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Hepatocellular carcinoma is characterized by high recurrence rates and poor prognosis. Cancer stem cells contribute to tumor heterogeneity, treatment resistance, and recurrence. This study aims to identify key genes associated with stemness and immune cell infiltration in HCC. We analyzed RNA sequencing data from The Cancer Genome Atlas to calculate mRNA expression-based stemness index in HCC. A weighted gene co-expression network analysis was performed to identify stemness-related gene modules. A single-sample gene set enrichment analysis was used to evaluate immune cell infiltration. Key genes were validated using RT-qPCR. The mRNAsi was significantly higher in HCC tissues compared to adjacent normal tissues and correlated with poor overall survival. WGCNA and subsequent analyses identified 10 key genes, including minichromosome maintenance complex component 2, cell division cycle 6, forkhead box M1, NIMA-related kinase 2, Holliday junction recognition protein, DNA topoisomerase II alpha, denticleless E3 ubiquitin protein ligase homolog, maternal embryonic leucine zipper kinase, protein regulator of cytokinesis 1, and kinesin family member C1, associated with stemness and low immune cell infiltration. These genes were significantly upregulated in HCC tissues. A functional enrichment analysis revealed their involvement in cell cycle regulation. This study identified 10 key genes related to stemness and immune cell infiltration in HCC. These genes, primarily involved in cell cycle regulation, may serve as potential targets for developing more effective treatments to reduce HCC recurrence and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features. Materials and Methods: The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay. Results: The PLK2 Crs15009-Crs963615 haplotype was under-represented in the GC group compared to that in the control group (Pcorr=0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM Trs228589-Ars189037-Grs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC. Conclusions: PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR- 23b-5p expression status could serve as a prognostic marker for survival in patients with GC. [ABSTRACT FROM AUTHOR]

• The review provides an in-depth analysis of polymorphisms in genes of the pathways that maintain genome stability, viz., DNA damage response, repair, cell cycle, apoptosis, and telomere maintenance, and discusses their implications in ovarian carcinogenesis. • The review also intersects with fields such as bioinformatics, broadening its relevance and use of computational tools and providing a detailed analysis of genetic association studies like case-control studies and meta-analyses. • It highlights the research gaps in studying these caretaker gene variants and includes novel perspectives to overcome the current challenges in SNP-based studies. Ovarian cancer (OC) is the deadliest gynecological malignancy among all female reproductive cancers. It is characterized by high mortality rate and poor prognosis. Genomic instability caused by mutations, single nucleotide polymorphisms (SNPs), copy number variations (CNVs), microsatellite instability (MSI), and chromosomal instability (CIN) are associated with OC predisposition. SNPs, which are highly prevalent in the general population, show a greater relative risk contribution, particularly in sporadic cancers. Understanding OC etiology in terms of genetic basis can increase the use of molecular diagnostics and provide promising approaches for designing novel treatment modalities. This will help deliver personalized medicine to OC patients, which may soon be within reach. Given the pivotal impact of SNPs in cancers, the primary emphasis of this review is to shed light on their prevalence in key caretaker genes that closely monitor genomic integrity, viz., DNA damage response, repair, cell cycle checkpoints, telomerase maintenance, and apoptosis and their clinical implications in OC. We highlight the current challenges faced in different SNP-based studies. Various computational methods and bioinformatic tools employed to predict the functional impact of SNPs have also been comprehensively reviewed concerning OC research. Overall, this review identifies that variants in the DDR and HRR pathways are the most studied, implying their critical role in the disease. Conversely, variants in other pathways, such as NHEJ, MMR, cell cycle, apoptosis, telomere maintenance, and PARP genes, have been explored the least. [ABSTRACT FROM AUTHOR]

