The Cytotoxic Effect of Cecropin A and Cecropin B on the MDA-MB-231 and M14K Tumour Cell Lines

The aim of the present in vitro study was to assess the tumoricidal potential of the following natural peptides belonging to the Cecropin family, namely Cecropin A and B, on a series of tumour cell lines: MDA-MB-231 (breast adenocarcinoma) and M14K (human mesothelioma). The experimental results reveal that the cytotoxic effects of the two peptides depend on their concentration. Their efficiency is significant at 120 μM concentrations and it persists even at 60 μM concentrations. The effects were insignificant at 30 μM concentrations. On the other hand, the cytotoxic potential was not significantly dependant on the type of peptide but more on the type of tumour cell line used. The MDA MB 231 line cells were much more sensitive to the action of Cecropins A and B than the M14K line cells. The prospects brought about by this experimental research consist of the collection of in vitro experimental data on the tumoricidal potential of these natural cytotoxic peptides on tumour cells. This will enable specialists to develop future in vivo experimental models in order to test the antitumor effect of these cytotoxic peptides. The ultimate goal would be the discovery of agents with efficient antitumor properties, i.e. with maximum tumoricidal effects and minimum toxic side effects.

Phenylacetylglutaminate and Phenylacetate in Combination Upregulate VDUP1, Cause Cell Cycle Blockade and Apoptosis in U87 Glioblastoma Cells

Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit the growth of neoplastic cells without growth inhibitory effect in normal cells. The aim of this study was to identify molecular pathways involved in the anti-proliferative effect of antineoplastons. Using a total human genome microarray we have found that 1) Vitamin D3 upregulated protein (VDUP1) is significantly upregulated in response to PG and PN in the U87 glioblastoma cells;2) Isobologram analysis shows that PG and PN act in an additive or synergistic manner to effectively suppress proliferation of U87 cells;3) PG and PN cause cell cycle arrest, changes in expression of several cell cycle genes and suppress expression and activity of the G2/M checkpoint kinase, CHK1. The multiple cellular targets possibly make these compounds effective anti-proliferative agents. We propose that PG and PN in combination target important cellular pathways and upregulate VDUP1 leading to detachment-induced apoptosis in cancer cells.

Potential of molecular chaperones for treating Alzheimer’s disease

Alzheimer’s disease(AD)is the most prevalent form of dementia,i.e.,progressive memory loss and profound cognitive dysfunction,resulting in a considerable societal burden.At the neuropathological level,the brains of AD patients exhibit amyloid-β(Aβ)plaques,neurofibrillary tangles,and neuroinflammation(Sala Frigerio and De Strooper,2016).

Application of Polygonum minus Extract in Enhancing Drought Tolerance in Maize by Regulating Osmotic and Antioxidant System

Drought stress is a major factor affecting plant growth and crop yield production.Plant extracts as natural biostimulants hold great potential to strengthen plants to overcome drought impacts.To explore the effect of Polygonum minus extract(PME)in enhancing drought tolerance in plants,a study was set up in a glasshouse environment using 10 different treatment combinations.PME foliar application were designed in CRD and effects were closely observed related to the growth,physiology,and antioxidant system changes in maize(Zea mays L.)under well-watered and drought conditions.The seaweed extract(SWE)was used as a comparison.Plants subjected to drought stress exhibited a significant reduction in fresh weight,dry weight,relative water content(RWC),and soluble sugar,but they stimulated the phenolic,flavonoid,proline,glutathione(GSH),malondialdehyde(MDA)and antioxidant enzyme(catalase,CAT;peroxidase,POD;superoxide dismutase,SOD)activities.Foliar application of PME improved fresh and dry weight(FW:33.1%~41.4%;DW:48.0%~43.1%),chlorophyll content(Chl b:87.9%~100.76%),soluble sugar(23.6%~49.3%),and soluble protein(48.6%~56.9%)as well as antioxidant enzyme activities(CAT and POD)compared to CK under drought conditions.while decreasing the level of MDA.Notably,the mitigating effect of PME application with high concentration was more effective than those of SWE.Our study reveals that PME could alleviate drought stress by regulating osmoprotectant content and antioxidant defense system and can be used as an economical and environmentally friendly biostimulants for promoting maize growth under drought stress.

