Search Results (114)

Background: Bacillus clausii SKB/BCL21 (MCC 0569) is a novel strain that shows promise as a probiotic for both human and animal healthcare. Objectives: The objective is to evaluate the safety profile of B. clausii SKB/BCL21 through genomic and toxicity assessments in Wistar rats, as well as to assess its efficacy as a probiotic in broiler chickens challenged with Clostridium perfringens. Methods: The identification of genus and species was performed using 16S rRNA and whole genome sequencing (WGS). A genomic analysis was conducted through bioinformatic screening of the B. clausii SKB/BCL21 genome to identify virulence factors, genes encoding toxins, mobile genetic elements, and antibiotic resistance genes. In vitro biosafety assays were conducted to evaluate mucin degradation, gelatinase, hemolytic activity, and DNase activity. The in vivo safety evaluation was performed by acute and subacute oral toxicity studies as per the OECD 423 guidelines. In efficacy testing broilers challenged with C. perfringens were administered with low dose (1 × 10⁸ cfu/kg of feed) and high dose (1 × 10⁹ cfu/kg of feed) of B. clausii SKB/BCL21. Performance metrics, such as average weight gain, feed conversion ratio (FCR), and mortality rates, were evaluated in comparison to a positive control group that received Virginiamycin 50% (15 ppm). Results: The isolate SKB/BCL21 was identified as Bacillus clausii based on 16S rRNA and whole genome sequencing (WGS). The bioinformatic analysis of the B. clausii SKB/BCL21 genome reveals that it lacks genes associated with toxins, mobile genetic elements, and virulence factors. However, it does contain intrinsic and non-transferable antibiotic resistance genes within its chromosomal DNA. In the acute toxicity study, an oral dose of 2000 mg/kg (400 billion cfu/kg) body weight was found to be nontoxic. The No Observed Adverse Effect Level (NOAEL) for B. clausii SKB/BCL21 was found to be 1000 mg/kg (200 billion cfu) body weight/day by oral route in the subacute toxicity study. The findings of in vivo toxicity studies indicate that there were no treatment-related changes in any of the endpoints assessed. The effects of low (1 × 10⁸ cfu/kg of feed) and high (1 × 10⁹ cfu/kg of feed) doses of B. clausii SKB/BCL21 on the growth performance metrics, including average weight gain, feed conversion ratio, and mortality rates in broiler chickens infected with C. perfringens, showed results similar to those of the positive control (Virginiamycin 50%, 15 ppm). Conclusions: Based on these preliminary studies, B. clausii SKB/BCL21 can serve as a potential alternative to antibiotic growth promotors in broiler production. These results suggest that the B. clausii SKB/BCL21 is safe and could be a potential probiotic for animal feed supplements. Full article

Diabetes mellitus represents a major global health burden, necessitating the development of safer and more effective therapeutic alternatives. Medicinal plants have gained increasing attention due to their bioactive compounds with potential hypoglycemic and antioxidant effects. The present study aimed to investigate the physicochemical characteristics, phytochemical composition, antioxidant capacity, and toxicological profile of hydroalcoholic tinctures obtained from Agrimonia pilosa Ledeb., Calendula arvensis L., and Polygonum hydropiper L. The tinctures were prepared by simple percolation using 70% ethanol and evaluated according to pharmacopoeial standards, including organoleptic properties, relative density, refractive index, alcohol content, and purity parameters. Phytochemical analysis was performed using thin-layer chromatography and spectrophotometric methods, highlighting the presence of flavonoids and polyphenolcarboxylic acids, with several bands showing chromatographic and spectral similarities to chlorogenic and caffeic acid standards. Antioxidant activity was assessed through total polyphenol and flavonoid content, with Polygonum hydropiper exhibiting the highest values. The hypoglycemic effect was evaluated using the oral glucose tolerance test in normoglycemic mice, demonstrating significant reductions in blood glucose levels, particularly for Agrimonia pilosa at higher doses. Acute toxicity studies indicated a low toxicity profile, with no mortality observed even at high doses (up to 9 g/kg body weight), corresponding to GHS category 5. However, subacute toxicity assessment revealed species-dependent effects, ranging from minimal hepatic changes for Calendula arvensis to moderate hepatotoxicity for Polygonum hydropiper and more pronounced hepatic, renal, and pancreatic alterations for Agrimonia pilosa. These findings suggest that the investigated tinctures possess significant hypoglycemic and antioxidant potential, with generally favorable safety profiles following acute administration. Nevertheless, prolonged use may induce organ-specific toxicity, highlighting the need for further pharmacological and clinical investigations to establish their therapeutic applicability and safety in diabetes management. Full article

