MiR‐221‐3p and miR‐92a‐3p enhances smoking‐induced inflammation in COPD

BackgroundSmoking is likely to facilitate airway inflammation and finally contributes to chronic obstructive pulmonary disease (COPD). This investigation was intended to elucidate miRNAs that were involved in smoking‐induced COPD.MethodsAltogether 155 COPD patients and 77 healthy volunteers were recruited, and their serum levels of miR‐221‐3p and miR‐92a‐3p were determined. Besides, human bronchial epithelial cells (16HBECs) were purchased, and they were treated by varying concentrations of cigarette smoke extract (CSE). The 16HBECs were, additionally, transfected by miR‐221‐3p mimic, miR‐92a‐3p mimic, miR‐221‐3p inhibitor or miR‐92a‐3p inhibitor, and cytokines released by them, including TNF‐α, IL‐8, IL‐1β, and TGF‐β1, were monitored using enzyme linked immunosorbent assay (ELISA) kits.ResultsChronic obstructive pulmonary disease patients possessed higher serum levels of miR‐221‐3p and miR‐92a‐3p than healthy volunteers (p < 0.05), and both miR‐221‐3p and miR‐92a‐3p were effective biomarkers in diagnosing stable COPD from acute exacerbation COPD. Moreover, viability of 16HBECs was undermined by CSE treatment (p < 0.05), and exposure to CSE facilitated 16HBECs’ release of TNF‐α, IL‐8, IL‐1β, and TGF‐β1 (p < 0.05). Furthermore, miR‐221‐3p/miR‐92a‐3p expression in 16HBECs was significantly suppressed after transfection of miR‐221‐3p/miR‐92a‐3p inhibitor (p < 0.05), which abated CSE‐triggered increase in cytokine production and decline in viability of 16HBECs (p < 0.05).ConclusionMiR‐221‐3p and miR‐92a‐3p were involved in CSE‐induced hyperinflammation of COPD, suggesting that they were favorable alternatives in diagnosing COPD patients with smoking history.     

Genetic research and clinical analysis of β‐globin gene cluster deletions in the Chinese population of Fujian province: A 14‐year single‐center experience

BackgroundHeterozygotes of HPFH and δβ thalassemia are clinically asymptomatic or have mild hemoglobin (Hb) values. However, when both HPFH and δβ‐thalassemia are coinherited with heterozygous β‐thalassemia, patients may progress to a clinical phenotype of thalassemia intermedia or thalassemia major. The purpose of this study was to characterize the genotypes and analyze the phenotypes of these disorders in Fujian Province, to offer advice for genetic counseling and accurate prenatal diagnosis in this region. A total of 55 001 subjects were participated in thalassemia screening. 142 subjects with HbF levels ≥10%, before the blood transfusion, were selected for further investigation.MethodsMultiplex ligation‐dependent probe amplification (MLPA) and Gap‐PCR were used to screen for three β‐globin gene cluster deletions: Chinese ^Gγ(^Aγδβ)⁰ thalassemia and Southeast Asia HPFH (SEA‐HPFH) deletion and 1357 bp deletion (NG‐000007.3:g.69997‐71353 del 1357).ResultsA total of 142 patients with HbF (≥10%) were enrolled to characterize the molecular basis of β‐globin gene cluster deletions in our study; 22 cases 0.04% (22/55 001) were definitively diagnosed with β‐globin gene cluster deletions. Ten cases were heterozygous for the Chinese ^Gγ(^Aγδβ)⁰‐thal mutations, 10 cases were heterozygous for SEA‐HPFH, and one case was compound heterozygous for SEA‐HPFH and the α‐thal mutation. The 1357 bp deletion (NG‐000007.3:g.69997‐71353 del 1357) was detected in one case. Moreover, the hemoglobin A₂ levels in patients who were heterozygous for Chinese ^Gγ(^Aγδβ)⁰‐thal were statistically lower than in cases with SEA‐HPFH deletion(p < 0.05).ConclusionIn Fujian Province, the prevalence of common β‐globin gene cluster deletions was 0.04%. What''s more, the most common β‐globin cluster deletions are the Chinese ^Gγ(^Aγδβ)⁰ and SEA‐HPFH.     