Inbreeding and genetic load in a pair of sibling grouse species:Tetrastes sewersowi and T.bonasia

Genetic load and inbreeding are recognized as important factors to be considered in conservation programs.Elevated levels of both can increase the risk of population extinction by negatively impacting fitness-related characters in many species of plants and animals,including humans(inbreeding depression).Genomic tech-niques are increasingly used in measuring and understanding genetic load and inbreeding and their importance in evolution and conservation.We used whole genome resequencing data from two sibling grouse species in subarctic Eurasia to quantify both.We found a large range of inbreeding measured as FROH(fraction of runs of homozygosity)in individuals from different populations of Chinese Grouse(Tetrastes sewerzowi)and Hazel Grouse(T.bonasia).FROH estimated from genome-wide runs of homozygosity(ROH)ranged from 0.02 to 0.24 among Chinese Grouse populations and from 0.01 to 0.44 in Hazel Grouse.Individuals from a population of Chinese Grouse residing in the Qilian mountains and from the European populations of Hazel Grouse(including samples from Sweden,Germany and Northeast Poland)were the most inbred(FROH ranged from 0.10 to 0.23 and 0.11 to 0.44,respectively).These levels are comparable to other highly inbred populations of birds.Hazel Grouse from northern China and Chinese Grouse residing in the Qinghai-Tibetan Plateau showed relatively lower inbreeding levels.Comparisons of the ratio between deleterious missense mutations and synonymous mutations revealed higher levels in Chinese Grouse as compared to Hazel Grouse.These results are possibly explained by higher fixation rates,mutational melt down,in the range-restricted Chinese Grouse compared to the wide-ranging Hazel Grouse.However,when we compared the relatively more severe class of loss-of-function muta-tions,Hazel Grouse had slightly higher levels than Chinese Grouse,a result which may indicate that purifying selection(purging)has been more efficient in Chinese Grouse on this class of mutations.

Biofilm formation in clinical isolates of nosocomial Acinetobacter baumannii and its relationship with multidrug resistance

Objective: To check biofilm formation by Acinetobacter baumannii(A. baumannii)clinical isolates and show their susceptibility to different antibiotics and investigate a possible link between establishment of biofilm and multidrug resistance.Methods: This study was performed on clinical samples collected from patients with nosocomial infections in three hospitals of Tehran. Samples were initially screened by culture and biochemical tests for the presence of different species of Acinetobacter. Identifications were further confirmed by PCR assays. Their susceptibilities to 11 antibiotics of different classes were determined by disc diffusion method according to Clinical and Laboratory Standards Institute guidelines. The ability to produce biofilm was investigated using methods: culture on Congo red agar, microtiter plate, and test tube method.Results: From the overall clinical samples, 156 specimens were confirmed to contain A. baumannii. The bacteria were highly resistant to most antibiotics except polymyxin B.Of these isolates, 10.26% were able to produce biofilms as shown on Congo red agar.However, the percentage of bacteria with positive biofilm in test tube, standard microtiter plate, and modified microtiter plate assays were 48.72%, 66.66%, and 73.72%, respectively. At least 92% of the biofilm forming isolates were multidrug resistant.Conclusions: Since most of the multidrug resistant strains produce biofilm, it seems necessary to provide continuous monitoring and determination of antibiotic susceptibility of clinical A. baumannii. This would help to select the most appropriate antibiotic for treatment.

The Effect of Antineoplastons A10 and AS2-1 and Metabolites of Sodium Phenylbutyrate on Gene Expression in Glioblastoma Multiforme

Antineoplastons are peptide and amino acid derivatives that occur naturally in the human body. They inhibit the growth of neoplastic cells without growth inhibition of normal cells. Phenylacetylglutaminate (PG) is an active ingredient of antineoplastons A10 and AS2-1 (ANP) and is also a metabolic by-product of phenylbutyrate (PB). The formulation of antineoplaston AS2-1 is a 4:1 mixture of phenylacetate (PN) and PG. Antineoplaston A10 is a 4:1 mixture of PG and isoPG. This study investigates the molecular mechanism of action of PG and PN. The Human U87 glioblastoma (GBM) cell line was used as the model system in this study. A total human gene array screen using the Affymetrix Human Genome plus 2.0 oligonucleotide arrays was performed using mRNA derived from U87 cells exposed to PG and PN. Pathway analysis was performed to allow the visualization of effect on metabolic pathways and gene interaction networks. Our preliminary results indicate that PG and PN interrupt signal transduction in RAS/MAPK/ERK and PI3K/AKT/PTEN pathways, interfere with cell cycle, decrease metabolism and promote apoptosis in human U87 GBM cells. The effect on multiple cellular pathways and targets, suggests that ANP and PB are promising candidates for clinical studies in GBM.

Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae

Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate(LNA) against carbapenemase-producing Klebsiella pneumoniae(KPC-KP). LNA alone exhibited bactericidal activity at 2.5%(V/V), and in combination with meropenem(MPM) at 1.25%(V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins,indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species(ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells.

Low back pain and osteoarthritis pain:a perspective of estrogen

Low back pain(LBP)is the world's leading cause of disability and is increasing in prevalence more rapidly than any other pain condition.Intervertebral disc(IVD)degeneration and facet joint osteoarthritis(FJOA)are two common causes of LBP,and both occur more frequently in elderly women than in other populations.Moreover,osteoarthritis(OA)and OA pain,regardless of the joint,are experienced by up to twice as many women as men,and this difference is amplified during menopause.Changes in estrogen may be an important contributor to these pain states.Receptors for estrogen have been found within IVD tissue and nearby joints,highlighting the potential roles of estrogen within and surrounding the IVDs and joints.In addition,estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression,indicating its potential use as a therapeutic agent for people with LBP and OA pain.This review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical findings.The potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.

Neural progenitor cell lines inhibit rat tumor growth in vivo

Current therapies for gliomas often fail to address their infiltrative nature. Conventional treatments leave behind small clusters of neoplastic cells, resulting in eventual tumor recurrence. In the present study, we have evaluated the antitumor activity of neural progenitor cells against gliomas when stereotactically injected into nucleus Caudatus of Fisher rats. We show that the rat neural progenitor cell lines HiB5 and ST14A,

Unique biogenesis and kinetics of hornwort Rubiscos revealed by synthetic biology systems

Hornworts are the only land plants that employ a pyrenoid to optimize Rubisco’s CO_(2) fixation,yet hornwort Rubisco remains poorly characterized.Here we assembled the hornwort Anthoceros agrestis Rubisco(AaRubisco)using the Arabidopsis thaliana SynBio expression system and observed the formation of stalled intermediates,prompting us to develop a new SynBio system with A.agrestis cognate chaperones.We successfully assembled AaRubisco and Rubisco from three other hornwort species.Unlike A.thaliana Rubisco,AaRubisco assembly is not dependent on RbcX or Raf2.Kinetic characterization reveals that hornwort Rubiscos exhibit a range of catalytic rates(3–10 s−1),but with similar affinity(∼30μM)and specificity(∼70)for CO_(2).These results suggest that hornwort Rubiscos do not comply with the long-held canonical catalytic trade-off observed in other land plants,providing experimental support that Rubisco kinetics may be phylogenetically constrained.Unexpectedly,we observed a 50%increase in AaRubisco catalytic rates when RbcX was removed from our SynBio system,without any reduction in specificity.Structural biology,biochemistry,and proteomic analysis suggest that subtle differences in Rubisco large-subunit interactions,when RbcX is absent during biogenesis,increases the accessibility of active sites and catalytic turnover rate.Collectively,this study uncovered a previously unknown Rubisco kinetic parameter space and provides a SynBio chassis to expand the survey of other Rubisco kinetics.Our discoveries will contribute to developing new approaches for engineering Rubisco with superior kinetics.

VEGFR2 inhibition hampers breast cancer cell proliferation via enhanced mitochondrial biogenesis

