Aspects Of Toxicity Research Articles

A Tau Pathogenesis-Based Network Pharmacology Approach for Exploring the Protections of Chuanxiong Rhizoma in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of neurodegenerative dementia and one of the top medical concerns worldwide. Currently, the approved drugs to treat AD are effective only in treating the symptoms, but do not cure or prevent AD. Although the exact causes of AD are not understood, it is recognized that tau aggregation in neurons plays a key role. Chuanxiong Rhizoma (CR) has been widely reported as effective for brain diseases such as dementia. Thus, we explored the protections of CR in AD by a tau pathogenesis–based network pharmacology approach. According to ultra-HPLC with triple quadrupole mass spectrometry data and Lipinski’s rule of five, 18 bioactive phytochemicals of CR were screened out. They were shown corresponding to 127 tau pathogenesis–related targets, among which VEGFA, IL1B, CTNNB1, JUN, ESR1, STAT3, APP, BCL2L1, PTGS2, and PPARG were identified as the core ones. We further analyzed the specific actions of CR-active phytochemicals on tau pathogenesis from the aspects of tau aggregation and tau-mediated toxicities. It was shown that neocnidilide, ferulic acid, coniferyl ferulate, levistilide A, Z-ligustilide, butylidenephthalide, and caffeic acid can be effective in reversing tau hyperphosphorylation. Neocnidilide, senkyunolide A, butylphthalide, butylidenephthalide, Z-ligustilide, and L-tryptophan may be effective in promoting lysosome-associated degradation of tau, and levistilide A, neocnidilide, ferulic acid, L-tryptophan, senkyunolide A, Z-ligustilide, and butylidenephthalide may antagonize tau-mediated impairments of intracellular transport, axon and synaptic damages, and neuron death (especially apoptosis). The present study suggests that acting on tau aggregation and tau-mediated toxicities is part of the therapeutic mechanism of CR against AD.

Biodegradation of Fumonisins by the Consecutive Action of a Fusion Enzyme.

Fumonisins (FBs) are toxic mycotoxins that commonly exist in food and feed. FBs can induce many aspects of toxicity, leading to adverse effects on human and animal health; therefore, investigating methods to reduce fumonisin contamination is necessary. In our study, we generated a recombinant fusion enzyme called FUMDI by linking the carboxylesterase gene (fumD) and the aminotransferase gene (fumI) by overlapping polymerase chain reaction (PCR). The fusion enzyme FUMDI was successfully, secretively expressed in the host Pichia pastoris (P. pastoris) GS115, and its expression was optimized. Our results demonstrated that the fusion enzyme FUMDI had high biodegradation activity of fumonisin B1 (FB1) and other common FBs, such as fumonisin B2 (FB2) and fumonisin B3 (FB3), and almost completely degraded 5 μg/mL of each toxin within 24 h. We also found that FUMDI enzyme and its reaction products had no negative effect on cell viability and did not induce cell apoptosis, oxidative stress, or endoplasmic reticulum (ER) stress in a human gastric epithelial cell line (GES-1). The results indicated that these FBs degradation products cannot have adverse effects in a cell model. In conclusion, a safe and efficient fumonisin-degrading enzyme was discovered, which could be a new a technical method for hazard control of FBs in the future.

The HSP40 chaperone Ydj1 drives amyloid beta 42 toxicity

Amyloid beta 42 (Abeta42) is the principal trigger of neurodegeneration during Alzheimer’s disease (AD). However, the etiology of its noxious cellular effects remains elusive. In a combinatory genetic and proteomic approach using a yeast model to study aspects of intracellular Abeta42 toxicity, we here identify the HSP40 family member Ydj1, the yeast orthologue of human DnaJA1, as a crucial factor in Abeta42‐mediated cell death. We demonstrate that Ydj1/DnaJA1 physically interacts with Abeta42 (in yeast and mouse), stabilizes Abeta42 oligomers, and mediates their translocation to mitochondria. Consequently, deletion of YDJ1 strongly reduces co‐purification of Abeta42 with mitochondria and prevents Abeta42‐induced mitochondria‐dependent cell death. Consistently, purified DnaJ chaperone delays Abeta42 fibrillization in vitro, and heterologous expression of human DnaJA1 induces formation of Abeta42 oligomers and their deleterious translocation to mitochondria in vivo. Finally, downregulation of the Ydj1 fly homologue, Droj2, improves stress resistance, mitochondrial morphology, and memory performance in a Drosophila melanogaster AD model. These data reveal an unexpected and detrimental role for specific HSP40s in promoting hallmarks of Abeta42 toxicity.

