In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which ...may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently and complemented with laboratory markers, modulates COVID-19 severity. The study included 265 COVID-19 patients. Polymorphism of GSTM1, GSTT1, Nrf2 rs6721961, GSTM3 rs1332018, GPX3 rs8177412, GSTP1 rs1695, GSTO1 rs4925, GSTO2 rs156697, SOD2 rs4880 and GPX1 rs1050450 genes was determined with appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) and organ damage (urea, creatinine, transaminases and LDH) markers, complete blood count and coagulation status (d-dimer, fibrinogen) were measured. We found significant association for COVID-19 progression for patients with lymphocytes below 1.0 × 109/L (OR = 2.97, p = 0.002). Increased IL-6 and CRP were also associated with disease progression (OR = 8.52, p = 0.001, and OR = 10.97, p < 0.001, respectively), as well as elevated plasma AST and LDH (OR = 2.25, p = 0.021, and OR = 4.76, p < 0.001, respectively). Of all the examined polymorphisms, we found significant association with the risk of developing severe forms of COVID-19 for GPX3 rs8177412 variant genotype (OR = 2.42, p = 0.032). This finding could be of particular importance in the future, complementing other diagnostic tools for prediction of COVID-19 disease course.
Objectives: Due to the role of oxidative stress in the pathophysiology of COVID-19, it is biologically plausible that inter-individual differences in patients' clinical manifestations might be ...affected by antioxidant genetic profile. The aim of our study was to assess the distribution of antioxidant genetic polymorphisms Nrf2 rs6721961, SOD2 rs4880, GPX1 rs1050450, GPX3 rs8177412, and GSTP1 (rs1695 and rs1138272) haplotype in COVID-19 patients and controls, with special emphasis on their association with laboratory biochemical parameters.
Methods: The antioxidant genetic polymorphisms were assessed by appropriate PCR methods in 229 COVID-19 patients and 229 matched healthy individuals.
Results: Among examined polymorphisms, only GSTP1 haplotype was associated with COVID-19 risk (p = 0.009). Polymorphisms of SOD2 and GPX1 influenced COVID-19 patients' laboratory biochemical profile: SOD2*Val allele was associated with increased levels of fibrinogen (p = 0.040) and ferritin (p = 0.033), whereas GPX1*Leu allele was associated with D-dimmer (p = 0.009).
Discussion: Our findings regarding the influence of SOD2 and GPX1 polymorphisms on inflammation and coagulation parameters might be of clinical importance. If confirmed in larger cohorts, these developments could provide a more personalized approach for better recognition of patients prone to thrombosis and those for the need of targeted antioxidant therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Although disturbance of redox homeostasis might be responsible for COVID-19 cardiac complications, this molecular mechanism has not been addressed yet. We have proposed modifying the effects of ...antioxidant proteins polymorphisms (superoxide dismutase 2 (
), glutathione peroxidase 1 (
), glutathione peroxidase 3 (
) and nuclear factor erythroid 2-related factor 2, (
)) in individual susceptibility towards the development of cardiac manifestations of long COVID-19. The presence of subclinical cardiac dysfunction was assessed via echocardiography and cardiac magnetic resonance imaging in 174 convalescent COVID-19 patients. SOD2,
,
and
polymorphisms were determined via the appropriate PCR methods. No significant association of the investigated polymorphisms with the risk of arrhythmia development was found. However, the carriers of variant
*T,
*C or
*A alleles were more than twice less prone for dyspnea development in comparison with the carriers of the referent ones. These findings were even more potentiated in the carriers of any two variant alleles of these genes (OR = 0.273, and
= 0.016). The variant
alleles were significantly associated with left atrial and right ventricular echocardiographic parameters, specifically LAVI, RFAC and RV-EF (
= 0.025,
= 0.009, and
= 0.007, respectively). Based on the relation between the variant
*T allele and higher levels of LV echocardiographic parameters, EDD, LVMI and GLS, as well as troponin T (
= 0.038), it can be proposed that recovered COVID-19 patients, who are the carriers of this genetic variant, might have subtle left ventricular systolic dysfunction. No significant association between the investigated polymorphisms and cardiac disfunction was observed when cardiac magnetic resonance imaging was performed. Our results on the association between antioxidant genetic variants and long COVID cardiological manifestations highlight the involvement of genetic propensity in both acute and long COVID clinical manifestations.
The basic aim of the investigation presented in this paper was to determine all relevant petrographical and geochemical characteristics of organic facies and their correlation with the lithological ...composition, sedimentation conditions and paleoenvironments. Application of geological and geochemical methods gives new insight into problems concerning determination of the potential and efficiency of petroleum source rocks.