Objective:Vascular endothelial growth factor(VEGF),apart from its predominant roles in angiogenesis,can enhance cancer cell proliferation,but its mechanisms remain elusive.The purpose of the present study was therefore to identify how VEGF regulates cancer cell proliferation.Methods:VEGF effects on cancer cell proliferation were investigated with the VEGF receptor 2 inhibitor,Ki8751,and the breast cancer cell lines,MCF-7 and MDA-MB-231,using flow cytometry,mass spectrometry,immunoblotting,and confocal microscopy.Data were analyzed using one-way analysis of variance followed by Tukey’s multiple comparison test.Results:VEGF blockade by Ki8751 significantly reduced cancer cell proliferation,and enhanced breast cancer cell apoptosis.Mass spectrometric analyses revealed that Ki8751 treatment significantly upregulated the expression of mitochondrial proteins,suggesting the involvement of mitochondrial biogenesis.Confocal microscopy and flow cytometric analyses showed that Ki8751 treatment robustly increased the mitochondrial masses of both cancer cells,induced endomitosis,and arrested cancer cells in the high aneuploid phase.VEGFR2 knockdown by sh RNAs showed similar effects to those of Ki8751,confirming the specificity of Ki8751 treatment.Enhanced mitochondrial biogenesis increased mitochondrial oxidative phosphorylation and stimulated reactive oxygen species(ROS)production,which induced cancer cell apoptosis.Furthermore,Ki8751 treatment downregulated the phosphorylation of Akt and PGC1α,and translocated PGC1αinto the nucleus.The PGC1αalterations increased mitochondrial transcription factor A(TFAM)expression and subsequently increased mitochondrial biogenesis.Conclusions:VEGF enhances cancer cell proliferation by decreasing Akt-PGC1α-TFAM signaling-mediated mitochondrial biogenesis,ROS production,and cell apoptosis.These findings suggested the anticancer potential of Ki8751 via increased mitochondrial biogenesis and ROS production.

Cancer cell migration： when red light switched to green

The doctrine of＇the golden mean＇ of the Confucian certainly applies at the molecular level to cell growth and migration. It is critically important for tissue architecture and homeostasis that cells stop prolifera- tion when reaching appropriate density and halt migration in a direction to avoid collision with others. This ＇red light＇ to hinder cell movement is essential for maintaining contact inhibition of locomotion （CIL）--a phe- nomenon that a cell ceases to continue moving in the same direction when it comes into contact with another cell. The concept of CIL emerged initially from the early work of Abercrombie and Heaysman in the 1950s.

Angiotensin Ⅱ stimulates expression of transcription factors c-Jun and c-Fos in cyclosporine induced human gingival fibroblasts

The present study demonstrates that the expression of c-Jun and c-Fos are elevated in gingival fibroblast cells treated with angiotensin Ⅱ and cyclosporine.The healthy human gingival tissues were collected and gingival fibroblasts were isolated and cultured.We used RT-PCR and Western blot analysis to identify the expression of c-Jun and c-Fos in cyclosporine and angiotensin II treated human gingival fibroblast cells.We found that angiotensin Ⅱ in combination with cyclosporine induces c-Jun and c-Fos expressions significantly;however,the angiotensin Ⅱ antagonist losartan inhibits the expression of c-Jun and c-Fos(p<0.01).The data suggest that angiotensin Ⅱ in combination with cyclosporine modulates the expression of c-Jun and c-Fos in human gingival fibroblast cells.

Sterilization of <i>Hibiscus rosa-sinensis</i>L. Vegetative Explants Sourced from Plants Grown in Open Environment and Influences of Organic Ingredients on <i>In Vitro</i>Direct Regeneration

This paper reports on the effects of organic ingredients in facilitating direct shoot regeneration from nodal explants of Hibiscus rosa-sinensis L. This paper also compares the sterilization conditions for 3 types of explants (node, internode, and shoot tip) harvested from an open field. The optimized sterilization conditions for the explants were 40% Clorox- 20 min exposure, 10% Clorox-15 min exposure, and 5% Clorox-40 min exposure for the node, internode and shoot tip, respectively. In the direct shoot regeneration using the nodal explants, we found MS medium containing 40 g/L sucrose, 0.3% (w/v) activated charcoal, and supplementations with myo-inositol, thiamine and nicotinic acid were suitable. The in vitro shoot survival rate was 30% with a mean leaf numbers of 2.68 produced, and a mean leaf length of 1.71 cm achieved after 5 weeks of culture on the modified medium.

We Should Apply a “One Health” Approach to Understand and Treat Alzheimer’s Disease

Despite many decades of researches and large numbers of clinical trials, there remain no effective treatments for Alzheimer’s disease, a major degenerative ageing brain disorder. The potential treatments have focused on targeting the accumulation of amyloid beta-peptide in the brains of patients, but without success in slowing the disease. Many studies have now identified a large range of pathological changes (i.e. altered immune activity, mitochondrial impairment, abnormal microbiome), and links to the external environment (i.e. associations with infections, the influence of air pollution). While the concept of One Health (which considers links between the environment and human disease) has traditionally been applied to the understanding of the human infectious disease, it is argued here that the One Health approach should be adopted for Alzheimer’s disease. This would provide a far more holistic understanding of the disease, and its relationship to a growing number of exogenous factors, as well as could potentially lead to new treatment options targeted at the confluence of external influences, and internal molecular pathways.