Transcription factors are inextricably linked with histone deacetylases leading to compact chromatin. The Forkhead transcription factor Fkh1 is mainly a negative transcriptional regulator which affects cell cycle control, silencing of mating-type cassettes and induction of pseudohyphal growth in the yeast Saccharomyces cerevisiae. Markedly, Fkh1 impinges chromatin architecture by recruiting large regulatory complexes. Implication of Fkh1 with transcriptional corepressor complexes remains largely unexplored. In this work we show that Fkh1 directly recruits corepressors Sin3 and Tup1 (but not Cyc8), providing evidence for its influence on epigenetic regulation. We also identified the specific domain of Fkh1 mediating Sin3 recruitment and substantiated that amino acids 51–125 of Fkh1 bind PAH2 of Sin3. Importantly, this part of Fkh1 overlaps with its Forkhead-associated domain (FHA). To analyse this domain in more detail, selected amino acids were replaced by alanine, revealing that hydrophobic amino acids L74 and I78 are important for Fkh1-Sin3 binding. In addition, we could prove Fkh1 recruitment to promoters of cell cycle genes CLB2 and SWI5. Notably, Sin3 is also recruited to these promoters but only in the presence of functional Fkh1. Our results disclose that recruitment of Sin3 to Fkh1 requires precisely positioned Fkh1/Sin3 binding sites which provide an extended view on the genetic control of cell cycle genes CLB2 and SWI5 and the mechanism of transcriptional repression by modulation of chromatin architecture at the G2/M transition. [ABSTRACT FROM AUTHOR]

Background: The clinical behavior of prostate cancer (PCa) is variable, and while the majority of cases remain indolent, 10% of patients progress to deadly forms of the disease. Current clinical predictors used at the time of diagnosis have limitations to accurately establish progression risk. Here we describe the development of a tumor suppressor regulated, cell-cycle gene expression based prognostic signature for PCa, and validate its independent contribution to risk stratification in several radical prostatectomy (RP) patient cohorts.Methods: We used RNA interference experiments in PCa cell lines to identify a gene expression based gene signature associated with Tmeff2, an androgen regulated, tumor suppressor gene whose expression shows remarkable heterogeneity in PCa. Gene expression was confirmed by qRT-PCR. Correlation of the signature with disease outcome (time to recurrence) was retrospectively evaluated in four geographically different cohorts of patients that underwent RP (834 samples), using multivariate logistical regression analysis. Multivariate analyses were adjusted for standard clinicopathological variables. Performance of the signature was compared to previously described gene expression based signatures using the SigCheck software.Results: Low levels of TMEFF2 mRNA significantly (p < 0.0001) correlated with reduced disease-free survival (DFS) in patients from the Memorial Sloan Kettering Cancer Center (MSKCC) dataset. We identified a panel of 11 TMEFF2 regulated cell cycle related genes (TMCC11), with strong prognostic value. TMCC11 expression was significantly associated with time to recurrence after prostatectomy in four geographically different patient cohorts (2.9 ≤ HR ≥ 4.1; p ≤ 0.002), served as an independent indicator of poor prognosis in the four RP cohorts (1.96 ≤ HR ≥ 4.28; p ≤ 0.032) and improved the prognostic value of standard clinicopathological markers. The prognostic ability of TMCC11 panel exceeded previously published oncogenic gene signatures (p = 0.00017).Conclusions: This study provides evidence that the TMCC11 gene signature is a robust independent prognostic marker for PCa, reveals the value of using highly heterogeneously expressed genes, like Tmeff2, as guides to discover prognostic indicators, and suggests the possibility that low Tmeff2 expression marks a distinct subclass of PCa. [ABSTRACT FROM AUTHOR]