B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D)-directed immunotherapies, chimeric antigen receptor T-cell (CAR-T) products, bispecific T-cell engagers (BsAbs), and antibody–drug conjugates (ADCs), have transformed the management of MM. Their adoption is now extending beyond tertiary centers following FDA modifications for CAR-T safety and the rapid uptake of off-the-shelf bispecifics suitable for community delivery. Clinicians outside specialist hubs must therefore be conversant with the full toxicity spectrum, including rare but high-consequence events, both for informed consent and for the work-up of post-therapy complications. In this narrative review, we report on the published literature around toxicities of approved and investigational BCMA- and GPRC5D-directed therapies, drawing on pivotal trial data, real-world cohorts, pharmacovigilance studies, and consensus management recommendations, with emphasis on practical recognition and risk mitigation. This review presents toxicities by a temporal pattern including acute (CRS, ICANS, infection, ocular, mucocutaneous), subacute (cranial nerve palsies, parkinsonism, myelitis, peripheral neuropathies IEC-associated enterocolitis and cardiovascular events), and long-term (prolonged cytopenias, second primary malignancies). We discuss validated risk stratification tools, such as the CAR-HEMATOTOX score, EASIX index, and multidisciplinary geriatric assessment, which predicts severe ICANS, infection, and resource utilization, supporting individualized pre-treatment planning. Safe delivery of immune therapies in community settings requires infrastructure for acute critical care, neurology, ophthalmology, infectious disease and long-term surveillance, but is achievable when paired with validated risk stratification and clear referral pathways. Full article

A phytopreparation based on the CO₂ extract of Arctium tomentosum Mill. root (AT) was evaluated for its safety and anti-inflammatory potential in Swiss albino mice. Acute and 28-day subacute oral toxicity studies demonstrated that AT, at doses up to 5000 mg/kg (acute) and 400 mg/kg (subacute), did not induce mortality, clinical signs of toxicity, or adverse effects on body weight, relative organ weights, or hematological and biochemical parameters. Histopathological analyses confirmed preserved tissue architecture in major organs, indicating the absence of structural toxicity. Anti-inflammatory activity was assessed using xylene-induced ear edema and LPS-induced systemic inflammation models. AT significantly reduced ear edema and suppressed the production of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in a dose-dependent manner. Additionally, AT exhibited potent hepatoprotective and nephroprotective effects, as reflected by the stabilization of ALT, AST, SCr, and BUN levels. Histological examination of inflamed tissues corroborated these findings. Overall, AT is well tolerated and demonstrates potent systemic anti-inflammatory and multi-organ protective properties, supporting its potential as a promising therapeutic candidate for inflammatory and oxidative stress-related conditions. Full article

