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Molecular Biology Reports Jun 2022This study served as the pioneer in studying the anti-cancer role of chicken cathelicidin peptides.
BACKGROUND
This study served as the pioneer in studying the anti-cancer role of chicken cathelicidin peptides.
METHODS AND RESULTS
Chicken cathelicidins were used as anticancer agent against the breast cancer cell line (MCF-7) and human colon cancer cell line (HCT116). In addition, the mechanism of action of the interaction of cationic peptides with breast cancer cell line MCF-7 was also investigated. An in vivo investigation was also achieved to evaluate the role of chicken cathelicidin in Ehrlich ascites cell (EAC) suppression as a tumor model after subcutaneous implantation in mice. It was found during the study that exposure of cell lines to 40 µg/ml of chicken cathelicidin for 72 h reduced cell lines growth rate by 90-95%. These peptides demonstrated down-regulation of (cyclin A1 and cyclin D genes) of MCF-7 cells. The study showed that two- and three-fold expression of both of caspase-3 and - 7 genes in untreated MCF-7 cells compared to treated MCF-7 cells with chicken cathelicidin peptides. Our data showed that chicken (CATH-1) enhance releasing of TNFα, INF-γ and upregulation of granzyme K in treated mice groups, in parallel, the tumor size and volume was reduced in the treated EAC-bearing groups. Tumor of mice groups treated with chicken cathelicidin displayed high area of necrosis compared to untreated EAC-bearing mice. Based on histological analysis and immunohistochemical staining revealed that the tumor section in Ehrlich solid tumor exhibited a strong Bcl2 expression in untreated control compared to mice treated with 10 & 20 µg of cathelicidin. Interestingly, low expression of Bcl2 were observed in mice taken 40 µg/mL of CATH-1.
CONCLUSIONS
This study drive intention in treatment of cancer through the efficacy of anticancer efficacy of chicken cathelicidin peptides.
Topics: Animals; Antineoplastic Agents; Cathelicidins; Cell Line, Tumor; Chickens; Humans; MCF-7 Cells; Mice; Neoplasms; Proto-Oncogene Proteins c-bcl-2
PubMed: 35449320
DOI: 10.1007/s11033-022-07267-7 -
Chemistry & Biodiversity May 2022Prostate cancer is the second most common malignancy in men and the development of effective therapeutic strategies remains challenging when more advanced,...
Prostate cancer is the second most common malignancy in men and the development of effective therapeutic strategies remains challenging when more advanced, androgen-independent or insensitive forms are involved. Accordingly, we have evaluated, using flow cytometry, confocal microscopy and image analysis, the anti-proliferative effects of (+)-2,3,9-trimethoxypterocarpan [(+)-PTC, 1] on relevant human prostate cancer cells as well as its capacity to control mitosis within them. In particular, the studies reported herein reveal that (+)-PTC exerts anti-proliferative activity against the PC-3 cell lines by regulating cell-cycle progression with mitosis being arrested in the prophase or prometaphase. Furthermore, it emerges that treatment of the target cells with this compound results in the formation of monopolar spindles, disorganized centrosomes and extensively disrupted γ-tubulin distributions while centriole replication remains unaffected. Such effects suggest (+)-PTC should be considered as a possible therapy for androgen-insensitive/independent prostate cancer.
Topics: Androgens; Cell Line; Humans; Male; Microtubules; Mitosis; Prostatic Neoplasms; Spindle Apparatus; Tubulin
PubMed: 35362194
DOI: 10.1002/cbdv.202200102 -
BMC Psychiatry Mar 2022The World Health Organization (WHO) proposed COVID-19 vaccination as an emergent and important method to end the COVID-19 pandemic. Since China started vaccination...
Subjective health status: an easily available, independent, robust and significant predictive factor at the prometaphase of vaccination programs for the vaccination behavior of Chinese adults.
BACKGROUND
The World Health Organization (WHO) proposed COVID-19 vaccination as an emergent and important method to end the COVID-19 pandemic. Since China started vaccination programs in December 2020, vaccination has spread to provinces and municipalities nationwide. Previous research has focused on people's vaccination willingness and its influencing factors but has not examined vaccination behavior. We examine the effectiveness of psychosocial factors in predicting vaccination behavior.
METHODS
A cross-sectional online survey was performed among Chinese adults on 8 May and 4 June 2021. The statistical analysis of the data included univariate analysis, receiver operator characteristics (ROC) analysis and ordinal multiclassification logistic regression model analysis.