Brain tumors are becoming a major cause of death. The classification of brain tumors has gone through restructuring with regard to some criteria such as the presence or absence of a specific genetic alteration in the 2016 central nervous system World Health Organization update. Two categories of genes with a leading role in tumorigenesis and cancer induction include tumor suppressor genes and oncogenes; tumor suppressor genes are inactivated through a variety of mechanisms that result in their loss of function. As for the oncogenes, overexpression and amplification are the most common mechanisms of alteration. Important cell cycle genes such as p53, ATM, cyclin D2, and Rb have shown altered expression patterns in different brain tumors such as meningioma and astrocytoma. Some genes in signaling pathways have a role in brain tumorigenesis. These pathways include hedgehog, EGFR, Notch, hippo, MAPK, PI3K/Akt, and WNT signaling. It has been shown that telomere length in some brain tumor samples is shortened compared to that in normal cells. As the shortening of telomere length triggers chromosome instability early in brain tumors, it could lead to initiation of cancer. On the other hand, telomerase activity was positive in some brain tumors. It is suggestive that telomere length and telomerase activity are important diagnostic markers in brain tumors. This review focuses on brain tumors with regard to the status of oncogenes, tumor suppressors, cell cycle genes, and genes in signaling pathways as well as the role of telomere length and telomerase in brain tumors. [ABSTRACT FROM AUTHOR]

Purpose DNA damage caused by radiation initiates biological responses affecting cell fate. DNA methylation regulates gene expression and modulates DNA damage pathways. Alterations in the methylation profiles of cell cycle regulating genes may control cell response to radiation. In this study we investigated the effect of ionizing radiation on the methylation levels of 22 cell cycle regulating genes in correlation with gene expression in 1321NI astrocytoma cell line. Methods 1321NI cells were irradiated with 2, 5 or 10 Gy doses then analyzed after 24, 48 and 72 h for cell viability using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliu bromide) assay. Flow cytometry were used to study the effect of 10 Gy irradiation on cell cycle. EpiTect Methyl II PCR Array was used to identify differentially methylated genes in irradiated cells. Changes in gene expression was determined by qPCR. Azacytidine treatment was used to determine whether DNA methylation affectes gene expression. Results Our results showed that irradiation decreased cell viability and caused cell cycle arrest at G2/M. Out of 22 genes tested, only CCNF and RAD9A showed some increase in DNA methylation (3.59% and 3.62%, respectively) after 10 Gy irradiation, and this increase coincided with downregulation of both genes (by 4 and 2 fold, respectively). Treatment with azacytidine confirmed that expression of CCNF and RAD9A genes was regulated by methylation. Conclusions 1321NI cell line is highly radioresistant and that irradiation of these cells with a 10 Gy dose increases DNA methylation of CCNF and RAD9A genes. This dose down-regulates these genes, favoring G2/M arrest. [ABSTRACT FROM AUTHOR]

Increased endopolyploidy is important for plant growth and development as well as for adaptation to environmental stresses. However, little is known about the role of reduced endopolyploidy, especially in root systems. In this report, endopolyploidy variations were examined in different types of barley ( Hordeum vulgare L.) roots, and the effects of phosphorus (P) deficiency and salinity (NaCl) stress on root endopolyploidy were also studied. The results showed that the endopolyploidy levels were lower in lateral roots than in either primary or nodal roots. The lower endopolyploidy in lateral roots was attributed to cortical cells. P deficiency reduced the endopolyploidy levels in lateral roots and mature zone of primary roots. By contrast, salinity had no effects on the endopolyploidy levels in either lateral or primary roots, but had a minor effect on nodal roots. Transcript analysis of cell cycle-related genes showed that multiple cell cycle-related genes were more highly expressed in lateral roots than in primary roots, suggesting their roles in lowering endopolyploidy. P deficiency reduced HvCCS52A1 transcripts in the mature zone of primary roots, but had little effect on the transcripts of 12 cell cycle-related genes in lateral roots, suggesting that endopolyploidy regulation differs between lateral roots and primary roots. Our results revealed that endopolyploidy reduction in root systems could be an integrated part of endopolyploidy plasticity in barley growth and development as well as in adaptation to a low P environment. [ABSTRACT FROM AUTHOR]

