Relationships between male secondary sexual traits, physiological state and offspring viability in the three-spined stickleback

Background Sexual signals produced by males play a central role in sexual selection, but the relationship between these traits and the quality of the bearer are often ambiguous. Secondary sexual traits may represent genetic quality of the bearer, resulting in positive relationships with physiological state, or may be costly to produce, showing trade-off with physiological state. A number of studies have explored the relationships between secondary sexual traits and other functional traits, but few have studied their fitness consequences. We studied the link between diverse physiological traits and both morphological and behavioural sexual traits and examined how their interplay influences offspring viability in the three-spined stickleback. Results Male sticklebacks showing nest building and courtship behaviour were smaller than those not investing in reproductive activities. There was no evidence that the expression of red nuptial colouration and the quality of courtship behaviour of males are positively related to their metabolic rates, swim ability, oxidative damage and mtDNA copy number. However, individuals showing larger red nuptial colour areas had higher levels of oxidative DNA damage in their sperm. Male courtship behaviour and aggressiveness, but not red colour area, were good predictors of offspring hatching and survival. Conclusions Our results suggest that, in our study population at the southern edge of the species’ distribution, sexual colouration of male sticklebacks was not a good indicator of their body state, but both courtship quality and aggressiveness during the courtship are reliable cues of their gamete quality, influencing the viability of their offspring. Thus, females that choose mates based on their courtship behaviour will have high fitness. In the study population, which represents a fast pace-of-life with high reproductive rate and short lifespan, sexual ornaments of males may not honestly signal their physiological and physical state because they invest at maximum in a single reproductive season despite high costs.

In pursuit of incorporation of markers of oxidative stress in traditional biochemical panels in clinical Chemistry: A risk assessment step in diagnosis and biotherapy

Chemical pathology (clinical chemistry/biochemistry) is the branch of laboratory medicine concerned with the detection of alterations in the chemical constituents and biochemical mechanisms, which ensure health, culminating in disease. The disease itself is a pattern of response to some insult or injury resulting in a disturbed function or structure. It is often difficult to ascertain precisely the point of transition from health to a disease state. Pathological changes, including metabolic and molecular perturbations, with the potential to progress to clinical disease, are also present in healthy populations, noteworthy are the reactive oxygen species such as hydroxyl radicals with the propensity to cause oxidative DNA damage. Biochemical profiles or panels such as liver function tests, renal function tests, bone profile, lipid profile, acid-base, and critical care have served as biomarkers employed in indicating the presence of or measuring the progress of the disease, as well as the effect of treatment. Oxidative stress, an imbalance between bio-available antioxidants and reactive species, is now widely recognized as accompanying most pathological states. Hence, the exclusion of antioxidant components in biochemical profiles appears a grave oversight. Basic components of the antioxidant system, glutathione (GSH), zinc, uric acid, ascorbic acid, and α-tocopherol, may be selected for incorporation. GSH is particularly important; as a scavenger for damaging oxidative intermediates in cells, it promises to be a good predictor of disease progression and prognosis. Including the antioxidant component into traditional profiles may aid physicians in more confidently ruling out disease, enabling further investigations, and/or reassuring patients. It is proposed that redefining the traditional profiles in chemical pathology by incorporating the indexes of the antioxidant system promises considerable improvement in the risk assessment process, in disease detection and recognition of the threshold of clinical concern in disease management and biotherapy.

The Response to Oxidative Damage Correlates with Driver Mutations and Clinical Outcome in Patients with Myelofibrosis

Myelofibrosis (MF) is the Philadelphia-negative myeloproliferative neoplasm characterized by the worst prognosis and no response to conventional therapy. Driver mutations in JAK2 and CALR impact on JAK-STAT pathway activation but also on the production of reactive oxygen species (ROS). ROS play a pivotal role in inflammation-induced oxidative damage to cellular components including DNA, therefore leading to greater genomic instability and promoting cell transformation. In order to unveil the role of driver mutations in oxidative stress, we assessed ROS levels in CD34+ hematopoietic stem/progenitor cells of MF patients. Our results demonstrated that ROS production in CD34+ cells from CALR-mutated MF patients is far greater compared with patients harboring JAK2 mutation, and this leads to increased oxidative DNA damage. Moreover, CALR-mutant cells show less superoxide dismutase (SOD) antioxidant activity than JAK2-mutated ones. Here, we show that high plasma levels of total antioxidant capacity (TAC) correlate with detrimental clinical features, such as high levels of lactate dehydrogenase (LDH) and circulating CD34+ cells. Moreover, in JAK2-mutated patients, high plasma level of TAC is also associated with a poor overall survival (OS), and multivariate analysis demonstrated that high TAC classification is an independent prognostic factor allowing the identification of patients with inferior OS in both DIPSS lowest and highest categories. Altogether, our data suggest that a different capability to respond to oxidative stress can be one of the mechanisms underlying disease progression of myelofibrosis.

