Cell Division Phase Research Articles

RhMYC2 controls petal size through synergistic regulation of jasmonic acid and cytokinin signaling in rose.

Petal size is determined by cell division and cell expansion. Jasmonic acid (JA) has been reported to be associated with floral development, but its regulatory mechanism affecting petal size remains unclear. Here, we reveal the vital role of JA in regulating petal size and the duration of the cell division phase via the key JA signaling component RhMYC2. We show that RhMYC2 expression is induced by exogenous treatment with methyl jasmonate and decreases from stage 0 to stage 2 of flower organ development, corresponding to the cell division phase. Furthermore, silencing RhMYC2 shortened the duration of the cell division phase, ultimately accelerating flowering opening and resulting in smaller petals. In addition, we determined that RhMYC2 controls cytokinin homeostasis in rose petals by directly activating the expression of the cytokinin biosynthetic gene LONELY GUY3 (RhLOG3) and repressing that of the cytokinin catabolism gene CYTOKININ OXIDASE/DEHYDROGENASE6 (RhCKX6). Silencing RhLOG3 shortened the duration of the cell division period and produced smaller petals, similar to RhMYC2 silencing. Our results underscore the synergistic effects of JA and cytokinin in regulating floral development, especially for petal size in roses.

The effect of site-specific recombinases XerCD on the removal of over-replicated chromosomal DNA through outer membrane vesicles in bacteria.

Outer membrane vesicles (OMVs) are universally produced by Gram-negative bacteria and play important roles in symbiotic and pathogenic interactions. The DNA from the lumen of OMVs from the Alphaproteobacterium Dinoroseobacter shibae was previously shown to be enriched for the region around the terminus of replication ter and specifically for the recognition sequence dif of the two site-specific recombinases XerCD. These enzymes are highly conserved in bacteria and play an important role in the last phase of cell division. Here, we show that a similar enrichment of ter and dif is found in the DNA inside OMVs from Prochlorococcus marinus, Pseudomonas aeruginosa, Vibrio cholerae, and Escherichia coli. The deletion of xerC or xerD in E. coli reduced the enrichment peak directly at the dif sequence, while the enriched DNA region around ter became broader, demonstrating that either enzyme influences the DNA content inside the lumen of OMVs. We propose that the intra-vesicle DNA originated from over-replication repair and the XerCD enzymes might play a role in this process, providing them with a new function in addition to resolving chromosome dimers.IMPORTANCEImprecise termination of replication can lead to over-replicated parts of bacterial chromosomes that have to be excised and removed from the dividing cell. The underlying mechanism is poorly understood. Our data show that outer membrane vesicles (OMVs) from diverse Gram-negative bacteria are enriched for DNA around the terminus of replication ter and the site-specific XerCD recombinases influence this enrichment. Clearing the divisome from over-replicated parts of the bacterial chromosome might be a so far unrecognized and conserved function of OMVs.

Proteomic analysis during seed development provides insight into the early establishment of seed dormancy in Xanthium strumarium.

This experiment was carried out to provide a comprehensive insight into the protein activities involved in dormancy establishment in seeds of common cocklebur (Xanthium strumarium), an annual plant with two dimorphic seeds contained in one casing known as a burr. These consist of a smaller dormant seed and a larger non-dormant seed. The proteome profile was compared between developing dormant and non-dormant seeds of Xanthium strumarium at five consecutive stages including three, 10, 20, 30, and 45 days after burr emergence (stages 1 to 5). We identified 6524 proteins in total, and approximately 3.6% of these were differentially abundant proteins (DAPs) between the two seed types. Both seed types showed fundamental changes in developmental programs during the examined stages. More than 38% of all DAPs were observed at the first stage, supporting the importance of the early developmental stage in seed fate determination. The detected DAPs at stage 1 were mainly associated with the cell division phase, which showed a delay in the dormant seeds. Over-representation of proteins responsible for cell wall biosynthesis, cytokinesis, and seed development were detected for non-dormant seeds at the first stage, while dormancy-associated proteins showed less abundance. Stage 3 was the critical stage for switching processes toward seed maturation and abscisic acid (ABA) signaling. Interestingly, higher abundance proteins in the mature non-dormant seed were mainly involved in the facilitation of seed germination. Taken together, the temporal pattern of the accumulated proteins in developing dormant seeds demonstrated a delay in the initiation of active cell division, enriched response to ABA, and defects in seed maturation. Moreover, stored proteins in the mature dormant seed delay germination but not dormancy induction. Finally, our results suggest that dormancy may be established at a stage of seed development earlier than previously thought.