RESULTS
Of the 1300 respondents, 761 (58.5%) were vaccinated. Univariate analysis showed that a high education level and good subjective health status were protective factors for vaccination behavior, while suffering from chronic diseases was a risk factor. ROC analysis showed that subjective health status (AUC = 0.625, 95% CI: 0.594-0.656, P < 0.001) was the best predictor of vaccination behavior. Logistic regression analysis with subjective health status as a dependent variable indicated that older age, female sex, depression, neurasthenia, obsession, hypochondriasis and chronic disease were significant risk factors, while positive coping tendencies were a significant protective factor.
CONCLUSION
Our study found a simple and effective marker, subjective health status, that can predict vaccination behavior. This finding can guide future epidemic prevention work.
Topics: Adult; COVID-19; COVID-19 Vaccines; China; Cross-Sectional Studies; Diagnostic Self Evaluation; Female; Humans; Pandemics; Prometaphase; Vaccination
PubMed: 35287644
DOI: 10.1186/s12888-022-03830-5 -
Frontiers in Oncology 2022Breast cancer (BRCA) has become the most frequently appearing, lethal, and aggressive cancer with increasing morbidity and mortality. Previously, it was discovered that...
BACKGROUND
Breast cancer (BRCA) has become the most frequently appearing, lethal, and aggressive cancer with increasing morbidity and mortality. Previously, it was discovered that the HAUS5 protein is involved in centrosome integrity, spindle assembly, and the completion of the cytoplasmic division process during mitosis. By encouraging chromosome misdivision and aneuploidy, HAUS5 has the potential to cause cancer. The significance of HAUS5 in BRCA and the relationship between its expression and clinical outcomes or immune infiltration remains unclear.
METHODS
Pan-cancer was analyzed by TIMER2 web and the expression differential of HAUS5 was discovered. The prognostic value of HAUS5 for BRCA was evaluated with KM plotter and confirmed with Gene Expression Omnibus (GEO) dataset. Following that, we looked at the relationship between the high and low expression groups of HAUS5 and breast cancer clinical indications. Signaling pathways linked to HAUS5 expression were discovered using Gene Set Enrichment Analysis (GSEA). The relative immune cell infiltrations of each sample were assessed using the CIBERSORT algorithm and ESTIMATE method. We evaluated the Tumor Mutation Burden (TMB) value between the two sets of samples with high and low HAUS5 expression, as well as the differences in gene mutations between the two groups. The proliferation changes of BRCA cells after knockdown of HAUS5 were evaluated by fluorescence cell counting and colony formation assay.
RESULT
HAUS5 is strongly expressed in most malignancies, and distinct associations exist between HAUS5 and prognosis in BRCA patients. Upregulated HAUS5 was associated with poor clinicopathological characteristics such as tumor T stage, ER, PR, and HER2 status. mitotic prometaphase, primary immunodeficiency, DNA replication, cell cycle related signaling pathways were all enriched in the presence of elevated HAUS5 expression, according to GSEA analysis. The BRCA microenvironment's core gene, HAUS5, was shown to be related with invading immune cell subtypes and tumor cell stemness. TMB in the HAUS5-low expression group was significantly higher than that in the high expression group. The mutation frequency of 15 genes was substantially different in the high expression group compared to the low expression group. BRCA cells' capacity to proliferate was decreased when HAUS5 was knocked down.
CONCLUSION
These findings show that HAUS5 is a positive regulator of BRCA progression that contributes to BRCA cells proliferation. As a result, HAUS5 might be a novel prognostic indicator and therapeutic target for BRCA patients.
PubMed: 35280773
DOI: 10.3389/fonc.2022.829777 -
Proceedings of the National Academy of... Mar 2022During mitosis, from late prophase onward, sister chromatids are connected along their entire lengths by axis-linking chromatin/structure bridges. During...
