The Role of Cytokines in the Peripheral Blood of Major Depressive Patients.

BACKGROUND: Recent technological advances offer an opportunity to further elucidate the complex cytokine network in Major Depressive Disorder (MDD). The objective of this study was to investigate the role of pro-inflammatory and anti-inflammatory cytokines in the mechanism of depressive disorders. Given the activating role of cytokines on the hypothalamic-pituitary-adrenal (HPA) axis, and the relevance of its regulation in MDD, we also analyzed the relationships between several cytokines and cortisol levels. METHODS: Twenty-five unipolar depressive patients and 20 healthy controls were recruited in this study. Flow cytometric bead array system (FCM-CBA) was used to examine the concentration of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, INF-α) in peripheral blood. Plasma Adrenocorticotropic Hormone (ACTH) and serum cortisol concentrations were detected. RESULTS: Compared with the controls, depressive patients had a significant increase in concentration of IL-2, TNF, serum cortisol, and TNF/IL-4 (p < 0.05). There was a significant positive correlation between serum cortisol and IL-2, as well as ACTH and IL-2 (p < 0.05) in depressive patients. There was a significant positive correlation between IL-2 and the Hamilton depression rating scale (HAMD) total scores in depressive patients, and also with TNF (p < 0.05). There was no significant difference in concentration of IL-4, IL-6, IL-10, and INF-α between two groups (p > 0.05). CONCLUSIONS: The present results suggest that depressive patients had an increase in concentration of some pro-inflammatory cytokines. Both IL-2 and TNF play important roles in the development of depressive disorders, and their concentration in peripheral blood may be used to evaluate the severity of depressive disorders.

Chromosome-scale genome assembly provides insights into flower coloration mechanisms of Canna indica.

Canna indica, which produce conspicuous and colorful flowers, are widely appreciated as ornamental plants. We used Pacific Biosciences sequencing (PacBio) and chromosome conformation capture (Hi-C) genome scaffolding to build a high-quality chromosome-scale genome assembly of C. indica and the genome assembly was 821Mb with a contig N50 of 48Mb assembled into nine chromosomes. The genome of C. indica was predicted to contain 31,130 genes and 30,816 genes were functionally annotated. Genome annotation identified 522 Mb (63.59 %) as repetitive sequences. Genome evolution analysis showed that whole-genome duplication occurred 53.4 million years ago. Transcriptome analysis revealed that petal coloration was linked with the expression of genes encoding enzymes involved in anthocyanin biosynthesis, carotenoid biosynthesis, and the methylerythritol phosphate (MEP) pathway. Furthermore, modules of co-expressed genes and hub genes were identified via weighted gene co-expression network analysis. These results suggested that, in Canna indica, deep red petal coloration was regulated by CHS2 and yellow petal coloration was associated with expression of ARF6 and NAC14. Considered together, the current study revealed a high-quality reference genome which may provide new insights into the molecular basis of flower coloration in Canna indica and help enhance the conservation and breeding of ornamental plants in general.

WT1 and Pax2 re-expression is required for epithelial-mesenchymal transition in 5/6 nephrectomized rats and cultured kidney tubular epithelial cells.

Mature tubular epithelial cells in the adult kidney can undergo epithelial-mesenchymal transition (EMT), a phenotypic change that is linked to the pathogenesis of renal interstitial fibrosis. EMT may be considered the reverse of mesenchymal-epithelial transition, which occurs during normal kidney development. The Wilms' tumor suppressor gene WT1 and the paired box 2 gene Pax2 are needed to induce mesenchymal-epithelial transition and play key roles in the progression of nephrogenesis. However, until now, WT1 and Pax2 have not been tested for their direct involvement in the process of renal tubular EMT. In this study, we explored the potential roles of WT1 and Pax2 in EMT that is induced in the remnant kidney of rats following 5/6 nephrectomy. We also examined WT1 and Pax2 in cultured renal tubular epithelial (NRK52E) cells treated with interleukin-1α and investigated the effects of blocking EMT using RNA interference. We showed that WT1 and Pax2 were re-expressed in the EMT models, and these were accompanied by decreased expression of E-cadherin and increased expression of vimentin, Snail and α-smooth muscle actin. Silencing WT1 and Pax2 by RNA interference blocked the interleukin-1α-induced EMT in the NRK52E cells, as reflected in the suppression of α-SMA and Snail expression, the restoration of E-cadherin expression and normal cell morphology. Our experiments suggested that the re-expression of WT1 and Pax2 in the tubular epithelial cells plays important roles in the promotion of EMT, and there may be therapeutic value in silencing Pax2 and WT1 to prevent or reverse renal fibrosis.