Prenatal diagnosis of thalassemia in 695 pedigrees from southeastern China: a 10‐year follow‐up study

Thalassaemia is highly prevalent in southeastern China. This 10‐year follow‐up study aimed to characterize the genotype and karyotype of thalassaemia in fetal samples derived from thalassemia carriers in Fujian province, southeastern China. A total of 476 prenatal samples from 472 couples carrying α‐thalassaemia traits and 224 samples from 223 couples carrying β‐thalassaemia traits were collected for STR analysis, detection of thalassemia genotypes and karyotyping. The common deletional α‐thalassemias and rare thalassemia genotypes were detected using Gap‐PCR assay, and the common β‐globin gene mutations were detected using PCR‐RDB assay. We detected 43.49% prevalence of α‐thalassaemia minor, 26.05% prevalence of α‐thalassaemia intermediate and major and 1.89% prevalence of rare form among the 476 prenatal samples from couples with α‐thalassaemia, and 85 fetuses with β‐thalassemia heterozygote, 16 with homozygote and 21 with double heterozygote, and a rare β^{IVS−2−654(C→T)}/Chinese G_γ (^Aγδβ)⁰ genotype among the 224 prenatal samples from couples with β‐thalassemia. Karyotyping showed 7 fetuses with abnormal karyotypes. Totally 153 pregnancies were terminated, and genetic diagnosis of thalassemia using fetal umbilical cord blood following induction of labor showed consistent results with prenatal diagnosis. No thalassemia phenotypes were identified in normal infants half a year after birth, and the infants with α‐thalassemia and β‐thalassemia minor had no or mild anemia symptoms, but normal development, while 15 babies with hemoglobin H disease presented moderate anemia symptoms. Our data suggest the pregestational screening of thalassemia, notably compound and rare forms of thalassemia, for couples carrying thalassemia traits.     

Differences of adrenal‐derived androgens in 5α‐reductase deficiency versus androgen insensitivity syndrome

Steroid 5α‐reductase type 2 deficiency (5α‐RD2) and androgen insensitivity syndrome (AIS) are difficult to distinguish clinically and biochemically, and adrenal‐derived androgens have not been investigated in these conditions using modern methods. The objective of the study was to compare Chinese patients with 5α‐RD2, AIS, and healthy men. Sixteen patients with 5α‐RD2, 10 patients with AIS, and 39 healthy men were included. Serum androgen profiles were compared in these subjects using liquid chromatography/tandem mass spectrometry (LC‐MS/MS). Based on clinical features and laboratory tests, 5α‐RD2 and AIS were diagnosed and confirmed by genotyping. Dihydrotestosterone (DHT) and testosterone (T) were both significantly lower in patients with 5α‐RD2 than AIS (p < 0.0001). The T/DHT ratio was higher in 5α‐RD2 (4.5–88.6) than AIS (13.4–26.7) or healthy men (7.6–40.5). Using LC‐MS/MS, a cutoff T/DHT value of 27.3 correctly diagnosed 5α‐RD2 versus AIS with sensitivity 93.8% and specificity 100%. Among the adrenal‐derived 11‐oxygenated androgens, 11β‐hydroxyandrostenedione (11OHA4) and 11‐ketoandrostenedione (11KA4) were also lower in patients with 5α‐RD2 than those of patients with AIS. In contrast, 11β‐hydroxytestosterone (11OHT) was higher in 5α‐RD2 than AIS. Furthermore, a 11OHT/11OHA4 cutoff value of 0.048 could also distinguish 5α‐RD2 from AIS. Thus, both elevated T/DHT values above 27.3 and the unexpected 11‐oxygenated androgen profile, with a 11OHT/11OHA4 ratio greater than 0.048, distinguished 5α‐RD2 from AIS. These data suggest that the metabolism of both gonadal and adrenal‐derived androgens is altered in 5α‐RD2.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Steroid 5α‐reductase type 2 deficiency (5α‐RD2) and androgen insensitivity syndrome (AIS) are difficult to distinguish.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study investigated adrenal‐derived androgens in 5α‐RD2, AIS, and healthy men by liquid chromatography/tandem mass spectrometry.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

The 11β‐hydroxyandrostenedione (11OHA4) and 11‐ketoandrostenedione (11KA4) were lower in patients with 5α‐RD2, whereas 11β‐hydroxytestosterone (11OHT) was higher in patients with 5α‐RD2.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The cutoff value of 11OHT/11OHA4 could be used to distinguish 5α‐RD2 from AIS.     

