We investigated whether a functional insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) influenced antipsychotic treatment. At baseline, and after 8 weeks of treatment with ...various antipsychotic medications, we assessed patients’ Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic-syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis. The ACE-I/D polymorphism was significantly associated with changes in PANSS psychopathology only (p < 0.05). Compared to ACE-II homozygous males, ACE-DD homozygous and ACE-ID heterozygous males manifested significantly greater decreases in PANSS positive score, PANSS excitement factor, and PANSS cognitive factor. ACE-DD homozygous females manifested higher decreases in PANSS depression factor compared to ACE-II homozygous and ACE-ID heterozygous females. The polymorphism’s effect size was estimated as moderate to strong, while its contribution to the PANSS psychopathology ranged from ~5.4 to 8.7%, with the lowest contribution observed for PANSS positive score changes and the highest for PANSS depressive factor changes. Our results indicate that ACE-I/D polymorphism had a statistically significant but weak gender-specific impact on psychopathology data, and showed no association between ACE-I/D polymorphism and metabolic-syndrome-related parameters.
The biologically active peptide angiotensin II is cleaved from angiotensinogen by the renin and the angiotensin-converting enzyme (ACE), an enzymatic cascade known as the renin-angiotensin system ...(RAS). RAS may be important in the etiology of nicotine dependence by influencing dopaminergic signaling. In the present study, the association between an insertion/deletion (I/D) polymorphism of ACE and nicotine dependence amongst patients with lung cancer was assessed. To date, several studies have shown the relevance of this polymorphic variant in both nicotine dependence and lung cancer. However, the present study is the first to address the potential role of the ACE-I/D polymorphism in nicotine dependence among patients with lung cancer. Genotyping was performed in 305 patients with lung cancer (males/females, 214/91). Significantly more male smokers had the ACE-I allele compared with male non-smokers (44.9 vs. 20.0%; P<0.05). The risk of smoking was ~5-fold higher for males with the ACE-I allele (ACE-II homozygous and ACE-ID heterozygous) vs. ACE-DD homozygous (odds ratio, 5.47; 95% confidence interval, 1.4-21.9; P=0.016). The pack-year smoking history in a subgroup of females with squamous cell carcinoma carrying the ACE-I allele was significantly lower compared with ACE-DD (37.1±14.1 vs. 57.0±29.1; F=4.5; P=0.046). The ACE-I/D polymorphism accounted for 17.6% of the smoking severity in this patient group (β, -0.42; multiple R
change, 0.176; P=0.046). These results suggest that the ACE-I/D polymorphism contributes to the risk of nicotine dependence and smoking severity in lung cancer patients in a sex-specific manner.
Addiction is a complex brain disease influenced by genetic, environmental, and neurological factors. Psychostimulants, cocaine, and methamphetamine influence different cell types in different brain ...regions, with a focus on the neurons responsible for rewarding effects in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Known markers for psychostimulant-induced neuronal plasticity in combination with droplet-based high-throughput single-cell sequencing divided the heterogeneity of cell populations in NAc and VTA into clusters, where all cells of the same type do not respond equally to exposure to psychostimulants. To explain psychostimulant-induced neuronal plasticity as changes in the amplitude and phase shifts of gene expression, we focused on epigenetic mechanisms of DNA and chromatin modifications, as well as DNA accessibility. We also comment on epitranscriptomics as a novel approach in the study of messenger RNA posttranslational modification, which regulates translation and potentially localized transcription in synapses in order to address the molecular chains that connect addiction from changes in gene expression to synaptic and, finally, neuronal plasticity.
