British Journal of Biomedical Science最新文献

Introduction: KISS1 play an essential role in human reproductive functions by regulating the hypothalamic-pituitary-gonadal axis. Loss-of-function mutations in this gene have been frequently identified in patients with different reproductive disorders. We hypothesised links between KISS1 polymorphisms and polycystic ovary syndrome (PCOS).

Materials and methods: In order to find links between KISS1 polymorphisms rs4889 C > G, rs12998 G > A, and rs35431622 A > G with PCOS, 770 blood samples were obtained from 385 control and 385 PCOS women. DNA was extracted, and genotyped for KISS1 variants by PCR.

Results: rs12998 G > A was linked to PCOS in dominant (p < 0.001), recessive (p < 0.001), co-dominant (p < 0.001), and allelic models (p < 0.001). In addition, rs4889 C > G was linked in recessive, dominant, co-dominant, and allelic models (p < 0.001). rs35431622 A > G was not linked to PCOS. Further analysis indicated that C-G-G haplotype was more common and G-A-G haplotype was less prevalent in cases compared with controls.

Conclusion: KISS1 variants rs12998 G > A and rs4889 C > G may be linked to the pathophysiology of PCOS.

Objectives. Patients with heart failure and reduced left ventricular ejection fraction (HFrEF) are prone to ventricular tachyarrhythmias. We tested whether biomarkers C-terminal Endothelin 1 (CT-ET1), midregional pro atrial natriuretic peptide (MR-proANP) and midregional pro adrenomedullin (MR-proADM) might improve risk stratification for arrhythmic death.Methods: This prospective observational study included 160 heart failure patients with ischaemic cardiomyopathy (ICM) or non-ischaemic, dilated cardiomyopathy (DCM) and 30 control patients without heart disease. Primary endpoint was arrhythmic death (ArD) or resuscitated cardiac arrest (resCA).Results: A total of 61 patients died during the median follow-up of 7.0 [5.2-8.4] years. An ArD or resCA was observed in 48 patients. Plasma levels of CT-ET1 (p = 0.002), MR-proANP (p < 0.001) and MR-proADM (p = 0.013) were significantly higher in ICM or DCM patients compared to controls. MR-proANP levels in ICM patients were associated with a significantly increased risk for ArD or resCA (hazard ratio (HR) = 1.42, [95%CI: 1.08-1.85], p = 0.011) in a multivariable Cox regression model. Plasma levels of CT-ET1 (HR = 1.07 [0.98-1.17], p = 0.113) and MR-proADM (HR = 1.80 [0.92-3.55], p = 0.087) were not associated with ArD or resCA in ICM patients. No significant association with ArD or resCA was found in DCM patients. Multivariable Cox regression showed that CT-ET1 (HR = 1.14 [1.07-1.22], p < 0.001), MR-proANP (HR = 1.64 [1.29-2.08], p < 0.001) and MR-pro ADM (HR = 2.06 [1.12-3.77], p = 0.020) were associated with a higher risk for overall mortality.Conclusion: Patients with HFrEF had elevated levels of CT-ET1, MR-proANP and MR-proADM. Plasma levels of MR-proANP are useful as predictor for arrhythmic death in patients with ICM.

Introduction: Cell biology studies, animal models and other data suggest a role for sirtuin-1 in the pathogenesis of rheumatoid arthritis (RA). We hypothesized the clinical significance of serum sirtuin-1 in this disease.Methods: Serum was obtained from 141 RA patients, 144 non-RA patients and 88 healthy controls. Sirtuin-1, anti-mutant citrulline vimentin antibody (anti-MCV), anti-cyclic citrulline polypeptide antibody (anti-CCP), rheumatoid factor and C-reactive protein were measured by immunological methods, and erythrocyte sedimentation rate was determined by the Westergren method.Results: All markers were higher in the RA group than in the non-RA group and the healthy control group (P < 0.01). The specificity of sirtuin-1 for the diagnosis of RA was 97% (the highest among all markers), sensitivity was 71%. In ROC curve analysis, the AUCs (95% CI) of sirtuin-1, anti-CCP and anti-MCV were 0.87 (0.82-0.91), 0.91 (0.88-0.94) and 0.92 (0.89-0.95) respectively (all p < 0.01). The combination of sirtuin-1and anti-MCV gave the highest Youden index of 0.79, whilst Cox regression showed sirtuin-1 and rheumatoid factor were the strongest independent predictors of RA.Conclusions: Serum sirtuin-1 is increased in RA, and may have a place is the diagnosis of this disease when combined with other markers.

