Reg2 treatment is protective but the induced Reg2 autoantibody is destructive to the islets in NOD mice.

Regenerating family protein 2 (Reg2) is a trophic factor which stimulates ß-cell replication and resists islet destruction. However, Reg2 also serves as an islet autoantigen, which makes it complicated to judge the effectiveness in treating diabetes. How Reg2 treatment behaves in non-obese diabetic (NOD) mice is to be investigated. NOD mice were treated with recombinant Reg2 protein, Complete Freund's adjuvant (CFA) + PBS and CFA+Reg2 vaccinations, CFA+PBS- and CFA+Reg2-immunized antisera, and single chain variable fragment (scFv)-Reg2 and mIgG2a-Reg2 antibodies. Glycemic level, bodyweight, serum Reg2 antibody titer, glucose tolerance, and insulin secretion were determined. Islet morphological characteristics, insulitis, cell apoptosis, islet cell components, and T cell infiltration were analyzed by histological examinations. The autoantigenicity of constructed Reg2C and Reg2X fragments was determined in healthy BALB/c mice, and the bioactivity in stimulating cell proliferation and survival was assessed in insulinoma MIN6 cells. Reg2 administration alleviated diabetes in NOD mice with improved glucose tolerance and insulin secretion but elevated serum Reg2 autoantibodies. Histomorphometry showed reduced inflammatory area, TUNEL signal and CD8 + T cell infiltration, and increased ß-cell proportion in support of the islet-protective effect of Reg2 treatment. CFA+PBS and CFA+Reg2 immunizations prevented diabetic onset and alleviated insulitis while injections of the antisera offered mild protections. Antibody treatments accelerated diabetic onset without increasing the overall incidence. Reg2C fragment depletes antigenicity, but reserves protective activity in streptozotocin (STZ)-treated MIN6 cells. In conclusion, Reg2 treatment alleviates type 1 diabetes (T1D) by preserving islet ß-cells, but induces Reg2 autoantibody production which poses a potential risk of accelerating diabetic progression.

Nanopore techniques as a potent tool in the diagnosis and treatment of endophthalmitis: a literature review.

Endophthalmitis is a serious ophthalmic disease characterized by changes in the eye's posterior segment, such as hypopyon and intraocular inflammation, vitritis being a hallmark. Infection-caused endophthalmitis can lead to irreversible vision loss, accompanied by eye pain or eye distention, and in the most severe cases the removal of the eyeball. Microorganisms such as bacteria, fungi, viruses, and parasites typically account for the disease and the entry pathways of the microbial can be divided into either endogenous or exogenous approaches, according to the origin of the etiological agents. Exogenous endophthalmitis can be derived from various occasions (such as post-operative complications or trauma) while endogenous endophthalmitis results from the bloodstream which carries pathogens to the eye. This review aims to summarize the application of new technology in pathogen identification of endophthalmitis so as to prevent the disease and better guide clinical diagnosis and treatment.

HLA correlates in a cohort of slow progressors from China: effects on HIV-1 disease progression.

We looked at our HIV + slow progressors cohort to determine if there were any human leukocyte antigen (HLA) correlates for protection. No statistically significant allelic differences were found between the HIV + and control cohorts using regression analysis, though trends were noted. Data for Elite Controllers showed an increased frequency of B*57. Likewise, no correlation was inferred with the clinical data of the HIV + cohort. We hypothesize that the protective effect of HLA alleles may have been lost over time.

Interleukin-17, produced by lymphocytes, promotes tumor growth and angiogenesis in a mouse model of breast cancer.

Previous studies have suggested that interleukin-17 (IL-17), an inflammatory cytokine expressed predominantly by Th17 cells, is highly expressed in tumor tissue and may help tumors to evade immune surveillance. In this study, the significance of IL-17 expression in the tumors of murine models of breast cancer was explored. BALB/c mice were injected with MA782/5S28102 or 4T1 breast cancer cell lines to establish breast tumors. The expression of IL-17 in tumor tissue was detected by western blotting 1 and 4 weeks later, which revealed that it increased with tumor progression (P<0.05). Additionally, tumor cells and tumor-infiltrating lymphocytes were isolated from tumor tissues and cultured for 5 days with stimulation by phorbol-12-myristate-13-acetate (PMA), anti­CD3 antibody and anti-CD28 antibody. Culture media from stimulated tumor cells or tumor-infiltrating lymphocytes were harvested and their concentrations of IL-17 were tested by ELISA. Tumor cells secreted low levels of IL-17 into the media; however, lymphocytes from tumor tissues secreted high levels of IL-17, with 4T1 tumors secreting higher levels of IL-17 than MA782 tumors (P<0.05). To evaluate the effect of IL-17 on the proliferation of tumor cells, 4T1 cells were cultured in the presence or absence of recombinant IL-17 and cell numbers were counted on day 5 of culturing. Ectopic IL-17 did not promote the proliferation of tumor cells in vitro. To further understand the effect of IL-17 expression within tumors, 4T1 tumor-bearing mice were injected with recombinant IL-17 or saline via the tail vein. Tumor size was measured up to 21 days following the initial infusion of IL-17. IL-17 infusion resulted in an increased tumor volume and microvascular density (as measured by the immunohistochemical detection of CD34 expression in microvessels; P<0.05). Therefore, IL-17 expression within tumor tissues appears to originate from tumor-infiltrating lymphocytes and is likely to promote tumor growth by enhancing angiogenesis.

