The association of LRP5 (rs556442) polymorphism with body composition and obesity in postmenopausal women

AimThe main of this study was to investigate the association between the rs566442 (V1119V) coding polymorphism of Low-density lipoprotein receptor-related protein 5 (LRP5) with obesity and basal metabolic rate in Iranian postmenopausal women.MethodsThis cross-sectional study was performed on 350 postmenopausal women with a mean age of 57.8 years (SD ± 6.14). Body composition was analyzed by bioelectrical impedance analysis (BIA) resistance. Obesity was defined based on Body mass index (BMI) ≥30 kg/m2. To determine the genotype of SNP (rs556442), PCR-RFLP assay was performed and confirmed by sequencing. DNA samples from participants were genotyped using the RFLP-PCR method.ResultsAmong the study population 37.1% (130) were obese. G allele had minor-allele frequency of 0.38% in our population. The frequency of genotypes in our study population was 12.9% (45 person) GG, 35.7% (125 person) AA and 51.4% (180) GA. After adjusting age and menopausal age, only basal metabolic rate showed significantly higher in GG group compare to other groups (p = 0.02). Our data showed basal metabolic rate was higher in obese women with GG genotype in comparison to obese women with AG and AA genotypes.DiscussionThe findings of this study suggest that the GG genotype of SNP (rs556442) could protective role in obese women through the association with BMR.     

Clinical,Angiographic Characteristics and In-Hospital Outcomes of Smoker and Nonsmoker Patients After Primary Percutaneous Coronary Intervention

BackgroundSmoking is a well-established cardiac risk factor there is dearth of Local data regarding clinical and angiographic characteristics of smoker patients.ObjectivesThis study was planned to assess the differences in the clinical characteristics, angiographic characteristics, and in-hospital outcomes of smokers and nonsmokers after primary percutaneous coronary intervention at a tertiary care hospital in Karachi, Pakistan.MethodsWe included patients between 40 and 80 years of age diagnosed with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention from July 1, 2017, to March 31, 2018. Clinical and angiographic characteristics and in-hospital outcomes were obtained from the cases submitted to the National Cardiovascular Data Registry's CathPCI (Catheterization–Percutaneous Coronary Intervention) Registry from our site.ResultsA total of 3,255 patients were included in this study. Smokers consist of 25.1% (817) of the total sample. A high majority of smokers were male, 98.8% (807), and smokers were relatively younger as compared to nonsmokers with a mean age of 52.89 ± 10.59 versus 55.98 ± 11.24 years; p < 0.001. Smokers had higher post-procedure TIMI (Thrombolysis In Myocardial Infarction) flow grade III: 97.8% (794) versus 95.53% (2,329); p = 0.037, and they had a relatively low mortality rate: 2.69% (22) versus 3.16% (77); p = 0.502.ConclusionsSmokers were predominantly male and around 3 years younger than nonsmokers. Diabetes mellitus and hypertension were less common among smokers and single-vessel disease was the more common angiographic finding for smokers as compared to 3-vessel disease for nonsmokers. No statistically significant differences in in-hospital outcomes were observed. ST-segment elevation myocardial infarction in smokers despite younger age and the low atherosclerotic risk profile, in our region, emphasize the need for nicotine addiction management and smoking cessation campaigns at large and for pre-discharge counseling.     

Antiprotozoal activity of diterpenoids isolated from Zhumeria majdae- absolute configuration by circular dichroism

PurposeZhumeria majdae, a unique species of the Zhumeria genus, is an endemic Iranian plant in the Lamiaceae family. Phytochemical investigation and biological activity of this plant are rarely reported. The current study aimed to find new antiprotozoal compounds from the roots of Z. majdae and to determine the absolute configuration of isolated compounds by circular dichroism.MethodsThe extraction process from roots and aerial parts of Z. majdae was carried out by hexane, ethyl acetate and methanol followed by testing their antiprotozoal effects against Leishmania donovani, Trypanosoma brucei rhodesiense, T. cruzi, and Plasmodium falciparum, respectively. Structure elucidation was done using 1D and 2D NMR spectroscopy and HREIMS spectrometry. In addition, experimental and theoretical circular dichroism spectroscopy was used to establish absolute configuration.ResultsIn comparison with aerial parts, the hexane extract from roots showed superior activity against T. b. rhodesiense, L. donovani and P. falciparum with IC₅₀ values of 5.4, 1.6 and 2.1 μg/ml, respectively. From eight abietane-type diterpenoids identified in roots, six were reported for the first time in the genus Zhumeria. 11,14-dihydroxy-8,11,13-abietatrien-7-one (6) exhibited a promising biological activity against P. falciparum (IC₅₀ 8.65 μM), with a selectivity index (SI) of 4.6, and lanugon Q (8) showed an IC₅₀ value of 0.13 μM and SI of 15.4 against T. b. rhodesiense.ConclusionAltogether, according to the results, of 8 isolated compounds, dihydroxy-8,11,13-abietatrien-7-one (6) and lanugon Q (8) exhibited a promising activity against T. b. rhodesiense and P. falciparum. In conclusion, these compounds could be potential candidates for further analysis and may serve as lead compounds for the synthesis of antiprotozoal agents. Open in a separate windowGraphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00345-w) contains supplementary material, which is available to authorized users.     

Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes

Most neurons in vertebrates make a developmental choice between two principal neurotransmitter phenotypes (glutamatergic versus GABAergic). Here we show that the homeobox gene Lbx1 determines a GABAergic cell fate in the dorsal spinal cord at early embryonic stages. In Lbx1-/- mice, the presumptive GABAergic neurons are transformed into glutamatergic cells. Furthermore, overexpression of Lbx1 in the chick spinal cord is sufficient to induce GABAergic differentiation. Paradoxically, Lbx1 is also expressed in glutamatergic neurons. We previously reported that the homeobox genes Tlx1 and Tlx3 determine glutamatergic cell fate. Here we show that impaired glutamatergic differentiation, observed in Tlx3-/- mice, is restored in Tlx3-/-Lbx1-/- mice. These genetic studies suggest that Lbx1 expression defines a basal GABAergic differentiation state, and Tlx3 acts to antagonize Lbx1 to promote glutamatergic differentiation.     

Symptomatic hepatitis B virus (HBV) reactivation despite reduced viral fitness is associated with HBV test and immune escape mutations in an HIV-coinfected patient

Two sequential hepatitis B virus (HBV) strains obtained before and during an icteric flare-up of an occult HBV infection in a patient coinfected with human immunodeficiency virus revealed HBV surface antigen (HBsAg) test escape mutations, although the patient had never received hepatitis B-specific immunoglobulin. In contrast to the high HBV DNA loads, recurrence of HBsAg, and resulting icteric hepatitis, phenotypic analysis of the mutated HBV strains revealed significantly reduced replication efficacies in vitro, compared with wild-type HBV. Therefore, immune escape in the transiently anti-HBs-positive patient appeared to be crucial for persistence and reactivation. Immune escape mutants evolved even without exogenous selective pressure, hampered detection in HBsAg screening, and might be transmitted during reactivation with high HBV loads.