Background: MicroRNAs (miRNAs) are naturally occurring posttranscriptional regulatory molecules that potentially play a role in endometriotic lesion development.Method: We evaluated the prevalence of miRNAs variants miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 in endometriosis in 260 cases and 260 controls. DNA was extracted and genotyping of the SNPs was carried out by PCR.Results: There was a significant association of rs2910164 and rs2292832 with increased rates of endometriosis under the dominant (p < 0.001), recessive (p < 0.05), co-dominant (p < 0.001), and allelic model (p < 0.001). Also, rs3746444 showed a borderline association with endometriosis under the recessive model (p = 0.05); however, rs11614913 was not linked to endometriosis. Further analysis indicated the significant association of miR-146a rs2910164 polymorphism genotypes (GG, GC, and CC) and miR-149 rs2292832 genotypes (CC and CT) with endometriosis severity in patients (p < 0.001). Additionally, haplotype frequency in cases compared to controls and Linkage disequilibrium (LD) between the mentioned SNPs was appraised.Conclusion: MiR-146a, miR-149 and miR-499 may have a role in the pathogenesis of endometriosis.

Introduction: We aimed to determine the analytical capabilities of a commonly used faecal immunochemical test (FIT) to detect faecal haemoglobin (Hb) in symptomatic people attending primary care in the context of the English NICE DG30 guidance.Materials and Methods: Data obtained from independent verification studies and clinical testing of the HM-JACKarc FIT method in routine primary care practice were analysed to derive performance characteristics.Results: Detection capabilities for the FIT method were 0.5 µg/g (limit of blank), 1.3 µg/g (limit of detection) and 3.0 µg/g (limit of quantitation). Of 33 non-homogenized specimens, 31 (93.9%) analysed in triplicate were consistently categorized relative to 10 µg/g, compared to all 33 (100%) homogenized specimens. Imprecision was higher (median 27.8%, (range 20.5% to 48.6%)) in non-homogenized specimens than in homogenized specimens (10.2%, (7.0 to 13.5%)). Considerable variation was observed in sequential clinical specimens from individual patients but no positive or negative trend in specimen degradation was observed over time (p = 0.26).Discussion: The FIT immunoassay evaluated is capable of detecting faecal Hb at concentrations well below the DG30 threshold of 10 µg/g and is suitable for application in this context. The greatest practical challenge to FIT performance is reproducible sampling, the pre-analytical step associated with most variability. Further research should focus on reducing sampling variability, particularly as post-COVID-19 guidance recommends greater FIT utilization.

Invasive fungal disease continues to be a cause of significant life-threatening morbidity and mortality in humans, particularly in those with a diminished immune system, such as with haematological malignancies. The mainstay of treating such life-threatening fungal infection has been antifungal drugs, including azoles, echinocandins and macrocyclic polyenes. However, like antibiotic resistance, antifungal resistance is beginning to emerge, potentially jeopardizing the effectiveness of these molecules in the treatment of fungal disease. One strategy to avoid this is the development of fungal vaccines. However, the inability to provoke a sufficient immune response in the most vulnerable immunocompromised groups has hindered translation from bench to bedside. This review will assess the latest available data and will investigate potential Aspergillus antigens and feasible vaccine techniques, particularly for vaccination of high-risk groups, including immunocompromised and immunosuppressed populations.

Mixed acute rejection is a clinicopathological entity that is difficult to accurately diagnose, and so may be under-reported. Allografts are lost more often than in either humoral or cellular rejection. The diagnosis requires both histological and immunological studies on renal biopsy and blood specimens from the transplant recipient to provide the required rescue therapy to abolish the allogeneic response against the graft. We present a clinical case report of an active mixed acute rejection driven by a de novo donor-specific complement-binding anti-DQB1*03:01 antibody and intraepithelial CD8 T-cells in a patient with a kidney transplant. The patient was diagnosed, treated, and followed up as per the local institution's procedure with a full recovery of graft function. Our case emphasises the challenge of a mixed acute rejection and supports the need to improve the post-transplant outcome of recipients and their grafts.