Cilj: Porod carskim rezom kontinuirano se povezuje s povećanim rizikom za pojavu komponenti metaboličkog sindroma kod ispitanika u općoj populaciji, dok su podatci za bolesnike sa shizofrenijom ...manjkavi i proturječni. U ovom smo istraživanju ispitali pridonosi li, i u kojoj mjeri, vrsta poroda vrijednostima indeksa tjelesne mase (ITM) te koncentracijama lipida i glukoze u plazmi na dvjema skupinama bolesnika sa shizofrenijom koji ne primaju terapiju: u bolesnika s prvom epizodom shizofrenije (N = 48) i u kroničnih bolesnika neadherentnih prema antipsihotičnoj terapiji (N = 83). Ispitanici i metode: Podatci o vrsti poroda i neadherentnosti prema antipsihotičnoj terapiji prikupljeni su iz autoanamneze i heteroanamneze. Određivanje ukupnog kolesterola, LDL kolesterola (engl. low density lipoprotein cholesterol), HDL kolesterola (engl. high density lipoprotein cholesterol), triglicerida i glukoze u plazmi realizirano je nakon 12-satnog gladovanja. Rezultati: Učestalost poroda carskim rezom iznosila je 8,4 %. Koncentracije triglicerida i vrijednosti ITM-a bile su značajno više u bolesnika rođenih carskim rezom u odnosu na bolesnike rođene vaginalnim porodom: 1,5 (0,6 – 4,3) vs. 1,1 (0,3 – 3,1); z = -2,21, p = 0,027. Vrsta poroda pridonosi s približno 3,3 % varijabilnosti koncentracija triglicerida. Zaključci: Naši rezultati upućuju da vrsta poroda utječe u manjoj mjeri na koncentracije triglicerida u plazmi u bolesnika sa shizofrenijom koji nisu na terapiji antipsihotičnim lijekovima. Porod carskim rezom predstavlja rizični čimbenik za povišene koncentracije triglicerida.
The type of delivery and antipsychotic medications could modulate clinical features of schizophrenia and nicotine dependence by affecting gut microbiota composition. In this study, we aimed to ...investigate whether the age of disease onset, severity of PANSS (Positive and Negative Syndrome Scale) psychopathology and nicotine dependence might be associated with the type of delivery among two groups of patients with schizophrenia without antipsychotic therapy: first-episode patients, and chronic patients, non-adherent to antipsychotic medications. Information regarding antipsychotic non-adherence, smoking status, and the type of delivery (vaginal delivery or caesarean delivery) was obtained from autoanamnestic and heteroanamnestic data. Age of disease onset was defined as age at the patient’s first hospital admission due to a psychotic episode at which the diagnosis of schizophrenia was used. PANSS evaluation data was taken during the acute state of the illness at the most recent hospitalization. Values of the age of disease onset, PANSS score and PANSS factor and prevalence of early (≤ 26 years) and late (> 26 years) disease onset did not differ significantly between patients born by caesarean delivery and vaginal delivery (p > 0.05). The prevalence of smokers was significantly higher among patients born by caesarean delivery (p = 0.012). The caesarean delivery is associated with ~9%-fold greater risk of nicotine dependence. We did not find any associations of the age of disease onset and PANSS psychopathology with the type of delivery among patients without therapy, but our results implicate that caesarean delivery might be a risk factor for nicotine dependence in that patient group.
Objectives:
The aim of this study was to investigate the expression of genes crucial for the quality of the oocyte and whether expression levels of these genes in cumulus cells can be biological ...markers for the quality of the oocyte, zygote or embryo, or even for achievement of pregnancy after the assisted reproductive technology procedure. We examined the expression profile of the anti-Müllerian hormone (AMH) gene and its respective receptors: anti-Müllerian hormone receptor type 2 (AMHR2), follicle-stimulating hormone receptor (FSHR) and androgen receptor (AR) in cumulus cells (CCs) surrounding the oocyte, as well as AMH concentrations in follicular fluid of the associated follicle. The obtained gene expression levels were correlated with the morphological quality of the associated oocyte, zygote and embryo as well as with assisted reproductive technology outcome following the intracytoplasmic sperm injection procedure.
Methods:
This study involved 129 cumulus cells and 35 follicular fluid samples, taken from 58 patients undergoing the intracytoplasmic sperm injection procedure. Oocytes, zygotes and embryos were assessed for morphological quality. The relative gene expression of AMH, AMHR2, FSHR and AR was calculated using the delta–delta Ct method. Anti-Müllerian hormone concentrations in follicular fluids were measured by enzyme-linked immunosorbent assay.
