PROTECTIVE EFFECT OF A NEW SUPEROXIDE-PRODUCING ENZYME COMPLEX FROM RASPBERRY IN RATS WITH THIRD-DEGREE THERMAL BURNS.

Thermal burns are the most common type of burn injuries. Medical treatment for burns is crucial, especially for third-degree burns and when a significant surface area of the body is affected. One of the most pressing issues in modern medicine is the search for new effective means to accelerate the healing of burn wounds. Oxygen radicals play a significant role in maintaining homeostasis, forming the body's resistance to infection, and ensuring the regeneration of organs and tissues. In this study, a superoxide (O2-)-producing enzyme (SPE) from raspberries was applied (topically to the skin, injected under the wound surface, with solution concentrations of 12.75% and 5%) after a third-degree thermal burn to determine its reparative effects on the skin. To assess the condition of the animals that had suffered burn injuries and the healing process, blood parameters were analyzed, and cytogenetic indices of bone marrow from the femur of the animals were studied: mitotic index, number of polyploid cells, and chromosomal aberrations. When analyzing hematological, cytogenetic, and histological parameters, significant differences were found between the «clean burn¼ groups and the groups in which SPE was used in different concentrations and methods of application. The use of SPE in both concentrations contributed to a reduction in the area of burn wounds compared to a «clean burn¼. The survival rate of animals for 30 days (before the end of the experiment) was 100% when using a 12.75% SPE solution and 50% when using a 5% SPE solution. The use of SPE led to significant differences in hematological parameters from the «clean burn¼ group throughout the entire duration of the experiment, showing a tendency to normalize the parameters. Under the influence of the 12.75% SPE solution, there was a tendency toward normalization of the mitotic index, along with a significant reduction in the percentage of polyploid cells and chromosomal aberrations, which may indicate its beneficial effects. This study found that a 12.75% SPE solution derived from raspberries was more effective and had healing properties on third-degree thermal burns, promoting rapid healing of the burn wound.

Maternal Exposure to Per- and Polyfluoroalkyl Substances and Offspring Chromosomal Abnormalities: The Japan Environment and Children's Study.

BACKGROUND: Although recent in vitro experimental results have raised the question of whether maternal exposure to per- and polyfluoroalkyl substances (PFAS) may be a potential environmental risk factor for chromosomal abnormalities, epidemiological studies investigating these associations are lacking. OBJECTIVES: This study examined whether prenatal PFAS exposure is associated with a higher prevalence of chromosomal abnormalities among offspring. METHODS: We used data from the Japan Environment and Children's Study, a nationwide birth cohort study, and employed logistic regression models to examine the associations between maternal plasma PFAS concentrations in the first trimester and the diagnosis of chromosomal abnormalities in all births (artificial abortions, miscarriages, stillbirths, and live births) up to 2 years of age. In addition, we examined associations with mixtures of PFAS using multipollutant models. RESULTS: The final sample consisted of 24,724 births with singleton pregnancies, of which 44 confirmed cases of chromosomal abnormalities were identified (prevalence: 17.8/10,000 births). When examined individually, exposure to perfluorononanoic acid (PFNA) and perfluorooctane sulfonic acid (PFOS) showed positive associations with any chromosomal abnormalities with age-adjusted odds ratios of 1.81 (95% CI: 1.26, 2.61) and 2.08 (95% CI: 1.41, 3.07) per doubling in concentration, respectively. These associations remained significant after Bonferroni correction, although they did not reach the adjusted significance threshold in certain sensitivity analyses. Furthermore, the doubling in all PFAS included as a mixture was associated with chromosomal abnormalities, indicating an age-adjusted odds ratio of 2.25 (95% CI: 1.34, 3.80), with PFOS as the predominant contributor, followed by PFNA, perfluoroundecanoic acid (PFUnA), and perfluorooctanoic acid (PFOA). DISCUSSION: The study findings suggested a potential association between maternal exposure to PFAS, particularly PFOS, and chromosomal abnormalities in offspring. However, the results should be interpreted cautiously, because selection bias arising from the recruitment of women in early pregnancy may explain the associations. https://doi.org/10.1289/EHP13617.

Characterization of cryptic complex chromosome rearrangements in balanced chromosomal rearrangement carriers and their PGT-SR clinical outcome assessments.