In making the qualitative and quantitative analyses of organic matter in this study various analytical methods were used (whole rock samples, kerogen concentrates; transmitted and reflected normal and fluorescent light). The type of organic facies was used as a criterion for the identification, accumulation and transformation of the organic matter. Paleobotanical studies of organic facies and palynofacies were used to identify types of vegetation and draw conclusions concerning the sedimentary environment.
Various types of organic facies and palynofacies were classified in relation to the origin of the organic matter. All sedimentary organic constituents of continental (huminite/vitrinite, inertinite, cuticle, wood fragments, tracheids, spores and pollen) and marine (mostly autochthonous-dinocysts, algae, foraminifera test linings, acritarchs and amorphous organic matter) origin have been grouped according to different classification systems. A summary of these classifications is proposed, with remarks on approximate corresponding coal macerals and selected kerogen types.
Degenerative spine conditions involve the gradual loss of normal structure and function of spine over time. They are usually caused by aging, but may also be the result of tumors, infections or ...arthritis. Pressure on the spinal cord and nerve roots caused by degeneration can be caused by herniated discs. Degenerative disc disease is one of the most common causes of low back and neck pain, and also one of the most misunderstood ones. Low back pain (LBP) is a common disorder affecting an increasing number of people worldwide, whose diagnosis is focused on the identification of triggering causes. First line therapy usually starts from conservative approaches, whereas second line treatments include a spectrum of minimally invasive techniques, before resorting to more invasive surgical approaches. Among minimally invasive techniques, percutaneous oxygen-ozone injections represent one of the most common and cost-effective procedures. Oxygen-ozone therapy is a minimally invasive treatment for lumbar disc herniation that uses the biochemical properties of the gas mixture of oxygen and ozone. Intradiscal, periradicular or intraarticular ozone therapy is used in patients that do not respond to standard conservative therapies for low back pain due to degenerative disc-induced lumbar disc herniation (LDH) or other degenerative process of nearby structures such as zygapophyseal articulations. All the interventional procedures for low back pain may be guided by ultrasound, computerized tomography or fluoroscopy.
Background: Autism spectrum disorders (ASD) are complex psychiatric disorders, with gene environment interaction being in the basis of their etiology. The association of perinatal complications and ...ASD is well established. Recent findings suggested that oxidative stress and polymorphism in genes encoding antioxidant enzymes might be involved in the development of ASD. Glutathione transferases (GSTs) have an important role in the antioxidant defense system. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms. Methods: The study included 113 ASD cases and 114 age- and sex group-matched healthy controls. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The questionnaire regarding prenatal and perinatal risk factors and complications was administered for all the subjects in the study. Results: The evaluated perinatal complications as a group significantly increased the risk of ASD odds ratio (OR) = 9.415; p = 0.000, as well as individual perinatal complications, such as prematurity (OR = 11.42; p = 0.001), neonatal jaundice (OR = 8.774; p = 0.000), respiratory distress syndrome (OR = 4.835; p = 0.047), and the use of any medication during pregnancy (OR = 2.413; p = 0.03). In logistic regression model, adding GST genotypes did not modify the significant effects found for prematurity and neonatal jaundice as risk factors in ASD. However, there was a significant interaction of GST genotype with medication use during pregnancy and the use of tocolytics during pregnancy, which was predictive of ASD risk only in carriers of GSTM1-null, as opposed to carriers of GSTM1-active genotype. Conclusion: Specific perinatal complications may be significant risk factors for ASD. GSTM1 genotype may serve as a moderator of the effect of some prenatal factors on the risk of ASD such as using medication during pregnancy. It may be speculated that different oxidative stress-related genetic and environmental factors could lead to development of ASD. Apart from etiological mechanisms, possible therapeutic implications in ASD are also discussed.Background: Autism spectrum disorders (ASD) are complex psychiatric disorders, with gene environment interaction being in the basis of their etiology. The association of perinatal complications and ASD is well established. Recent findings suggested that oxidative stress and polymorphism in genes encoding antioxidant enzymes might be involved in the development of ASD. Glutathione transferases (GSTs) have an important role in the antioxidant defense system. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms. Methods: The study included 113 ASD cases and 114 age- and sex group-matched healthy controls. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The questionnaire regarding prenatal and perinatal risk factors and complications was administered for all the subjects in the study. Results: The evaluated perinatal complications as a group significantly increased the risk of ASD odds ratio (OR) = 9.415; p = 0.000, as well as individual perinatal complications, such as prematurity (OR = 11.42; p = 0.001), neonatal jaundice (OR = 8.774; p = 0.000), respiratory distress syndrome (OR = 4.835; p = 0.047), and the use of any medication during pregnancy (OR = 2.413; p = 0.03). In logistic regression model, adding GST genotypes did not modify the significant effects found for prematurity and neonatal jaundice as risk factors in ASD. However, there was a significant interaction of GST genotype with medication use during pregnancy and the use of tocolytics during pregnancy, which was predictive of ASD risk only in carriers of GSTM1-null, as opposed to carriers of GSTM1-active genotype. Conclusion: Specific perinatal complications may be significant risk factors for ASD. GSTM1 genotype may serve as a moderator of the effect of some prenatal factors on the risk of ASD such as using medication during pregnancy. It may be speculated that different oxidative stress-related genetic and environmental factors could lead to development of ASD. Apart from etiological mechanisms, possible therapeutic implications in ASD are also discussed.