Results:
The results yielded suggest a relationship between AMH, AR and oocyte morphology: AMH and AR gene expression levels in CCs surrounding morphologically optimal oocytes were significantly lower than in CCs surrounding oocytes with suboptimal morphology (p = 0.011 and p = 0.008, respectively). Statistically significant positive correlation was found between mRNA expression levels of AMH and FSHR (p < 0.001), AMH and AR (p = 0.001), AMHR2 and FSHR (p < 0.001), AMHR2 and AR (p < 0.001), as well as between FSHR and AR (p < 0.001).
Conclusion:
Assessed results point to AMH and AR relation with oocyte maturity, but not with its fertilization potential, or with embryo quality.
Couples with infertility issues have been assisted by
fertilization reproduction technologies with high success rates of 50-80%. However, complications associated with ovarian stimulation remain, ...such as ovarian hyperstimulation. Oocyte quality is a significant factor impacting the outcome of
fertilization procedures, but other processes are also critical for fertilization success. Increasing evidence points to aberrant inflammation as one of these critical processes reflected in molecular changes, including glycosylation of proteins. Here we report results from a MALDI-TOF-MS-based glycomic profiling of the total IgG and total proteome N-glycomes isolated from the follicular fluid obtained from patients undergoing fertilization through either (1) assisted reproduction by modified natural cycle or (2) controlled ovarian stimulation (GnRH antagonist, GnRH Ant) protocols. Significant inflammatory-related differences between analyzed N-glycomes were observed from samples and correlated with the ovarian stimulation protocol used in patients.
Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) gene polymorphisms have been extensively evaluated as predisposing factors to human reproductive disorders. However, ...the evidence available is inconsistent. Therefore, we performed a systematic review and meta-analysis to provide the first comprehensive synopsis of case-control studies that investigated the association of MMP and TIMP gene polymorphisms with disorders that influence fertility and pregnancy complications. Literature search was performed using PubMed and Scopus databases. We included 42 case-control studies in the systematic review for the following disorders: adenomyosis, endometriosis, hypertensive disorders of pregnancy, preterm birth and recurrent spontaneous abortion. Although a large number of MMP and TIMP gene polymorphisms were tested, no exclusive and unambiguous risk factors were identified for any of the disorders. The majority of statistically significant associations were confirmed in just one study. Additionally, we performed two meta-analyses for MMP9 rs3918242 polymorphism in endometriosis/adenomyosis and preeclampsia but found no association with either disorder. Considering the modest associations and conflicting results between individual case-control studies, new data is needed for further research of this subject.
•A large number of MMP and TIMP SNPs were tested as predisposing factors to fertility disorders.•The aim of the study was to conduct a systematic review and meta-analysis of MMP and TIMP SNPs.•No unambiguous risk factors were identified for any of the disorders.
Lung cancer is the most common second primary cancer. We investigated whether the TNF-alpha-308 and TNF-alpha-238 polymorphisms were associated with the susceptibility and severity of lung cancer as ...the second primary cancer (LC2).
This study included 104 patients from the group LC2. The control subjects included 2 groups. The first control group (LC1) comprised 201 unrelated patients with lung cancer as a first primary cancer. The second control group (HC) comprised 230 healthy blood donors, matched for sex and age to the study group.
The frequencies of the TNF-alpha-238 polymorphism GG genotype and the G allele were higher in the LC2 group than in the LC1 group, but the differences did not reach significance (p=0.054 and p=0.057, respectively). Similar differences were found in the TNF-alpha-238 polymorphism GG genotype and G allele between the LC2 group and the HC group (p=0.054 and p=0.057, respectively). In terms of the different types of lung cancer, patients with a second primary NSCLC (non-small cell lung cancer) more frequently had TNF-alpha-238 polymorphism GG genotypes and G alleles than patients with a first primary NSCLC (the differences approached statistical significance: p=0.060, p=0.064, respectively). All (100%) patients of group LC2 (n=104) had the GG genotype and the G allele. GG genotype was exclusive and no A allele was found in group LC2.
TNF-alpha-238 polymorphism GG genotype and the G allele could have a promotional effect on the development of NSCLC in the group of patients with LC2.
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