During mitosis, from late prophase onward, sister chromatids are connected along their entire lengths by axis-linking chromatin/structure bridges. During prometaphase/metaphase, these bridges ensure that sister chromatids retain a parallel, paranemic relationship, without helical coiling, as they undergo compaction. Bridges must then be removed during anaphase. Motivated by these findings, the present study has further investigated the process of anaphase sister separation. Morphological and functional analyses of mammalian mitoses reveal a three-stage pathway in which interaxis bridges play a prominent role. First, sister chromatid axes globally separate in parallel along their lengths, with concomitant bridge elongation, due to intersister chromatin pushing forces. Sister chromatids then peel apart progressively from a centromere to telomere region(s), step-by-step. During this stage, poleward spindle forces dramatically elongate centromere-proximal bridges, which are then removed by a topoisomerase IIα–dependent step. Finally, in telomere regions, widely separated chromatids remain invisibly linked, presumably by catenation, with final separation during anaphase B. During this stage increased separation of poles and/or chromatin compaction appear to be the driving force(s). Cohesin cleavage licenses these events, likely by allowing bridges to respond to imposed forces. We propose that bridges are not simply removed during anaphase but, in addition, play an active role in ensuring smooth and synchronous microtubule-mediated sister separation. Bridges would thereby be the topological gatekeepers of sister chromatid relationships throughout all stages of mitosis.
Topics: Anaphase; Cell Cycle Proteins; Chromatids; Chromosomal Proteins, Non-Histone; DNA Topoisomerases, Type II; Humans; Sister Chromatid Exchange; Cohesins
PubMed: 35235450
DOI: 10.1073/pnas.2123363119 -
Cancer Research Communications Dec 2021Polo-like kinase (PLK) family members play important roles in cell cycle regulation. The founding member PLK1 is oncogenic and preclinically validated as a cancer...
Polo-like kinase (PLK) family members play important roles in cell cycle regulation. The founding member PLK1 is oncogenic and preclinically validated as a cancer therapeutic target. Paradoxically, frequent loss of chromosome 5q11-35 which includes PLK2 is observed in basal-like breast cancer. In this study, we found that PLK2 was tumor suppressive in breast cancer, preferentially in basal-like and triple-negative breast cancer (TNBC) subtypes. Knockdown of PLK1 rescued phenotypes induced by PLK2-loss both and . We also demonstrated that PLK2 directly interacted with PLK1 at prometaphase through the kinase but not the polo-box domains of PLK2, suggesting PLK2 functioned at least partially through the interaction with PLK1. Furthermore, an improved treatment response was seen in both Plk2-deleted/low mouse preclinical and PDX TNBC models using the PLK1 inhibitor volasertib alone or in combination with carboplatin. Re-expression of PLK2 in an inducible PLK2-null mouse model reduced the therapeutic efficacy of volasertib. In summary, this study delineates the effects of chromosome 5q loss in TNBC that includes PLK2, the relationship between PLK2 and PLK1, and how this may render PLK2-deleted/low tumors more sensitive to PLK1 inhibition in combination with chemotherapy.
Topics: Humans; Mice; Animals; Triple Negative Breast Neoplasms; Genes, Tumor Suppressor; Biomarkers; Protein Serine-Threonine Kinases
PubMed: 35156101
DOI: 10.1158/2767-9764.crc-21-0106 -
Current Biology : CB Mar 2022Proper segregation of chromosomes during mitosis depends on "amphitelic attachments"-load-bearing connections of sister kinetochores to the opposite spindle poles via...
Proper segregation of chromosomes during mitosis depends on "amphitelic attachments"-load-bearing connections of sister kinetochores to the opposite spindle poles via bundles of microtubules, termed as the "K-fibers." Current models of spindle assembly assume that K-fibers arise largely from stochastic capture of microtubules, which occurs at random times and locations and independently at sister kinetochores. We test this assumption by following the movements of all kinetochores in human cells and determine that most amphitelic attachments form synchronously at a specific stage of spindle assembly and within a spatially distinct domain. This biorientation domain is enriched in bundles of antiparallel microtubules, and perturbation of microtubule bundling changes the temporal and spatial dynamics of amphitelic attachment formation. Structural analyses indicate that interactions of kinetochores with microtubule bundles are mediated by non-centrosomal short microtubules that emanate from most kinetochores during early prometaphase. Computational analyses suggest that momentous molecular motor-driven interactions with antiparallel bundles rapidly convert these short microtubules into nascent K-fibers. Thus, load-bearing connections to the opposite spindle poles form simultaneously on sister kinetochores. In contrast to the uncoordinated sequential attachments of sister kinetochores expected in stochastic models of spindle assembly, our model envisions the formation of amphitelic attachments as a deterministic process in which the chromosomes connect with the spindle poles synchronously at a specific stage of spindle assembly and at a defined location determined by the spindle architecture. Experimental analyses of changes in the kinetochore behavior in cells with perturbed activity of molecular motors CenpE and dynein confirm the predictive power of the model.