Association of alpha‐thalassemia and Glucose‐6‐Phosphate Dehydrogenase deficiency with transcranial Doppler ultrasonography in Nigerian children with sickle cell anemia

BackgroundStroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha‐thalassemia and glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha‐thalassemia and G6PD(A⁻) variant with abnormal TCD velocities among Nigerian children with SCA.MethodsOne hundred and forty‐one children with SCA were recruited: 72 children presented with normal TCD (defined as the time‐averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha‐thalassemia (the α‐3.7 globin gene deletion) was determined by multiplex gap‐PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism—polymerase chain reaction.ResultsThe frequency of α‐thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α‐/ α α: 41.7%, α ‐/ α ‐: 11.1%] versus 21/69 (30.4%) [α‐/ α α: 27.5%, α ‐/ α ‐: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α‐thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20–0.78, p = 0.007]. However, the frequencies of G6PDA⁻ variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).ConclusionOur study reveals the protective role of α‐thalassemia against the risk of abnormal TCD in Nigerian children with SCA.     

Circular RNA circβ‐catenin aggravates the malignant phenotype of non‐small‐cell lung cancer via encoding a peptide

BackgroundMore and more evidences demonstrate that circular RNAs (circNRAs) can encode protein. As a circRNA with translation capabilities, outcomes of circβ‐catenin in non‐small cell lung cancer (NSCLC) still need to be explored.MethodThe research methods of circβ‐catenin in the article include qRT‐PCR, wound healing assay, CCK‐8, colony formation, and Transwell assay. Western blotting and immunofluorescence were provided to detect protein expression levels and peptide encoded by circβ‐catenin, respectively.ResultsA prominently higher circβ‐catenin expression was found in NSCLC tissues. Silencing of circβ‐catenin was able to inhibit NSCLC cell migrating, invasive, and proliferative phenotypes. Overexpression of circβ‐catenin could enhance the migrating, invasive, and proliferative phenotypes of NSCLC cells. Importantly, circβ‐catenin was found to encode a peptide in NSCLC cells. Silencing or overexpression of circβ‐catenin could reduce or increase β‐catenin protein expression via suppressing the degradation of β‐catenin.ConclusionCircβ‐catenin could promote NSCLC cell malignant phenotypes via peptide‐regulated β‐catenin pathway. Our study provided a new understanding for the mechanisms of NSCLC.     

Arctigenin inhibits apoptosis,extracellular matrix degradation,and inflammation in human nucleus pulposus cells by up‐regulating miR‐483‐3p

BackgroundArctigenin (ATG) is the active ingredient of the Chinese herbal medicine Arctium lappa, with anti‐inflammatory and antioxidant effects. Excessive inflammation and cell apoptosis are important causes of intervertebral disc degeneration (IDD). Hence, this study probed into the possible role of ATG in IDD.MethodsInterleukin (IL)‐1β (10 ng/ml) was adopted to induce human nucleus pulposus cells (HNPCs) as a cell model for IDD. The effects of different concentrations of ATG (0, 2, 5, 10, 20, 50 μmol/L) on the viability of HNPCs and effects of ATG (10, 50 μmol/L) on the viability of IL‐1β‐induced HNPCs were detected by cell counting kit‐8 (CCK‐8). After IL‐1β‐induced HNPCs were transfected with miR‐483‐3p inhibitor and/or treated with ATG, cell viability and apoptosis were determined by CCK‐8 and flow cytometry; the expressions of miR‐483‐3p, extracellular matrix (ECM)‐related genes, and inflammation‐related genes were measured by quantitative real time polymerase chain reaction (qRT‐PCR), and expressions of ECM/apoptosis/NF‐κB pathway‐related proteins were quantified by Western blot.ResultsATG had no significant effect on the viability of HNPCs but could promote the viability of IL‐1β‐induced HNPCs. ATG inhibited apoptosis, ECM degradation, inflammation, and activation of NF‐κB pathway in HNPCs induced by IL‐1β, but promoted the expression of miR‐483‐3p. MiR‐483‐3p inhibitor reversed the above‐mentioned regulatory effects of ATG.ConclusionArctigenin suppresses apoptosis, ECM degradation, inflammation, and NF‐κB pathway activation in HNPCs by up‐regulating miR‐483‐3p.     

