Genetic variants are associated with altered clinical outcome of patients with sepsis and cardiovascular diseases. Common gene signaling pathways may be involved in the pathophysiology of these ...diseases. A better understanding of genetic commonality among these diseases may enable the discovery of important genes, signaling pathways, and therapeutic targets for these diseases. We investigated the common genetic factors by a systematic search of the literature. Twenty-four genes (ADRB2, CD14, FGB, FV, HMOX1, IL1B, IL1RN, IL6, IL10, IL17A, IRAK1, MASP2, MBL, MIR608, MIF, NOD2, PCSK9, PPARG, PROC, SERPINE1, SOD2, SVEP1, TF, TIRAP, TLR1) were extracted as reported genetic variations associated with altered outcome of both sepsis and cardiovascular diseases. Of these genes, the adverse allele (or combinations) was same in nine (ADRB2, FV, HMOX1, IL6, MBL, MIF, NOD2, PCSK9, SERPINE1), and the effect appears to be in the same direction in both sepsis and cardiovascular disease. Shared gene signaling pathways suggest that these are true biological results and could point to overlapping drug targets in sepsis and cardiovascular disease.
CD24 is a highly glycosylated protein with a small protein core that is linked to the plasma membrane via a glycosyl‐phosphatidylinositol anchor. CD24 is primarily expressed by immune cells but is ...often overexpressed in human tumors. In cancer, CD24 is a regulator of cell migration, invasion and proliferation. Its expression is associated with poor prognosis and it is used as cancer stemness marker. Recently, CD24 on tumor cells was identified as a phagocytic inhibitor (“do not eat me” signal) having a suppressive role in tumor immunity via binding to Siglec‐10 on macrophages. This finding is reminiscent of the demonstration that soluble CD24‐Fc can dampen the immune system in autoimmune disease. In the present review, we summarize recent progress on the role of the CD24‐Siglec‐10 binding axis at the interface between tumor cells and the immune system, and the role of CD24 genetic polymorphisms in cancer. We describe the specific function of cytoplasmic CD24 and discuss the presence of CD24 on tumor‐released extracellular vesicles. Finally, we evaluate the potential of CD24‐based immunotherapy.
Objective
Immunoglobulin-A vasculitis (IgAV) is an inflammatory disease that affects small blood vessels. This study was performed to identify an association between protein tyrosine phosphatase ...non-receptor type 22 (PTPN22) + 788G > A (rs33996649), transforming growth factor-beta (
TGF-β
) -509C > T (rs18004069), interleukin 1-beta
(IL-1
β)
-
511C > T (rs16944), interleukin 5 (
IL-5
) -746C/T (rs2069812), and angiotensin-converting enzyme (ACE) I/D (rs4646994) gene polymorphisms, susceptibility to IgAV, as well as the mRNA levels of IL-1β, IL-1β, and TGF-β
.
Method
A total of 53 patients with IgAV and 50 healthy controls were enrolled. PTPN22, TGF-β, IL-1β, ACE gene polymorphisms, ACE gene I/D polymorphisms, and mRNA expression levels were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method, allele-specific PCR, and real-time PCR with TaqMan kits, respectively.
Results
PTPN22
,
TGF-β
,
IL-1β
,
IL-5
, and
ACE
variants showed no genotype or allele differences between patients with IgAV and controls. Increased levels of
IL-1β and TGF-β
mRNA expressions were observed in patients with IgAV (p < 0.001). Patients with the IL-1β AG genotype showed significantly increased amounts of arthritis than patients with non-AG (p = 0.004). Age at disease onset was found to be significantly different in patients with IgAV according to the presence of TGF-β TT genotype (p = 0.047)
.
Conclusion
Polymorphisms in PTPN22, TGF-β, IL-5, IL-1β, and ACE genes are unlikely to confer susceptibility to IgAV. However, the presence of the AG genotype of IL-1β is associated with susceptibility to IgAV-related arthritis. This is the first study to report a significant increase in serum mRNA levels of IL-1β and TGF-β in IgAV patients, supporting a susceptibility to IgAV in childhood.
Human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin stalk of group 1 influenza A viruses (IAVs) are biased for IGHV1-69 alleles that use phenylalanine (F54) but not leucine ...(L54) within their CDRH2 loops. Despite this, we demonstrated that both alleles encode for human IAV bnAbs that employ structurally convergent modes of contact to the same epitope. To resolve differences in lineage-expandability, we compared F54 vs L54 as substrate within humanized mice where antibodies develop with human-like CDRH3 diversity but are restricted to single V
H
-genes. While both alleles encoded for bnAb precursors, only F54 IGHV1-69 supported elicitation of heterosubtypic serum bnAbs following immunization with a stalk-only nanoparticle vaccine. L54 IGHV1-69 was unproductive, co-encoding for anergic B cells and autoreactive stalk antibodies that were cleared from B cell memory. Moreover, human stalk antibodies also demonstrated L54-dependent autoreactivity. Therefore, IGHV1-69 polymorphism, which is skewed ethnically, gates tolerance and vaccine-expandability of influenza bnAbs.
Human broadly neutralizing antibodies (bnAbs) against influenza virus preferentially use F54 IGHV1-69 as opposed to the L54 allele of this antibody V
H
-gene. Sangesland et al. show that while both alleles encode for affinity to the same target, L54 IGHV1-69 also imparts autoreactivity, dampening vaccine-expandability in a humanized mouse model.
The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or ...pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism-based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.
Purpose
One of the causes of infertility is circadian rhythm disorders. This study aimed to investigate
Clock 3111 T/C
and
Period3 VNTR
(variable number tandem repeat) gene polymorphisms and these ...gene proteins, some biochemical parameters, and circadian rhythm hormones in infertile women.
Methods
Thirty-five infertile women and thirty-one healthy fertile women were included. Blood samples were taken in the mid-luteal phase. DNAs obtained from peripheral blood were analyzed using polymerase chain reaction-restriction fragment length polymorphism methods. Follicle-stimulating hormone, LH (luteinizing hormone), estradiol, prolactin, free triiodothyronine, fT4 (free thyroxine), thyroid-stimulating hormone, testosterone, cortisol, progesterone, prolactin, ferritin, vitamin B12, and folate levels in serum samples were determined by the electrochemiluminescence immunoassay method. Melatonin,
Clock
, and
Period3
protein levels were determined with ELISA kits.
Results
There was a significant difference in the frequency of
Period3
DD (
Per3
4/4
)
genotype
between the groups. The
Clock
protein level of the infertile group was higher than the fertile group.
Clock
protein levels of the fertile group were positively correlated with estradiol levels and negatively correlated with LH, prolactin, and fT4 levels.
PER3
protein levels of the infertile group were negatively correlated with LH levels. Melatonin levels of the fertile group were positively correlated with progesterone levels and negatively correlated with cortisol levels. Melatonin levels of the infertile group were positively correlated with LH levels and negatively correlated with cortisol levels.
Conclusion
Per3
4/4
genotype may be an independent risk factor in infertile women. Different correlation results found in fertile and infertile women can form the basis for future studies.
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