Reversal of alopecia areata, osteoporosis follow treatment with activation of Tgr5 in mice.

BACKGROUND: Alopecia areata is an autoimmune hair loss disease with infiltration of pro-inflammatory cells into hair follicles. The role of Tgr5 in dermatitis has attracted considerable attention. The present study aimed to investigate the effect of Tgr5 in the development of Alopecia areata. METHODS: The study utilized a comparison control group design with four groups of wild-type group, wild-type+INT777 group, Tgr5-/- group, and Tgr5-/-+INT777 group. The mice were treated with INT777 (30 mg/kg/day) or the carrier solution (DMSO) intraperitoneally for 7 weeks, and the back skin was collected and analyzed by histology and immunohistochemistry staining. The lumbar vertebrae 4 has also been analyzed by DXA and Micro-CT. RESULTS: Tgr5-/- mice displayed the decreasingly significant in hair area and length, skin thickness, and the ratio of anagen and telogen, collagen, and mast cell number and loss the bone mass than WT group. After treating with INT777, the appearance of alopecia areata and bone microstructure has improved. Immunohistochemistry and qPCR analysis showed that activation of Tgr5 can down-regulate the express of JAK1, STAT3, IL-6, TNF-α, and VEGF. CONCLUSION: These findings indicate that activation of Tgr5 mediated amelioration of alopecia areata and osteoporosis by down-regulated JAK1-STAT3 signaling pathway.

A Systematic Review and Meta-analysis of Prevalence of Biopsy-Proven Lupus Nephritis.

OBJECTIVES: This study aims to conduct a meta-analysis to clarify the epidemiologic characteristics of biopsy-proven lupus nephritis (BPLN), including those relating to its prevalence and prognosis. PATIENTS AND METHODS: A literature search for relevant studies was conducted in the electronic databases of PubMed, Google Scholar, Embase, and Cochrane trial register. The following search terms were used for original articles published between January 1982 and April 2016: "lupus nephritis" or systemic lupus erythematosus ('SLE') or 'systemic lupus erythematous' and "pathology" or 'epidemiology' or prevalence or incidence. Pooled estimates with 95% confidence intervals were calculated. RESULTS: Nineteen studies were included (mean age of SLE patients at renal biopsy: ~30 years). Of total BPLN patients, 85% were females. BPLN developed in 29% of SLE patients, and accounted for 60% of secondary glomerular diseases in renal biopsy databases. BPLN prevalence among SLE patients was higher in Saudi Arabia compared with pooled Europe/USA data (43% vs 26%, p<0.05). Pooled BPLN prevalence among secondary glomerular diseases patients was higher in Asian/Latin American countries than in Europe (63% vs 34%, p<0.05). Overall five-, 10- and 20-year survival rates of BPLN patients were 94%, 86%, and 71%, respectively, which were higher than those before 1995 (84%, 72%, and 52%, respectively) and lower than those after 1995 (96%, 89%, and 80%, respectively) (all p<0.05). Class IV nephritis, present in 40% of BPLN patients, was a risk factor for renal failure that contributed to poor prognosis. CONCLUSION: Lupus nephritis is a common complication of young female patients with SLE, and the most prevalent etiology of secondary glomerular diseases. Attention should be paid to class IV nephritis due to its high frequency and association with poor prognosis.

Modulation of the immune response in rheumatoid arthritis with strategically released rapamycin.

Rheumatoid arthritis (RA) is a chronic inflammatory disease, which is associated with symptoms, including synovial membrane inflammatory pain, joint synovitis and stiffness. However, there are no effective methods available to cure this disease. In the present study, rapamycin was used to modulate immunity in RA. To limit the cytotoxicity of rapamycin, rapamycin was loaded into well­characterized biocompatible nanoparticles. In vitro, rapamycin particles downregulated the activation of dendritic cell surface markers, including CD80+ and CD40+, upon interacting with macrophages. The rapamycin particles reduced the secretion of inflammatory cytokines, including interleukin (IL)­6, tumor necrosis factor (TNF) and IL­1ß, which are characteristic of RA. In vivo, the rapamycin particles decreased the symptoms of RA in mice, and the production of inflammatory cytokines was associated with the occurrence of RA. The present study partially revealed the interactions between rapamycin and two types of immune cell in RA disease, and may potentially offer a solution to improve the treatment of RA.

Hypoxia inducible factor-1 alpha promotes mesangial cell proliferation in lupus nephritis.