Network analysis and experimental pharmacology study explore the protective effects of Isoliquiritigenin on 5-fluorouracil-Induced intestinal mucositis.

5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs for malignant tumors. However, intestinal mucositis caused by 5-FU is a severe dose-limiting toxic effect and even leads to treatment interruption. Isoliquiritigenin (ISL) is one of the main active compounds of licorice, which is a traditional Chinese herbal medicine commonly used in inflammation and gastrointestinal diseases. It is speculated that ISL have protective effects on intestinal mucositis. However, no such studies have been reported. Therefore, to investigate the impact of ISL on 5-Fu-induced intestinal mucositis, a strategy based on network prediction and pharmacological experimental validation was proposed in this study. Firstly, the targets and mechanism of ISL in alleviating 5-Fu-induced gastrointestinal toxicity were predicted by network analysis. And the results were further confirmed by molecular docking. Then, a mouse model of intestinal mucositis was established by intraperitoneal injection of 5-FU (384 µmol/kg) to verify the prediction of network analysis. The network analysis results suggested that PTGS2 (Prostaglandin G/H synthase 2) and NOS2 (Nitric oxide synthase, inducible) might be the critical targets of ISL for reducing the intestinal toxicity of 5-FU. In addition, KEGG and GO enrichment analysis revealed that the HIF-1, TNF, MAPK, IL-17, PI3K-Akt, Ras, NF-kappa B signaling pathway, and biological processes of the inflammatory response, apoptosis regulation, NO production and NF-kappa B transcription factor activity might be involved in the mechanism of ISL against intestinal mucositis. Subsequent animal experiments showed that ISL could reduce the weight loss, leukopenia and mucosal damage caused by 5-FU. Compared with the intestinal mucositis model, the protein expressions of PTGS2, NOS2, TNFα (Tumor necrosis factor-alpha) and NF-κB p65 (nuclear factor kappa-B P65) were decreased after ISL treatment. In conclusion, this study is the fist time to find that ISL can attenuate 5-FU-induced intestinal mucositis in mice. Its anti-mucositis effect may be through regulating TNF/NF-κB pathway and inhibiting inflammatory mediators PTGS2 and NOS2. It will provide a potential candidate for the prevention and treatment of chemotherapy-induced intestinal mucositis.

Emerging tendency towards autoimmune process in major depressive patients: a novel insight from Th17 cells.

Evidence indicates that there is an emerging tendency towards autoimmunity occuring in major depressive disorder (MDD). The aim of our study is to investigate the mechanism of autoimmune process in MDD from a novel insight of Th17 cells, which have been identified as the significant activators of autoimmunity. We included 40 patients with MDD and 30 healthy control subjects. An indirect immunofluorescence test was used for the detection of serum antinuclear antibodies (ANA), and revealed that the patient group was positive more frequently than the control group. By flow cytometric analysis, depressed subjects revealed a significant increase in peripheral Th17 cell number, and an obvious decrease in T-reg cell number, showing an imbalance of Th17/Treg ratio compared to healthy controls. We also found a higher level of RORγt (retinoic acid-related orphan receptor-γt, the specific transcription factor of Th17 cell) mRNA expression in peripheral blood lymphocytes by RT-PCR and serum concentration of IL-17 by ELISA in patients. In conclusion, our study showed a potential role of Th17 cells in the autoimmune process in MDD patients, thus contributing to the existing evidence of autoimmune inclination in MDD.

Urine particles analysis: performance evaluation of Sysmex UF-1000i and comparison among urine flow cytometer, dipstick, and visual microscopic examination.

INTRODUCTION: Our objective was to evaluate a newly invented urine flow cytometer, and select an optimal strategy for urinalysis in clinical practice. METHODS: The performance of UF-1000i was evaluated in both control material and patient samples. A total of 1631 specimens were collected and analysed by visual microscopy examination (VME), UF-1000i flow cytometer (Sysmex Medical Electronics Co, Kobe, Japan) and an automated dipstick reflectometer Clinitek Atlas (Bayer Corp, Elkhart, USA). RESULTS: UF-1000i showed good imprecision performance for the main parameters in urine particles with CV values less than 20%. The results from UF-1000i correlated well with VME for erythrocytes (r = 0.96), leukocytes (r = 0.98), and epithelial cell (r = 0.84). The area under the receiver operating curve (AUC) was 0.879, 0.903, 0.783, and 0.817 respectively for erythrocytes, leukocytes, bacteria and CAST in UF-1000i. While in Clinitek Atlas, the AUC was 0.848, 0.803, 0.761, and 0.754 respectively. Sensitivity of combination of the two methods for screening remained at 98% as compared to VME alone, while reducing the visual review rate down to 40%. CONCLUSION: UF-1000i is capable of reproducible measurement of urine particles in the clinically relevant range and shows its advantage over Atlas. Combination of the two methods is an optimal strategy for urine sample screening.