Safe-and-Sustainable-by-Design Framework Based on a Prospective Life Cycle Assessment: Lessons Learned from a Nano-Titanium Dioxide Case Study.

Safe-and-sustainable-by-design (SSbD) is a concept that takes a systems approach by integrating safety, sustainability, and functionality throughout a product’s the life cycle. This paper proposes a framework based on a prospective life cycle assessment for early safety and sustainability assessment. The framework’s purpose is to identify environmental sustainability and toxicity hotspots early in the innovation process for future SSbD applicability. If this is impossible, key performance indicators are assessed. Environmental sustainability aspects, such as global warming potential (GWP) and cumulative energy demand (CED), and toxicity aspects, such as human toxicity potential and freshwater ecotoxicity potential, were assessed upon applying the framework on a case study. The case study regarded using nano-titanium dioxide (P25-TiO2) or a modified nano-coated version (Cu2O-coated/P25-TiO2) as photocatalysts to produce hydrogen from water using sunlight. Although there was a decrease in environmental impact (GWP and CED), the modified nano-coated version had a relatively higher level of human toxicity and freshwater eco-toxicity. For the presented case study, SSbD alternatives need to be considered that improve the photocatalytic activity but are not toxic to the environment. This case study illustrates the importance of performing an early safety and environmental sustainability assessment to avoid the development of toxic alternatives.

A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin.

Curcuma longa Linn. (C. longa), popularly known as turmeric, belongs to the Zingiberaceae family and has a long historical background of having healing properties against many diseases. In Unani and Ayurveda medicine, C. longa has been used for liver obstruction and jaundice, and has been applied externally for ulcers and inflammation. Additionally, it is employed in several other ailments such as cough, cold, dental issues, indigestion, skin infections, blood purification, asthma, piles, bronchitis, tumor, wounds, and hepatic disorders, and is used as an antiseptic. Curcumin, a major constituent of C. longa, is well known for its therapeutic potential in numerous disorders. However, there is a lack of literature on the therapeutic potential of C. longa in contrast to curcumin. Hence, the present review aimed to provide in-depth information by highlighting knowledge gaps in traditional and scientific evidence about C. longa in relation to curcumin. The relationship to one another in terms of biological action includes their antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, cardioprotective, immunomodulatory, antifertility, antimicrobial, antiallergic, antidermatophytic, and antidepressant properties. Furthermore, in-depth discussion of C. longa on its taxonomic categorization, traditional uses, botanical description, phytochemical ingredients, pharmacology, toxicity, and safety aspects in relation to its major compound curcumin is needed to explore the trends and perspectives for future research. Considering all of the promising evidence to date, there is still a lack of supportive evidence especially from clinical trials on the adjunct use of C. longa and curcumin. This prompts further preclinical and clinical investigations on curcumin.

Environmental Impact Assessment of Sustainable Pig Farm via Management of Nutrient and Co-Product Flows in the Farm