BACKGROUND: Evidence has accumulated that hypoxia plays a significant role in the pathogenesis and progression of both acute renal injury and chronic renal disease. However, little was known about the effects of hypoxia on lupus nephritis (LN). In the current study, we investigated the expression of hypoxia inducible factor-1 alpha (HIF-1α) in LN. METHODS: Renal biopsies from 22 LN patients and 20 patients with renal carcinoma were obtained. In situ HIF-1α expression was examined by immunohistochemical staining, and the relationship between HIF-1α and clinical/pathological features was analyzed. HIF-1α expression in kidney from both MRL/lpr and C57BL/6 mice was detected by immunohistochemical technology. Dimethyloxaloylglycine (DMOG), an inhibitor of HIF-degrading prolylhydroxylases, was utilized to prevent HIF-1α degradation in mouse mesangial cells (MCs). After DMOG treatment, the proliferation and apoptosis rates of mouse MCs were determined. RESULTS: LN patients showed larger amounts of HIF-1α in both glomerular and tubulointerstitial areas. The levels of intraglomerular HIF-1α were closely associated with renal pathology activity index and clinical manifestations in LN patients. In MRL/lpr mice, intraglomerular HIF-1α-positive cells were also significantly increased. Interestingly, the levels of HIF-1α positively correlated with cell density in glomerulus in both LN patients and MRL/lpr mice. Upon treatment with DMOG, the proliferation of MCs was upregulated, and apoptosis was downregulated. CONCLUSION: HIF-1α is highly expressed in both glomerular and tubulointerstitial tissues in LN, especially in proliferative LN. HIF-1α may promote MCs growth through the induction of proliferation and inhibition of apoptosis, and hence plays an important role in the pathogenesis of LN.

[Clinical features and prognosis of patients with lupus nephritis].

OBJECTIVE: To explore the clinical features and prognosis of patients with lupus nephritis (LN) in a large multicenter lupus cohort of Jiangsu Province. METHODS: Medical records of 2 078 systemic lupus erythematosus (SLE) inpatients from 15 hospitals at the first admission from 1999 to 2012 were reviewed and classified into two groups with LN or without. The clinical features between two groups were compared with Mann-Whitney U or Chi-square test and potentially associated factors tested by Cox regression. RESULTS: A total of 883 (42.5%) hospitalized lupus patients were diagnosed as LN. And the median age at disease onset of LN patients was lower than that of those without LN [(30 ± 11) vs (32 ± 12) years, P < 0.01]. Cardiopulmonary involvement, neuropsychiatric disorder, gastrointestinal dysfunction, hematologic disease, ophthalmopathy, SLEDAI score > 9 at admission and SLE disease activity index (SLEDAI) score > 9 at discharge were more often seen in patients with LN compared to those without LN (31.5%, 7.9%, 13.9%, 69.0%, 1.5%, 77.4%, 29.8% vs 18.8%, 5.1%, 6.8%, 63.1%, 0.3%, 43.1%, 8.1%, all P < 0.01). The mortality rates at 1 or 5 years after first admission were both significantly higher in LN patients than those without LN (7.2%, 15.0% vs 3.1%, 6.3%, P < 0.01). Independent predictors for mortality in patients with LN were neuropsychiatric involvement[hazard ratio (HR) 2.46], SLEDAI score > 9 at discharge (HR 2.34), increased serum creatinine (HR 2.21) and elevated alanine aminotransferase and (or) aspartate transaminase (HR 2.09) whereas glucocorticosteroid therapy (HR 0.18) was a protective factor. CONCLUSION: LN is one common complication of SLE patients during an early stage. And LN patients are more prone to present other vital organ involvement, higher disease activity and worse treatment outcomes. When accompanied with neuropsychiatric involvement, increased serum creatinine or elevated transaminase, worse prognosis is expected. Glucocorticosteroid treatment may offer some benefits.

Report of 12 cases of ankylosing spondylitis patients treated with Tripterygium wilfordii.

OBJECTIVE: Description of the clinical response of 12 consecutive cases of disease-active ankylosing spondylitis (AS) treated with the herbal medicine Tripterygium wilfordii Hook f (TwHf; lei gong teng, thunder god vine), which has been reported in controlled studies to be effective in rheumatoid arthritis (RA). METHODS: The clinical status of 12 patients with active AS who were started on 60 mgday(-1) of a commercial tablet preparation of TwHf extract. were monitored at weeks 1, 3, and 6. RESULTS: Compared to baseline, there was significant improvement in mean values of physician assessment, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and Bath ankylosing spondylitis global score (BAS-G) at weeks 3 and 6, with no changes in liver enzymes or complete blood count (CBC). CONCLUSION: A placebo-controlled double-blind study for Tripterygium is warranted. Until then, this particular report should be considered as case reports and not an endorsement of the use of Tripterygium in clinical practice.