Background: Cohesin complex is responsible for sister chromatid cohesion. STAG1/STAG2 is part of the complex, which is regulated by PDS5B. Alterations in these genes were described in tumors. PDS5B is a negative regulator of cell proliferation. We aimed to assess molecular alterations in these genes in oral squamous cell carcinoma (OSCC) and predict their expression by the expression of 84 cell cycle genes. In addition, we investigated whether pds5b protein expression impacted ki-67 and p53 immunopositivity.Methods: We assessed loss of heterozygosity (LOH) at STAG1 and STAG2 loci in 15 OSCC using three polymorphic markers. Associations between the immunoexpression of pds5b and ki-67 and p53 were tested in 62 samples. Differences between transcriptional levels of STAG1, STAG2, and PDS5B between OSCC and normal oral mucosa (NM) were evaluated by qPCR. An 84 cell cycle genes qPCR array was carried with OSCC samples, and STAG1, STAG2, and PDS5B were independently used as response variables in multiple linear regression models.Results: Loss of heterozygosity in at least one marker was observed in three samples. pds5b, p53, and ki-67 were highly expressed, and no association was found between pds5b immunoexpression and ki-67 or p53 (P > 0.05). OSCC and NM showed similar transcriptional levels of STAG1, STAG2, and PDS5B. STAG1 and CUL3 expression seem to be related (P = 0.004).Conclusions: There is LOH at STAG1 and STAG2 loci in OSCC, but OSCC and NM showed similar transcriptional levels of STAG1, STAG2, and PDS5B. pds5b immunoexpression in OSCC was high, but it was not associated with proliferation cell index. [ABSTRACT FROM AUTHOR]

Aims Cell cycle dysregulation is important in tumorigenesis. Transcriptional silencing of cell cycle regulatory genes, due to DNA methylation, is a common epigenetic event in malignancies. As 2 O 3 has been shown to induce cell cycle arrest and also to be a potential hypomethylating agent. Our study aimed to investigate DNA methylation patterns of cell cycle regulatory genes promoters, the effects of Arsenic trioxide (As 2 O 3 ) on the methylated genes and cell cycle distribution in colorectal cancer (CRC) cell lines. Main methods The methylation-specific PCR (MSP) and/or restriction enzyme-based methods were used to study the promoter methylation patterns of 24 cell cycle regulatory genes in CRC cell lines. Gene expression level and cell cycle distribution were determined by Real-time PCR and flow cytometric analyses, respectively. Key findings Our methylation analysis indicated that only promoters of RBL1 (p107), CHFR and p16 genes were aberrantly methylated in three cell lines. As 2 O 3 significantly decreased DNA methylation in promoter regions of these genes and restored their expression. We found that As 2 O 3 significantly reduced the expression of DNA methyltransferase 1 (DNMT1) and increased arsenic methyltransferase (AS3MT). Furthermore, As 2 O 3 altered transcriptional activity of several unmethylated cell cycle regulatory genes including cyclin B 1, E1, D1, GADD45A and p21. Cell cycle flow cytometry analysis showed As 2 O 3 induced G2/M arrest in all three cell lines. Significance These data suggest that demethylation and alteration in the expression level of the cell cycle-related genes may be possible mechanisms in As 2 O 3 -induced cell cycle arrest in colorectal cancer cells. [ABSTRACT FROM AUTHOR]

Purpose The analysis of gene expression, especially those involved in cell cycle control, can help to discover mechanisms determining the outcome of radiation treatment. The main purpose of this study was to examine the expression level of genes responsible for cell cycle regulation in samples of the head and neck cancer, obtained during surgery. Methods Postsurgical samples of SCC of head and neck region were collected. Over 80 genes were analysed using cell cycle quantitative real-time RT-PCR Array method. Presence of 14 high-risk HPV types DNA in frozen or paraffin-embedded tumour pathological samples was also assessed. To correlate gene expression with selected pathological features and clinical outcome we used different hierarchical clustering method. Results Hierarchical clustering demonstrated the association between gene expression within certain clusters and gender, tumour site, T stage, N stage, grade, pathological subtype or tumour recurrence. Conclusions Despite some limitations we were able to identify gene clusters that allowed to classify patients according to selected clinical features and occurrence of tumour recurrence. The results of the analysis also confirm that the incidence of HPV infection among the patients from Upper Silesia is relatively low, whereas HPV negative tumours, likely associated with smoking, appeared dominant. [ABSTRACT FROM AUTHOR]