Cross‐reactivity between tick and wasp venom can contribute to frequent wasp sensitization in patients with the α‐Gal syndrome

Backgroundα‐Gal syndrome (AGS) is a food allergy with severe delayed allergic reactions, mediated by IgE‐reactivity to galactose‐α1,3‐galactose (α‐Gal). AGS is strongly associated with tick bites. An increased incidence of venom sensitization has been found in AGS patients. Here, we evaluated the frequency of wasp sensitization in Swedish AGS patients and the possible cross‐reactivity between wasp venom and tick proteins.MethodsSera from 136 Swedish AGS patients and 29 wasp‐positive non‐AGS control sera were analyzed for IgE‐reactivity against wasp venom (Vespula spp.), the European tick Ixodes ricinus (Streptavidin ImmunoCAP), α‐Gal and total IgE by ImmunoCAP. The presence of α‐Gal on wasp venom proteins (Vespula vulgaris) was investigated by western blot (WB), and possible cross‐reactivity between wasp venom and tick proteins by enzyme‐linked immunosorbent assay and WB. Involvement of cross‐reactive carbohydrate domains (CCDs) was also assessed.ResultsWasp sensitization was present in 54% of AGS patients, although the IgE levels were low. Wasp sensitized patients had higher IgE levels to α‐Gal and total IgE levels compared to non‐wasp sensitized AGS patients. α‐Gal was not detected in wasp venom, but cross‐reactivity between wasp and tick proteins was demonstrated which was not dependent on CCDs. The same cross‐reactivity was also observed in the control sera. Furthermore, 17 putative cross‐reactive peptides were identified using an in silico approach.ConclusionsFor the first time, cross‐reactivity between wasp venom and tick proteins has been described. This may be a reason why the majority of Swedish AGS patients, who have all been tick bitten, are also sensitized against wasp.     

Upregulation of CD3ζ and L‐selectin in antigen‐specific cytotoxic T lymphocytes by eliminating myeloid‐derived suppressor cells with doxorubicin to improve killing efficacy of neuroblastoma cells in vitro

BackgroundAgglomeration of myeloid‐derived suppressor cells (MDSCs) in tumors impedes immunotherapeutic effects. Doxorubicin (DOX) is currently the most specific drug used for the selective removal of MDSCs. Here, we study the feasibility and mechanism of eliminating MDSCs by DOX to improve antigen‐specific cytotoxic T lymphocyte (CTL)‐killing neuroblastoma (NB) cells in vitro.MethodsCTL and MDSC were prepared; then, CTLs, NB cells, MDSCs, and DOX were mixed and cultivated in different collocation patterns and divided into different groups. The levels of cluster of differentiation 3ζ chain (CD3ζ) and L‐selectin in CTL in different groups were detected. Thereafter, the killing rate of NB cells and secretion of interleukin‐2 and interferon‐γ were measured and compared.ResultsBy real‐time polymerase chain reaction (PCR) and Western blot test respectively, the proliferation and killing effect of CTLs on NB cells were all inhibited by MDSC through downregulating CD3ζ (p = 0.002; p = 0.001) and L‐selectin (p = 0.006; p < 0.001). However, this inhibitory effect was reversed by DOX. Significant differences were observed in the levels of interleukin‐2 (p < 0.001), interferon‐γ (p < 0.001), and the killing rate (p < 0.001) among the groups, except between the CTL +SK‐N‐SH and CTL +SK‐N‐SH +DOX groups (p > 0.05).ConclusionsTargeted elimination of MDSCs by DOX can improve Ag‐specific CTL killing of NB cells in vitro by upregulating CD3ζ and L‐selectin. This study provides a novel method to enhance the immunotherapeutic effects of NB.     