The growing global protein demand and environmental concerns from conventional animal agriculture have driven the exploration of sustainable alternative protein sources. Single-cell proteins (SCPs) from microbial fermentation offer a promising solution. This study comprehensively evaluated the nutritional value and safety profile of SCP produced from Ralstonia eutropha H16 through integrated in vitro and in vivo assessments. Nutritional analyses revealed a high crude protein content of 71.87 ± 5.05 g/100 g dry weight, with total amino acids of 53.67 ± 1.05 g/100 g. The essential amino acid content was 24.38 ± 0.51 g/100 g, accounting for 45% of the total amino acids. An essential amino acid index (EAAI) of 1.46 ± 0.04 and an amino acid score (AAS) of 0.83 ± 0.06 confirmed its classification as a high-quality protein source according to FAO/WHO standards. In vivo rat feeding trials demonstrated an adjusted protein efficiency ratio (PER) of 1.81, exceeding common plant proteins such as wheat (0.8–1.1). True digestibility (TD) reached 85.73%, with a biological value (BV) of 49.37%, net protein utilization (NPU) of 42.33%, and protein digestibility-corrected amino acid score (PDCAAS) of 0.71. Comprehensive safety assessments included chemical contaminant screening, acute oral toxicity studies in rats and mice, in vitro chromosome aberration tests, and erythrocyte micronucleus tests. Heavy metals and aflatoxin B₁ levels were below regulatory limits. Acute oral toxicity studies established LD₅₀ values exceeding 10,000 mg/kg body weight in both rodent species, classifying this protein source as practically non-toxic. The 28-day sub-acute toxicity study showed no significant adverse effects at low doses (6.25% protein replacement). Both genotoxicity assays (mammalian cell chromosome aberration assay and mammalian erythrocyte micronucleus test) returned negative results. These findings establish R. eutropha H16-derived SCP as a safe, nutritious, and sustainable protein source with considerable potential for feed and food applications, contributing to global food security and environmental sustainability. Full article

Quinazolinone derivatives are well-known anticancer agents; anticancer properties are also part of the broad spectrum of biological activity of coumarins. Conjugates containing quinazolin-4(3H)-one and coumarin fragments linked by polymethylene bridges of varying lengths were designed to improve properties of both parental compounds and create new anticancer or antibacterial agents. 3-{3-[(4-Methyl-2-oxo-2H-chromen-7-yl)oxy]propyl}quinazolin-4(3H)-one was synthesized as the base compound. It demonstrated moderate cytotoxicity against leukemia (K562 and HL60) and neuroblastoma (SH-SY5Y) cells in vitro, combined with relatively low acute, subacute, and chronic toxicity in vivo. Conjugates with various substituents and linkers were then synthesized to evaluate the structure–activity relationship. A study of the synthesized compounds on cell cultures showed that the introduction of a methyl substituent into the benzene ring of the coumarin fragment led to both an increase in cytotoxicity and expansion of its spectrum of action. Testing of the hybrids against Gram-positive and Gram-negative bacteria revealed that the introduction of halogens into the quinazoline fragment in the compounds or the elongation of the linker led to the emergence of pronounced antibacterial properties, which were most clearly manifested against Acinetobacter baumanii. The possibility of directing activity of quinazoline-4(3H)-one–coumarin hybrids by varying the substituents and the length of the linker was shown. Full article

The active constituents of essential plant oils (EOAIs), monoterpenoid carvacrol and monoterpene p-cymene, are widely distributed in many aromatic plants and their products. They differ in that carvacrol has a phenolic functional group. The numerous pharmacological effects of these two EOAIs are well known. In different doses/concentrations, they exhibit analgesic, neuroprotective, vasorelaxant, anti-inflammatory, antiviral, antibacterial and antiparasitic effects. The acute toxicity of carvacrol and p-cymene in rats and the free-living nematode Caenorhabditis elegans was investigated. Furthermore, the impact of subacute administration of these two terpenes on general health, CNS integration, i.e., motor coordination and balance of rats, as well as their effects on the movement of adult C. elegans, was also examined. The aim was to compare the effects and describe in more detail the selective toxicity of carvacrol and p-cymene. The calculated LD₅₀ value of carvacrol was 790.15 ± 1.15 mg/kg, while the LD₅₀ value of p-cymene is above 3000 mg/kg. Tested doses of carvacrol and p-cymene administered for 28 days (50, 100, and 200 mg/kg) did not exert any effect on the CNS of rats or cause any clinical disorders. LC₅₀ value of carvacrol for adult C. elegans was 184.13 ± 1.51 μM and for p-cymene 1268 ± 1.65 μM. In subacute testing, carvacrol showed negative effects on C. elegans reproduction, distance traveled, movement speed and rotational index at lower concentrations than p-cymene, indicating higher toxicity, which may be due to its phenolic structure. On the other hand, although less toxic to C. elegans, p-cymene exhibited a specific effect on worm motility, with more rolling which should be further investigated, and can be a consequence of cuticle damage or loss of orientation. Full article

