6-Shogaol induces apoptosis in acute lymphoblastic leukaemia cells by targeting p53 signalling pathway and generation of reactive oxygen species

Combination therapies, using medicinal herbs, are broadly recommended to attenuate the chemotherapy adverse effects. Based on our previous findings considering the anti-leukaemic effects of ginger extract on acute lymphoblastic leukaemia (ALL) cells, the present study was aimed to investigate the anti-cancer role of this pharmaceutical plant on ALL mice models. Moreover, we worked towards identifying the most anti-leukaemic derivative of ginger and the mechanism through which it may exert its cytotoxic impact. In vivo experiments were performed using five groups of six C57BL/6 nude mice, and the anti-leukaemic activity of ginger extract alone or in combination with methotrexate (MTX) was examined. Results showed increased survival rate and reduced damages in mice brain and liver tissues. Subsequently, MTT assay demonstrated synergistic growth inhibitory effect of 6-shogaol (6Sh) and MTX on ALL cell lines and patients primary cells. Eventually, the molecular anti-neoplastic mechanism of 6Sh was evaluated using Bioinformatics. Flow cytometry illustrated 6Sh-mediated apoptosis in Nalm-6 cells confirmed by Western blotting and RT-PCR assays. Further analyses exhibited the generation of reactive oxygen species (ROS) through 6Sh. The current study revealed the in vivo novel anti-leukaemic role of ginger extract, promoted by MTX. Moreover, 6-shogaol was introduced as the major player of ginger cytotoxicity through inducing p53 activity and ROS generation.     

Enhancement of seminiferous tubular growth and spermatogenesis in testes of rats recovering from early hypothyroidism: a quantitative study

Testicular weight and DNA content were markedly reduced (63 and 69%) in weanling Long-Evans rat pups rendered hypothyroid from birth by administration of propylthiouracil (PTU), a reversible goitrogen. These growth deficits worsened to >80% by continuing hypothyroidism beyond weaning, to days 50 and 90. Recovery of thyroid function, brought about by discontinuing PTU at weaning, resulted in a paradoxical stimulation of testis growth, amounting to increased weight (40%), DNA content (60%) and size by 90 days, compared to age-matched controls. In the 25-day or older hypothyroid rats, testicular structure was immature and spermatogenesis markedly delayed, as evident by closed lumen and significantly reduced diameter of seminiferous tubules (38%), thickness of germinal layer (70%), and number of primary spermatocytes (86%), compared to control. Hypothyroidism did not alter the number of tubules per testis cross section. In the 90-day recovery rats, numbers of seminiferous tubules were unchanged but tubular diameter was significantly (20%) larger than in controls and spermatogenesis appeared very active as indicated by significantly increased germinal layer thickness (22%) and total number and density of primary spermatocytes (55% and 40%). The results show that although postnatal hypothyroidism is deleterious for testicular growth and spermatogenesis, recovery from this condition leads to enhanced seminiferous tubular growth and spermatogenesis.     

An in silico analysis on the photoproteins Mnemiopsin 1 and Mnemiopsin 2 to explain the experimental results

Mnemiopsin 1 (Mn1) and Mnemiopsin 2 (Mn2) are photoproteins found in Mnemiopsis leidyi. We have tried to answer the question of whether the structural features of photoproteins can explain the observed activity data. According to the activity measurements data, they have the same characteristic wavelength. However, the initial intensity of Mn2 is significantly higher than that of Mn1, and decay time of Mn1 (0.92 s⁻¹) is lower than that of Mn2 (1.46 s⁻¹). The phylogenetic analysis demonstrates that, compared with Obelin and Aequorin from Obelia longissima and Aequorea victoria, respectively, a gene modification event may have caused the expansion of the N-terminal side of all photoproteins from M. leidyi. An in silico study has shown that the stability of the photoprotein–substrate complex of Mn2 is higher than that of Mn1, indicating a higher affinity of the substrate for Mn2 compared with Mn1. It was revealed that the active EF-hand loops 1 and III in Mn2 is locally more rigid compared with those in Mn1. We concluded that different stability of the photoprotein complexes leads to different initial intensity. While different patterns of the local dynamics of loops I and III may influence the decay rate.     

Fullerenol [60] Nano-cages for Protection of Crops Against Oxidative Stress: A Critical Review

Journal of Plant Growth Regulation - Fullerenols are carbon nanoparticles that have been declared as free radical sponges. There is a need to take a prudent path toward its applications in various...     

The Human Cathelicidin LL-37, a Defensive Peptide Against Rotavirus Infection

International Journal of Peptide Research and Therapeutics - LL-37 is a 37 amino acid long cationic peptide belonging to the cathelicidin family of antimicrobial peptides. Limited investigations...     

Plant growth-promoting Bacillus sp. strain SDA-4 confers Cd tolerance by physio-biochemical improvements,better nutrient acquisition and diminished Cd uptake in Spinacia oleracea L.