Genotoxic and histopathological alterations in rats exposed to herbal liquors

The increase in consumption of herbal liquors in Nigeria is a cause for alarm. These are consumed with the mis-conception that they are without toxic effects. The aim of this study is to investigate the genotoxic and histopathological alterations in rats exposed to herbal liquors. Female rats were exposed to herbal liquors for 6 weeks. The histopathological and genotoxic evaluation were done to assess extent of damage. Pathological examination revealed incidences of aggregates chronic inflammatory cell infiltrates in the heart of Jedi treated group while the heart of the other groups had no abnormalities. The histologic sections of the kidney tissue revealed congested vessels while the lung showed reduction in air filled alveolar spaces with infiltration of alveoli and interstitium by aggregates of inflammatory cells indnadicating moderate to severe pulmonary inflammation. Histologic sections of lung tissue in rats treated with herbal liquors reveals congestion of pulmonary vessels and interstitial hemorrhages. Genotoxic evaluation of rat lymphocytes exposed to herbal liquors via comet assay shows that rats administered with the different herbal liquors developed significant (p < 0.05) as revealed in the % DNA in tail, % DNA in head, olive moment, tail length and tail moment which indicates the presence of DNA strand breaks and a marker for oxidative DNA damage. This result reveals that herbal liquors contain substances that produce reactive oxygen species that have pathological effect on certain organs as well as inducing DNA strand breaks that could compromise the integrity of the DNA which can lead to mutation.

Effect of Imidocarb Application on Oxidative DNA Damage Caused by Anaplasmosis

This study was aimed to evaluate DNA fragmentation by using Comet assay in naturally infected sheep with Anaplasmosis before and after treatment with the Comet method, which shows DNA damage specifically. In the study, blood samples were collected from 10 Anaplosmosis infected and 10 healthy sheep. The anaplosmosis was diagnosed by clinical signs and symptoms. The infection was confirmed by Giemsa staining. The blood was collected from control group and infected group before and after the treatment, from the vena jugularis with the appropriate method. The DNA fragmentation was checked by using the Comet assay of blood cells. The data were analysed throught ANNOVA one-way. The result showed higher DNA fragmentation in sick animals diagnosed with anaplasmosis; tail length and tail moment values were found to be statistically significantly higher than the control group. When the data obtained after imidocarb (IMD) application were compared with obtained during the disease, a decreased DNA damage and tail moment was determined, however, these values higher than control. In this study, DNA damage and the extent of this damage were investigated by the Comet assay method using a healthy control group before and after treatment in animals with Anaplasmosis. When the findings obtained from the study were evaluated, it was seen that Anaplasma agents caused DNA damage and with the imidocarb application given for treatment, DNA damage was reduced and results close to healthy individuals were obtained.

Radiation nephropathy: Dose, management, and population risk

Radiation nephropathy is renal injury caused by a sufficient dose of irradiation. It can result from external beam irradiation or internal irradiation as might occur from therapeutic radioisotopes. Its usual clinical presentation is as chronic kidney disease occurring some months after irradiation, and it can evolve to end-stage-renal-disease. While the immediate cellular injury from irradiation depends on radiolysis of water and oxidative DNA damage, there is no conclusive evidence for chronic persistent oxidative stress or inflammation as the cause of the multi-tissue scarring that ensues. Antagonists of the renin-angiotensin system are effective treatments for experimental radiation nephropathy but their preferential value in human clinical medicine is unproven.