Enhancing Accumulation and Penetration Efficiency of Next-Generation Antibiotics to Mitigate Antibiotic Resistance in Pseudomonas aeruginosa PAO1

This study explores the efficacy of advanced antibiotic compounds against P. aeruginosa, focusing on Antibiotic B, an enhanced derivative of Ceftriaxone. The study measured the intracellular uptake of Antibiotic B and introduced a novel adjuvant, Influximax, which augmented its antibacterial activity. Results showed a diminished potential for resistance emergence with Antibiotic B, particularly when used in combination with Influximax. The study suggests that optimizing antibiotic delivery into bacterial cells and leveraging syner-gistic adjuvant combinations can enhance drug resistance combat. .

Health Impacts and Mechanisms of Per- and Polyfluoroalkyl Substances (PFAS) from Epidemiological to Toxicological

This research provides a comprehensive analysis of the health impacts of Per- and Polyfluoroalkyl Substances (PFAS) through an integration of epidemiological and toxicological studies. The study identifies significant correlations between PFAS exposure and adverse health outcomes, including thyroid dysfunction, elevated cholesterol levels, and increased risk of specific cancers. Utilizing a mixed-methods approach, the research combines a systematic review and meta-analysis of recent literature with in vitro and in vivo toxicological experiments. The epidemiological analysis reveals increased risks of thyroid dysfunction, cholesterol elevation, and certain cancers among PFAS-exposed individuals. Toxicological findings further corroborate these results, showing dose-dependent cytotoxic effects in human cell lines and endocrine disruption in rodent models. The study emphasizes the importance of regulatory measures to mitigate PFAS exposure and the urgent need for more comprehensive research into their long-term effects. The integration of epidemiological and toxicological data underscores the significant health risks posed by PFAS, highlighting the necessity of immediate action to limit exposure and develop safer alternatives.

Selection and Screening of Superior Genotypes for Quality Planting Stock Based on Vegetative Growth Performance of Some Selected 12-Year-Old Acacia Species

Production of quality wood is a big problem in forestry plantation since trees grown in plantation of some high value temperate and tropical hardwood species tend to produce low value, short butt logs and bolts due to crooked stems, low fork heights and delayed shedding of lower branches. Result from existing Acacia plantation in Malaysia indicated that most existing Acacia plantation trees especially Acacia auriculiformis and Acacia mangium, fork very heavily which leads to the formation of multiple leaders more than one and some are fork so close to the ground that they will produce little to no merchantable wood. In this context, a research study was initiated to select and recommend the best performing tree species or provenance suited for timber production in Malaysia with respect to growth and other characteristics. Species/provenance/progeny test was conducted on four species of Acacia namely, A. mangium, A. auriculiformis, A. crassicarpa and A. aulococarpa, each with 4 provenances originated from Papua New Guinea (PNG) and Queensland (QL). The growth performance of the provenances was monitored in terms of some quantitative and qualitative characteristics to evaluate the genetic variation and growth performance of a base breeding population. 20 progenies for each species were selected and randomly planted with 16 trees representing each progenies in a trial plot laid out in a randomized complete block design consisting of four blocks as replication. The study showed that there were significant different (p mangium performed better compared to other Acacia species in all of the aspect tested and it was followed by A. crassicarpa, A. aulococarpa and A. auriculiformis. There were also significant differences between provenance within regions and progenies within provenances in all quantitative and qualitative traits tested in this study. Generally, provenance and progenies selected from PNG excelled those from QL both in quantitative and qualitative characteristics. The top performing progenies of Acacia species are CG 1854 of (Bensbach WP) and KN000107 (SW of Boset WP) of A. mangium, BVG2609 (Bensbach WP) of A. crassicarpa, BVG 00835 (WP Morehead) and MM1016 (Arufi E Morehead WP) of A. aulococarpa and JSL363 (Wenlock River) and BVG 2657 (Bansbach) of A. auriculiformis.

Stress granules: friend or foe in neurodegenerative disorders?

Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis,despite the diversity in clinical symptoms,share a striking feature at the cellular level:the accumulation of insoluble aggregates of misfolded proteins that are sequestered in intraneuronal inclusion bodies.Besides mutations in disease-associated proteins that render them aggregation-prone,the decline of protein homeostasis(i.e.proteostasis)with aging is also believed to be a contributing factor to the accumulation of protein aggregates.