This study evaluates the environmental impact assessment of sustainable pig farm via management of nutrient and co-product flows in the farm. Manure management and biogas production are among the most promising pathways towards fully utilizing organic waste within a circular bioeconomy as the most environmentally friendly solution mitigating gaseous emissions and producing bioenergy and high-quality bio-fertilizers. The concept of farm management includes rearing pig, growing all the feeds needed, and managing the nutrients and co-product flows in the farm. A consequential life cycle assessment (LCA) was performed to examine three scenarios in which all the generated manure is used as fertilizer for barley cultivation and mineral fertilizer is used where necessary (SC1); produced surplus straw is used for thermal energy generation and maize is used for sale, substituting maize biomass in the market (SC2); and all co-products are circulated in a closed system (SC3). The functional unit (FU) was defined as a “farm with 1000 fattening pigs at farm gate”. The analysis showed that heat generation from wheat, barley and legumes straw has a significantly higher positive environmental impact than the use of these cereal straw for biogas production. The partial replacement of mineral fertilizers with digestate has positive environmental effects in terms of abiotic depletion, photochemical oxidation, terrestrial ecotoxicity, freshwater aquatic ecotoxicity, human toxicity, and marine aquatic ecotoxic aspects. The amount of digestate generated on a farm is not sufficient to completely eliminate the use of mineral fertilizers for plant fertilization. The generated pig manure (SC1) and digestate (SC2) is only enough for the fertilization of 8.3% of the total cultivated land of farm applying 22.9 t/ha rate.

Pre-weaning fluoxetine exposure caused anti-depressant like behavior at adulthood via perturbing tryptophan metabolism in rats.

The perinatal depression exposes the child to antidepressants during vulnerable window of development, which can chronically impact the mental wellbeing of new born. Active pharmaceuticals are not tested for this long term neurobehavioral aspect of toxicity during drug development process. Keeping this in view, the current study was designed to study the effect of pre-weaning fluoxetine exposure on depression-like behavior of the offspring upon attaining adulthood using FST (Forced swim test). Additionally, the brain tryptophan, 5-HT (5-hydroxytryptamine) and its metabolite 5-HIAA (5-hydroxyindoleacetic acid) levels were quantified using Enzyme linked Immunosorbent Assay (ELISA), while expression of SERT (serotonin receptor), 5-HT1A receptor, TPH (tryptophan hydroxylase) genes were monitored using qPCR. Our data showed that pre-weaning fluoxetine (10, 50 or 100mg/kg) exposure decreased depression-like behavior. The 5-HT and 5-HIAA levels showed declining trend. However, the 5-HT synthetic precursor i.e. tryptophan levels were found to be significantly elevated in both brain and plasma as compared to control rats. The gene expression study did not reveal any significant alterations as compared to control. In conclusion, the present study demonstrate that pre-weaning fluoxetine exposure decreased depression-like behavior upon adulthood via perturbing tryptophan metabolism.

A Concise Review on Toxicity and Pharmacological Aspects of Foeniculum vulgare with Emphasis on Anti-Cancer Potential

The recent advancements in field of genomics and synthetic biology has paved the way for determination and utilization of pharmaceutical properties of beneficial plants. Foeniculum vulgare is a member of Apiaceae family, commonly known as fennel. It is globally distributed aromatic medicinal herb. F. vulgare falls in the category of World’s most important medicinal herb because of its economic status and pharmaceutical industrial applications. It has been used as herbal treatment for a longer period of time as an effective medicine to cure different ailments such as liver pain, kidney disorders, swollen stomach, abdominal pain, and mouth ulcerand no documented severe side effects reported. Essential oil, flavonoids and phenolic compounds are major chemical constituents of F.vulgare. Volatile and non-volatile compounds of this plant are responsible for its biological activities. The Pharmacological experiments performed by in vitro and in vivo models, revealed that F. vulgare has strong therapeutic effects. This review is supposed to shed the light on anti-bacterial, antioxidant, antidiabetic, antifungal, antimicrobial, antianxiety, hepatoprotective, memory protective, acaricidal, anti-cancer, anti-inflammatory and anti-mutagenic activities.

Acanthospermum hispidum DC: An Updated Review on Phytochemistry and Biological Activities.

