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Aflatoxin B₁ (AFB₁) is a pre-carcinogenic molecule produced by toxigenic fungi and is widely harmful to public health. Algae extracts are sub-cellular pilot plants rich in bioactive substances that aid detoxification. This study aimed to reduce AFB₁-toxicity in biological tissues of administrated rats using two algae extracts, Spirulina (SPR) and Amphora (AMR). Algae extracts were prepared using an aqueous system, concentrated, and lyophilized before being administrated to rats. The extract contents of total phenolic and flavonoids were determined to indicate their bioactive content and antioxidant potency. The animal experiment was designed in 8 groups as the control negative and control positive (AFB₁; 20 μg/kg BW/day); groups 3 and 4 were designed for control positive of algae applied at high doses for toxicity evaluation. Otherwise, four groups were classified as G5 and G6 for rats administrated by AFB_1, followed by 50 and 100 mg/kg Spirulina extract, respectively. The G7 and G8 were administrated with an AFB1 dose followed by amphora treatment at 50 and 100 mg extract/kg, respectively. The results showed a significant content of algae extracts of phenolic compounds (27.36 ± 1.75 and 39.55 ± 1.14 mg GAE/g DW for the SPR and AMR, respectively), with a valuable antioxidant activity. For rats treated only with the SPR or AMR extracts, no tissue changes were recorded for the liver, kidney, pancreas, or testis. Again, the biochemical parameters of these groups are recorded without harmful impacts, particularly for the tumor markers of AFP, TNF-α, CEA, and ALP. Once more, a higher extract concentration was more effective in AFB₁-toxicity reduction, particularly for the SPR on the liver and kidney tissues. The SPR extract manifested a protective impact in sensitive tissue against the AFB₁ effect, particularly in the testis. The results recommend the application of SPR extract at 100 mg/kg bw as an effective treatment for AFB₁-toxicity regulation (as pharmaceutical or nutraceutical) involved in daily habits.

Thymoquinone is the main active compound derived from the essential oil of the Nigella sativa plant seed. While thymoquinone is an antioxidant, it has been reported in several studies that thymoquinone has dose-dependent pro-oxidant activity with the Fenton reaction in the presence of transition elements such as iron and copper. This study aimed to investigate cytotoxic, apoptotic, genotoxic, and reactive oxygen species (ROS) generating effects of thymoquinone treated with copper in colon cancer cells. HT-29 cells were treated with pro-oxidant-acting doses of thymoquinone alone and together with the non-toxic dose of Copper (II) Sulfate for 24 h. Cytotoxic, apoptotic, genotoxic, and ROS production activities were analyzed by MTT viability test, Acridine Orange/Ethidium Bromide (AO/EB) staining, alkaline single cell gel electrophoresis and H2DCF-DA assay, respectively. Viability results showed that thymoquinone and copper synergistically affect cancer cells, and DNA damage was increased with the synergic effect. The intracellular ROS was increased when thymoquinone and copper were applied together. Applying redox-active copper (II) with thymoquinone increases DNA damage, apoptosis, and cell death by increasing the amount of intracellular ROS through pro-oxidant activity. Treatments targeting copper-related pathways may open new therapeutic avenues for cancer treatment.

Background

Infertility has been observed as one of the major issues in humans, one known risk factor is heavy metals.

Methods

The main focus of the present research was to assess the toxic effect of hexavalent chromium (Cr (VI)) on sperm and its mitigation by Nigella sativa seed extract (NS) and its conjugated silver nanoparticles (NS + NP). In the present study, we administered 1.5 mg/kg body of Cr (VI) orally in mice for 60 days routinely, to induce toxicity in testes and effect on sperm production and motility in male mice. NS and NS + NP (50 mg/kg body weight) were administered to evaluate protective action against Cr (VI). The sperm were analyzed by computer-assisted semen analysis (CASA) and chromium concentration in testicular tissue was measured via the atomic absorption spectrophotometer.

Results

The CASA analysis showed that Cr (VI) was directly linked with a decline in sperm concentration, motility, distance, velocity, straightness, and head beat frequency attributes. However, the administration of Nigella sativa seed extract and its green synthesized silver nanoparticles improved sperm concentration, motility, distance, velocity, straightness, and head beat frequency. The chromium content in the testes of Cr-exposed animals significantly increased, which negatively affected sperm parameters. However, Nigella sativa and Nigella sativa conjugated silver nanoparticles appeared to help in the removal of Cr content from testes hence improving the sperm parameters in exposed mice.

Conclusion

The decrease in Cr concentration improved sperm quality and quantity, hence, improve male fertility.

Attempts were made to evaluate the purified bioactive compounds of Xenorhabdus nematophila against Meloidogyne incognita. In order to extract the purified compounds, a solid-supported liquid-liquid extraction system with a flow rate (1 mL/min) was used to purify bioactive molecules. Compounds were individually collected concentrated and evaluated against M. incognita. Among 25 fractions the L19 fraction, exhibited 98% inhibition in egg hatching and mortality of juveniles. The biomolecules were identified through Liquid Chromatography- Mass Spectroscopy (LC-MS) technique. To decipher the mode of action of compounds, molecular docking studies were performed with potential protein targets such as acetylcholinesterase, β-1,4-endoglucanase, glutathione S-transferase-1, cytochrome c oxidase, G-protein coupled receptor and Fatty acid and retinol-binding proteins of M. incognita. The results revealed that among eight compounds from the L19 fraction, malonate and pidopidon exhibited greater binding affinity towards the selected protein targets of M. incognita. In vitro studies with malonate and pidopidon against M. incognita showcased a 99% reduction in egg hatching and juvenile mortality. Moreover, greenhouse experiments revealed that malonate compounds not only reduced 94% of the M. incognita population but also enhanced the plant growth parameters in tomato by 60%. Hence the present study stands novel in exploiting the nematicidal compounds from X. nematophila giving limelight to explore pidopidon and malonate as novel nematicidal compounds for the management of M. incognita.