Cadmium (Cd) is highly toxic metal for plant metabolic processes even in low concentration due to its longer half-life and non-biodegradable nature. The current study was designed to assess the bioremediation potential of a Cd-tolerant phytobeneficial bacterial strain Bacillus sp. SDA-4, isolated, characterized and identified from Chakera wastewater reservoir, Faisalabad, Pakistan, together with spinach (as a test plant) under different Cd regimes. Spinach plants were grown with and without Bacillus sp. SDA-4 inoculation in pots filled with 0, 5 or 10 mg kg⁻¹ CdCl₂-spiked soil. Without Bacillus sp. SDA-4 inoculation, spinach plants exhibited reduction in biomass accumulation, antioxidative enzymes and nutrient retention. However, plants inoculated with Bacillus sp. SDA-4 revealed significantly augmented growth, biomass accumulation and efficiency of antioxidative machinery with concomitant reduction in proline and MDA contents under Cd stress. Furthermore, application of Bacillus sp. SDA-4 assisted the Cd-stressed plants to sustain optimal levels of essential nutrients (N, P, K, Ca and Mg). It was inferred that the characterized Cd-tolerant PGPR strain, Bacillus sp. SDA-4 has a potential to reduce Cd uptake and lipid peroxidation which in turn maintained the optimum balance of nutrients and augmented the growth of Cd-stressed spinach. Analysis of bioconcentration factor (BCF) and translocation factor (TF) revealed that Bacillus sp. SDA-4 inoculation with spinach sequestered Cd in rhizospheric zone. Research outcomes are important for understanding morpho-physio-biochemical attributes of spinach-Bacillus sp. SDA-4 synergy which might provide efficient strategies to decrease Cd retention in edible plants and/or bioremediation of Cd polluted soil colloids.     

Advances in Salt Tolerance of Some Major Fiber Crops Through Classical and Advanced Biotechnological Tools: A Review

Journal of Plant Growth Regulation - Plant biofibers are of great economic and commercial importance. Among various fiber producing crops, cotton (Gossypium hirsutum L.), hemp (Cannabis sativa L.),...     

Elucidating Cd-mediated distinct rhizospheric and in planta ionomic and physio-biochemical responses of two contrasting Zea mays L. cultivars

Cadmium (Cd) in soil–plant system can abridge plant growth by initiating alterations in root zones. Hydroponics and rhizoboxes are useful techniques to monitor plant responses against various natural and/or induced metal stresses. However, soil based studies are considered more appropriate in order to devise efficient food safety and remediation strategies. The present research evaluated the Cd-mediated variations in elemental dynamics of rhizospheric soil together with in planta ionomics and morpho-physio-biochemical traits of two differentially Cd responsive maize cultivars. Cd-sensitive (31P41) and Cd-tolerant (3062) cultivars were grown in pots filled with 0, 20, 40, 60 and 80 µg/kg CdCl₂ supplemented soil. The results depicted that the maize cultivars significantly influenced the elemental dynamics of rhizosphere as well as in planta mineral accumulation under applied Cd stress. The uptake and translocation of N, P, K, Ca, Mg, Zn and Fe from rhizosphere and root cell sap was significantly higher in Cd stressed cv. 3062 as compared to cv. 31P41. In sensitive cultivar (31P41), Cd toxicity resulted in significantly prominent reduction of biomass, leaf area, chlorophyll, carotenoids, protein contents as well as catalase activity in comparison to tolerant one (3062). Analysis of tolerance indexes (TIs) validated that cv. 3062 exhibited advantageous growth and efficient Cd tolerance due to elevated proline, phenolics and activity of antioxidative machinery as compared to cv. 31P41. The cv. 3062 exhibited 54% and 37% less Cd bio-concentration (BCF) and translocation factors (TF), respectively in comparison to cv. 31P41 under highest Cd stress regime. Lower BCF and TF designated a higher Cd stabilization by tolerant cultivar (3062) in rhizospheric zone and its potential use in future remediation plans.     

Liquid–liquid phase separation of Tau by self and complex coacervation

The liquid–liquid phase separation (LLPS) of Tau has been postulated to play a role in modulating the aggregation property of Tau, a process known to be critically associated with the pathology of a broad range of neurodegenerative diseases including Alzheimer''s Disease. Tau can undergo LLPS by homotypic interaction through self‐coacervation (SC) or by heterotypic association through complex‐coacervation (CC) between Tau and binding partners such as RNA. What is unclear is in what way the formation mechanisms for self and complex coacervation of Tau are similar or different, and the addition of a binding partner to Tau alters the properties of LLPS and Tau. A combination of in vitro experimental and computational study reveals that the primary driving force for both Tau CC and SC is electrostatic interactions between Tau‐RNA or Tau‐Tau macromolecules. The liquid condensates formed by the complex coacervation of Tau and RNA have distinctly higher micro‐viscosity and greater thermal stability than that formed by the SC of Tau. Our study shows that subtle changes in solution conditions, including molecular crowding and the presence of binding partners, can lead to the formation of different types of Tau condensates with distinct micro‐viscosity that can coexist as persistent and immiscible entities in solution. We speculate that the formation, rheological properties and stability of Tau droplets can be readily tuned by cellular factors, and that liquid condensation of Tau can alter the conformational equilibrium of Tau.     

The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate

Inflammatory cytokines exert different effects on hematopoietic stem cells (HSCs), lead to the development of various cell lineages in bone marrow (BM) and are thus a differentiation axis for HSCs. The content used in this article has been obtained by searching PubMed database and Google Scholar search engine of English-language articles (1995–2020) using “Hematopoietic stem cell,” “Inflammatory cytokine,” “Homeostasis,” and “Myelopoiesis.” Inflammatory cytokines are involved in the differentiation and proliferation of hematopoietic progenitors to compensate for cellular death due to inflammation. Since each of these cytokines differentiates HSCs into a specific cell line, the difference in the effect of these cytokines on the fate of HSC progenitors can be predicted. Inhibitors of these cytokines can also control the inflammatory process as well as the cells involved in leukemic conditions. In general, inflammatory signaling can specify the dominant cell line in BM to counteract inflammation and leukemic condition via stimulating or inhibiting hematopoietic progenitors. Therefore, detection of the effects of inflammatory cytokines on the differentiation of HSCs can be an appropriate approach to check inflammatory and leukemic conditions and the suppression of these cytokines by their inhibitors allows for control of homeostasis in stressful conditions.