Petal size is controlled by the MYB73/TPL/HDA19-miR159-CKX6 module regulating cytokinin catabolism in Rosa hybrida

The size of plant lateral organs is determined by well-coordinated cell proliferation and cell expansion. Here, we report that miR159, an evolutionarily conserved microRNA, plays an essential role in regulating cell division in rose (Rosa hybrida) petals by modulating cytokinin catabolism. We uncover that Cytokinin Oxidase/Dehydrogenase6 (CKX6) is a target of miR159 in petals. Knocking down miR159 levels results in the accumulation of CKX6 transcripts and earlier cytokinin clearance, leading to a shortened cell division period and smaller petals. Conversely, knocking down CKX6 causes cytokinin accumulation and a prolonged developmental cell division period, mimicking the effects of exogenous cytokinin application. MYB73, a R2R3-type MYB transcription repressor, recruits a co-repressor (TOPLESS) and a histone deacetylase (HDA19) to form a suppression complex, which regulates MIR159 expression by modulating histone H3 lysine 9 acetylation levels at the MIR159 promoter. Our work sheds light on mechanisms for ensuring the correct timing of the exit from the cell division phase and thus organ size regulation by controlling cytokinin catabolism.

Kaempferol and its derivatives: Biological activities and therapeutic potential

Kaempferol, a natural plant-origin flavonoid, exhibits therapeutic anti-inflammatory, antioxidant, anticancer, antidiabetic, and neuroprotective properties. Kaempferol acts within several distinct mechanisms like apoptotic induction in cancer cells, enzymatic inhibition, signalling pathway inhibition, and downregulation in cell viability during the G2/M phase of cell division. This review summarizes the therapeutic effects of kaempferol against several health ailments. The recent progress on kaempferol obtained from fruits and vegetables as an antioxidant, anti-inflammatory, anticancer, antidiabetic, and neuroprotective agent and its mechanisms of action are also discussed. In addition, kaempferol has been reported to be present in wastes and byproducts from post-fruit and vegetable processing. Thus, a paradigm shift towards valorizing fruits and vegetable industrial wastes/byproducts to obtain bioactive kaempferol can support the circular economy pillar for generating wealth from waste and for finding a sustainable alternative source.

Walther Flemming: life path and scientific legacy

The main stages of Walther Flemming life and activity are considered in the article. Walther Flemming (21.04.1843–4.08.1905) is German biologist, anatomist, one of the most famous histologists of the 19th century and the founder of cytogenetics. He studied medicine at four famous universities of the German Empire – in Göttingen, Tübingen, Berlin and Rostock. After defending his thesis, in 1868 he started teaching anatomy and histology at Würzburg, Amsterdam and Rostock universities, Germany and Charles Ferdinand University, the Czech Republic. During the last 25 years of his life, he was a professor of anatomy at the Christian Albrecht University in Kiel, Germany and headed one of its departments – the anatomical institute.
 At the beginning of W. Flemming scientific activity, his research mostly concerned histology and anatomy, as well as the development of histological methods and fixation of microscopic specimens. However, the main works of the scientist are devoted to study cell division process and the chromosomes distribution in daughter nuclei. He firstly introduced the concept of “mitosis”, which he studied on stained microscopic preparations, using salamander epithelial cells as a source of biological material. W. Flemming described the processes in the nucleus, distinguished “progressive” and “regressive” phases of cell division. He demonstrated that the cells contain areas that absorb basophilic dyes. These areas were later called chromatin; other structures remained unstained under such conditions and were therefore called achromatin. W. Flemming studied the structure and functions of the spindle during cell division, and he also studied the polar structure, which he called centriole. The scientist found that indirect division usually occurs not only in vertebrates, but also in invertebrates and protists. He established that two successive, morphologically distinct divisions of nuclear occur during spermatogenesis, resulting in the division of chromatin into two daughter cells. Thus, W. Flemming’s research contributed to the development of cell biology and its branches.

