[Advances of nanomaterials applied in ophthalmic treatment].

Nanomaterials have been used in many aspects of ophthalmic treatment. By emphasizing the ubiquitous characteristics of nanoparticles and composites, we first explained their relatively mature applications in drug delivery. Then we reviewed the research on nanomaterials in regenerative medicine and gene therapy in recent years. We also discussed the main limitations of the wider application of nanomaterials in ophthalmology: stability, biotoxicity and preclinical-clinical differences. The development of efficient and non-toxic nanomaterials, combined with appropriate transportation systems and application occasions, will provide more possibilities for the future application of nanomaterials in ophthalmic treatments.

[Transcriptome profiling of differentiated lenses through RNA sequencing].

Objective: To gain insight into the transcriptional landscape including mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) of the differentiated lens. Methods: Experiment research. The total RNAs of the differentiated lenses were extracted and purified. Total RNAs of 16-week, 23-week, and 25-week differentiated lenses were then sequenced using Illumina HiSeq 2500, and analyzed using bioinformatics tools. The top expressed and differentially expressed mRNAs and lncRNAs were screened. The expressions of overlap genes among the 16-week, 23-week, and 25-week lenses were analyzed by Venn diagram. The expression tendency of lens-specific genes was obtained and verified with real-time polymerase chain reaction. Results: A total of 67 518 311 mapped reads were obtained from differentiated lenses at 16 weeks, 99 440 160 at 23 weeks, and 67 262 320 at 25 weeks. The gene overlap expression analysis showed 740 of the top 1 000 highly expressed mRNAs, 170 of the top 300 highly expressed lncRNAs, and 69 of the top 100 highly expressed circRNAs overlapping expressed in lenses at 16, 23, and 25 weeks, respectively. Lens specific gene expression analysis revealed that the expression of crystallin (CRY) AA, CRYGA, CRYGB, CRYGC, CRYGD, CRYGEP, and CRYGS was upregulated, while the expression of gap junction (GJ) A3 and GJA8 was downregulated with the differentiation of lenses. Conclusion: The lens transcriptome profile shows that more than half of the high expressed mRNA, lncRNA and circRNA at different differentiation stages are overlapping expressed, and all of them have high expression of lens specific protein genes, such as CRY, GJ etc. (Chin J Ophthalmol, 2020, 56: 356-363).

ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. METHODS: The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro. RESULTS: The patients were well-controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL-5, IL-13 and IL-9 in response to IL-25, IL-33 plus IL-2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL-5, IL-13 and IL-9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment. CONCLUSION: The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK-STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.

Mesenchymal stem cells and immunomodulation: current status and future prospects.

The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application. An understanding of the biological properties of MSCs will clarify the mechanisms of MSC-based transplantation for immunomodulation. In this review, we summarize the preclinical and clinical studies of MSCs from different adult tissues, discuss the current hurdles to their use and propose the future development of pluripotent stem cell-derived MSCs as an approach to immunomodulation therapy.

Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities.

BACKGROUND: Chronic sinusitis (CRS) is a common otorhinolaryngologic disease that is frequently encountered in everyday practice, but there is a lack of precise data regarding the prevalence of CRS in developing countries. We performed a national investigation in China to determine the prevalence and associated factors of CRS. METHODS: We conducted a cross-sectional investigation in 2012. A stratified four-stage sampling method was used to select participants randomly from seven cities in mainland China. All participants were interviewed face-to-face via a standardized questionnaire. Unconditional logistic regression analyses were conducted to examine the association between smoking and sinusitis after adjusting for socio-demographic factors. RESULTS: This study included a total of 10 636 respondents from seven cities. The overall prevalence of CRS was 8.0% and ranged from 4.8% to 9.7% in seven centres. Chronic sinusitis affected approximately 107 million people in mainland China. Chronic sinusitis was particularly prevalent among people with specific medical conditions, including allergic rhinitis, asthma, chronic obstructive pulmonary disease and gout. The prevalence was slightly higher among males (8.79%) than females (7.28%) (P = 0.004), and the prevalence varied by age group, ethnicity and marital status and education (P < 0.05), but not by household per capita income or living space (P > 0.05). Both second-hand tobacco smoke and active smoking were independent risk factors for CRS (P = 0.001). CONCLUSIONS: Chronic sinusitis is an important public health problem in China. Our study provides important information for the assessment of the economic burden of CRS and the development and promotion of public health policies associated with CRS particularly in developing countries.