Several reports have presented that balanced chromosomal rearrangements (BCRs) carriers with normal phenotypes may be carriers of complex rearrangements. However, the incidence and PGT clinical outcomes of cryptic complex chromosome rearrangements (CCCRs) in individuals with BCRs is remain unknown. We recruited a cohort of 1,264 individuals with BCR carriers from 2016 to 2021 at the Reproductive and Genetic Hospital of CITIC Xiangya. Peripheral blood was collected for karyotyping and genomic DNA extraction and the PGT-SR clinical outcomes of CCCRs carriers were analyzed and compared with those of BCR carriers. Our findings revealed that 3.6% (45/1,264) of BCR carriers had CCCRs, involving 3-25 breakpoints on 1-3 chromosomes. Furthermore, when mate-pair sequencing was employed, 63.3% (19/30) of CCCR carriers were found to have chromosome rearrangements that were different from those identified by the MicroSeq technique. And the transferable embryo rate of CCCR carriers with 3 chromosomes was significantly lower than that of CCCR carriers with only 1-2 chromosomes. In this research, we revealed that some of the BCR carriers were actually CCCR carriers, and the prognosis of PGT in CCCR carriers with one or two chromosomes is better than that of CCCR carriers with three chromosomes.

Exploring the link between chromosomal polymorphisms and reproductive abnormalities.

OBJECTIVE: This work aimed to investigate the potential correlation between chromosomal polymorphisms and various reproductive abnormalities. METHODS: We examined 21,916 patients affected by infertility who sought care at the Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University between January 2018 and December 2022. A total of 2227 individuals identified as chromosomal polymorphism carriers constituted the polymorphism group, and 2245 individuals with normal chromosome karyotypes were randomly selected to form a control group. Clinical manifestations, histories of spontaneous miscarriage, abnormal reproductive developments, fetal abnormalities, and male sperm quality anomalies were statistically compared between these two groups. RESULTS: Of the 21,916 patients analyzed, 2227 displayed chromosomal polymorphism, representing a 10.16% detection rate. Amongst the male patients, 1622 out of 10,827 exhibited polymorphisms (14.98%), whereas 605 out of 11,089 females showed polymorphisms (5.46%). Female carriers in the polymorphism group, showed statistically significant increased rates of spontaneous abortion (29.75% vs. 18.54%), fetal anomalies (1.32% vs. 0.81%), and uterine abnormalities compared with the control group (1.32% vs. 0.81%). Male carriers in the polymorphism group had higher rates of spontaneous abortion in partners (22.87% vs. 10.37%), fetal anomalies (1.97% vs. 0.25%), compromised sperm quality (41.74% vs. 7.18%), testicular underdevelopment (2.28% vs. 0.92%), and hypogonadotropic hypogonadism (0.62% vs. 0.37%) compared with the control group. CONCLUSION: Chromosomal polymorphisms may have a certain negative effect on reproductive irregularities, including spontaneous abortions, fetal anomalies, and reduced sperm quality in males. Their clinical effects deserve further investigation.

Comparative analysis of cyto-genotoxicity of zinc using the comet assay and chromosomal abnormality test.

In this study, the toxicity of the trace element zinc (Zn) in Allium cepa L. test material was examined. Toxicity was investigated in terms of physiological, cytogenetic, biochemical, and anatomical aspects. Germination percentage, root length, weight gain, mitotic index (MI), micronucleus (MN) frequency, chromosomal abnormalities (CAs), malondialdehyde (MDA), proline and chlorophyll levels, superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and meristematic cell damage were used as indicators of toxicity. Additionally, the comet test was used to measure the degree of DNA damage. Four groups of A. cepa bulbs-one for control and three for applications-were created. While the bulbs in the treatment groups were germinated with Zn at concentrations of 35, 70, and 140 mg/L, the bulbs in the control group were germinated with tap water. Germination was carried out at room temperature for 72 h and 144 h. When the allotted time was over, the root tips and leaf samples were collected and prepared for spectrophotometric measurements and macroscopic-microscopic examinations. Consequently, Zn treatment led to significant reductions in physiological indicators such as weight gain, root length, and germination percentage. Zn exposure caused genotoxicity by decreasing the MI ratios and increasing the frequency of MN and CAs (p < 0.05). Zn promoted various types of CAs in root tip cells. The most observed of CAs was the sticky chromosome. Depending on the dose, Zn was found to cause an increase in tail lengths in comet analyses, which led to DNA damage. Exposure to Zn led to a significant decrease in chlorophyll levels and an increase in MDA and proline levels. It also promoted significant increases in SOD and CAT enzyme activities up to 70 mg/L dose and statistically significant decreases at 140 mg/L dose. Additionally, Zn exposure caused different types of anatomical damage. The most severe ones are epidermis and cortex cell damage. Besides, it was found that the Zn dose directly relates to all of the increases and decreases in physiological, cytogenetic, biochemical, and anatomical parameters that were seen as a result of Zn exposure. As a result, it has been determined that the Zn element, which is absolutely necessary in trace amounts for the continuation of the metabolic activities of the organisms, can cause toxicity if it reaches excessive levels.

Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study.

Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004-2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (Pinteraction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.

Bleomycin-induced chromosomal aberrations in Epstein-Barr virus-transformed human lymphoblastoid cells.

We have evaluated the induction of complete (i.e., without open ends) and incomplete (i.e., with non-rejoined or open ends) chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) in human lymphoblastoid cells immortalized with the Epstein-Barr virus (EBV). An EBV-induced lymphoblastoid cell line (T-37) was exposed to BLM (10-200 µg/mL) for 2 h at 37ºC, and chromosomal aberrations were analyzed 24 h after treatment, using PNA-FISH with pan-telomeric and pan-centromeric probes. Both complete (multicentrics, rings, compound acentric fragments, and interstitial deletions) and incomplete (incomplete chromosomes or IC, and terminal acentric fragments or TAF) chromosomal aberrations increased significantly in BLM-exposed cells, although the concentration-response relationship was non-linear. Of the acentric fragments (ace) induced by BLM, 40 % were compound fragments (CF, ace +/+). TAF (ace, +/-) and interstitial fragments (IAF, ace -/-) were induced at similar frequencies (30 %). 230 ICE were induced by BLM, of which 52 % were IC and 48 % TAF. The average ratio between total incomplete chromosome elements (ICE) and multicentrics was 1.52. These findings suggest that human lymphoblastoid cells exhibit less repair capacity than human lymphocytes, with respect to BLM-induced ICE, and that chromosomal incompleteness is a common event following exposure of these cells to BLM.

Trends in the cytogenetic and immunologic status of healthy persons; Kazakhstan, 2007-2022.

Environmental pollution can affect immune health and genome stability. We have studied the immunological and cytogenetic status of healthy urban (Almaty City, which has high levels of air pollution) and rural residents of southern Kazakhstan, over the past 15 years. Differences between the groups in plasma immunoglobulin levels and chromosomal aberration frequencies were noted. Over the 15-year study period, decreases of immunoglobulin levels and increases of chromosomal aberration frequencies were observed and correlated with place of residence and ecological status of the region of residence; both ecological deterioration and the coronavirus pandemic are likely to have had negative effects.

Performance evaluation of noninvasive prenatal testing on 24 chromosomes in a cohort of 118,969 pregnant women in Sichuan, China.

OBJECTIVE: This study aimed to comprehensively analyze the detection capacity of non-invasive prenatal testing (NIPT) for chromosomal abnormalities of all 24 chromosomes, as well as high-risk indications for pregnancy and the fetal fraction, in a large cohort. METHODS: We retrospectively enrolled 118,969 pregnant women who underwent NIPT at Sichuan Provincial Maternity and Child Health Care Hospital from March 2019 to June 2022. The sensitivity, specificity, positive predictive value, negative predictive value, and positive chromosomal abnormality rate were calculated. The fetal fraction based on gestational age, maternal body mass index, and number was examined. RESULTS: NIPT demonstrated > 99% sensitivity and specificity for almost all of the common trisomies (T21, T18, and T13), sex chromosomal aneuploidies, rare autosomal trisomies, and microdeletion/microduplication syndromes. Positive predictive values varied from 12.0% to 89.6%. Advanced maternal age was associated with an increased risk of three major aneuploidies. The fetal fraction was positively correlated with gestational age and negatively correlated with the maternal body mass index. CONCLUSIONS: NIPT can be used to effectively screen for chromosomal abnormalities across all 24 chromosomes. Advanced maternal age is a risk factor for high-risk pregnancy, and careful consideration of the fetal fraction is essential during NIPT.

Cellular toxicity of calcium propionate in human lymphocyte.