Cytogenetic activity of a mutagenic factor with high damaging capacity in winter wheat

The analysis of cytological abnormalities is an important method for identifying the potential of a chemical as a mutagen for future heritable genetic changes, the level of genotype-mutagen interaction and site-specific activity for the nature and/or different concentrations of the mutagen. The research aims to determine the limits of the variability of genotypes of different origins, especially those with wide ecological and genetic variability, and to show the interaction between the variety and the mutagen. Winter wheat grains of several varieties (Balaton, Borovytsia, Zelenyi Hai, Zoloto Ukrainy, Kalancha, Niva Odeska, Polianka, Pochayna) were treated with dimethyl sulphate at concentrations of 0.0125%, 0.025%, 0.05%, and exposure was 24 hours. The cytogenetic activity was studied by the frequency and spectrum of chromosomal rearrangements in the corresponding phases of cell division, depending on the variety and concentration of the mutagen as the main factors affecting these parameters, as well as the main features of the spectrum, such as the overall rate of chromosomal rearrangements, the number of fragments and double fragments, bridges, micronuclei, and lagging chromosomes. The studied concentrations of the supermutagen were found to have a significant effect on all analysed parameters and can be classified as optimal and high concentration levels in terms of the effect on cytological activity and mitotic problems for the factor, despite previous studies. The variety factor has a much greater impact on the nature and frequency of certain types of aberrations than an increase in the mutagen concentration, it was characterised by a much greater site-specific effect than other chemical agents, and various variants in mutagenic effects were identified according to the subject’s genotype. It was generalised that the features that reproduced the effect of the mutagen, according to the discriminant analysis, were the total frequency, the frequency of fragments and double fragments, and bridges. In practical use in the genetic improvement of plants and for obtaining valuable traits, the optimal concentrations are 0.0125%, and 0.025%, which is planned to be further confirmed on a wider range of genotypes and by mutation studies for the next (second or third) generations

Dual Targeted Nanoparticles for the Codelivery of Doxorubicin and siRNA Cocktails to Overcome Ovarian Cancer Stem Cells.

Most anticancer treatments only induce the death of ordinary cancer cells, while cancer stem cells (CSCs) in the quiescent phase of cell division are difficult to kill, which eventually leads to cancer drug resistance, metastasis, and relapse. Therefore, CSCs are also important in targeted cancer therapy. Herein, we developed dual-targeted and glutathione (GSH)-responsive novel nanoparticles (SSBPEI-DOX@siRNAs/iRGD-PEG-HA) to efficiently and specifically deliver both doxorubicin and small interfering RNA cocktails (siRNAs) (survivin siRNA, Bcl-2 siRNA and ABCG2 siRNA) to ovarian CSCs. They are fabricated via electrostatic assembly of anionic siRNAs and cationic disulfide bond crosslinking-branched polyethyleneimine-doxorubicin (SSBPEI-DOX) as a core. Interestingly, the SSBPEI-DOX could be degraded into low-cytotoxic polyethyleneimine (PEI). Because of the enrichment of glutathione reductase in the tumor microenvironment, the disulfide bond (-SS-) in SSBPEI-DOX can be specifically reduced to promote the controlled release of siRNA and doxorubicin (DOX) in the CSCs. siRNA cocktails could specifically silence three key genes in CSCs, which, in combination with the traditional chemotherapy drug DOX, induces apoptosis or necrosis of CSCs. iRGD peptides and "sheddable" hyaluronic acid (HA) wrapped around the core could mediate CSC targeting by binding with neuropilin-1 (NRP1) and CD44 to enhance delivery. In summary, the multifunctional delivery system SSBPEI-DOX@siRNAs/iRGD-PEG-HA nanoparticles displays excellent biocompatibility, accurate CSC-targeting ability, and powerful anti-CSC ability, which demonstrates its potential value in future treatments to overcome ovarian cancer metastasis and relapse. To support this work, as exhaustive search was conducted for the literature on nanoparticle drug delivery research conducted in the last 17 years (2007-2023) using PubMed, Web of Science, and Google Scholar.