Naja species bite is the commonest cause for consultation to Remote Envenomation Consultancy Services in Malaysia. Envenomation by Naja species may result in neuroparalysis and cardiotoxic effects including arrhythmias, hypertension, tachycardia, atrioventricular blocks, ventricular tachycardia, and ventricular fibrillation. We report a case of cardiotoxicity as an early manifestation following an equatorial spitting cobra, Naja sumatrana bite, preceding early paralytic envenomation manifestation. A 14-year-old boy presented to an emergency department with mild local envenomation. ECG showed multiple ventricular premature complexes. Subsequently patient developed ptosis. Complete resolution of ptosis and resumption of normal sinus rhythm occurred following administration of the appropriate antivenom. The patient was discharged well after two days of hospitalization. The patient's ECG findings and neurotoxic manifestation suggested acute systemic envenomation. High index of suspicion for cardiotoxicity with close serial monitoring is recommended to ensure timely administration of antivenom.

In tropical nations, snakebite envenomation is a significant public health issue with negative human and social effects. This is due to three factors: 1) more species of the most hazardous snakes are present; 2) emergency medical assistance is not readily available; and 3) inadequate health care. The problems caused by snakebite envenomation have been partially resolved by immunotherapy. An extensive collection of medicinal herbs is recognized to have antivenomous properties in traditional medicine. However, very few species have undergone scientific investigation, and even fewer have had their active components separated and structurally and functionally defined. In this work, the anti-venom potential of hot and cold aqueous extracts from Pittosporum neelgherrense is evaluated using an in-vitro model. The experimental results showed that 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-(11.20), 1-Undecanol (16.38), Lauryl acetate (18.25), and Cyclotridecane (19.14) were phytochemical substances whose chemical structures were recognized by GCMS. The Direct and Indirect hemorrhagic activity was found to be completely neutralized by P. neelgherrense extract (44.61% hot plant extract & 55.38% cold plant extract) and the zone (2.4 mm), respectively. The neutralization of venoms was indicated by the zone (0.5–0.9 cm) of hydrolysis production of proteolytic activity. Additionally, the results of the gelatine liquefaction study demonstrated that clot formation was not triggered by venom at low concentrations (50:50) but was instead brought on by higher concentrations. The present study suggested that the neutralization of venom by hot water extracts of P. neelgherrense is a potentially therapeutic application.

Implementation of the next-generation technologies for gene sequencing of venom duct transcriptome has provided a large number of peptide sequences of marine cone snails. Emerging technologies on computational platforms are now rapidly evolving for the accurate predictions of the 3D structure of the polypeptide using the primary sequence. The current report aims to integrate the information derived from these two technologies to develop the concept of structure-aided function assignment of Conus peptides. The proof of the concept was demonstrated using the transcriptomic peptide Am931 of C. amadis. The 3D structure of Am931 was computed using Density Functional Theory (DFT) and the quality of the predicted structure was confirmed using 2D NMR spectroscopy of the corresponding synthetic peptide. The computed structure of Am931 aligns with the active site motif of thioredoxins, possess catalytic disulfide conformation of (+, −)AntiRHHook and selectively modulate the N-terminal Cys3 thiol. These structural features indicate that Am931 may act as a disulfide isomerase and modulate the oxidative folding of conotoxins. Synthetic peptide Am931 provides proof-of-function by exhibiting catalytic activity on the oxidative folding of α-conotoxin ImI and improving the yield of native globular fold. The approach of integration of new technologies in the Conus peptide research may help to accelerate the discovery pipeline of new/improved conotoxin functional.

Yangzheng mixture has been used as an adjuvant tumor therapy as a traditional Chinese medicine in clinical. However, less is known about the activity of Yangzheng mixture. In our study, we explored the anti-tumor activity of Yangzheng mixture for HCC in vitro and in vivo. The effects of Yangzheng mixture on HCC biological behaviors were assessed using colony formation assay, EdU staining, cell cycle assay, Annexin V/PI staining, and wound healing assay. Migration and invasion of HCC cells were further evaluated via transwell assays, while molecular mechanisms were investigated through western blotting and immunofluorescence staining. Additionally, the anticancer effect of Yangzheng mixture in vivo were examined using H22 xenograft and H22 metastatic hepatocellular carcinoma models. Our results revealed that Yangzheng mixture inhibited colony formation, EdU incorporation, cell migration, and invasion, while arresting cell cycle at the G2-M phase in Bel-7402 and SMMC-7721 cells. Mechanistic studies demonstrated that Yangzheng mixture showed a markedly inhibition on Bel-7402 and SMMC-7721 cells with higher NLRP3 expression. We further confirmed that Yangzheng mixture could activate NLRP3 inflammasome through NF-κB by western blotting and immunofluorescence staining. Additionally, Yangzheng mixture inhibited β-catenin nucleus translocation and reversed EMT process. In vivo, the H22 xenograft model depicted that Yangzheng mixture significantly reduced tumor size and weight compared with control. Moreover, H22 lung metastasis model showed that Yangzheng mixture significantly inhibited liver cancer cell spreading to lungs in mice. Overall, our finding revealed that Yangzheng mixture inhibited HCC proliferation and migration in vitro and in vivo by reversing EMT via NF-κB/NLRP3/β-catenin pathway. These results may serve new therapeutic evidences for Yangzheng mixture application in clinical.