Calcium propionate is the chemical substance added to food in order to prolong the shelf-life of factory made foods by inhibiting the development of bacteria, fungi and other microorganisms. The objective of this study was to investigate the ability of calcium propionate to induce cytotoxic and genotoxic effects in lymphocytes. Oxidative stress induction by calcium propionate was also studied. Four concentrations of calcium propionate (0.5, 1.0, 1.5 and 2.0 mg/ml) were applied in lymphocytes for 24 and 48 h treatment. It studied cytotoxic and genotoxic effects by MTT assay, chromosome culture technique, and micronucleus assay. Oxidative stress induction was studied by superoxide dismutase (SOD) activity assay. The results showed that lymphocyte viability was decreased significantly by calcium propionate at 1.5 and 2.0 mg/ml (p < 0.05). Calcium propionate induced chromosome aberration at 1.0, 1.5 and 2.0 mg/ml and sister chromatid exchange at 1.5 and 2.0 mg/ml (p < 0.05). It induced micronucleus formation at 0.5, 1.0, 1.5 and 2.0 mg/ml (p < 0.05). The calcium propionate concentrations of 0.5 - 1.0 mg/ml and 1.5 - 2.0 mg/ml could reduce SOD activity inhibition (p < 0.05). Calcium propionate induced oxidative stress in lymphocytes. It can be concluded that calcium propionate induces genotoxic risk and oxidative stress in lymphocytes. Based on this study and the positive results, consumers should be made aware that calcium propionate should be considered a genotoxic compound. The awareness of food preservative usage and the educational program must take place frequently for good human health in the community.

Cytogenetics and the Revolution of Optical Genome Mapping in the Diagnosis of Diseases.

The study of chromosomal shape, characteristics, and behavior in somatic cell division (mitosis) during growth and development and in germ cell division (meiosis) during reproduction is known as cytogenetics. Many techniques can be used for cytogenetics, including fluorescent in situ hybridization (FISH), spectral karyotyping (SKY), multicolor FISH (M-FISH), microarray, and optical genome mapping (OGM). OGM is a novel genome-wide method that can identify structural variants (SVs) and copy number variants (CNVs) with only one test. Genomic structural information that is difficult to obtain with DNA sequencing can be promptly obtained with OGM, in which large molecule lengths can be mapped at a reasonable cost. OGM is increasingly being used to investigate chromosome abnormalities in genetic disorders and human cancer, but it was first utilized in genome assembly and research. According to recent research, OGM is capable of identifying every clinically significant variation seen in trials using conventional care. OGM is being utilized to identify genomic abnormalities in patients with malignancies and constitutional illnesses. It is regarded as a revolution in the field of cytogenetics. Rather than sequencing DNA, OGM relies on DNA labeling. Currently, the OGM technique with the Saphyr system from Bionano Genomics is a widely utilized platform for cytogenetic analysis. In conclusion, OGM can now be considered a highly reliable method for the identification of chromosomal abnormalities in the diagnosis of tumors and hematological diseases.

[Prenatal diagnosis of a fetus with 15q11q13 complex duplication syndrome and a literature review].

OBJECTIVE: To explore the clinical features and genetic etiology of a fetus with 15q11q13 complex duplication syndrome. METHODS: A fetus diagnosed with 15q11q13 duplication syndrome at Ningbo Women and Children's Hospital on April 19, 2023 was selected as the study subject. Clinical data was collected, and the fetus was subjected to invasive prenatal diagnosis including G-banded karyotyping and chromosomal microarray analysis (CMA). Following the discovery of chromosomal duplication, trio-whole exome sequencing was carried out to exclude single base variants and confirm the parental original of the duplication. Optical genome mapping was also performed to delineate the structural arrangement of the duplication. Relevant literature was searched in the PubMed, Wanfang Medical Network and CNKI databases using "15q11q13", "duplication", "hexasomy" and "Six fold repetition" as the key words from January 1, 2000 to August 1, 2023 for a review of previously reported 15q11q13 hexasomy cases. This study was approved by the Ningbo Women & Children's Hospital (Ethics No. EC2020-048). RESULTS: The fetus was found to have a mosaicism karyotype of 48,X?,+mar,+idic(15)(q13)[33]/47,X?,+idic(15)(q13)[17]. CMA and trio-WES have all shown a six-fold duplication in the PWS/AS critical region (PWACR) at 15q11.2q13.2 and quadruple duplication of 15q13.2q13.3 region, which have derived from its mother and formed supernumerary marker chromosomes (SMCs). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 15q11.2q13.2 sixfold duplication was classified as pathogenic, whilst the 15q13.2q13.3 quadruple duplication was classified as variant of uncertain significance. Literature search has identified 11 cases of 15q11q13 duplication involving hexasomy of the PWACR, with all cases showing mental retardation, language delay and hypotonia, and most of them also had motor retardation, epilepsy and mild facial dysmorphism. CONCLUSION: Hexasomy for the PWACR combined with tetrasomy of 15q13.2q13.3 probably underlay the left hand polydactyly, polyhydramnios and intrauterine growth retardation in this fetus.