Acanthospermum hispidum DC is a medicinal plant present in America, Africa, Australia, India, Hawaii, and Brazil. In Brazil, the species is used in the treatment of gastrointestinal, respiratory disorders and has expectorant action. In the literature, there are studies on the chemical composition of the species, with reports of the presence of alkaloids, flavonoids, hydrolyzable tannins, terpenes, and steroids. In addition, several studies have reported in vitro and in vivo studies that prove the biological properties of extracts and compounds isolated from different organs of the A. hispidum plant, including hepatoprotectors, antioxidants, antimicrobials and antiparasitic. The objective of this review is to update the knowledge about the phytochemical, pharmacological and toxicity aspects of A. hispidum, and to contribute to the recognition of the species and direct new studies. An extensive bibliographic search was conducted in different scientific databases. The presence of different chemical constituents in A. hispidum has been identified, among these constituents are flavonoids, tannins, terpenes, and steroids. Additionally, antimicrobial and antiparasitic activities were mainly attributed to the species, and other activities not previously described were presented, such as anticholinesterase, antioxidant, hepatoprotective, and hypoglycemic, all based on results of in vitro and in vivo studies. Finally, no reports of toxic effects were found in the in vitro and in vivo tests. After analyzing the articles, it was evidenced that other experiments with different models using animals are essential to evaluate the possible mechanisms of action of the extracts and compounds isolated of A. hispidum. Therefore, this review may contribute to the recognition of the importance of A. hispidum and its potential as a medicinal plant and may also guide the conduct of future research regarding the constituents, biological activities, and toxicity of the species.

The Toxic Side of Nanotechnology: An Insight into Hazards to Health and the Ecosystem

: The objective of the present article is to provide an insight into the toxicity aspects of nanoparticles on health and the ecosystem, along with risk assessment and monitoring. After a detailed screening of various research reports from peer-reviewed journals, books, and research news, the article was prepared. Nanotechnology's various significant advantages over conventional technologies have been explored for diverse research and commercial needs, such as cosmetics, medical, pharmaceuticals, biotechnology, electronics, catalysts, and robotics. However, nanotechnology has several challenging elements for health, environment, society, economic growth, and unpredictable consequences due to its unknown nature, which needs to be identified. Therefore, in this review, an attempt has been made to cover the two most important aspects of the toxicity of nanoparticles, i.e., influence on health and the ecosystem. The health hazards to various organs, especially lungs, gastro-intestinal tract and dermis, and aquatic organisms, have been elaborated. Furthermore, various ecotoxicological aspects, including mechanism of ecotoxicity, ecotoxicological challenges, and solutions to be undertaken by ecotoxicologists, are discussed. Finally, risk assessments related to the approaches that can be used for the optimization of nanotechnology are also mentioned. It is high time that nanotechnology gets reconsideration and uncompromising attention at the public and private level regarding its use, handling, storage, proper treatment, and disposal. Also, risk analysis and establishment of regulatory guidelines for the optimization and safe practice of nanotechnology for humans less harmful to the environment are recommended.

Photodegradation of propranolol in surface waters: An important role of carbonate radical and enhancing toxicity phenomenon

Antihypertensive propranolol (PRO) is frequently detected in surface waters and has adverse effects on aquatic organisms. In this study, its photochemical fate in surface water with the aspect of kinetics, products and toxicity were investigated employing steady-state photochemistry experiments and ecotoxicity tests. The results showed that photodegradation of PRO was enhanced in river water than that in phosphate buffer where dissolved organic matter (DOM), NO3−, and HCO3− played important roles. DOM accelerated the photodegradation mainly through generation of excited triplet-state DOM while NO3− played dual roles in the photodegradation. The reaction between excited triplet-state PRO and HCO3− can generate carbonate radical (CO3·-) to promote the photodegradation. The second-order reaction rate constant between PRO and CO3·- was determined to be (3.4 ± 0.8) × 108 M−1 s−1. Eight photodegradation products were identified in the studied river water sample. Finally, the toxicity evaluated by Vibrio fischeri increased after photodegradation and three photodegradation products were responsible for the increasing toxicity, which was concluded from the significant correlation between toxicity parameters and quantity of the photodegradation products.

Adverse effects of the toxic industrial dye malachite green on the antioxidant and antimicrobial properties of Allium cepa L.

