Transcriptome and Proteome Analyses Reveal Stage-Specific DNA Damage Response in Embryos of Endangered Sturgeon

DNA damage during early life stages may have a negative effect on embryo development, inducing malformations that have long-lasting effects during adult life. Therefore, in the current study, we analyzed the effect of DNA damage induced by genotoxicants (camptothecin (CPT) and olaparib) at different stages of embryo development. We analyzed the survival, DNA fragmentation, transcriptome, and proteome of the endangered sturgeon Acipenser ruthenus. Sturgeons are non-model fish species that can provide new insights into the DNA damage response and embryo development. The transcriptomic and proteomic patterns changed significantly after exposure to genotoxicants in a stage-dependent manner. The results of this study indicate a correlation between phenotype formation and changes in transcriptomic and proteomic profiles. CPT and olaparib downregulated oxidative phosphorylation and metabolic pathways, and upregulated pathways involved in nucleotide excision repair, base excision repair, and homologous recombination. We observed the upregulated expression of zona pellucida sperm-binding proteins in all treatment groups, as well as the upregulation of several glycolytic enzymes. The analysis of gene expression revealed several markers of DNA damage response and adaptive stress-response, which could be applied in toxicological studies on fish embryo. This study is the first complex analysis of the DNA damage response in endangered sturgeons.

Toxicological and safety evaluations of Weissella cibaria strain CMU in animal toxicity and genotoxicity

Weissella cibaria belongs to the Lactobacillaceae family and has been isolated from traditional fermented foods and saliva of children with good oral health. Previous investigations have shown that W. cibaria CMU (Chonnam Medical University) is expected to be safe based on results of in silico and in vitro analyses. However, there is a lack of studies assessing its safety in vivo. A toxicological safety evaluation of W. cibaria CMU was performed using an acute oral safety study in rats, a 14-day oral range finding study, a subsequent 13-week oral toxicity study in rats and a genetic toxicity battery (in vitro bacterial reverse mutation, in vitro chromosome aberration in Chinese Hamster Ovary cells and in vivo micronucleus study in mice). The results of the studies in rats showed that the acute lethal dose of W. cibaria CMU is > 5000 mg/kg body weight (bw)/day (1.8 × 109 CFU/kg bw/day) and the 14-day or 13-week no observed adverse effect level (NOAEL) is 5000 mg/kg bw/day (1.8 × 109 CFU/kg bw/day), the highest dose administered. W. cibaria CMU was non-mutagenic in the bacterial reverse mutation test and non-clastogenic or aneugenic in vitro and in vivo. In conclusion, the toxicological studies performed demonstrated W. cibaria CMU to be a safe strain to consume. This study is the first study examining the potential of a W. cibaria strain to cause genetic toxicity and subchronic toxicity in rats according to the Organization for Economic Cooperation and Development guidelines.

A systematic ethnobotanical review of Adhatoda vasica (L.), Nees.

Adhatoda vasica (L.), Nees belonging to the family Acanthaceae is a shrub with opposite ascending branches. The plant has been used in the indigenous system of medicine in India for near about 2500 years. It is a well-known plant as a drug in Ayurvedic and Unani medicines. Traditionally it was used for the treatment of various acute and chronic diseases and showed strong pharmacological activity particularly for bronchial infections, cough, bacterial infections, reproductive disorders, cardiac diseases and many more. Various phytochemicals like alkaloids, flavonoids, tannins, etc. were obtained from Adhatoda vasica (A. vasica). The active constituent of the plant is vasicine, l-vasicinone, deoxyvasicine, maiontone, vasicinolone and vasicinol etc. This review consists of updated information on the phyto-constituents isolated from A. vasica and their potential role in the treatment of various ailments traditionally and medically. Based on the critical review it was concluded that there is not sufficient scientifically strong evidence to explain that A. vasica extract, could be harmful to human beings especially in pregnant women. Major data on traditional uses as well as toxicological studies, evaluated various correctness, relevance, importance, and reliability for the overall evaluation of A. vasica safety. Numerous clinical trials are conducted around the globe on the herbal formulations of vasaka. This review includes strong data about phytochemical and ethnopharmacological studies that indicate that A. vasica is a versatile native plant of the Indian subcontinent having a commercial reputation and thus can be encouraged for diversified applications like medicinal and other potential uses.

What Do We Know about Antimicrobial Activity of Astaxanthin and Fucoxanthin?

Astaxanthin (AST) and fucoxanthin (FUC) are natural xanthophylls, having multidirectional activity, including antioxidant, anti-inflammatory, and anticancer. Both compounds also show antimicrobial activity, which is presented in this review article. There are few papers that have presented the antimicrobial activity of AST. Obtained antimicrobial concentrations of AST (200–4000 µg/mL) are much higher than recommended by the European Food Safety Authority for consumption (2 mg daily). Therefore, we suggest that AST is unlikely to be of use in the clinical treatment of infections. Our knowledge about the antimicrobial activity of FUC is better and this compound acts against many bacteria already in low concentrations 10–250 µg/mL. Toxicological studies on animals present the safety of FUC application in doses 200 mg/kg body weight and higher. Taking available research into consideration, a clinical application of FUC as the antimicrobial substance is real and can be successful. However, this aspect requires further investigation. In this review, we also present potential mechanisms of antibacterial activity of carotenoids, to which AST and FUC belong.