Evaluation of genotoxicity and teratogenicity of phillyrin.

Phillyrin is extracted from Forsythia suspensa (Thunb.) Vahl, is significantly higher in (unripe Forsythiae Fructus) Qing qiao than in (ripe Forsythiae Fructus) Lao qiao fruits of the plant. However, the toxicity of phillyrin has not been adequately investigated. The study investigates the genetic and teratogenic effects of phillyrin to determine its safety profile. Assessing the genotoxicity and teratogenicity of phillyrin involved various tests, such as the bacterial reverse mutation assay, mammalian erythrocyte micronucleus assay, spermatocyte chromosome aberration assay, and teratogenicity assay. The results demonstrated that phillyrin exhibited no discernible impact on the following: number of colonies that spontaneously revert for Salmonella typhimurium TA 97, TA98, TA100, TA102, and TA1535, frequency of bone marrow polychromatic erythrocytes, and the rate of chromosomal aberrations. In the teratogenicity test, the pregnant rats exhibited no signs of toxicity or abnormal changes, and the growth, embryonic development, and visual anatomy of each pup were normal. In comparison with the negative control group, there were no significant differences in fetal body weight, mortality, deformity rate, malformed nest rate, gravid uterus weight, average number of fetuses per litter, fetal body length, or visceral and skeletal development in each dose group. In conclusion, these findings provide evidence that phillyrin does not exhibit genotoxic or teratogenic effects, supporting its potential safety for pharmacological applications.

Mutagenicity and Genotoxicity Assessment of Leuconostoc lactis DMLL10 Isolated from Kimchi.

Leuconostoc lactis DMLL10 is a microorganism specific to kimchi fermentation. In this study, we sought to evaluate the toxicity of this strain, which was newly isolated from kimchi, to determine its safety as a food ingredient. Bacterial reverse mutation assay, chromosomal aberration assay, and mammalian cell in vitro micronucleus assay were performed to assess the genetic toxicity of Leu. lactis DMLL10. The strain did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, or Escherichia coli WP2uvrA, with or without metabolic activation of S9 mixture. The oral administration of Leu. lactis DMLL10 also did not significantly increase the number of micronucleated polychromatic erythrocytes, or the mean ratio of polychromatic to total erythrocytes. Additionally, Leu. lactis DMLL10 did not cause a significant chromosomal aberration in CHU/IL cells in the presence or absence of S9 activation. Therefore, Leu. lactis DMLL10 can be suggested as a functional food ingredient with reliability and safety.

Combined biological effects of CBCT and therapeutic X-ray dose on chromosomal aberrations of lymphocytes.

BACKGROUND AND PURPOSE: Cone beam computed tomography (CBCT) is routinely used in radiotherapy to localize target volume. The aim of our study was to determine the biological effects of CBCT dose compared to subsequent therapeutic dose by using in vitro chromosome dosimetry. MATERIALS AND METHODS: Peripheral blood samples from five healthy volunteers were irradiated in two phantoms (water filled in-house made cylindrical, and Pure Image CTDI phantoms) with 6 MV FFF X-ray photons, the dose rate was 800 MU/min and the absorbed doses ranged from 0.5 to 8 Gy. Irradiation was performed with a 6 MV linear accelerator (LINAC) to generate a dose-response calibration curve. In the first part of the investigation, 1-5 CBCT imaging was used, in the second, only 2 Gy doses were delivered with a LINAC, and then, in the third part, a combination of CBCT and 2 Gy irradiation was performed mimicking online adapted radiotherapy treatment. Metaphases were prepared from lymphocyte cultures, using standard cytogenetic techniques, and chromosomal aberrations were evaluated. Estimate doses were calculated from chromosome aberrations using dose-response curves. RESULTS: Samples exposed to X-ray from CBCT imaging prior to treatment exhibited higher chromosomal aberrations and Estimate dose than the 2 Gy therapeutic (real) dose, and the magnitude of the increase depended on the number of CBCTs: 1-5 CBCT corresponded to 0.04-0.92 Gy, 1 CBCT + 2 Gy to 2.32 Gy, and 5 CBCTs + 2 Gy to 3.5 Gy. CONCLUSION: The estimated dose based on chromosomal aberrations is 24.8% higher than the physical dose, for the combination of 3 CBCTs and the therapeutic 2 Gy dose, which should be taken into account when calculating the total therapeutic dose that could increase the risk of a second cancer. The clinical implications of the combined radiation effect may require further investigation.