The lower expression of circulating miR‐210 and elevated serum levels of HIF‐1α in ischemic stroke; Possible markers for diagnosis and disease prediction

Background Stroke, either due to ischemia or hemorrhage, causes acute neurological damages to the brain. There is shortage of reliable biomarkers for ischemic stroke (IS), and we therefore investigated the serum concentrations of microRNA‐210 (miR‐210) and hypoxia inducible factor‐1α (HIF‐1α), as possible diagnostic and/or prognostic markers for IS.MethodsSerum samples were acquired from 52 IS patients and their healthy counterparts at five time points: upon admission, 24 and 48 h after admission, upon discharge and 3 months later. Serum levels of miR‐210 and HIF‐1α were respectively analyzed using real time RT‐PCR and ELISA. Diagnostic and prognostic accuracy tests were performed to assess the value of suggested biomarkers.ResultsIS patients demonstrated higher levels of serum HIF‐1α and lower miR‐210 in comparison to the healthy subjects. MiR‐210 was suggested to be a weak diagnostic biomarker at the time of admission (AUC = 0.61; p = 0.05), while HIF‐1α was an acceptable diagnostic marker for IS (AUC = 0.73; p < 0.0001). The higher expression of miR‐210 and lower levels of HIF‐1α were associated with better survivals in IS patients.ConclusionsSerum miR‐210 is a weak diagnostic marker of IS. Serum HIF‐1α is a better biomarker in diagnosing IS patients but further work in larger groups, including those with hemorrhagic stroke is necessary to confirm its diagnostic utility. Similarly, the prognostic potentiality of miR‐210 and HIF‐1α was acceptable but needs bigger sample size and longer follow‐up to be statistically confirmed.     

Association of tumor necrosis factor alpha ‐308 single nucleotide polymorphism with SARS CoV‐2 infection in an Iraqi Kurdish population

Uncovering risk factors playing roles in the severity of Coronavirus disease 2019 (Covid‐19) are important for understanding pathoimmunology of the disease caused by severe acute respiratory syndrome Coronavirus 2 (SARS CoV‐2). Genetic variations in innate immune genes have been found to be associated with Covid‐19 infections. A single‐nucleotide polymorphism (SNP) in a promoter region of tumor necrosis factor alpha (TNF‐α) gene, TNF‐α −308G>A, increases expression of TNF‐α protein against infectious diseases leading to immune dysregulations and organ damage. This study aims to discover associations between TNF‐α −308G>A SNP and Covid‐19 infection. Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) was used for genotyping a general Kurdish population and Covid‐19 patients. The homozygous mutant (AA) genotype was found to be rare in the current studied population. Interestingly, the heterozygous (GA) genotype was significantly (p value = 0.0342) higher in the Covid‐19 patients than the general population. This suggests that TNF‐α −308G>A SNP might be associated with Covid‐19 infections. Further studies with larger sample sizes focusing on different ethnic populations are recommended.     

Anticardiolipin and anti‐beta 2‐glycoprotein I antibodies in patients with unexplained articular manifestations

ObjectiveTo determine the frequency of antiphospholipid antibodies (aPL) in patients with unexplained articular manifestations.Material and MethodsThree hundred thirteen patients suffering from arthritis or arthralgia without evident cause and 266 healthy blood donors (HBD) were included in the study. Anticardiolipin antibodies (aCL) and anti‐beta 2‐glycoprotein I antibodies (aβ2GPI) were measured by ELISA.ResultOut of the 313 patients, 250 were females and 63 were males. The mean age of patients was 49 ± 14 years (17–87 years). One hundred eleven patients have arthralgia and 202 have arthritis. The frequency of aCL and/or aβ₂GPI (24.9%) was significantly higher in patients than in HBD (10.9%). The frequency of aβ2GPI was 23.6% in patients and 9.4% in the control group (p < 10⁻³). aβ2GPI‐IgA was significantly more frequent in patients than in the control group (20.4% vs. 7.5%, p < 10⁻³). aβ2GPI was most commonly observed than aCL in patients (23.6% vs. 6.4%, p < 10⁻⁶). IgA isotype of aβ2GPI was the most frequent in 20.4% of patients while IgG and IgM were detected in 5.4% and 2.9% respectively.ConclusionThis study showed that aPL were common in patients with articular manifestations and were mainly directed against β₂GPI. The role of these antibodies remains to be specified.     