The therapeutic importance of Allium cepa L. has been well established through ethnobotanical studies. Malachite Green is a highly toxic dye that finds extensive use in the textile industry as a fabric colorant. A. cepa was treated with malachite green solutions (20mg/l and 40mg/l) for 45 days. The roots actively take up malachite green and impede the plant's growth in root length, shoot length and fresh weight. A. cepa is rich in bioactive compounds, which have superior antioxidant and antimicrobial properties. We observe that the antimicrobial activities decrease by 36% for Staphylococcus aureus and 31% for Escherichia coli on the treatment of A. cepa bulbs with 40 mg/l malachite green. Antioxidant activity was similarly lowered by 61% under the toxic effects of the dye. Reduction in the efficacy of A. cepa in terms of the critical medicinal properties and general retardation in growth is a cause of concern. This article reports a previously unknown aspect of malachite green toxicity and presents the effect of any dye on the medicinal properties of A. cepa for the first time.

Curcumin nanoformulations: Beneficial nanomedicine against cancer.

Curcumin is a phytochemical achieved from the plant turmeric. It is extensively utilized for the treatment of several types of diseases such as cancers. Nevertheless, its efficiency has been limited because of rapid metabolism, low bioavailability, poor water solubility, and systemic elimination. Scientists have tried to solve these problems by exploring novel drug delivery systems such as lipid-based nanoparticles (NPs) (e.g., solid lipid NPs, nanostructured lipid carriers, and liposomes), polymeric NPs, micelles, nanogels, cyclodextrin, gold, and mesoporous silica NPs. Among these, liposomes have been the most expansively studied. This review mainly focuses on the different curcumin nanoformulations and their use in cancer therapy in vitro, in vivo, and clinical studies. Despite the development of curcumin-containing NPs for the treatment of cancer, potentially serious side effects, including interactions with other drugs, some toxicity aspects of NPs may occur that require more high-quality investigations to firmly establish the clinical efficacy.

Unravelling the Immune Modulatory Effect of Indian Spices to Impede the Transmission of COVID-19: A Promising Approach.

Months after WHO declared COVID-19 as a Global Public Health Emergency of International Concern, it does not seem to be flattening the curve as we are still devoid of an effective treatment modality and vaccination is in the first phase in many countries. Amid such uncertainty, being immune is the best strategy to defend against corona attacks. As the whole world is referring back to immune-boosting traditional remedies, interest is rekindled in the Indian system of Medicine, which is gifted with an abundance of herbal medicines as well as remedies. Among them, spices (root, rhizome, seed, fruit, leaf, bud, and flower of various plants used to add taste and flavors to food) are bestowed with immense medicinal potential. A plethora of clinical as well as preclinical studies reported the effectiveness of various spices for various ailments. The potential immune-boosting properties together with their excellent safety profiles are making spices the current choice of phytoresearch as well as the immune-boosting home remedies during these sceptical times. The present review critically evaluates the immune impact of various Indian spices and their potential to tackle the novel coronavirus, with comments on the safety and toxicity aspects of spices.

Ex vivo pulmonary assay applied for screening of toxicity potential of chemicals

Acute inhalation toxicity testing for chemical classification and labeling has been performed using animal models, however, these models have limited predictibility of the toxicity on the respiratory system. Thus, non-animal models have been emerging as alternatives for preclinical assessment of respiratory toxicity of chemicals, comprising in chemico, in vitro, ex vivo, and in silico approaches. In this study, we characterized and evaluated the applicability of a new ex vivo bovine bronchial model for addressing key aspects of pulmonary toxicity. Standardized bronchial fragments were cultured at an air-liquid interface for seven days showing cell viability, morphology, and function during the ex vivo time of cultivation. Different exposure ways, liquid or aerosol exposure, were also studied using paraformaldehyde (PFA) as a positive control. In a concentration-dependent manner, a decrease in tissue viability was observed for aerosols instead of direct liquid exposure upon tissue surface. Moreover, PFA exposure allowed the addressment of several damage biomarkers, including epithelium thickness, mitochondrial activity, ROS production, and caspase-3 activation. Besides, the bronquial tissue was exposed to chemicals from different UN GHS inhalation toxicity categories and presented a concentration-dependent response for most of the evaluated materials. The proposed airway ex vivo model represents a low-cost and reproducible tool applicable for pulmonary toxicity assessment of chemicals.