Performance evaluation of a particle-enhanced turbidimetric cystatin C assay using the Abbott Aeroset analyser and assessment of cystatin C-based equations for estimating glomerular filtration rate in chronic kidney disease.

INTRODUCTION: Measurement of glomerular filtration rate (GFR) is critical for the diagnosis and stratification of chronic kidney disease (CKD). Recent studies have shown that cystatin C is superior to creatinine for the detection of impaired GFR, and several cystatin C-based equations for estimating GFR have been developed for this clinical application. We conducted the present study to assess the applicability of cystatin C as a routine clinical laboratory index and to determine the performance of cystatin C-based equations in estimating GFR in CKD patients in China. METHODS: Performance evaluation of particle-enhanced turbidimetric cystatin C assay on the Abbott Aeroset analyser was carried out according to the National Committee for Clinical Laboratory document EP10-A2. Estimated GFR, which was generated from cystatin C-based equations, was compared with measured GFR, which was detected by plasma clearance of 99mTc-DTPA. RESULTS: Our cystatin C assay showed a very low total imprecision and linearity drift. All eight cystatin C-based GFR estimating equations underestimated or overestimated GFR as compared with GFR determined by 99mTc-DTPA clearance. CONCLUSION: Although the cystatin C assay is acceptable for routine clinical laboratory monitoring, none of the existing cystatin C-based equations were ideal for estimating GFR in Chinese CKD patients.

[Role of angiotensin II and JAK2 signal pathway in transdifferentation of renal tubular cells in mice after acute ischemic followed by reperfusion].

OBJECTIVE: To investigate the effect of angiotensin (Ang)II and its Janns-activated kinase-2 (JAK2) signal pathway in transdifferentiation of renal tubular cells under the challenge of acute ischemic reperfusion injury. METHODS: Models of acute ischemic reperfusion injury were established and the level of local AngII, a key element of renin-angiotensin system (RAS), in kidney was measured using radioimmunity technique. The expression of alpha-smooth muscle actin (alpha-SMA), a phenotype of mesenchymal cells, was detected by RT-PCR and immunohistochemistry methods. Renal tubule cells (NRK-52E) were cultured with various concentration of AngII, followed by blocking of PD123319, AngII receptor 2 antagonist, and AG490, an inhibitor of JAK2 signal pathway. RESULTS: AngII of kidney tissue increased immediately after acute ischemic-reperfusion injury, in time dependent fashion. Expression of alpha-SMA in renal tubule cells was found at 48 hours after ischemic-reperfusion injury and in NRK-52E cells treated by high concentration of AngII and was dose and time dependent. The peak of alpha-SMA expression was seen after 30 minute treatment at the dose of 10(-9) mol/L, which was interrupted by both of PD123319 and AG490. CONCLUSIONS: Transdifferentiation of renal tubular epithelial cells occurs under acute ischemic-reperfusion injury. Local renin-angiotensin system may play a role in the transdifferentiation of TEC through AT2 receptor and its JAK2 signal pathway.

Current classification and status of primary immunodeficiency diseases in Taiwan.

The incidence of primary immunodeficiency diseases (PIDD) in Taiwan is estimated at 2.17 per 100,000 live births. This is much lower than in Sweden, with 8.4 per 100,000 live births. Patients with critical combined T-cell and B-cell immunodeficiency (CID) seem to be under-diagnosed because of delayed referrals to a tertiary care center which is able to organize a cooperative transplantation team encompassing, at least, a pediatric hematologist and a immunologist for severe combined immunodeficiency (SCID) classified as "pediatric emergency". Moreover, there are rare reported cases of adult-onset (over 18-years-old) common variable immunodeficiency (CVID). These cases are possibly treated as autoimmune diseases, but not PIDD. To date around the world, 206 kinds of PIDD have been found and 110 causal genetic effects were identified. Although epidemiological studies show wide geographical and racial variations in the prevalence and distribution of PIDD, we believe in Taiwan that those patients with Mendelian susceptibility to mycobacteria disease (MSMD), belonging to "congenital phagocyte defect", are often treated as isolated refractory mycobacterial infections or chronic granulomatous disease. Also, "diseases of innate immunity" and "autoimflammatory disorders" are not yet identified. To manage patients with hemophagocytic lymphohisticytosis syndromes, one of "disease of immune dysregulation, stem cell transplantation will be considered if there is poor response to chemotherapy. Patients with PIDD need better access to specialized clinical, laboratory and therapeutic resources.