Frequency of serological markers of rheumatoid arthritis in patients with IgA anti‐β2 glycoprotein I antibodies

AimTo determine the frequency of serological markers of RA in patients with anti‐β2 glycoprotein I antibodies (aβ2GPI) of IgA isotype.Material and MethodsA retrospective study was conducted on 67 patients with aβ2GPI‐IgA. Ninety healthy blood donors (HBD) were used as a control group. IgG anti‐cyclic citrullinated peptides antibodies (CCP‐Ab) and rheumatoid factors (RF) IgG, IgA, and IgM were detected by enzyme‐linked immunosorbent assay (ELISA).ResultsSeventeen patients and eight HBD had CCP‐Ab and/or RF (25.4% vs. 8.9%, p = 0.005, CI 95% [14.95; 35.79], odds ratio = 3.5). The frequency of CCP‐Ab was significantly higher in patients than in healthy subjects (14.9% vs. 3.3%, p = 0.009). IgA isotype of RF was significantly higher in patients than in controls (7.5% vs. 0%, p = 0.02). In male patients, CCP‐Ab and/or RF were more frequent than in healthy male subjects (37.5% vs. 11.8%, p = 0.02). In patients, no correlation was found between the levels of aβ2GPI‐IgA and CCP‐Ab (r = 0.082, p = 0.51). There was no correlation between the level aβ2GPI‐IgA and the level of the isotypes of RF (IgG, IgA, and IgM) in patients (r = 0.1, p = 0.37; r = 0.17, p = 0.17 and r = 0.07, p = 0.59 respectively).ConclusionFrequencies of CCP‐Ab and RF are high in patients with aβ2GPI‐IgA suggesting that these patients are susceptible to developing RA.     

β1‐receptor polymorphisms and junctional ectopic tachycardia in children after cardiac surgery

Junctional ectopic tachycardia (JET) is a potentially life‐threatening postoperative arrhythmia in children with specific congenital heart defects and can contribute significantly to postoperative morbidity for at‐risk populations. In adults, β1‐adrenergic receptor (ADRB1) and β2‐adrenergic receptor (ADRB2) genotypes have been associated with increased risk for arrhythmias. However, their association with arrhythmia risk in children is unknown. We aimed to test associations between ADRB1 and ADRB2 genotypes and postoperative JET in patients with congenital heart defects. Children who underwent cardiac surgery were genotyped for the ADRB1 p.Ser49Gly (rs1801252; c.145A>G), p.Arg389Gly (rs1801253; c.1165C>G), ADRB2 p.Arg16Gly (rs1042713; c.46A>G), and p.Glu27Gln (rs1042714; c.79G>C) polymorphisms. The occurrence of postoperative JET was assessed via cardiologist‐interpreted electrocardiograms. Genotype associations with JET were analyzed via logistic regression, adjusted for clinical variables associated with JET, with separate analysis in patients not on a β‐blocker. Of the 343 children included (median age 8 months, 53% boys, 69% European ancestry), 45 (13%) developed JET. The Arg389Arg genotype was not significantly associated with JET in the overall population (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 0.96–4.03, p = 0.064), but was nominally associated in patients not taking a β‐blocker (n = 324, OR = 2.25, 95% CI = 1.05–4.80. p = 0.034). None of the other variants were associated with JET. These data suggest that the ADRB1 Arg389Arg genotype may predict risk for JET following cardiac surgery in pediatric patients in the absence of β‐blockade. Whether treatment with a β‐blocker ameliorates this association requires further research.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

ADRB variants have been associated with arrhythmias in an adult population; however, the contribution of these variants to postoperative arrhythmia risk in children with congenital heart disease is unknown.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Is there an association among ADRB1 Ser49Gly, ADRB1 Arg389Gly, ADRB2 Arg16Gly, or ADRB2 Gln27Glu genotypes and postoperative junctional ectopic tachycardia (JET) occurrence in children undergoing cardiac surgery?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

ADRB1 Arg389Arg genotype may help predict risk for JET following cardiac surgery in pediatric patients in the absence of β‐blockade.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

These findings serve as a foundation for further study of postoperative JET risk and ADRB1 Arg389Arg genotype and suggest a potential role of β‐blockade in reducing genotype‐mediated risk for JET in ADRB1 Arg389Arg genotype patients.     