Background:
Autism spectrum disorders (ASD) are a heterogeneous group of developmental disorders, with different levels of symptoms, functioning, and comorbidities. Recent findings suggested that ...oxidative stress and genetic variability in glutathione S-transferases (GSTs) might increase the risk of ASD development. We aimed to determine whether GST polymorphisms influence the severity of symptoms as well as the cognitive and adaptive abilities in children with ASD.
Methods:
The sample included 113 ASD cases. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The clinical characteristics were determined with Autism Diagnostic Interview-Revised (ADI-R) in all of the participants. In non-verbal participants, we explored the adaptive functioning using the Vineland Adaptive Behavior Scale II, while in verbal participants, we used the Wechsler Abbreviated Scale of Intelligence (WASI).
Results:
It was shown that the
GSTA1
*
CC
genotype was a predictor of a lower non-verbal communication impairment as well as of a lower chance of having seizures during life.
GSTM1-active
genotype predicted a higher adaptive functioning. The predictive effect of
GSTA1, GSTM1
, and
GSTT1
genotype was moderated by exposure during pregnancy (maternal smoking and medication). The
GSTP1
*
IleIle
genotype was significantly associated to a better cognitive functioning in children with ASD.
Conclusion:
Besides the complex gene-environment interaction for the specific risk of developing ASD, there is also a possible complexity of interactions between genetic and environmental factors influencing the level of symptoms and impairment in people with ASD. Detoxification and antioxidant enzymes, such as GSTA1, might contribute to the core of this complexity.
Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities ...of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferases
,
,
,
(
and
), and
were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity.
polymorphisms were determined by appropriate PCR methods. Among six
polymorphisms analyzed in this study,
rs1695 and
were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variant
-
allele exhibit lower odds of COVID-19 development (
= 0.002), contrary to carriers of variant
genotype which have higher odds for COVID-19 (
= 0.024). Moreover, combined
(
and
) and
genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (
= 0.001 and
= 0.025, respectively). Further studies are needed to clarify the exact roles of specific glutathione S-transferases once the SARS-CoV-2 infection is initiated in the host cell.
Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae ...propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods. Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying
or
allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of
and
alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined
genotype. Moreover, individuals carrying combined
genotype were more prone to developing long-COVID "brain fog", while this probability further enlarged if the
allele was also present. The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.
To evaluate the changes in serum neuron specific enolase and protein S-100B, after carotid endarterectomy performed using the conventional technique with routine shunting and patch closure, or ...eversion technique without the use of shunt.
Prospective non-randomized study included 43 patients with severe (>80%) carotid stenosis undergoing carotid endarterectomy in regional anesthesia. Patients were divided into two groups: conventional endarterectomy with routine use of shunt and Dacron patch (csCEA group) and eversion endarterectomy without the use of shunt (eCEA group). Protein S-100B and NSE concentrations were measured from peripheral blood before carotid clamping, after declamping and 24 hours after surgery.
Neurologic examination and brain CT findings on the first postoperative day did not differ from preoperative controls in any patients. In csCEA group, NSE concentrations decreased after declamping (P<0.01), and 24 hours after surgery (P<0.01), while in the eCEA group NSE values slightly increased (P=ns), accounting for a significant difference between groups on the first postoperative day (P=0.006). In both groups S-100B concentrations significantly increased after declamping (P<0.05), returning to near pre-clamp values 24 hours after surgery (P=ns). Sub-group analysis revealed significant decline of serum NSE concentrations in asymptomatic patients shunted during surgery after declamping (P<0.05) and 24 hours after surgery (P<0.01), while no significant changes were noted in non-shunted patients (P=ns). Decrease of NSE serum levels was also found in symptomatic patients operated with the use of shunt on the first postoperative day (P<0.05). Significant increase in NSE serum levels was recorded in non-shunted symptomatic patients 24 hours after surgery (P<0.05).
Variations of NSE concentrations seemed to be influenced by cerebral perfusion alterations, while protein S-100B values were unaffected by shunting strategy. Routine shunting during surgery for symptomatic carotid stenosis may have the potential to prevent postoperative increase of serum NSE levels, a potential marker of brain injury.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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