Radioligand therapy (RLT) offers the ability to deliver radiation to specific cells based on the presence of certain targets. RLT with [¹⁷⁷Lu]Lu-DOTATATE was approved in 2018 by the US Food and Drug Administration (FDA) for patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). As RLT has become integrated into clinical practice, understanding the presence of and management strategies associated with acute, subacute, or delayed toxicities is essential to optimize patient outcomes. In this review article, we consider the risk factors for complications and any preventative strategies that may be employed. We present an overview of the toxicities that could occur during or soon after RLT infusion and discuss recommended management strategies, both from the literature and from experience in the clinical administration of RLT for patients with GEP-NETs. We highlight the importance of robust procedures for handling emergency situations and the potential for radioactive contamination from patients’ bodily fluids. Furthermore, the potential for delayed toxicities is also considered. In addition to toxicities and management, we also review the practical radiation safety precautions that are important both during and following RLT treatment. Full article

Dromedary camels possess unique anatomical, physiological, and metabolic adaptations that enable survival in arid environments; however, these same adaptations make them highly sensitive to nutritional imbalance under modern feeding conditions. This review synthesizes current knowledge on nutritional pathologies and metabolic disorders in camels, emphasizing the links between diet composition, foregut fermentation, mineral status, and systemic health. Imbalances in energy and carbohydrates predispose camels to subacute and acute acidosis, negative energy balance, and ketosis-like syndromes, particularly when rapidly fermentable feeds are introduced without adequate fiber or water. Protein and nitrogen disorders, including ammonia toxicity and impaired urea recycling, arise from mismatches between degradable protein, fermentable energy, hydration, and mineral availability. Widespread deficiencies of phosphorus, copper, cobalt, zinc, selenium, and vitamins A and E remain major constraints, leading to pica, poor microbial fermentation, oxidative stress, immunosuppression, reproductive failure, and skeletal disorders. Nutritional disturbances frequently extend beyond the gastrointestinal tract, forming a gut–liver–kidney metabolic axis characterized by hepatic dysfunction, renal compromise, and systemic oxidative stress. The review also addresses gastrointestinal impaction, foreign-body ingestion, toxic plant consumption, and feeding on human food waste as emerging nutritional challenges, particularly in peri-urban systems. Advances in diagnostic ultrasonography, feed evaluation techniques, probiotics, mineral–vitamin supplementation, and omics-based approaches are discussed as tools for improving early diagnosis and precision nutrition. Despite growing research interest, the lack of camel-specific feeding standards and reliance on cattle-based recommendations remain critical gaps. This review highlights the need for species-specific nutrient requirement models, sustainable rangeland management, and integrative research to support the health, resilience, and productivity of camels under changing environmental and production systems. Full article

Fine particulate matter (PM2.5)-induced ovarian damage has attracted widespread attention, but differences in cytotoxicity and underlying mechanisms of water-soluble (WS-PM2.5) and water-insoluble (WIS-PM2.5) fractions are unclear. To investigate potential effects of PM2.5 from livestock farming environments on animal ovaries, PM2.5 samples were collected from large-scale cattle barns. There were significant differences between fractions regarding elemental composition, proportion of water-soluble ions, polycyclic aromatic hydrocarbon content, and endotoxin concentrations. Based on transcriptome sequencing results, in a cowshed PM2.5 exposure model (rats), differentially expressed ovarian mRNAs were significantly enriched in signaling pathways such as cytokine interaction and the Hippo pathway, with the expression of thioredoxin-interacting protein (Txnip) significantly increased. In vitro (primary rat ovarian granulosa cells), short-term exposure to WS-PM2.5 (12 h) significantly induced inflammatory factor release, acute oxidative stress, mitochondrial dysfunction, and intracellular Ca²⁺ overload, with characteristics of rapid acute injury. However, extended (24 h) WIS-PM2.5 exposure had greater disruptive effects on estrogen homeostasis, intracellular enzyme release (LDH), and mitochondrial structure (subacute characteristics). Furthermore, downregulating Txnip expression via inhibitors effectively mitigated cowshed PM2.5-induced ovarian granulosa cell toxicity, oxidative stress, and mitochondrial and hormonal dysfunction. In summary, solubility of cowshed PM2.5 components affected cytotoxic characteristics, and Txnip was a key factor linking oxidative stress to granulosa cell damage. The study provided a mechanistic basis and potential targets for preventing and controlling PM2.5-induced ovarian damage in livestock environments. Full article