Mesenchymal stem cells derived from human induced pluripotent stem cells modulate T-cell phenotypes in allergic rhinitis.

BACKGROUND: Human induced pluripotent stem cells (iPSCs) possess remarkable self-renewal capacity and the potential to differentiate into novel cell types, such as mesenchymal stem cells (MSCs). iPSC-MSCs have been shown to enhance tissue regeneration and attenuate tissue ischaemia; however, their contribution to the immune regulation of Th2-skewed allergic rhinitis (AR) and asthma remains unclear. OBJECTIVE: This study compared the immunomodulatory effects of iPSC-MSCs and bone marrow-derived MSCs (BM-MSCs) on lymphocyte proliferation, T-cell phenotypes and cytokine production in peripheral blood mononuclear cells (PBMCs) in patients with AR, and investigated the possible molecular mechanisms underlying the immunomodulatory properties of iPSC-MSCs. METHODS: In co-cultures of PBMCs with iPSC-MSCs or BM-MSCs, lymphocyte proliferation was evaluated using 3H-thymidine (3H-TdR) uptake, carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE) assays; the regulatory T-cell (Treg) phenotype was determined by flow cytometry, and cytokine levels were measured using an enzyme-linked immunosorbent assay. The immunomodulatory properties of both MSCs were further evaluated using NS398 and transwell experiments. RESULTS: Similar to BM-MSCs, we determined that iPSC-MSCs significantly inhibit lymphocyte proliferation and promote Treg response in PBMCs (P < 0.05). Accordingly, the cytokine milieu (IFN-γ, IL-4, IL-5, IL-10 and IL-13) in the supernatants of PBMCs changed significantly (P < 0.05). The immunomodulatory properties of iPSC-MSCs and BM-MSCs were associated with prostaglandin E2 (PGE2) production and cell-cell contact. CONCLUSIONS: These data demonstrate that iPSC-MSCs are capable of modulating T-cell phenotypes towards Th2 suppression through inducing Treg expansion, suggesting that iPSC-MSCs can be used as an alternative candidate to adult MSCs to treat allergic airway diseases.

Combined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma.

Glaucoma is a progressive neuropathy characterized by loss of vision as a result of retinal ganglion cell (RGC) death. There are no effective neuroprotectants to treat this disorder. Brain-derived neurotrophic factor (BDNF) is well known to transiently delay RGC death in ocular hypertensive eyes. The CNS-specific leucine-rich repeat protein LINGO-1 contributes to the negative regulation to some trophic pathways. We thereby examined whether BDNF combined with LINGO-1 antagonists can promote long-term RGC survival after ocular hypertension. In this study, intraocular pressure was elevated in adult rats using an argon laser to photocoagulate the episcleral and limbal veins. BDNF alone shows slight neuroprotection to RGCs after a long-term progress of 4 weeks following the induction of ocular hypertension. However, combination of BDNF and LINGO-1-Fc prevents RGC death in the same condition. We further identified that (1) LINGO-1 was co-expressed with BDNF receptor, TrkB in the RGCs, and (2) BDNF combined with LINGO-1-Fc activated more TrkB in the injured retina compared to BDNF alone. These results indicate that the combination of BDNF with LINGO-1 antagonist can provide long-term protection for RGCs in a chronic ocular hypertension model. TrkB may be the predominant mediator of this neuroprotection.

Brain interleukin asymmetries and paw preference in mice.

The two sides of the brain are differently involved in the modulation of immune responses as demonstrated by lesion and behavioral approaches. To study the interactions between cerebral cortex cytokines and brain lateralization, three groups of BALB/c mice were selected on the basis of their performance in the paw preference test (left-pawed, ambidextrous and right-pawed) and the levels of interleukin-1beta and interleukin-6 were measured in the two cerebral cortices after an intraperitoneal saline or lipopolysaccharide. Generally, right cortices had higher interleukin-1beta and interleukin-6 levels than left cortices for both saline and lipopolysaccharide-treated mice. A strong correlation between the levels of interleukin-1beta and interleukin-6 in right and left cortices and behavioral lateralization was observed. For the saline-treated mice: in their left cortices, interleukin-1beta levels were higher for ambidextrous mice than for right-pawed mice (P<0.05); in their right cortices, interleukin-6 levels were higher for ambidextrous mice than for right-/left-pawed mice, and right-pawed mice have higher levels of interleukin-6 than left-pawed mice (P<0.01). In their left cortices, interleukin-6 levels are higher for left-pawed mice than for both ambidextrous and right-pawed mice (P<0.01). In their left cortices, interleukin-6 levels are higher for left-pawed mice than for both ambidextrous and right-pawed mice (P<0.01). The quadratic curve equations showed that the levels of interleukin-1beta and interleukin-6 in the right/left cortices had a highly significant correlation with paw preference scores in both normal and lipopolysaccharide-treated mice. In conclusion, the present report demonstrated that the basal levels of interleukin-1beta and interleukin-6 were higher in the right cortex than left cortex in mice. There was a strong correlation between the levels of interleukin-1beta and interleukin-6 and behavioral lateralization, and cytokine asymmetries had a strong correlation with the direction and the intensity of behavioral lateralization.

