Autoantibodies to apolipoprotein A-1 as a biomarker of cardiovascular autoimmunity

Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.

Curcumin induces differentiation of embryonic stem cells through possible modulation of nitric oxide-cyclic GMP pathway

Curcumin,an active ingredient of dietary spice used in curry,has been shown to exhibit anti-oxidant,anti-inflammatory and anti-proliferative properties.Using EB directed differentiation protocol of H-9 human em-bryonic stem(ES)cells;we evaluated the effect of cur-cumin(0-20μmol/L)in enhancing such differentiation.Our results using real time PCR,western blotting and immunostaining demonstrated that curcumin signifi-cantly increased the gene expression and protein levels of cardiac specific transcription factor NKx2.5,cardiac troponin I,myosin heavy chain,and endothelial nitric oxide synthase during ES cell differentiation.Further-more,an NO donor enhanced the curcumin-mediated induction of NKx2.5 and other cardiac specific proteins.Incubation of cells with curcumin led to a dose depend-ent increase in intracellular nitrite to the same extent as giving an authentic NO donor.Functional assay for second messenger(s)cyclic AMP(cAMP)and cyclic GMP(cGMP)revealed that continuous presence of cur-cumin in differentiated cells induced a decrease in the baseline levels of cAMP but it significantly elevated baseline contents of cGMP.Curcumin addition to a cell free assay significantly suppressed cAMP and cGMP degradation in the extracts while long term treatment of intact cells with curcumin increased the rates of cAMP and cGMP degradation suggesting that this might be due to direct suppression of some cyclic nucleo-tide-degrading enzyme(phosphodiesterase)by curcu-min.These studies demonstrate that polyphenol curcu-min may be involved in differentiation of ES cells partly due to manipulation of nitric oxide signaling.

Beyond monogenetic rare variants:tackling the low rate of genetic diagnoses in predominantly antibody deficiency

Predominantly antibody deficiency(PAD)is the most prevalent form of primary immunodeficiency,and is characterized by broad clinical,immunological and genetic heterogeneity.Utilizing the current gold standard of whole exome sequencing for diagnosis,pathogenic gene variants are only identified in less than 20% of patients.While elucidation of the causal genes underlying PAD has provided many insights into the cellular and molecular mechanisms underpinning disease pathogenesis,many other genes may remain as yet undefined to enable definitive diagnosis,prognostic monitoring and targeted therapy of patients.Considering that many patients display a relatively late onset of disease presentation in their 2^(nd) or 3^(rd) decade of life,it is questionable whether a single genetic lesion underlies disease in all patients.Potentially,combined effects of other gene variants and/or non-genetic factors,including specific infections can drive disease presentation.In this review,we define(1)the clinical and immunological variability of PAD,(2)consider how genetic defects identified in PAD have given insight into B-cell immunobiology,(3)address recent technological advances in genomics and the challenges associated with identifying causal variants,and(4)discuss how functional validation of variants of unknown significance could potentially be translated into increased diagnostic rates,improved prognostic monitoring and personalized medicine for PAD patients.A multidisciplinary approach will be the key to curtailing the early mortality and high morbidity rates in this immune disorder.

Inhibition of tumor autophagy:a strategy to improve antitumor immunity?

In a study recently published in Nature,Lawson et al.confirm several pathways previously implicated in tumor cell sensitivity to cytotoxic T lymphocytes(CTLs),and identify autophagy as an additional pathway involved in mediating tumor immune evasion.1 Autophagy is a regulated and conserved multistep process that enables cells to degrade and recycle intracellular components and is critical for cellular homeostasis.Autophagy has recently been associated with tumor immune evasion in pancreatic ductal adenocarcinoma,2 whereby this process selectively targeted the degradation of major histocompatibility complex I(MHC-I),limiting recognition,and anti-tumor responses by CTLs.Here,Lawson et al.identify an additional role for autophagy in tumor immune evasion,by mediating resistance to cytokine-mediated cell death.

Inhibition of tumor autophagy: a strategy to improve antitumorimmunity?

In a study recently published in Nature,Lawson et al.confirm several pathways previously implicated in tumor cell sensitivity to cytotoxic T lymphocytes(CTLs),and identify autophagy as an additional pathway involved in mediating tumor immune evasion.1 Autophagy is a regulated and conserved multistep process that enables cells to degrade and recycle intracellular components and is critical for cellular homeostasis.Autophagy has recently been associated with tumor immune evasion in pancreatic ductal adenocarcinoma,2 whereby this process selectively targeted the degradation of major histocompatibility complex I(MHC-I),limiting recognition,and anti-tumor responses by CTLs.Here,Lawson et al.identify an additional role for autophagy in tumor immune evasion,by mediating resistance to cytokine-mediated cell death.

Increased Oocyte Production after Acupuncture Treatment during Superovulation Process in Mice

Objective To investigate whether acupuncture treatment during superovulation process improves ovarian response and increases egg production. Methods ICR female mice aged 12 -5 weeks were divided into control group, anaesthesia group and acupuncture group. Female mice were injected intraperitoneally with pregnant mare＇s serum gonadotropin （PMSG）, followed by human chorionic gonadotropin （hCG） injection 56 h later. Anaesthesia group and acupuncture group were anaesthetized three times by injecting 10% nembutal solution according to 7.5-10.0μl/g weight. Acupuncture group was treated three times with puncture Sanyinjiao Points（SP6） under anaesthesia. After 17 h of hCG injection, eggs were recovered and ovaries were isolated. Matured eggs were counted, ovarian histology and expression of follicle stimulating hormone receptor（FSH-R） in ovary were analyzed. Results Acupuncture treatment statistically increased the number of ovulated eggs. Histological section showed that some matured follicles left in the ovaries of control and anaesthesia groups after ovulation. On the contrary, all matured follicles ruptured and converted into corpus lutea in Acupuncture group. Expression of FSH-R in ovary was decreased in acupuncture group compared with those of the two others. Conclusion Acupuncture treatment during superovulation process improves ovarian response so as to increase egg production. The positive effect of acupuncture may be associated with regulated FSH-R expression.