NK cells in hepatitis B virus infection: a potent target for immunotherapy

Viruses, including hepatitis B virus (HBV), are the most prevalent and infectious agents that lead to liver disease in humans. Hepatocellular carcinoma (HCC) and cirrhosis of the liver are the most serious complications arising from prolonged forms of hepatitis B. Previous studies demonstrated that patients suffering from long-term HBV infections are unable to eradicate HBV from hepatocytes completely. The mechanisms responsible for progression of these forms of infection have not yet been clarified. However, it seems that there are differences in genetic and immunological parameters when comparing patients to subjects who successfully clear HBV infections, and these may represent the causes of long-term infection. Natural killer (NK) cells, the main innate immune cells that target viral infections, play important roles in the eradication of HBV from hepatocytes. NK cells carry several stimulatory and inhibitor receptors, and binding of receptors with their ligands results in activation and suppression of NK cells, respectively. The aim of this review is to address the recent information regarding NK cell phenotype, functions and modifications in hepatitis B. This review addresses the recent data regarding the roles of NK cells as novel targets for immunotherapies that target hepatitis B infection. It also discusses the potential to reduce the risk of HCC or cirrhosis of the liver by targeting NK cells.     

Predictors of mortality in medically treated patients with congestive heart failure of nonrheumatic etiology and reduced systolic function

ObjectiveWe investigated the prognostic value of various parameters on the mortality of patients with nonrheumatic chronic heart failure and left ventricular (LV) systolic dysfunction.MethodsThis study included 132 consecutive patients with congestive heart failure and reduced LV systolic function without rheumatic valve disease. The primary outcome was mortality. Mean follow-up was 38 ± 6 months.ResultsDuring the follow-up period there were 47 deaths (35.6%). The age (64.1 ± 13.5 vs. 58.7 ± 11.8 years, P = 0.019), left bundle branch block (44.7% vs. 18.8%, P = 0.002), urea concentration (11.4 ± 5.3 vs. 8.9 ± 4.6 mmol/L, P = 0.006), LV end-diastolic and end-systolic dimensions (6.7 ± 0.8 vs. 6.4 ± 0.8 cm, P = 0.025 and 5.5 ± 0.8 vs. 4.9 ± 0.8 cm, P < 0.001, respectively), grade 3–4 mitral regurgitation (40.4 vs. 22.4%, P < 0.001), fractional shortening (16.7 ± 5.3% vs. 19.8 ± 5.7%, P = 0.002) and LV ejection fraction (32.9 ± 8.5% vs. 38.7 ± 11.3%, P = 0.003) were different between non-survivors and survivors. Multivariate analysis identified severity of mitral regurgitation (OR = 1.99, 95% CI 1.18–3.34; P = 0.009), age (OR = 1.07, 95% CI 1.02–1.12; P = 0.01) and LV end-systolic dimension (OR = 1.09, 95% CI 1.02–1.16; P = 0.014) as independent correlates of mortality.ConclusionsIn medically treated patients with nonrheumatic chronic heart failure and left ventricular systolic dysfunction, severity of mitral regurgitation, age and enlarged LV end-systolic dimension were independently associated with increased risk of death.     

The effect of obstructive sleep apnea on the increased risk of cardiovascular disease: a systematic review and meta-analysis

Neurological Sciences - Obstructive sleep apnea (OSA) is a disorder characterized by intermittent airway obstruction during sleep. The association between OSA and the incidence of cardiovascular...     

Anticonvulsive effect of atorvastatin on pentylenetetrazole‐induced seizures in mice: the role of nitric oxide pathway

Atorvastatin has shown to possess neuroprotective, antiexcitotoxic, and antiepileptic effects besides its cholesterol‐lowering properties. Nitric oxide (NO) may be responsible for a group of these effects. In the present study, a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice was used to investigate the anticonvulsive effects of atorvastatin through NO‐dependent pathways. Atorvastatin (5 mg/kg) significantly increased the seizure threshold (P < 0.001). Moreover, L‐arginine (a precursor of NO) significantly (P < 0.01) potentiated the anticonvulsive effects of subeffective doses of atorvastatin (1 mg/kg). Finally, L‐NAME [L‐arginine methyl ester dihydrochloride], a nonspecific NO synthase inhibitor, completely abolished the anticonvulsive properties of atorvastatin. Our findings demonstrated the role of atorvastatin as an anticonvulsive agent and showed the effects to be mediated through NO‐related pathways.     

The effect of garlic on lipid profile and glucose parameters in diabetic patients: A systematic review and meta-analysis

Purpose

Several studies have been published about the effect of garlic on lipid profile and blood glucose in diabetic patients. Which, the results mostly contradict with each other. This study aimed to investigate the effect of garlic on lipid profile and serum glucose levels in diabetic patients using a systematic review and meta-analysis.

Quality of life of hemodialysis and renal transplantation patients

The quality of life of patients with end-stage renal disease is an important indicator of disease burden. To achieve a better quality of life, some medical treatment might be replaced by other approaches. The aim of this study was to compare the quality of life of renal-transplanted and hemodialysis patients in Iran. Two hundred hemodialysis and 200 renal transplantation patients were recruited from 5 major hospitals and renal patients' support society in Tehran, Iran. The data were collected using the Persian versions of the Ferrans and Powers Quality of Life Index-Dialysis and Transplantation Version. The quality-of-life mean scores of renal transplantation patients were significantly better compared with those of the hemodialysis patients (21.36 [SD, 4.06] vs 20.35 [SD, 5.14]; P = .03). The questionnaire demonstrated significant differences in health/functioning and familial subscale of quality of life between the transplanted and hemodialysis patients (p < .05). The better quality of life of transplant patients, in comparison with hemodialysis patients, is an important reason for advising kidney transplants in renal failure patients. To improve the patients' quality of life, kidney transplantation might be effective for the end-stage renal disease. With regard to socioeconomic problem in most of the patients with renal failure, comprehensive insurance and referral to renal and transplanted patients' support society are suggested for those who have undergone different renal replacement therapies.     