The effects of microRNAs on glucocorticoid responsiveness.

PURPOSE: Glucocorticoids (GCs) are of wide usage in the clinical treatment of lymphoblastic malignancies such as acute lymphoblastic leukemia. However, individually distinctive responsiveness to the GC therapy may attenuate their clinical efficacy, and more reliable predictor for GC resistance is still eagerly needed. Recent studies indicate that microRNAs (miRNAs), which demonstrate regulatory functions targeting mRNAs during the post-transcription, involved in the regulation of GCs sensitivity through several mechanisms, especially adjusting the magnitude of GC receptors (GRs), which mediates the cellular effects of GCs and plays a pivotal role in GCs sensitivity, inspiring that special miRNAs pattern could serve as the biomarkers to predict GC sensitivity and bring forth potential strategies for overcoming drug resistance. In this review, we discuss related miRNAs and their diverse effects exerted on multifaceted complexity of GCs responsiveness for further exploiting the molecular mechanism of GC resistance and future construction of the molecular diagnostic method and reverse GC resistance. METHODS: We have reviewed and searched for eligible literature relating to the effects of microRNAs on GC responsiveness from systematic PubMed searches. RESULTS: GC response can be mediated by miRNAs through influence on GC signaling pathway, leading to diverse glucocorticoid responsiveness. Mutations in miRNA gene also influence GC response. As well, GCs regulate the function of several miRNAs, and suggesting a bidirectional influence among them. CONCLUSIONS: It is possible and necessary that miRNAs serve as stable biomarkers and GC resistant patients would benefit from an effective and early screening test.

MicroRNA-185-5p restores glucocorticoid sensitivity by suppressing the mammalian target of rapamycin complex (mTORC) signaling pathway to enhance glucocorticoid receptor autoregulation.

Overexpression of microRNA-185-5p (miR-185-5p) in glucocorticoid (GC)-sensitive acute lymphoblastic leukemia (ALL) was identified using a microarray and reverse transcription polymerase chain reaction and was further confirmed in ALL cell lines. A reporter assay confirmed that the Rictor-one component of mammalian target of rapamycin complex 2 (mTORC2) is a target of miR-185-5p. Decreased mTORC activity was also confirmed in GC-sensitive patients. Overexpression of miR-185-5p significantly enhanced GC sensitivity in CEM-C1 cells (GC resistance) by increasing the rate of cell apoptosis and cycle arrest, and decreasing cell survival, accompanied by a decrease in mTORC activity and an increase in GC-induced glucocorticoid receptor (GR) expression. Rapamycin, an mTORC1 inhibitor, showed similar effects to miR-185-5p. These results demonstrated that miR-185-5p enhances GC sensitivity via suppression of mTORC activity by enhancing GR autoupregulation and that miR-185-5p is a potential target for the diagnosis and reversion of GC resistance.

Prevalence and genotype distribution of human papillomavirus in 961,029 screening tests in southeastern China (Zhejiang Province) between 2011 and 2015.

Human papillomavirus infection plays a key role in the development of cervical cancer. To establish a foundation for HPV-based screening and vaccination programs, we investigated the HPV prevalence and genotypic distributions in Chinese women from Zhejiang Province. Between 2011 and 2015, a total of 961,029 samples from 2021 clinical hospitals were tested HPV genotype by a PCR-based hybridization gene chip assay, and 443,890 samples were evaluated cervical cytology by liquid-based cytology analysis. Our results showed that the positive rate for HPV was 20.54%, which ranged from 28.72% to 17.81% and varied by year of recruitment. Age-specific prevalence showed a "two-peak" pattern, with the ≤20-year-old group presenting the highest HPV infection rate, followed by 61-70-year-old group. Overall, the most prevalent genotypes were HPV16, 52 and 58. Additionally, the odds ratios for the prevalence of the HR-HPV, LR-HPV and HPV-negative groups with abnormal cytology were 12.56, 3.21 and 0.06, respectively. Among genotypes, HPV 16 has been found to have the highest OR, followed by HPV58, 18, 52. Here, we present data regarding the prevalence and type distribution of HPV infection, which can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs.

