blood test with determination of urea, creatinine and cystatin C, immunological (TNFα, IL-18, MCP-1, IgM and IgG antibodies to cytomegalovirus infection (CMVI) in blood serum, IL-1β and IL-17A in urine) examination methods. Thus, it was found that the concentration of cystatin C in the blood serum was inversely proportional to the glomerular filtration rate in the kidneys – with a decrease in kidney function in sick children, a twofold increase was noted, that is, the accumulation of cystatin C in the blood. An increase in the concentration of IL-18 in serum and IL-1β in urine relative to the control group in CGN was an indicator of the severity of an autoimmune reaction, and a relatively low concentration of cytokines in both blood and urine in CGN with CMVI indicated suppression of the specific antiviral immunity of CMVI. It was found that an increase in serum MCP-1 by 1.4 times in group 1 and 2.9 times in group 2 of CGN with CMVI is an indicator of viral kidney damage. A significantly high concentration of IL-17A in urine in CGN with CMVI indicated local cytokine production in the kidneys and acted as an indicator of the prognosis of the outcome of CGN.

Comparative Analysis of Natural vs. Synthetic Antioxidants in Nigeria

Purpose: The aim of the study was to assess the comparative analysis of natural vs. synthetic antioxidants in Nigeria. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: The study indicated that natural antioxidants, derived from plant sources such as fruits, vegetables, and herbs, are often preferred for their bioavailability and health benefits, including their ability to neutralize free radicals and reduce oxidative stress. They are associated with lower toxicity and potential health-boosting properties, such as reducing the risk of chronic diseases. On the other hand, synthetic antioxidants, which are chemically manufactured, tend to have a more stable and consistent potency, making them more effective in industrial applications like food preservation. However, concerns about their long-term health effects, including potential toxicity and adverse side effects, have led to a growing preference for natural alternatives. While both types play important roles in protecting cells from damage, natural antioxidants are often seen as safer, though their effectiveness can vary depending on the source and concentration. Implications to Theory, Practice and Policy: Free radical theory of aging, phytochemical hypothesis and toxicology of food additives may be used to anchor future studies on the comparative analysis of natural vs. synthetic antioxidants in Nigeria. In practical terms, health professionals should advocate for the incorporation of natural antioxidants into dietary guidelines, emphasizing foods rich in these beneficial compounds, such as fruits, vegetables, and herbs. From a policy perspective, there is a pressing need for regulatory frameworks that impose stricter guidelines on the use of synthetic antioxidants in food products, prioritizing safety assessments and considering long-term health impacts.

Emerging Cationic Nanovaccines

Cationic vaccines of nanometric sizes can directly perform the delivery of antigen(s) and immunomodulator(s) to dendritic cells in the lymph nodes. The positively charged nanovaccines are taken up by antigen-presenting cells (APCs) of the lymphatic system often originating the cellular immunological defense required to fight intracellular microbial infections and the proliferation of cancers. Cationic molecules imparting the positive charges to nanovaccines exhibit a dose-dependent toxicity which needs to be systematically addressed. Against the coronavirus, mRNA cationic nanovaccines evolved rapidly. Nowadays cationic nanovaccines have been formulated against several infections with the advantage of cationic compounds granting protection of nucleic acids in vivo against biodegradation by nucleases. Up to the threshold concentration of cationic molecules for nanovaccine delivery, cationic nanovaccines perform well eliciting the desired Th 1 improved immune response in the absence of cytotoxicity. A second strategy in the literature involves dilution of cationic components in biocompatible polymeric matrixes. Polymeric nanoparticles incorporating cationic molecules at reduced concentrations for the cationic component often result in an absence of toxic effects. The progress in vaccinology against cancer involves in situ designs for cationic nanovaccines. The lysis of transformed cancer cells releases several tumoral antigens, which in the presence of cationic nanoadjuvants can be systemically presented for the prevention of metastatic cancer. In addition, these local cationic nanovaccines allow immunotherapeutic tumor treatment.

Methamphetamine-induced cardiotoxicity: in search of protective transcriptional mechanisms.

Crystalline methamphetamine hydrochloride is an illegal drug with ahigh addictive potential, better known by its colloquial name "ice" or "crystal meth". The abuse of this drug has led to significant health problems worldwide. Like other amphetamine-type stimulants, chronic consumption of methamphetamine leads to direct toxic effects on the central nervous system, causing cognitive impairment, depressive behavior, and other severe neurological or psychiatric symptoms. Besides its neurotoxicity, the drug exhibits numerous deleterious effects on the cardiovascular system, including hypertension, accelerated atherosclerosis, vasospasm-induced acute coronary syndromes, sudden cardiac death, and dilated cardiomyopathy with congestive heart failure and left ventricular dysfunction. The excessive release of catecholamines upon methamphetamine exposure causes vasoconstriction and vasospasm, which ultimately lead to hypertension, tachycardia, endothelial dysfunction, and cardiotoxicity. While numerous studies have focused on transcription factors expressed in the brain that cause the neurotoxic effects of the drug, much less is known about transcription factors involved in the development of methamphetamine-induced heart failure. In this article, we provide an overview of the Janus kinase-signal transducer and activator of transcription3 (JAK-STAT3) pathway involved in ischemia/reperfusion injury in the myocardium, which may be activated by the vasospasm-inducing action of the drug. However, much more work is needed to decipher the precise role of STAT protein family members, including the potentially cardioprotective STAT3, in the pathogenesis of methamphetamine-induced cardiotoxicity.