Effective combination of aligned nanocomposite nanofibers and human unrestricted somatic stem cells for bone tissue engineering

Aim:

Bioartificial bone tissue engineering is an increasingly popular technique to solve bone defect challenges. This study aimed to investigate the interactions between matrix composition and appropriate cell type, focusing on hydroxyapatite (HA), to achieve a more effective combination for bone regeneration.

Methods:

Human unrestricted somatic stem cells (USSCs) were isolated from placental cord blood. The cellular and molecular events during the osteo-induction of USSCs were evaluated for 21 d under the following conditions: (1) in basal culture, (2) supplemented with hydroxyapatite nanoparticle (nHA) suspension, and (3) seeded on electrospun aligned nanofibrous poly-ɛ-caprolactone/poly-L-lactic acid/nHA (PCL/PLLA/nHA) scaffolds. The scaffolds were characterized using scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR) and tensile test.

Results:

Maintenance of USSCs for 21 d in basal or osteogenic culture resulted in significant increase in osteoblast differentiation. With nHA suspension, even soluble osteo-inductive additives were ineffective, probably due to induced apoptosis of the cells. In contrast to the hindrance of proliferation by nHA suspension, the scaffolds improved cell growth. The scaffolds mimic the nanostructure of natural bone matrix with the combination of PLLA/PCL (organic phase) and HA (inorganic phase) offering a favorable surface topography, which was demonstrated to possess suitable properties for supporting USSCs. Quantitative measurement of osteogenic markers, enzymatic activity and mineralization indicated that the scaffolds did not disturb, but enhanced the osteogenic potential of USSCs. Moreover, the alignment of the fibers led to cell orientation during cell growth.

Conclusion:

The results demonstrated the synergism of PCL/PLLA/nHA nanofibrous scaffolds and USSCs in the augmentation of osteogenic differentiation. Thus, nHA grafted into PCL/PLLA scaffolds can be a suitable choice for bone tissue regeneration.     

Elevated cerebrospinal fluid tumour necrosis factor is associated with acute and long‐term neurocognitive impairment in cerebral malaria

Systemic tumour necrosis factor‐α (TNF‐α) may contribute to the pathogenesis of cerebral malaria (CM) by promoting endothelial activation and parasite sequestration. However, less is known about the role of central nervous system (CNS) TNF‐α in CM. We assessed plasma (n=249) and cerebrospinal fluid (CSF) (n=167) TNF‐α levels in Ugandan children with CM, plasma TNF‐α in Ugandan community control children (n=198) and CSF TNF‐α in North American control children who had recovered from leukaemia (n=13). Plasma and CSF TNF‐α were measured by magnetic bead assay. We compared plasma and CSF TNF‐α levels in children with CM to mortality, acute and chronic neurologic deficits and long‐term neurocognitive impairment. Plasma and CSF TNF‐α levels were higher in CM than control children (P<.0001 for both). CSF TNF‐α levels were higher in children who had neurologic deficits at discharge or 6‐month follow‐up (P≤.05 for both). Elevated CSF but not plasma TNF‐α was associated with longer coma duration (Spearman's rho .18, P=.02) and deficits in overall cognition in children 5 years and older (β coefficient ?.74, 95% CI ?1.35 to ?0.13, P=.02). The study findings suggest that CNS TNF‐α may be involved in the development of acute and chronic neurologic and cognitive sequelae in children with CM.     

Acute myeloid leukaemia: expression of MYC protein and its association with cytogenetic risk profile and overall survival

Acute myeloid leukaemia (AML) is a clinically aggressive disease with marked genetic heterogeneity. Cytogenetic abnormalities provide the basis for risk stratification into clinically favourable, intermediate, and unfavourable groups. There are additional genetic mutations, which further influence the prognosis of patients with AML. Most of these result in molecular aberrations whose downstream target is MYC. It is therefore logical to study the relationship between MYC protein expression and cytogenetic risk groups. We studied MYC expression by immunohistochemistry in a large cohort (n = 199) of AML patients and correlated these results with cytogenetic risk profile and overall survival (OS). We illustrated differential expression of MYC protein across various cytogenetic risk groups (p = 0.03). Highest expression of MYC was noted in AML patients with favourable cytogenetic risk group. In univariate analysis, MYC expression showed significant negative influence of OS in favourable and intermediate cytogenetic risk group (p = 0.001). Interestingly, MYC expression had a protective effect in the unfavourable cytogenetic risk group. In multivariate analysis, while age and cytogenetic risk group were significant factors influencing survival, MYC expression by immunohistochemistry methods also showed some marginal impact (p = 0.069). In conclusion, we have identified differential expression of MYC protein in relation to cytogenetic risk groups in AML patients and documented its possible impact on OS in favourable and intermediate cytogenetic risk groups. These preliminary observations mandate additional studies to further investigate the routine clinical use of MYC protein expression in AML risk stratification. Copyright © 2016 John Wiley & Sons, Ltd.