The nucleolar protein pescadillo (PES) controls biogenesis of the 60S ribosomal subunit through functional interactions with Block of Proliferation 1 (BOP1) and WD Repeat Domain 12 (WDR12) in plants. In this study, we determined protein characteristics and in planta functions of BOP1 and WDR12, and characterized defects in plant cell growth and proliferation caused by a deficiency of PeBoW (PES-BOP1-WDR12) proteins. Dexamethasone-inducible RNAi of BOP1 and WDR12 caused developmental arrest and premature senescence in Arabidopsis, similar to the phenotype of PES RNAi. Both the N-terminal domain and WD40 repeats of BOP1 and WDR12 were critical for specific associations with 60S/80S ribosomes. In response to nucleolar stress or DNA damage, PeBoW proteins moved from the nucleolus to the nucleoplasm. Kinematic analyses of leaf growth revealed that depletion of PeBoW proteins led to dramatically suppressed cell proliferation, cell expansion, and epidermal pavement cell differentiation. A deficiency in PeBoW proteins resulted in reduced cyclin-dependent kinase Type A activity, causing reduced phosphorylation of histone H1 and retinoblastoma-related (RBR) protein. PeBoW silencing caused rapid transcriptional modulation of cell-cycle genes, including reduction of E2Fa and Cyclin D family genes, and induction of several KRP genes, accompanied by downregulation of auxin-related genes and up-regulation of jasmonic acid-related genes. Taken together, these results suggest that the PeBoW proteins involved in ribosome biogenesis play a critical role in plant cell growth and survival, and their depletion leads to inhibition of cell-cycle progression, possibly modulated by phytohormone signaling. [ABSTRACT FROM AUTHOR]

Background: We reported previously that root elongation in Arabidopsis is promoted by exogenous proline, raising the possibility that this amino acid may modulate root growth. Results: To evaluate this hypothesis we used a combination of genetic, pharmacological and molecular analyses, and showed that proline specifically affects root growth by modulating the size of the root meristem. The effects of proline on meristem size are parallel to, and independent from, hormonal pathways, and do not involve the expression of genes controlling cell differentiation at the transition zone. On the contrary, proline appears to control cell division in early stages of postembryonic root development, as shown by the expression of the G2/M-specific CYCLINB1;1 (CYCB1;1) gene. Conclusions: The overall data suggest that proline can modulate the size of root meristematic zone in Arabidopsis likely controlling cell division and, in turn, the ratio between cell division and cell differentiation. [ABSTRACT FROM AUTHOR]

We evaluated genetic variants in 51 candidate genes encoding proteins that interact with HIV-1 during the virus life cycle for association with HIV-1 outcomes in an African cohort.Using a nested case-control study within a cohort of heterosexual HIV-1-serodiscordant couples, we genotyped 475 haplotype-tagging single-nucleotide polymorphisms (tagSNPs) and 18 SNPs previously associated with HIV-1 transmission and/or progression (candidate SNPs) in 51 host genes. We used logistic and Cox proportional hazard regression with adjustment for sex, age, and population stratification to detect SNP associations with HIV-1 acquisition, plasma HIV-1 set point, and a composite measure of HIV-1 disease progression. Significant thresholds for tagSNP, but not candidate SNP, associations were subjected to Bonferroni correction for multiple testing.We evaluated 491 HIV-1-infected and 335 HIV-1-uninfected individuals for 493 SNPs, 459 of which passed quality control filters. Candidate SNP PPIA rs8177826 and tagSNP SMARCB1 rs6003904 were significantly associated with HIV-1 acquisition risk (odds ratio = 0.14, P = 0.03, and odds ratio = 2.11, Pcorr = 0.01, respectively). Furthermore, the TT genotype for CCR5 rs1799988 was associated with a mean 0.2 log10 copies per milliliter lower plasma HIV-1 RNA set point (P = 0.04). We also identified significant associations with HIV-1 disease progression for variants in FUT2 and MBL2.Using a targeted gene approach, we identified variants in host genes whose protein products interact with HIV-1 during the virus replication cycle and were associated with HIV-1 outcomes in this African cohort. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe co-expression correlations of cell cycle regulatory genes in multiple myeloma (MM) and plasma cell leukemia (PCL). Our results highlight the presence of dynamic equilibrium between co-expression of activator and inhibitor gene sets. Moreover inhibitor set is more sensitive to the activator changes, not vice versa. We have shown that CDKN2A expression is associated with short-term survival in newly diagnosed MM patients (survival was 30.3±3.9months for ‘low’ expressed and 7.5±5.6months for ‘high’ expressed group, p<0.0001). Moreover low-expression CDKN2A group showed time-to-progression benefit in newly diagnosed patients (remission was 20.8±3.6months for ‘low’ and 8.4±2.7months for ‘high’ expressed group, p<0.0001) as well as in whole studied cohort of MM patients (remission was 20.8±2.8months for ‘low’ and 9.8±1.1months for ‘high’ expressed group, p<0.0001). The overexpression of inhibitors can be explained as a compensatory reaction to growing “oncogenic stress”. [ABSTRACT FROM AUTHOR]