Studi Penggunaan Safranin dan Kolkisin dalam Pengamatan Kromosom pada Sel Akar Bawang Bombay (Allium cepa Var)

Based on the results of initial observations it was found that the use of safranin and colchicine showed less than optimal results. The purpose of this study was to observe the phases of mitotic division seen in the use of safranin and colchicine in onion (Allium cepa Var) root cells. The stages of the research included the stages of making preparations, namely root growth, root cutting, fixation, maceration, staining, and squashing. and continued with the observation of the phase of mitotic division which appeared microscopically. The data obtained were from the results of observing the cleavage phase in the chromosomes of the onion root cells, then analyzed descriptively and then comparatively to show what cleavage phases were due to safranin and colchicine staining with different soaking times. Based on the observed cell division phase of onion (Allium cepa Var) roots, safranin was more effective than colchicine with 30 minutes of soaking time.

Inhibition of cell cycle-dependent hyphal and biofilm formation by a novel cytochalasin 19,20‑epoxycytochalasin Q in Candida albicans

Biofilm-mediated drug resistance is a key virulence factor of pathogenic microbes that cause a serious global health threat especially in immunocompromised individuals. Here, we investigated the antihyphal and antibiofilm activity of 19,20‑epoxycytochalasin Q (ECQ), a cytochalasin actin inhibitor isolated from medicinal mushroom Xylaria sp. BCC1067 against Candida albicans. Remarkably, 256 µg/ml of ECQ inhibited over 95% of C. albicans hyphal formation after 24 h-treatment. Combined ECQ and lipid-based biosurfactant effectively enhanced the antihyphal activity, lowering required ECQ concentrations. Hyphal fragmentation and reduction of biofilm biomass, shown by SEM and AFM visualization of ECQ-treated biofilms, were well corelated to the reduced metabolic activities of young and 24 h-preformed C. albicans biofilms. Induced intracellular accumulation of reactive oxygen species (ROS) also occurred in accompany with the leakage of shrunken cell membrane and defective cell wall at increasing ECQ concentrations. Transcriptomic analyses via RNA-sequencing revealed a massive change (> 1300 genes) in various biological pathways, following ECQ-treatment. Coordinated expression of genes, associated with cellular response to drugs, filamentous growth, cell adhesion, biofilm formation, cytoskeleton organization, cell division cycle, lipid and cell wall metabolisms was confirmed via qRT-PCR. Protein–protein association tool identified coupled expression between key regulators of cell division cyclin-dependent kinases (Cdc19/28) and a gamma-tubulin (Tub4). They coordinated ECQ-dependent hyphal specific gene targets of Ume6 and Tec1 during different phases of cell division. Thus, we first highlight the antihyphal and antibiofilm property of the novel antifungal agent ECQ against one of the most important life-threatening fungal pathogens by providing its key mechanistic detail in biofilm-related fungal infection.

Stability of asymmetric cell division: A deformable cell model of cytokinesis applied to C. elegans

Cell division during early embryogenesis is linked to key morphogenic events such as embryo symmetry breaking and tissue patterning. It is thought that the physical surrounding of cells together with cell intrinsic cues act as a mechanical “mold,” guiding cell division to ensure these events are robust. To quantify how cell division is affected by the mechanical and geometrical environment, we present a novel computational mechanical model of cytokinesis, the final phase of cell division. Simulations with the model reproduced experimentally observed furrow dynamics and describe the volume ratio of daughter cells in asymmetric cell divisions, based on the position and orientation of the mitotic spindle. For dividing cells in geometrically confined environments, we show how the orientation of confinement relative to the division axis modulates the volume ratio in asymmetric cell division. Further, we quantified how cortex viscosity and surface tension determine the shape of a dividing cell and govern bubble-instabilities in asymmetric cell division. Finally, we simulated the formation of the three body axes via sequential (a)symmetric divisions up until the six-cell stage of early C. elegans development, which proceeds within the confines of an eggshell. We demonstrate how model input parameters spindle position and orientation provide sufficient information to reliably predict the volume ratio of daughter cells during the cleavage phase of development. However, for egg geometries perturbed by compression, the model predicts that a change in confinement alone is insufficient to explain experimentally observed differences in cell volume. This points to an effect of the compression on the spindle positioning mechanism. Additionally, the model predicts that confinement stabilizes asymmetric cell divisions against bubble-instabilities.