Association between mutations of the luteinizing hormone ß subunit and female infertility.

To explore the association between mutations of Trp8Arg and Ile15Thr in the luteinizing hormone (LH) gene and female infertility, primary female infertility patients (n=60) and normal healthy women (n=60) were screened for mutations Trp8Arg and Ile15Thr in the LH-ß subunit gene by polymerase chain reaction-restriction fragment length polymorphism, and associations were examined between the mutations and female infertility. The results showed that there were significant differences in the allele and genotype frequencies of Trp8Arg and Ile15Thr between the two groups (P<0.05). A significant difference was noted in the LH level among women with different genotypes (P<0.05), and the LH level was highest in women who were homozygous for both mutations. However, there were no significant differences in FSH level and FSH/LH ratio among subjects with different genotypes (P>0.05). In conclusion, polymorphisms of Trp8Arg and Ile15Thr in the LH-ß subunit gene occur in infertile women. The polymorphisms correlate with female infertility and may be a risk factor in the pathogenesis of female infertility.

Polymorphisms in estrogen receptor-α are associated with idiopathic female infertility.

To investigate the relationship between polymorphisms in the estrogen receptor-α (ERα) gene and unexplained female infertility, restriction fragment length polymorphism (RFLP) analysis of ERα was employed in 150 females with idiopathic infertility (study group) and 150 healthy, age-matched females of proven fertility (control group). The results showed that the ERα allele frequencies differed significantly between the study and control groups (P=0.001). The allele identified by PvuII (P) restriction was detected more frequently in the study group (49.0% of individuals) compared to the control group (31.0%; P=0.001), while the allele identified by XbaI (X) restriction was detected less frequently in the study group (19.7%) compared to the control group (35.7%, P=0.001). A similar phenomenon was observed for the distribution of the TA alleles. The TA13 allele was more common in the study group (24.7 vs. 6.7% in controls; P=0.001), while the TA15 allele was less common in the study group (15.3 vs. 27.3% in controls; P=0.034). To conclude, polymorphisms in the ERα gene are associated with idiopathic female infertility. In particular, the P and TA13 alleles may represent significant risk factors, while the X and TA15 alleles may be protective factors.

Extensive HLA-driven viral diversity following a narrow-source HIV-1 outbreak in rural China.

Obstacles to developing an HIV-1 vaccine include extensive viral diversity and lack of correlates of protective immunity. High mutation rates allow HIV-1 to adapt rapidly to selective forces such as antiretroviral therapy and immune pressure, including HIV-1-specific CTLs that select viral variants which escape T-cell recognition. Multiple factors contribute to HIV-1 diversity, making it difficult to disentangle the contribution of CTL selection without using complex analytical approaches. We describe an HIV-1 outbreak in 231 former plasma donors in China, where a narrow-source virus that had contaminated the donation system was apparently transmitted to many persons contemporaneously. The genetic divergence now evident in these subjects should uniquely reveal how much viral diversity at the population level is solely attributable to host factors. We found significant correlations between pair-wise divergence of viral sequences and HLA class I genotypes across epitope-length windows in HIV-1 Gag, reverse transcriptase, integrase, and Nef, corresponding to sites of 140 HLA class I allele-associated viral polymorphisms. Of all polymorphic sites across these 4 proteins, 24%-56% were sites of HLA-associated selection. These data confirm that CTL pressure has a major effect on inter-host HIV-1 viral diversity and probably represents a key element of viral control.

[Epidemiologic study and HLA analysis of highly exposed to HIV but persistently seronegative subjects (HEPS) in commercial blood donors in China].

BACKGROUND: To investigate epidemiology and HLA typing of highly exposed to HIV but persistently seronegative subjects (HEPS) in commercial blood donors in China. METHODS: This was a cohort study for epidemiologic characteristics of highly exposed but persistently seronegative subjects. PCR with sequence-specific primer and PCR-SSP for HLA typing were applied. RESULTS: Eight HEPS were identified. Compared HLA typing with seropositive couple, high frequency of HLA-a24, HLA-B40 genotyping was observed. CONCLUSION: Highly exposed to HIV but persistently seronegative subjects in commercial blood donors in China had high frequency of HLA-A24 and HLA-B40 genotype.