We investigated spatio-temporal variations in cell division and the occurrence of endoreduplication in cells of tuber mustard stems during development. Cells in the stem had 8C nuclei (C represents DNA content of a two haploid genome), since it is an allotetraploid species derived from diploid Brassica rapa (AA) and B. nigra (BB), thus indicating the occurrence of endoreduplication. Additionally, we observed a dynamic change of cell ploidy in different regions of the swollen stems, with a decrease in 4C proportion in P4-1 and a sharp increase in 8C cells that became the dominant cell type (86.33% at most) in the inner pith cells. Furthermore, cDNAs of 14 cell cycle genes and four cell expansion genes were cloned and their spatial transcripts analysed in order to understand their roles in stem development. The expression of most cell cycle genes peaked in regions of the outer pith (P2 or P3), some genes regulating S/G2 and G2/M ( BjCDKB1;2, BjCYCB1;1 and BjCYCB1;2) significantly decrease in P5 and P6, while G1/S regulators ( BjE2Fa, BjE2Fb and BjE2Fc) showed a relative high expression level in the inner pith (P5) where cells were undergoing endoreduplication. Coincidentally, BjXTH1and BjXTH2 were exclusively expressed in the endoreduplicated cells. Our results suggest that cells of outer pith regions (P2 and P3) mainly divide for cell proliferation, while cells of the inner pith expand through endoreduplication. Endoreduplication could trigger expression of BjXTH1 and BjXTH2 and thus function in cell expansion of the pith tissue. [ABSTRACT FROM AUTHOR]

Growth of tomato fruits is determined by cell division and cell expansion, which are tightly controlled by factors that drive the core cell cycle. The cyclin-dependent kinases (CDKs) and their interacting partners, the cyclins, play a key role in the progression of the cell cycle. In this study the role of CDKA1, CDKB1, and CDKB2 in fruit development was characterized by fruit-specific overexpression and down-regulation. CDKA1 is expressed in the pericarp throughout development, but is strongly up-regulated in the outer pericarp cell layers at the end of the growth period, when CDKB gene expression has ceased. Overexpression of the CDKB genes at later stages of development and the down-regulation of CDKA1 result in a very similar fruit phenotype, showing a reduction in the number of cell layers in the pericarp and alterations in the desiccation of the fruits. Expression studies revealed that CDKA1 is down-regulated by the expression of CDKB1/2 in CDKB1 and CDKB2 overexpression mutants, suggesting opposite roles for these types of CDK proteins in tomato pericarp development. [ABSTRACT FROM PUBLISHER]