Inhibition of peptidoglycan synthesis is sufficient for total arrest of staphylococcal cell division

Bacterial cell wall biosynthesis is the target of many important antibiotics. Its spatiotemporal organization is closely coordinated with cell division. However, the role of peptidoglycan synthesis within cell division is not fully understood. Even less is known about the impact of antibiotics on the coordination of these two essential processes. Visualizing the essential cell division protein FtsZ and other key proteins in Staphylococcus aureus, we show that antibiotics targeting peptidoglycan synthesis arrest cell division within minutes of treatment. The glycopeptides vancomycin and telavancin completely inhibit septum constriction in all phases of cell division. The beta-lactam oxacillin stops division progress by preventing recruitment of the major peptidoglycan synthase PBP2 to the septum, revealing PBP2 as crucial for septum closure. Our work identifies cell division as key cellular target of these antibiotics and provides evidence that peptidoglycan synthesis is the essential driving force of septum constriction throughout cell division of S. aureus.

The Study on Sea Buckthorn (Genus Hippophae L.) Fruit Reveals Cell Division and Cell Expansion to Promote Morphogenesis.

Due to its unique flavor and high antioxidant content, the sea buckthorn (genus Hippophae L.) fruit is increasingly favored by consumers. Developing from the perianth tube, the sea buckthorn fruit varies greatly among species in both size and shape. However, the cellular regulation mechanism of sea buckthorn fruit morphogenesis remains unclear. This study presents the growth and development patterns, morphological changes, and cytological observations of the fruits of three Hippophae species (H. rhamnoides ssp. sinensis, H. neurocarpa, and H. goniocarpa). The fruits were monitored every 10-30 days after anthesis (DAA) for six periods in their natural population on the eastern margin of the Qinghai-Tibet Plateau in China. The results showed that the fruits of H. rhamnoides ssp. sinensis and H. goniocarpa grew in a sigmoid mode, while H. neurocarpa grew in an exponential mode under the complex regulation of cell division and cell expansion. In addition, cellular observations showed that the mesocarp cells of H. rhamnoides ssp. sinensis and H. goniocarpa were larger in the area with prolonged cell expansion activity, while H. neurocarpa had a higher cell division rate. Elongation and proliferation of the mesocarp cells were found to be essential factors affecting the formation of fruit morphology. Finally, we established a preliminary cellular scenario for fruit morphogenesis in the three species of sea buckthorn. Fruit development could be divided into a cell division phase and a cell expansion phase with an overlap between 10 and 30 DAA. In particular, the two phases in H. neurocarpa showed an additional overlap between 40 and 80 DAA. The description of the sea buckthorn fruit's transformation and its temporal order may provide a theoretical basis to explore the growth mechanism of fruits and regulate their size through certain cultivation techniques.

Cytogenotoxic effects of 3-epicaryoptin in Allium cepa L. root apical meristem cells.

Diterpenoid 3-epicaryoptin (C26H36O9) is abundant in the leaves of Clerodendrum inerme, a traditionally used medicinal plant, and has insect antifeedant activities. Here, we aim to explore the cytogenotoxic effects of compound 3-epicaryoptin in Allium cepa root apical meristem cells. 3-epicaryoptin (concentrations of 100, 150, and 200µgmL-1) and the standard compound colchicine (200µgmL-1) were applied to A. cepa roots for 2, 4, and 4 + 16h (4-h treatment followed by 16-h recovery). Cytogenotoxicity was analyzed by studying the root growth retardation (RGR), mitotic index (MI), and chromosomal aberrations. The result showed statistically significant (p < 0.01), concentration-dependent RGR effects of 3-epicaryoptin treatment compared with the negative control. A study of cell frequency in different phases of cell division observed a significant (p < 0.001) increase in the metaphase cell percentage (66.2 ± 0.58%, 150µgmL-1), which subsequently caused an increase in the frequency of MI (12.29 ± 0.34%, 150µgmL-1) at 4h of 3-epicaryoptin treatment and that was comparable with the colchicine action. The cytological study revealed that the 3-epicaryoptin treatment could induce different types of chromosomal abnormalities, such as colchicine-like metaphase, vagrant chromosomes, sticky chromosomes, anaphase bridge, lagging chromosomes, multipolar anaphase-telophase, and an increased frequency of micronuclei and polyploid cells. These findings indicate that 3-epicaryoptin is cytogenotoxic, and thus, C. inerme should be used with caution in traditional medicine.