Cell atavistic transition: Paired box 2 re-expression occurs in mature tubular epithelial cells during acute kidney injury and is regulated by Angiotensin II.

The regeneration of tubular epithelial cells (TECs) after acute kidney injury (AKI) is crucial for the recovery of renal structure and function. The mechanism by which quiescent TECs re-obtain a potential to regenerate remains unknown. In this study, we observed a transient re-expression of embryonic gene Paired box 2 (Pax2) in adult rat TECs in vivo during ischemia-reperfusion induced AKI and most Pax2 positive TECs co-expressed kidney injury molecule-1 (KIM-1), a tubular injury marker. The re-expression of Pax2 was accompanied by increased levels of intrarenal Angiotensin II, which is a crucial injury factor of AKI. Furthermore, we also found a temporary re-expression of Pax2 in NRK-52E cells under the stimulation of Angiotensin II. This stimulatory effect could be blocked by PD123319 (Angiotensin II type 2 receptor (AT2R) inhibitor) and AG490 (Janus Kinase 2 (JAK2) inhibitor). As Pax2 is essential for the phenotypic conversion from mesenchymal stem cells to TECs during kidney development, we proposed that the re-expression of Pax2 in mature TECs may be an indicator of "atavistic" transition which mimics but reverses the processes of development of TECs. This could be proved by that a progenitor marker, CD24, was also found to be transiently expressed shortly after the expression of Pax2 in NRK-52E cells stimulated with Angiotensin II. The expression of CD24 was also suppressed by PD123319 and AG490. Moreover, knockdown of Pax2 by RNA interference could significantly reduce the expression of CD24 in NRK-52E cells stimulated with Angiotension II. Those findings suggest that mature TECs can trans-differentiate into progenitor-like cells by "atavistic transition", which may participate in the recovery of tissue structure and Pax2 may play a pivotal role in this process. That might have important implications for further understanding of tubular regeneration after injury.

Loss of polycystin-1 inhibits Bicc1 expression during mouse development.

Bicc1 is a mouse homologue of Drosophila Bicaudal-C (dBic-C), which encodes an RNA-binding protein. Orthologs of dBic-C have been identified in many species, from C. elegans to humans. Bicc1-mutant mice exhibit a cystic phenotype in the kidney that is very similar to human polycystic kidney disease. Even though many studies have explored the gene characteristics and its functions in multiple species, the developmental profile of the Bicc1 gene product (Bicc1) in mammal has not yet been completely characterized. To this end, we generated a polyclonal antibody against Bicc1 and examined its spatial and temporal expression patterns during mouse embryogenesis and organogenesis. Our results demonstrated that Bicc1 starts to be expressed in the neural tube as early as embryonic day (E) 8.5 and is widely expressed in epithelial derivatives including the gut and hepatic cells at E10.5, and the pulmonary bronchi at E11.5. In mouse kidney development, Bicc1 appears in the early ureteric bud and mesonephric tubules at E11.5 and is also expressed in the metanephros at the same stage. During postnatal kidney development, Bicc1 expression gradually expands from the cortical to the medullary and papillary regions, and it is highly expressed in the proximal tubules. In addition, we discovered that loss of the Pkd1 gene product, polycystin-1 (PC1), whose mutation causes human autosomal dominant polycystic kidney disease (ADPKD), downregulates Bicc1 expression in vitro and in vivo. Our findings demonstrate that Bicc1 is developmentally regulated and reveal a new molecular link between Bicc1 and Pkd1.

Nuclear HSP90 regulates the glucocorticoid responsiveness of PBMCs in patients with idiopathic nephrotic syndrome.