Comprehensive Analysis of Aldehyde Dehydrogenases (ALDHs) and Its Significant Role in Hepatocellular Carcinoma

Oxidative DNA damage is closely related to the occurrence and progression of cancer. Oxidative stress plays an important role in alcohol-induced hepatocellular carcinoma (HCC). Aldehyde dehydrogenase (ALDH) is a family of enzymes that plays an essential role in the reducing oxidative damage. However, how ALDHs family affects alcohol-related HCC remains obscure. We aimed to explore the correlation between the differential expression of ALDHs in patients with HCC and pathological features, as well as the relationship between ALDHs and prognosis, and finally analyze the possible mechanism of ALDHs in targeted therapy of HCC. The data of HCC were downloaded from The Cancer Genome Atlas (TCGA) database. This research explored the expression and prognostic values of ALDHs in HCC using Oncomine, UALCAN, Human Protein Atlas, cBioPortal, Kaplan–Meier plotter, GeneMANIA, Tumor Immune Estimation Resource, GEPIA databases, and WebGestalt. Low mRNA and protein expressions of ALDHs were found to be significantly associated with tumor grade and clinical cancer stages in HCC patients. In particular, the loss of ALDH expression is more obvious in Asians, and its effect on prognosis is far more significant than that in the White race. Our findings play an important role in the study of prognostic markers and anti-liver cancer therapeutic targets for the members of the ALDHs family, especially in patients with liver cancer in Asia.

Oxidative DNA Damage of Peripheral Blood Cells and Blood Plasma Сell-Free DNA as an Indicator of the Oxidative Stress Level in Children with Autism Spectrum Disorders and Schizophrenia

Background: pathogen heterogeneity and complexity are the main obstacles for schizophrenia and autism spectrum disorders (ASD) differential diagnosis in children. The role of oxidative stress in the molecular mechanisms of schizophrenia and autism pathogenesis is beyond doubt. Free radicals that accumulate during stress can cause oxidative modifications and the formation of breaks in the сell-free DNA (cfDNA) and nuclear DNA of blood cells. To date, it has been proven that 8-hydroxy-2’- deoxyguanosine (8-OHdG) can be considered as an oxidative stress biomarker. However, it is still unclear how pronounced the genotoxic consequences of oxidative stress are in ASD of varying severity and in childhood onset schizophrenia (COS). Objective: to study the relationship between the oxidative DNA damage level in peripheral blood cells and the circulating cell-free DNA characteristics with the severity of COS and the course of ASD in children. Patients and methods: blood samples of 96 patients with childhood autism (CA — F84.0 according to ICD-10), atypical autism (AA — F84.1 according to ICD-10) and with childhood onset schizophrenia (COS — F20.8 according to ICD-10) were obtained from the Child Psychiatry Department of the Mental health research center. Blood samples of the control group (34 people) — from the collection of samples of the Research Centre for medical Genetics. The selection of patients was carried out using the clinical and psychopathological method. Cell-free DNA was isolated by extraction with organic solvents. The concentration of cfDNA was determined fluorimetrically. The level of 8-OHdG in cell-free DNA was determined by binding of the corresponding antibodies on membrane filters, endonuclease activity was determined by radial diffusion in a gel. G0-peripheral blood lymphocytes were isolated by gradient centrifugation. The level of 8-OHdG and the level of the phosphorylated form of histone H2AX (yH2AX) in G0-peripheral blood lymphocytes were analyzed in fixed cells by flow cytofluorometry using appropriate antibodies. Statistical processing was carried out using Microsoft Office Excel, Statistica 6.0, StatGraph. Results and conclusions: oxidative stress has different severity in ASD, occurring in severe form (AA) and mild/moderate form (CA). In CA, the level of oxidative damage to the DNA of lymphocytes tends to increase, but does not reach statistically significant level; the level of oxidative damage to cfDNA does not differ from the control. In AA and, to an even stronger extent, in COS, the level of oxidative damage to the DNA of cells and cfDNA is significantly increased, which indicates the development of systemic oxidative stress, which is not compensated by the body’s antioxidant system. The level of 8-OHdG in the composition of the cfDNA and DNA of the nuclei of peripheral blood cells can be a marker of oxidative stress, which is important not only for diagnosing the severity of the pathological process, but also for treatment regimens development for COS and ASD in children.