Naturally occurring horse model of miscarriage reveals temporal relationship between chromosomal aberration type and point of lethality.

Chromosomal abnormalities are a common cause of human miscarriage but rarely reported in any other species. As a result, there are currently inadequate animal models available to study this condition. Horses present one potential model since mares receive intense gynecological care. This allowed us to investigate the prevalence of chromosomal copy number aberrations in 256 products of conception (POC) in a naturally occurring model of pregnancy loss (PL). Triploidy (three haploid sets of chromosomes) was the most common aberration, found in 42% of POCs following PL over the embryonic period. Over the same period, trisomies and monosomies were identified in 11.6% of POCs and subchromosomal aberrations in 4.2%. Whole and subchromosomal aberrations involved 17 autosomes, with chromosomes 3, 4, and 20 having the highest number of aberrations. Triploid fetuses had clear gross developmental anomalies of the brain. Collectively, data demonstrate that alterations in chromosome number contribute to PL similarly in women and mares, with triploidy the dominant ploidy type over the key period of organogenesis. These findings, along with highly conserved synteny between human and horse chromosomes, similar gestation lengths, and the shared single greatest risk for PL being advancing maternal age, provide strong evidence for the first animal model to truly recapitulate many key features of human miscarriage arising due to chromosomal aberrations, with shared benefits for humans and equids.

De Novo Cancer Mutations Frequently Associate with Recurrent Chromosomal Abnormalities during Long-Term Human Pluripotent Stem Cell Culture.

Human pluripotent stem cells (hPSCs) are pivotal in regenerative medicine, yet their in vitro expansion often leads to genetic abnormalities, raising concerns about their safety in clinical applications. This study analyzed ten human embryonic stem cell lines across multiple passages to elucidate the dynamics of chromosomal abnormalities and single-nucleotide variants (SNVs) in 380 cancer-related genes. Prolonged in vitro culture resulted in 80% of the lines acquiring gains of chromosome 20q or 1q, both known for conferring an in vitro growth advantage. 70% of lines also acquired other copy number variants (CNVs) outside the recurrent set. Additionally, we detected 122 SNVs in 88 genes, with all lines acquiring at least one de novo SNV during culture. Our findings showed higher loads of both CNVs and SNVs at later passages, which were due to the cumulative acquisition of mutations over a longer time in culture, and not to an increased rate of mutagenesis over time. Importantly, we observed that SNVs and rare CNVs followed the acquisition of chromosomal gains in 1q and 20q, while most of the low-passage and genetically balanced samples were devoid of cancer-associated mutations. This suggests that recurrent chromosomal abnormalities are potential drivers for the acquisition of other mutations.

Contribution of AurkA/TPX2 Overexpression to Chromosomal Imbalances and Cancer.

The AurkA serine/threonine kinase is a key regulator of cell division controlling mitotic entry, centrosome maturation, and chromosome segregation. The microtubule-associated protein TPX2 controls spindle assembly and is the main AurkA regulator, contributing to AurkA activation, localisation, and stabilisation. Since their identification, AurkA and TPX2 have been described as being overexpressed in cancer, with a significant correlation with highly proliferative and aneuploid tumours. Despite the frequent occurrence of AurkA/TPX2 co-overexpression in cancer, the investigation of their involvement in tumorigenesis and cancer therapy resistance mostly arises from studies focusing only on one at the time. Here, we review the existing literature and discuss the mitotic phenotypes described under conditions of AurkA, TPX2, or AurkA/TPX2 overexpression, to build a picture that may help clarify their oncogenic potential through the induction of chromosome instability. We highlight the relevance of the AurkA/TPX2 complex as an oncogenic unit, based on which we discuss recent strategies under development that aim at disrupting the complex as a promising therapeutic perspective.