Egg toxic compounds in the animal kingdom. A comprehensive review.

Covering: 1951 to 2022Packed with nutrients and unable to escape, eggs are the most vulnerable stage of an animal's life cycle. Consequently, many species have evolved chemical defenses and teamed up their eggs with a vast array of toxic molecules for defense against predators, parasites, or pathogens. However, studies on egg toxins are rather scarce and the available information is scattered. The aim of this review is to provide an overview of animal egg toxins and to analyze the trends and patterns with respect to the chemistry and biosynthesis of these toxins. We analyzed their ecology, distribution, sources, occurrence, structure, function, relative toxicity, and mechanistic aspects and include a brief section on the aposematic coloration of toxic eggs. We propose criteria for a multiparametric classification that accounts for the complexity of analyzing the full set of toxins of animal eggs. Around 100 properly identified egg toxins are found in 188 species, distributed in 5 phyla: cnidarians (2) platyhelminths (2), mollusks (9), arthropods (125), and chordates (50). Their scattered pattern among animals suggests that species have evolved this strategy independently on numerous occasions. Alkaloids are the most abundant and widespread, among the 13 types of egg toxins recognized. Egg toxins are derived directly from the environment or are endogenously synthesized, and most of them are transferred by females inside the eggs. Their toxicity ranges from ρmol kg-1 to mmol kg-1, and for some species, experiments support their role in predation deterrence. There is still a huge gap in information to complete the whole picture of this field and the number of toxic eggs seems largely underestimated.

Ecodesign coupled with Life Cycle Assessment to reduce the environmental impacts of an industrial enzymatic cleaner

The application of life cycle assessment (LCA) through ecodesign strategies enables making informed choices on the sustainability of products and services. Accordingly, in this work we quantify the environmental impacts associated with the life cycle of an enzymatic multipurpose cleaner to provide guidance on how producers and consumers can boost the implementation of more sustainable production and consumption patterns. LCA methodology with primary data is applied. To enable future comparison, 1 kg of detergent in its container is used as a functional unit, and cradle-to-grave system boundaries are set according to the reference "detergents and cleaning products" Product Category Rules (PCR). The environmental impacts are grouped into upstream, core and downstream life cycle phases, and seven impact categories are analyzed. Regarding the upstream stage, the degreaser 3-butoxy-2-propanol has the larger environmental load in 4 of 7 categories analyzed. During the core stage, electricity, natural gas and road transport of raw materials are the main contributors, while road transport has the largest share in 6 of the 7 downstream impact categories. Considering a cradle-to-grave boundary, a CO 2 -eq footprint of 0.76 kg per kg of packaged detergent is obtained, where energy consumption and transportation are the main impact drivers. Five ecodesigned scenarios are proposed to lower the overall environmental footprint of the enzymatic cleaner, including the use of renewable energy, higher volume packaging, the use of recycled packaging, the use of renewable surfactants from vegetal origin instead of petrochemically derived ones and the change from road transport for distribution to railway transport are analyzed. Among the proposed new scenarios aimed lower the cradle-to-grave environmental impacts, enlarging packaging volume results the most effective choice, lowering the impacts by 8–38% (global warming reduction by 25%). On the contrary, the substitution of the petroleum-based surfactant by one based on palm kernel oil increases the impacts by 4–16%. Overall, using larger packaging and the adoption of railway transportation are the most effective measures to reduce the impacts. As the followed PCR does not take into account the impacts generated after the use phase, we encourage its extension to the complete life cycle so toxicity and biodegradability aspects can also be considered. Covering from the extraction of raw materials, to production, transport, use and end-of-life, this work may pave the path toward the adoption of responsible production and consumption patterns in the cleaning sector. .

A Comprehensive Review on the Heavy Metal Toxicity and Sequestration in Plants.