Purpose: To investigate whether an adaptive response can be induced in mice which were pre-exposed to 900 MHz radiofrequency fields. Materials and methods: Adult male Kunming mice were exposed to 900 MHz radiofrequency fields (RF) at power intensities of 12, 120 and 1200 μμW/cm2 for 1 h/day for 14 days and then subjected to whole body gamma-irradiation. The results were compared with those in unexposed control animals and those exposed to gamma-irradiation alone (without pre-exposure to RF). The extent of survival and hematopoietic tissue damage (assessed in the form of nucleated colony forming cells in the bone marrow and colony forming cells in the spleen of lethally irradiated ''recipient'' mice) as well as the expression of cell cycle-related genes were investigated. Results: The results indicated a significant increase in survival time, reduction in the hematopoietic tissue damage in RF pre-exposed mice which were gamma-irradiated (as compared with those exposed to gamma-radiation alone). This was accompanied by significantly increased expression of cell cycle-related genes, namely, cyclin-D1, cyclin-E, cyclin-DK4 and cyclin-DK2 in hematopoietic cells. Conclusions: Pre-exposure of mice to 900 MHz radiofrequency fields has resulted in a significant reduction in hematopoietic damage caused by subsequent exposure to ionising radiation. This phenomenon appears to be similar to that of the ''adaptive response'' which is well documented in scientific literature. [ABSTRACT FROM AUTHOR]

Abstract: In this work, we modify the superparamagnetic clustering algorithm (SPC) by adding an extra weight to the interaction formula that considers which genes are regulated by the same transcription factor. With this modified algorithm which we call SPCTF, we analyze the Spellman et al. microarray data for cell cycle genes in yeast, and find clusters with a higher number of elements compared with those obtained with the SPC algorithm. Some of the incorporated genes by using SPCFT were not detected at first by Spellman et al. but were later identified by other studies, whereas several genes still remain unclassified. The clusters composed by unidentified genes were analyzed with MUSA, the motif finding using an unsupervised approach algorithm, and this allow us to select the clusters whose elements contain cell cycle transcription factor binding sites as clusters worthy of further experimental studies because they would probably lead to new cell cycle genes. Finally, our idea of introducing the available information about transcription factors to optimize the gene classification could be implemented for other distance-based clustering algorithms. [Copyright &y& Elsevier]

Abstract: Objectives: We aimed to investigate the expression profile of cell cycle genes in the mandibular condyle on mechanical strain and natural growth, and quantify their expression intensity. Methods: Three hundred and fifty 35 days old Sprague–Dawley rats were randomly divided into experimental groups fitted with bite-jumping appliances and control groups. Groups were sacrificed at days 1, 3, 7, 9, 14, 30, and 33. Then, condyles were dissected and total RNA was extracted for microarray analysis. Results: Thirty-nine known cell cycle genes were present in the condyle, where Cyclin D1, PCNA, and Wnt5a were differentially expressed. Reverse transcriptase-PCR confirmed that Wnt5a showed a 2-fold increase on experimental day 1, Cyclin D1 showed a 2-fold increase on experimental day 1 and a 3-fold increase on experimental day 14, while PCNA shows 2.2-fold increase both on experimental days 9 and 30. PCNA, Cyclin D1, and Wnt5a were all expressed by cells in both the proliferative layer and erosive zone. Conclusion: Mandibular advancement leads to the expression of Cyclin D1 that accelerates entry to the S phase. The increased level of PCNA indicates increased DNA replication of MSC. Then, elevated level of Wnt5a indicates the commitment of MSC to the chondrogenic lineage. [Copyright &y& Elsevier]

Ovarian cancer remains a highly lethal disease. The molecular pathology of ovarian carcinomas is heterogeneous and involves various putative precursor lesions and multiple pathways of development. Dysregulation of cell cycle control, in particular G1-S-phase transition, is implicated in the pathogenesis of most human cancers, including epithelial ovarian cancer (EOC). The regulatory pathways controlling cell cycle phases include several oncogenes and tumor suppressor genes which display a range of abnormalities with potential usefulness as markers of evolution or treatment response in ovarian cancer. This review summarizes the current knowledge about these alterations in borderline and malignant tumors of the ovary. We focalized our attention on the genes involved in the regulation of the G1 phase and the G1-S phase transition of the cell cycle, two crucial steps in the cell cycle control. In particular the role of cyclins, cyclindependent kinases (CDKs), CDKs inhibitors (CKIs) and retinoblastoma family members has been reviewed. [ABSTRACT FROM AUTHOR]