Resistance to glucocorticoid (GC) is a challenge for the treatment of patients with idiopathic nephrotic syndrome (INS). Most of the effects of GC are mediated by the GC receptor (GR). Heat shock protein 90 (HSP90) is an important molecular chaperone for the GR and is supposed to be the key factor in regulating GC effects. In a previous study, we found that both the expression and nuclear distribution of HSP90 were increased in GC resistant INS patients. The aim of this study is to explore how these phenomena contribute to GC resistance in INS patients. Healthy subjects and INS patients with different GC responses were recruited. The total HSP90 expression was determined by reverse transcription-PCR and flow cytometric analysis. Western blot analysis was used to evaluate the expression of nuclear HSP90. Co-immunoprecipitation and electrophoretic mobility gel shift assays were performed to explore the interaction between HSP90 and the GR in the nucleus as well as the DNA-binding activity of GR. We induced the upregulation of the expression of total HSP90 in PBMCs by treatment with interleukin-6 in vitro and found that the nuclear HSP90 level, the DNA-binding activity of the GR and the cell apoptotic responsiveness to GC remained unchanged. Furthermore, an increased nuclear HSP90 was demonstrated mainly by binding to GR in the nucleus, while the DNA-binding activity of the GR dramatically decreased in GC resistant INS patients. The present results suggest that the accumulation of HSP90 in the nucleus potentially hinders DNA-binding activity and transactivation, which may contribute to GC resistance in patients with INS.

Glucocorticoid receptor auto-upregulation and its relation with glucocorticoid sensitivity in idiopathic nephrotic syndrome.

BACKGROUND: Resistance to glucocorticoid (GC) treatment is a significant clinical problem in many diseases. Most effects of GC are mediated by glucocorticoid receptor (GR). Multiple promoters have been found in GR gene, which results in different exons 1 s. In human leukemia cell lines, GC response is thought to be related with promoter usage and auto-upregulation of GR. In this study, we investigated whether GR could be auto-induced in peripheral blood mononuclear cells (PBMCs) and whether an inability to upregulate the GR is related with GC resistance in idiopathic nephrotic syndrome (INS). METHODS: Reverse transcription-PCR was applied to measure the mRNA expression of GR transcripts (GR exons 1A, 1B, 1C, and GR), and real-time PCR was used to confirm these results. GR protein expression was analyzed by Western blot. RESULTS: Following GC treatment, both GR exon 1A and GR in PBMCs were increased in vitro, while GR exons 1B and 1C showed no significant changes. In patients with INS, the glucocorticoid-sensitive group expressed more GR exon 1A and less GR exon 1C than the glucocorticoid-resistant group, but the total GR showed no significant difference. CONCLUSIONS: GR is auto-induced in PBMCs in vitro and GR promoter 1A is involved in this mechanism; however the auto-upregulation of GR is not related with glucocorticoid response in patients with INS.

CARMA3 is crucial for EGFR-Induced activation of NF-κB and tumor progression.

EGF activates NF-κB, and constitutively activated NF-κB contributes to EGFR mutation-associated tumorigenesis, but it remains unclear precisely how EGFR signaling leads to NF-κB activation. Here we report that CARMA3, a caspase recruitment domain (CARD)-containing scaffold molecule, is required for EGF-induced NF-κB activation. CARMA3 deficiency impaired the activation of the IKK complex following EGF stimulation, resulting in a defect of EGF-induced IκBα phosphorylation and NF-κB activation. We found that CARMA3 and Bcl10 contributed to several characteristics of EGFR-associated malignancy, including proliferation, survival, migration, and invasion. Most importantly, CARMA3 contributed to tumor growth in vivo. Our findings elucidate a crucial link between EGFR-proximal signaling components and the downstream IKK complex, and they suggest a new therapeutic target for treatment of EGFR-driven cancers.

Depression, another autoimmune disease from the view of autoantibodies.

Immune dysregulation is very common in major depression (MD) patients, with these individuals incurring increased risk for development of chronic inflammatory disease or autoimmune disease. Meanwhile, depressive symptoms have been found at a high prevalence in autoimmune disease. This apparent convergence suggests they may share a common pathogenic factor, or a close interaction innate. Recent studies have found that autoantibodies play an important role in the pathogenesis of depression both in animal models and human. Here, we suggest that depression, in nature, can be regarded as autoimmune disease caused by various autoantibodies, which broadens our understanding of depression, and brings about new fields for research and clinical implications of the disease.

Epigenetic programming of diverse glucocorticoid response and inflammatory/immune-mediated disease.

Glucocorticoid plays a fundamental role in maintaining immune homeostasis. Resistance to glucocorticoids is a potential etiology of inflammatory/immune-mediated disease. Most of the glucocorticoid effects are mediated by glucocorticoid receptor (GR), which has a complicated promoter region with multiple promoters. Studies have found that the methylation pattern of GR promoter is highly individual, which may contribute to the diverse glucocorticoid responds. Early life is a critical time for epigenetic programming of the body in which methylation imprints are established. Here we propose a hypothesis that connects the adverse early life events and the development of inflammatory/immune-mediated disease through an epigenetic mechanism, the methylation of GR gene.