Plantain (Musa paradisiaca L.) is a tropical monocotyledonous, succulent plant of the Musaceae family commonly grown for food in the tropical regions of the African, Asian, and South American continents, where its parts are also sought for ethnomedicinal purposes in the treatment of burns, inflammation, and diabetes, among others. In the present preliminary exploratory study, the ethanol extract of the underutilized Musa paradisiaca peel (MPE) was evaluated for its in vitro inhibitory effects on α-amylase and α-glucosidase, as well as its in vivo hypoglycemic activity and potential biochemical toxicity. MPE (100, 200, 400 mg/kg) was orally administered to normal experimental rats for 30 days, following which the lipid profile, antioxidant status, and serum/tissue indices of hepatic, renal, and cardiac functions were evaluated. MPE produced significant inhibition (p < 0.05) of α-amylase (37%) and α-glucosidase (46%) at 120 µg/mL in vitro. The effect was lower than that of acarbose (IC₅₀ = 44.4 ± 1.14 and 15.60 ± 0.01 µg/mL, respectively). A modest blood glucose-lowering effect of MPE was observed at the highest tested dose (400 mg/kg) following subacute oral administration. During this treatment period, no biochemical alterations of toxicological importance were caused by MPE, as the organ–body weight ratio and serum/tissue indicators of organ function/damage were not adversely altered. In conclusion, MPE demonstrated inhibitory activity against both α-amylase and α-glucosidase, which may contribute to its potential hypoglycemic effects. Additionally, the findings indicate that the peel extract is non-toxic in rats following sub-acute administration at doses up to 400 mg/kg body weight. Further studies involving diabetic models and chronic exposure will substantiate and extend these preliminary observations. Full article

Background: Thunbergia alata is employed in traditional medicine to treat culture-bound syndromes such as “susto” (fright) or “espanto” (fearfulness). These conditions may correlate with depressive disorders. However, there is no evidence that this species has antidepressant properties. Aims: To characterize the antidepressant-like effect of an aqueous extract of T. alata in different paradigms and to analyze the role of brain monoamines in such actions. Methods: Independent groups of mice were treated with saline or the extract (1, 5, 10, 50, and 100 mg/kg; p.o.) and evaluated in the tail suspension (TST) and forced swimming tests (FST). Biochemical mechanisms were analyzed using inhibitors of monoamine synthesis, ligands of serotonergic receptors, and in vitro assays of MAO-A and MAO-B activity. Acute and sub-acute toxicity was evaluated. Results: The extract significantly reduced the immobility time of mice in both the TST and the FST, without affecting locomotor activity, as did the prototypical antidepressant desipramine. PCPA, AMPT, and NAN-190 abolished the extract’s effects on despair, while serotonergic ligands (8-OH-DPAT, fluoxetine, and pindolol) facilitated their antidepressant action. T. alata inhibited MAO-A and B activity. High doses of the extract produced no change in organ morphology; LD₅₀ was >2000 mg/kg. Conclusions: This is the first study to demonstrate that an aqueous extract of T. alata produces antidepressant effects mediated by the monoamine brain levels, especially serotonin. In addition to its use in culture-bounded syndromes, the present findings of safety and efficacy give support to the proposal that T. alata may be used in the treatment of depression. Full article