Heavy metal (HM) toxicity has become a global concern in recent years and is imposing a severe threat to the environment and human health. In the case of plants, a higher concentration of HMs, above a threshold, adversely affects cellular metabolism because of the generation of reactive oxygen species (ROS) which target the key biological molecules. Moreover, some of the HMs such as mercury and arsenic, among others, can directly alter the protein/enzyme activities by targeting their –SH group to further impede the cellular metabolism. Particularly, inhibition of photosynthesis has been reported under HM toxicity because HMs trigger the degradation of chlorophyll molecules by enhancing the chlorophyllase activity and by replacing the central Mg ion in the porphyrin ring which affects overall plant growth and yield. Consequently, plants utilize various strategies to mitigate the negative impact of HM toxicity by limiting the uptake of these HMs and their sequestration into the vacuoles with the help of various molecules including proteins such as phytochelatins, metallothionein, compatible solutes, and secondary metabolites. In this comprehensive review, we provided insights towards a wider aspect of HM toxicity, ranging from their negative impact on plant growth to the mechanisms employed by the plants to alleviate the HM toxicity and presented the molecular mechanism of HMs toxicity and sequestration in plants.

Impact of Metallic, Quantum Dots and Carbon-Based Nanoparticles on Quality and Storage of Albumin Products for Clinical Use

Albumin is the most versatile carrier protein in plasma, possessing multiple functions; a reduced amount of albumin in the body is associated with different kinds of diseases such as hypovolemia and hypoproteinemia. The demand for albumin increased for various indications in shocks, burns, cardiopulmonary bypass, acute liver failure and research applications. Several potential problems associated with the preparation and administration of this substance arise from purity, sterilization process and vascular membrane permeability. The present review discusses the potential of metallic, quantum dots and carbon-based nanocarriers to improve the quality of blood products and the effect of these nanoparticles on albumin products. The effects of these nanoparticles on albumin products with a focus on toxicity aspects, structural alteration, stressing conditions, stabilizing agents and unwanted leakage are highlighted. Our literature review indicated the enhanced efficiency of AuNPs in metallic nanoparticles and better performance of negatively charged QDs on albumin products, which provided important information for possible safe use in medical applications. Moreover, among carbon-based nanoparticles, GO had relatively improved effects on albumin unwanted leakage and fibrillation. This review suggests an agenda for scientists to use and design nanoparticles to improve albumin products for various applications.

Intestinal toll-like receptor 4 knockout alters the functional capacity of the gut microbiome following irinotecan treatment.

Irinotecan can cause high levels of diarrhea caused by toxic injury to the gastrointestinal microenvironment. Toll-like receptor 4 (TLR4) and the gut microbiome have previously been implicated in gastrointestinal toxicity and diarrhea; however, the link between these two factors has not been definitively determined. We used a tumor-bearing, intestinal epithelial cell (IEC) TLR4 knockout model (Tlr4ΔIEC) to assess microbiome changes following irinotecan treatment. We then determined if a fecal microbiota transplant (FMT) between Tlr4ΔIEC and wild-type (WT) mice altered irinotecan-induced gastrointestinal toxicity. MC-38 colorectal cancer cells were injected into WT and Tlr4ΔIEC mice. Fecal samples were collected prior to tumor inoculation, prior to irinotecan treatment and at cull. 16S rRNA gene sequencing was used to assess changes in the microbiome. Next, FMT was used to transfer themicrobiome phenotype between Tlr4ΔIEC and WT mice prior to irinotecan treatment. Gastrointestinal toxicity symptoms were assessed. In study 1, there were no compositional differences in the microbiome between Tlr4ΔIEC and WT mice at baseline. However, predicted functional capacity of the microbiome was different between WT and Tlr4ΔIEC at baseline and post-irinotecan. In study 2, Tlr4ΔIEC mice were protected from grade 3 diarrhea. Additionally, WT mice who did not receive FMT had more colonic damage in the colon compared to controls (P = 0.013). This was not seen in Tlr4ΔIEC mice or WT mice who received FMT (P > 0.05). Tlr4ΔIEC and WT had no baseline compositional microbiome differences, but functional differences at baseline and following irinotecan. FMT altered some aspects of irinotecan-induced gastrointestinal toxicity.