APOE gene ɛ4 allele (388C‐526C) effects on serum lipids and risk of coronary artery disease in southern Chinese Hakka population

ObjectiveTo analyze the relationship of Apolipoprotein E (APOE) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene polymorphisms with coronary artery disease (CAD).Methods1,129 CAD patients and 1,014 non‐CAD controls were included in the study, and relevant information and medical records were collected. The single‐nucleotide polymorphisms (SNPs) were analyzed, including rs429358, rs7412 in APOE gene and rs2306283, rs4149056 in SLCO1B1 gene.ResultsThe CAD patients’ average age was 66.3 ± 10.7 years, while 65.5 ± 12.0 years in controls. The frequencies of APOE allele ɛ3, ɛ4, and ɛ2 were 83.01%, 10.08%, and 6.91% respectively. There were statistically significant differences in genotype ɛ3/ɛ4 (χ² = 8.077, p = 0.005) in CAD patients compared with the controls. The SLCO1B1 genotype *1b/*1b and haplotype *1b showed the highest frequency in the study sample. Moreover, ε4 carriers had significantly lower HDL‐C, Apo‐A1 levels than ε3 carriers among CAD patients, while ε2 carriers showed lower LDL‐C, Apo‐B level, and higher Apo‐A1/Apo‐B level than ε3 and ε4 carriers. In controls, ε2 carriers showed lower LDL‐C and Apo‐B level, higher Apo‐A1, and Apo‐A1/Apo‐B level than ε4 carriers. Logistic regression analysis showed that high LDL‐C and Apo‐B level, low HDL‐C level, smoking, and the ε4 allele were risks for the presence of CAD.ConclusionsAPOE ε4 allele may be associated with susceptibility to CAD in southern Chinese Hakka population. It indicated that the APOE SNPs rs429358 and rs7412 are associated with CAD, but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene.     

Novel long noncoding RNA LINC02323 promotes cell growth and migration of ovarian cancer via TGF‐β receptor 1 by miR‐1343‐3p

BackgroundThis study was aimed at investigating the effects of long noncoding RNA (lncRNA) LINC02323 in ovarian cancer and its possible mechanism.MethodsMicroarray analysis and QPCR were utilized to identify lncRNA LINC02323 expression in patients with ovarian cancer. MTT assay was used for analysis of ovarian cancer cell proliferation. Western blot was utilized to investigate its possible mechanism.ResultsIn patients with ovarian cancer, lncRNA LINC02323 expression was up‐regulated and miR‐1343‐3p expression was down‐regulated. Over‐expression of lncRNA LINC02323 promoted cell growth and reduced LDH activity levels in vitro model by suppression of miR‐1343‐3p expression. Down‐regulation of lncRNA LINC02323 reduced cell growth and increased LDH activity levels in vitro model by induction of miR‐1343‐3p expression. Over‐expression of miR‐1343‐3p reduced cell growth and reduced LDH activity levels in vitro model by suppression of TGF‐β receptor. Down‐regulation of miR‐1343‐3p promoted cell growth and reduced LDH activity levels in vitro model by induced of TGF‐β receptor.ConclusionOur findings show that Novel long noncoding RNA LINC02323 promotes cell growth of ovarian cancer via TGF‐β receptor 1 by miR‐1343‐3p.     

Profuse telangiectasias in an immunocompetent patient misleading presentation revealing a hepatosplenic‐Tγδ‐cell lymphoma

Here we present the case of an hepato‐splenic‐Tγδ‐cell lymphoma interestingly occurring in a non‐immunocompromised patient, with profuse telangiectasias giving originally misleading orientation towards the diagnosis of B angiotropic lymphoma.