Topics: Chromosome Segregation; Humans; Kinetochores; Microtubules; Mitosis; Spindle Apparatus
PubMed: 35108523
DOI: 10.1016/j.cub.2022.01.013 -
Journal of Natural Products Jan 2022Natural products, which are enzymatically biosynthesized, have a broad range of biological activities. In particular, many flavonoids are known to contribute to human...
Natural products, which are enzymatically biosynthesized, have a broad range of biological activities. In particular, many flavonoids are known to contribute to human health with low toxicity. We previously reported that novel benzo[]thiophenyl (BT) flavones with a 10π-electron BT ring B replacing the usual 6π-electron phenyl ring showed potent antiproliferative activity against human tumor cell lines. Interestingly, the activity profiles against cell cycle progression of the BT-flavones totally changed depending on the combination of substituents at the C-3 and C-5 positions. This finding encouraged an extension of these studies on the impact of BT to related flavonoids, such as chalcones, isoflavones, and aurones. Accordingly, 10 isoflavones, 29 chalcones, and four aurones were synthesized and evaluated for antiproliferative activity against five human tumor cell lines including a multi-drug-resistant cell line. Among these compounds, BT-isoflavone , BT-chalcones , , , , and , and BT-aurone displayed significant antiproliferative effects against all tested tumor cell lines. The structure-antiproliferative activity relationships clearly demonstrated the importance of BT instead of phenyl as ring B for the isoflavone and chalcones, but not the aurones. Flow cytometry and immunocytochemical studies demonstrated that the active BT-flavonoids led to cell cycle arrest at the prometaphase by induction of multipolar spindle formation. The present studies should contribute greatly to the synthesis and functional analysis of biologically active flavonoid derivatives for chemical space expansion.
Topics: Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Electrons; Flavonoids; Humans; Mitosis; Structure-Activity Relationship; Thiophenes
PubMed: 35026948
DOI: 10.1021/acs.jnatprod.1c00867 -
Methods in Molecular Biology (Clifton,... 2022This paper describes an easy method to enrich the harvest of adherent mammalian cells at each stage of mitosis (from prometaphase to cytokinesis) by combining Eg5...
This paper describes an easy method to enrich the harvest of adherent mammalian cells at each stage of mitosis (from prometaphase to cytokinesis) by combining Eg5 inhibition using dimethylenastron (DMA) with mitotic shake-off, followed by timed release from the drug.
Topics: Animals; Cytokinesis; HeLa Cells; Humans; Mammals; Mitosis; Prometaphase; Survivin
PubMed: 34972948
DOI: 10.1007/978-1-0716-1904-9_7 -
Horticulture Research Dec 2021Seedlessness is a valuable agronomic trait in watermelon (Citrullus lanatus) breeding. Conventional less seed watermelons are mainly triploid, which has many...
Seedlessness is a valuable agronomic trait in watermelon (Citrullus lanatus) breeding. Conventional less seed watermelons are mainly triploid, which has many disadvantages due to unbalanced genome content. Less seed watermelon can be achieved at the diploid level when certain reproductive genes are mutated or by chromosome translocation, which leads to defects during meiosis. However, the formation mechanism of diploid less seed watermelons remains largely unknown. Here, we identified a spontaneous mutant line, watermelon line "148", which can set seeds normally when self-pollinated. A total of 148 × JM F hybrid plants exhibited seed number reductions to 50.3% and 47.3% of those of the two parental lines, respectively, which are considered to be less seed. Examination of pollen viability and hybridization experiments revealed that F hybrids produce semisterile pollen and ovules. Further cytological observations indicated that semisterility was a result of a reciprocal translocation of chromosomes, which exhibited one quadrivalent ring of four chromosomes at prometaphase I during meiosis. RT-qPCR analysis indirectly confirmed that the semisterile phenotype is caused by chromosome translocation rather than disruption of specific meiotic gene expression. F population genetic analysis indicated that the "148" watermelon line is a homozygous translocation and that the less seed phenotype of the F hybrid is prompted by one chromosome fragment translocation. The translocated fragment was further fine mapped to a 2.09 Mb region on chromosome 6 by whole-genome resequencing and genetic map cloning procedures. Our work revealed that a 2.09 Mb chromosome fragment translocation on chromosome 6, causing meiotic defects at metaphase I during meiosis, leads to diploid less seed watermelon. Our findings provide a new promising method for less seed watermelon breeding at the diploid level, as well as a fragment size reference for breeding less seed watermelon through artificially induced chromosome translocation.
PubMed: 34848689
DOI: 10.1038/s41438-021-00687-9