Characterization of Transcriptome Dynamics during Early Fruit Development in Olive (Olea europaea L.).

In the olive (Olea europaea L.), an economically leading oil crop worldwide, fruit size and yield are determined by the early stages of fruit development. However, few detailed analyses of this stage of fruit development are available. This study offers an extensive characterization of the various processes involved in early olive fruit growth (cell division, cell cycle regulation, and cell expansion). For this, cytological, hormonal, and transcriptional changes characterizing the phases of early fruit development were analyzed in olive fruit of the cv. 'Picual'. First, the surface area and mitotic activity (by flow cytometry) of fruit cells were investigated during early olive fruit development, from 0 to 42 days post-anthesis (DPA). The results demonstrate that the cell division phase extends up to 21 DPA, during which the maximal proportion of 4C cells in olive fruits was reached at 14 DPA, indicating that intensive cell division was activated in olive fruits at that time. Subsequently, fruit cell expansion lasted as long as 3 weeks more before endocarp lignification. Finally, the molecular mechanisms controlling the early fruit development were investigated by analyzing the transcriptome of olive flowers at anthesis (fruit set) as well as olive fruits at 14 DPA (cell division phase) and at 28 DPA (cell expansion phase). Sequential induction of the cell cycle regulating genes is associated with the upregulation of genes involved in cell wall remodeling and ion fluxes, and with a shift in plant hormone metabolism and signaling genes during early olive fruit development. This occurs together with transcriptional activity of subtilisin-like protease proteins together with transcription factors potentially involved in early fruit growth signaling. This gene expression profile, together with hormonal regulators, offers new insights for understanding the processes that regulate cell division and expansion, and ultimately fruit yield and olive size.

Cyclin-dependent kinases in cancer: Role, regulation, and therapeutic targeting.

Regulated cell division is one of the fundamental phenomena which is the basis of all life on earth. Even a single base pair mutation in DNA leads to the production of the dysregulated protein that can have catastrophic consequences. Cell division is tightly controlled and orchestrated by proteins called cyclins and cyclin-dependent kinase (CDKs), which serve as licensing factors during different phases of cell division. Dysregulated cell division is one of the most important hallmarks of cancer and is commonly associated with a mutation in cyclins and CDKs along with tumor suppressor proteins. Therefore, targeting the component of the cell cycle which leads to these characteristics would be an effective strategy for treating cancers. Specifically, Cyclin-dependent kinases (CDKs) involved in cell cycle regulation have been identified to be overexpressed in many cancers. Many studies indicate that oncogenesis occurs in cancerous cells by the overactivity of different CDKs, which impact cell cycle progression and checkpoint dysregulation which is responsible for development of tumor. The development of CDK inhibitors has emerged as a promising and novel approach for cancer treatment in both solid and hematological malignancies. Some of the novel CDK inhibitors have shown remarkable results in clinical trials, such as-Ribociclib®, Palbociclib® and Abemaciclib®, which are CDK4/6 inhibitors and have received FDA approval for the treatment of breast cancer. In this chapter, we discuss the molecular mechanism through which cyclins and CDKs regulate cell cycle progression and the emergence of cyclins and CDKs as rational targets in cancer. We also discuss recent advances in developing CDK inhibitors, which have emerged as a novel class of inhibitors, and their associated toxicities in recent years.

Complete identity and expression of StfZ, the cis-antisense RNA to the mRNA of the cell division gene ftsZ, in Escherichia coli.

Bacteria regulate FtsZ protein levels through transcriptional and translational mechanisms for proper cell division. A cis-antisense RNA, StfZ, produced from the ftsA-ftsZ intergenic region, was proposed to regulate FtsZ level in Escherichia coli. However, its structural identity remained unknown. In this study, we determined the complete sequence of StfZ and identified the isoforms and its promoters. We find that under native physiological conditions, StfZ is expressed at a 1:6 ratio of StfZ:ftsZ mRNA at all growth phases from three promoters as three isoforms of 366, 474, and 552 nt RNAs. Overexpression of StfZ reduces FtsZ protein level, increases cell length, and blocks cell division without affecting the ftsZ mRNA stability. We did not find differential expression of StfZ under the stress conditions of heat shock, cold shock, or oxidative stress, or at any growth phase. These data indicated that the cis-encoded StfZ antisense RNA to ftsZ mRNA may be involved in the fine tuning of ftsZ mRNA levels available for translation as per the growth-phase-specific requirement at all phases of growth and cell division.