A Narrative Review on the Phytochemistry, Pharmacology and Therapeutic Potentials of Clinacanthus nutans (Burm. f.) Lindau Leaves as an Alternative Source of Future Medicine

The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant’s extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this review paper compiles all the available contemporary data from this subtropical herb on its phytochemistry and pharmacological activities with a view towards garnering further interest in exploring its use in cardiovascular and renal diseases.

DETERMINATION OF CHEMICAL AND TOXICOLOGICAL CHARACTERISTICS OF WATER QUALITY IN RECREATIONAL AREAS ON THE MATYRA RIVER

В работе приведены и проанализированы данные химических и токсикологических исследований воды р. Матыра Липецкой области. Отмечены превышения допустимых значений по органолептическим показателям, а также по сульфатам, аммоний-иону и нитритам. Кроме того, было проведено определение относительной токсичности с помощью метода, основанного на регистрации изменений оптической плотности культуры водоросли хлорелла ( Chlorella vulgaris ). В результате биотестирования показано, что все пробы воды проявили токсичность, которая проявляется в стимуляции роста культуры хлорелла. Такая стимуляция роста свидетельствует о том, что исследованные пробы содержат легкоусвояемые органические и неорганические соединения. При сравнении полученных значений концентраций с предыдущими исследованиями отмечена отрицательная динамика по всем определяемым загрязняющим веществам, что свидетельствует о снижении качества воды. The paper presents and analyzes the data of chemical and toxicological studies of the water of the Matyra river of the Lipetsk region. Excess of permissible values for organoleptic parameters, as well as for sulfates, ammonium ion and nitrites were noted. In addition, the relative toxicity was determined using a method based on the registration of changes in the optical density of the Chlorella (Chlorella vulgaris) algae culture. The results of the bioassay showed that all water samples demonstrated toxicity, which manifests itself in stimulating the growth of chlorella culture. Such growth stimulation indicates that the samples studied contain easily digestible organic and inorganic compounds. When comparing the obtained concentration values with previous studies, negative dynamics was noted for all identified pollutants, which indicates a decrease in water quality.

Identification of a Thyroid Hormone Derivative as a Pleiotropic Agent for the Treatment of Alzheimer’s Disease

The identification of effective pharmacological tools for Alzheimer’s disease (AD) represents one of the main challenges for therapeutic discovery. Due to the variety of pathological processes associated with AD, a promising route for pharmacological intervention involves the development of new chemical entities that can restore cellular homeostasis. To investigate this strategy, we designed and synthetized SG2, a compound related to the thyroid hormone thyroxine, that shares a pleiotropic activity with its endogenous parent compound, including autophagic flux promotion, neuroprotection, and metabolic reprogramming. We demonstrate herein that SG2 acts in a pleiotropic manner to induce recovery in a C. elegans model of AD based on the overexpression of Aβ42 and improves learning abilities in the 5XFAD mouse model of AD. Further, in vitro ADME-Tox profiling and toxicological studies in zebrafish confirmed the low toxicity of this compound, which represents a chemical starting point for AD drug development.

Antitumor Potential of Annona muricata Linn. An Edible and Medicinal Plant in Mexico: In Vitro, In Vivo, and Toxicological Studies

Annona muricata (Am) is a plant used in traditional Mexican medicine to treat cancer. In this study, ethanol extracts of Am collected in Acapulco and Tecpan from Guerrero state were evaluated orally on Balb/c mice inoculated with 4T1 cells, for cytotoxic activity (CA) on 4T1 cells, in brine shrimp lethality assay (BSLA), and for acute oral toxicity in mice. In addition, ethanol extracts were subjected to high-performance liquid chromatography (HPLC) with diode array detection. Results showed that the extracts collected in December in Acapulco (AcDe) and Tecpan (TeDe) exhibited the most significant antitumor and cytotoxic activity. In the BSLA, the most important effect was observed in the extracts from Acapulco and Tecpan collected in June (AcJu) and August (TeAg), respectively. The samples from Acapulco (AcJu, and AcAg) and Tecpan (TeJu and TeAg) showed the highest toxicity. The analysis of the extracts, AcDe and TeDe, by HPLC revealed that flavonoids, rutin, narcissin, and nicotinflorin were the major components. These findings suggest that extracts from Am collected in Acapulco and Tecpan in the month of December may be an important source to obtain flavonoid glycosides with anticancer potential specifically against breast cancer. This also supports the use of Am to treat cancer in Mexican traditional medicine.

Zebrafish Embryos and Larvae as Alternative Animal Models for Toxicity Testing

Prerequisite to any biological laboratory assay employing living animals is consideration about its necessity, feasibility, ethics and the potential harm caused during an experiment. The imperative of these thoughts has led to the formulation of the 3R-principle, which today is a pivotal scientific standard of animal experimentation worldwide. The rising amount of laboratory investigations utilizing living animals throughout the last decades, either for regulatory concerns or for basic science, demands the development of alternative methods in accordance with 3R to help reduce experiments in mammals. This demand has resulted in investigation of additional vertebrate species displaying favourable biological properties. One prominent species among these is the zebrafish (Danio rerio), as these small laboratory ray-finned fish are well established in science today and feature outstanding biological characteristics. In this review, we highlight the advantages and general prerequisites of zebrafish embryos and larvae before free-feeding stages for toxicological testing, with a particular focus on cardio-, neuro, hepato- and nephrotoxicity. Furthermore, we discuss toxicokinetics, current advances in utilizing zebrafish for organ toxicity testing and highlight how advanced laboratory methods (such as automation, advanced imaging and genetic techniques) can refine future toxicological studies in this species.