Anthracyclines are widely used chemotherapeutic agents with proven efficacy against a broad range of malignancies, but their clinical utility is limited by a well-documented, dose-dependent cardiotoxicity. While this toxicity has traditionally been attributed to direct cardiomyocyte injury, emerging evidence highlights the pivotal role of cardiac fibroblasts (CFs) in the development and progression of anthracycline-induced cardiotoxicity. This review examines the diverse effects of anthracycline focusing on doxorubicin (DOX) and CFs across the temporal phases of cardiac injury. DOX activates fibroblast-driven extracellular matrix remodeling and promotes fibrosis through enhanced collagen production and the induction of cellular senescence, thereby exacerbating early myocardial inflammation and dysfunction. Clinically, anthracycline cardiotoxicity may present as acute (within days), subacute (within weeks), or chronic progressive forms manifesting either early (within one year) or late (up to decades post-treatment). While early manifestations may be reversible with timely detection and management, late-phase cardiotoxicity is often irreversible, characterized by declining left ventricular ejection fraction and heart failure. A deeper understanding of the molecular and cellular contributions of CFs may uncover novel therapeutic targets to prevent or attenuate anthracycline-related cardiac damage. Full article

Background/Objectives: Our work was designed to study the physicochemical properties, safety profile, pharmacokinetics, and prophylactic efficacy of an original iodine–dextrin-based pharmaceutical formulation (PA), both alone and in combination with azithromycin (AZ), in a murine model of LPS-induced sepsis. Methods/Results: UV–vis and ¹H-NMR spectroscopy confirmed the formation of a stable iodine–dextrin complex, with triiodide anions stabilized by hydrogen bonding and donor–acceptor interactions. No clinical signs of acute toxicity were observed at doses up to 5000 mg/kg, and subacute administration (62.5 and 125 mg/kg) showed no adverse effects on hematological or biochemical parameters. A mild, non-pathological enlargement of thyrocytes and parallel increases in TSH, T3, and T4 levels were observed at 125 mg/kg, consistent with physiological adaptation to iodine. Pharmacokinetic analysis revealed high oral bioavailability (~92%), prolonged half-life (~21 h), and wide tissue distribution with low clearance. In the sepsis model, pretreatment with AZ+PA alleviated clinical symptoms, maintained body weight, and significantly improved hematological parameters, reducing WBCs and CRP levels. The combination also decreased plasma IL-6 and TNF-α concentrations more effectively than either agent alone, indicating a synergistic anti-inflammatory effect. Histological analysis confirmed that PA, particularly in combination with AZ, mitigated LPS-induced tissue injury in the liver, kidney, and lungs. Conclusions: These findings suggest that PA is a safe, bioavailable compound with immunomodulatory properties that enhance azithromycin’s protective effects during systemic inflammation. This supports its potential use as a prophylactic agent in clinical settings, such as preoperative immune modulation to prevent sepsis-related complications. Full article

Povidone-iodine (PVP-I), a widely used aquaculture disinfectant, remains poorly understood in terms of sublethal toxicity and damage reversibility. This study employed Macrobrachium rosenbergii as the model organism to evaluate the acute toxicity and sublethal effects of PVP-I through a 4-day exposure experiment followed by a 7-day depuration period. Acute toxicity tests enabled the determination of 24–96 h median lethal concentrations (LC₅₀), with the 96 h LC₅₀ being 5.67 mg/L and the safe concentration (SC) being 1.37 mg/L. Based on this, three sublethal concentrations (1.14, 1.89, and 2.84 mg/L) were tested over a 4-day exposure followed by a 7-day depuration period. Investigated endpoints included gill ultrastructure, apoptosis, and antioxidant and immune-related gene expression. Subacute exposure at 1.89 and 2.84 mg/L induced mitochondrial vacuolization, upregulated apoptosis-related genes (Cyt-c, Caspase-3, Bok), and downregulated antioxidant gene expression (SOD, CAT, GSH-Px). The high-concentration group also showed sustained Toll-like receptor (Toll) gene overexpression and acid phosphatase (ACP) gene suppression. After depuration, antioxidant gene expression normalized; however, apoptotic markers in gill tissue remained impaired. Overall, high PVP-I concentrations cause irreversible gill damage via mitochondrial-mediated apoptosis, whereas lower concentrations (≤1.14 mg/L) allow for greater recovery. These results offer crucial toxicodynamic insights for safer PVP-I use and risk assessment in M. rosenbergii aquaculture. Full article