Memantine enhances the cisplatin-induced apoptosis in A2780 ovarian cancer cells via CyclinD1 and hTERT inhibition

Cisplatin is the first-line treatment for ovarian cancer. Therefore, the use of effective compounds with synergistic effects can be considered a new strategy. Memantine is an NMDA receptors blocker which is overexpressed in cancers, including ovarian cancer and thus can be an efficient adjunct in cancer treatment. In this study, the MTT test, Flow cytometry, and DAPI staining was used to examine the combined effect of cisplatin with memantine. A study on Cyclin D1 and hTERT expression levels were conducted by qRT-PCR, and also cell cycle study of treated cells was performed. Our findings demonstrated that memantine enhances cytotoxicity in A2780 ovarian cancer cells. Apoptosis was also enhanced in cells treated with the combination of memantine and cisplatin. Memantine reduced the expression of Cyclin D1 and hTERT in A2780 cells and decreased the number of cancer cells in the cell cycle's growth and division phase. Our study suggests that memantine can be considered a potent adjuvant in the treatment of ovarian cancer.

Anti-Mitoticpotential Identification of Nyale (Eunice sp.) in The Tourism Area of Kuta Beach, Lombok Island, West Nusa Tenggara

BACKGROUND: BauNyale festival is a Lombok tradition that originated in the Kuta beach tourism area in Central Lombok. The locals of Lombok Island gathered in this location to harvest marine worms known as Nyale (Eunice sp.). The ability of marine worms to act as anticancer agents has received little attention in Indonesia. AIM: This study aimed to examine the biomolecules compounds of Nyale as antimitotic candidates. METHODS: This was a preliminary study using post-test only with a control group design. The sample of this study was Nyale (Eunice sp.), and sea urchin (Tripneustes ventricosus) collected from Kuta beach, Central Lombok. The Nyale was extracted with 96% ethanol as the solvent. Gas Chromatography-Mass Spectrometry (GCMS) was used to determine the content of bioactive compounds. Sea urchin embryos were divided into four treatment groups (control; 10 mg, 100 mg, and 1000 mg; 1000 mg of Nyale extract). After 2 h of fertilization incubation, the number of cell division phases (2–32 cells) was counted. The data were analyzed using ANOVA. RESULTS: The results of the GCMS test revealed that there were ten different compounds in the Nyale ethanol extract. There was a tendency for cleavage when testing the anti-mitotic potential of Nyale extract in each group. There was a significant difference in the percentage of cell changes in all treatments (control, 10 mg, 100 mg, and 1000 mg) (p &lt; 0.005). CONCLUSION: Bioactive compounds found in marine worms (nyale) influence the percentage of cell division (anti-mitotic) in sea urchin embryos.

Exploring key developmental phases and phase-specific genes across the entirety of anther development in maize.

Anther development from stamen primordium to pollen dispersal is complex and essential to sexual reproduction. How this highly dynamic and complex developmental process is controlled genetically is not well understood, especially for genes involved in specific key developmental phases. Here we generated RNA sequencing libraries spanning 10 key stages across the entirety of anther development in maize (Zea mays). Global transcriptome analyses revealed distinct phases of cell division and expansion, meiosis, pollen maturation, and mature pollen, for which we detected 50, 245, 42, and 414 phase-specific marker genes, respectively. Phase-specific transcription factor genes were significantly enriched in the phase of meiosis. The phase-specific expression of these marker genes was highly conserved among the maize lines Chang7-2 and W23, indicating they might have important roles in anther development. We explored a desiccation-related protein gene, ZmDRP1, which was exclusively expressed in the tapetum from the tetrad to the uninucleate microspore stage, by generating knockout mutants. Notably, mutants in ZmDRP1 were completely male-sterile, with abnormal Ubisch bodies and defective pollen exine. Our work provides a glimpse into the gene expression dynamics and a valuable resource for exploring the roles of key phase-specific genes that regulate anther development.