Changes in photoassimilate partitioning between source and sink organs significantly affect fruit development and size. In this study, a comparison was made of tomato plants (Solanum lycopersicum L.) grown under a low fruit load (one fruit per truss, L1 plants) and under a standard fruit load (five fruits per truss, L5 plants), at morphological, biochemical, and molecular levels. Fruit load reduction resulted in increased photoassimilate availability in the plant and in increased growth rates in all plant organs analysed (root, stem, leaf, flower, and fruit). Larger flower and fruit size in L1 plants were correlated with higher cell number in the pre-anthesis ovary. This was probably due to the acceleration of the flower growth rate since other flower developmental parameters (schedule and time-course) remained otherwise unaffected. Using RT-PCR, it was shown that the transcript levels of CYCB2;1 (cyclin) and CDKB2;1 (cyclin-dependent kinase), two mitosis-specific genes, strongly increased early in developing flower buds. Remarkably, the transcript abundance of CYCD3;1, a D-type cyclin potentially involved in cell cycle regulation in response to mitogenic signals, also increased by more than 5-fold at very early stages of L1 flower development. By contrast, transcripts from fw2.2, a putative negative regulator of cell division in tomato fruit, strongly decreased in developing flower bud, as confirmed by in situ hybridization studies. Taken together, these results suggest that changes in carbohydrate partitioning could control fruit size through the regulation of cell proliferation-related genes at very early stages of flower development. [ABSTRACT FROM PUBLISHER]

Purpose: One of the most common malignancies peculiar to female health with few symptoms, low response to therapy, difficult diagnosis, frequent relapse, and high mortality, is ovarian cancer. Thus, our experiment, using Human amniotic fluid mesenchymal stem cells (hAFMSCs) as a therapeutic tool, aims to find an efficient treatment approach for patients suffering from SKOV3 ovarian cancer. Material & Methods: In this study, we obtained 5 ml amniotic fluid from 16–20 week pregnant women who underwent amniocentesis for routine prenatal diagnosis by karyotyping in Al‐Zahra Hospital of Tabriz University of Medical Sciences, Iran. Using trans wells in 24 wells plate, hAFMSCs were isolated from all samples, co‐cultured with SKOV3 ovarian cancer cell line, and characterized via flow cytometry and RT‐PCR. Human skin fibroblast cells (HSFCs) were isolated and used as a negative control. SKOV3 and HSFCs' viability after 5 days was evaluated by MTT assay. Cell cycle and apoptotic genes were analyzed by real‐time PCR. Results: We successfully isolated and characterized hAFMSCs through it positivity for CD44 and CD90 specific mesenchymal stem cell markers and negativity for CD31 and CD45. Oct4 and NANOG were evaluated by RT‐PCR as pluripotency markers, and visualized on 2% gel electrophoresis. We established hAFMS cell lines after 5 days of co‐culturing the SKOV3 cells, viability was decreased; however, HSFCs did not show toxicity by MTT assay. The genes indicated upregulation and high expression by a real‐time PCR. Conclusions: Our findings showed that hAFMSCs have natural tumor tropism, and can release soluble factors in a cell culture, which cause an efficient anticancer effect. Thus, we can use hAFMSCs for complete anticancer therapy on SKOV3 cell line at cell culture condition and possibly in vivo in the near future. [ABSTRACT FROM AUTHOR]

Description of the molecular biology of plant and animal cell cycles highlights similarities and critical differences. The cell cycle is a point of control in both growth and development and deepening understanding of underlying processes and mechanisms may have many practical applications. [ABSTRACT FROM PUBLISHER]