[Selective distribution of IL-1 beta and IL-6 contents in the right and left cortices of Balb/c mice].

The purpose of the present work was to study the different distribution of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) contents in the right and left cortices, which may be related to the differences in immunomodulatory functions between the two cerebral cortices. Samples of tissue homogenate were prepared from the left and right cerebral cortices of the Balb/c mice and IL-1 beta, and IL-6 contents were measured using ELISA kits. Both IL-1 beta (P < 0.01) and IL-6 (P < 0.001) contents of the right cortex were higher than those of the left. After injection of LPS, the IL-6 content of the left cortex increased. No statistically significant difference of IL-1 beta contents was found between the two cerebral cortices, while the IL-6 content of the right cortex was higher than that of the left (P < 0.01), suggesting that some cytokines are probably involved in the differences between the right and left cerebral immunomodulatory functions in mice.

[Experimental study on yiqi-huoxue therapy of liver fibrosis].

UNLABELLED: The experimental hepatic fibrosis was treated with YiQi (reinforcing Qi, YQ) Huoxue (activating blood circulation, HX) principle which was consisted of astragalus membranaceus, Ligusticum wallichii, paeonia lactiflora, etc. After stimulation with CCl4 over four months, the Wistar rat developed liver fibrosis. Rats were divided into the normal control, the toxifying control, YQHX group and HX group. The experimental period lasted over four months. RESULTS: (1) Mortality of animal: Both toxifying control and HX group reached 50%, while YQHX group was 16% only. These results suggest that YQHX agents could strengthen the body resistance; (2) The determination of serum SGPT: The mean levels in toxifying control were 39.3 +/- 39, in HX group 43.7 +/- 12.9, while in YQHX group 29.0 +/- 7.6 (units/Lserum). These results indicated that YQHX agents had the function of protecting the liver and lowering the activity of SGPT (P less than 0.01); (3) Measuring the contents of hepatic collages: The mean levels in toxifying control was 38.9 +/- 3.3 (mg/g liver), while in HX group and YQHX group 28.7 +/- 2.2 and 22.7 +/- 1.1 (mg/g liver) respectively. The results indicated that the YQHX agents had the best results in treating hepatic fibrosis; (4) Observation with hepatic histopathology: The degree of hepatocyte degeneration and necrosis in YQHX group was milder than that in toxifying and HX group. These observations revealed that YQHX agents possessed the function of protecting liver. There was severe liver fibrosis in toxifying control, but the degree of liver fibrosis in YQHX group was significantly milder than that in toxifying control.(ABSTRACT TRUNCATED AT 250 WORDS)

[Detection of cytomegalovirus (CMV) DNA sequence in biopsy samples of cervical cancer].

Biopsy samples of the cervical cancer and cervicitis were analysed by HCMV-DNA hybridization method. The results indicated that HCMV-DNA was detected in 21 (36%) of 59 cervical cancer and 6 (21%) of 28 cervicitis specimens, using 32P-DNA probe containing transformation gene (14% of total genome) to hybridize. None of 25 cervical cancer and 19 cervicitis samples showed positive HCMV-DNA, using 32P-DNA probe without transformation gene (76% of total genome). The preliminary results show that the sequence of CMV transformation gene is present in about one third of cervical cancer and one fifth of cervicitis biopsy samples tested. This detection rate is lower than that of Taiwan Province and Africa, and slightly higher than that of the USA and Finland. The relation between the HCMV and cervical cancer is being further studied.

[Prostaglandin E (PGE) and gastric carcinoma].

Since 1984, an experimental and clinical study on the relation between PGE and gastric carcinoma has been performed by determining PGE content in the bioptic gastric mucosa and plasma. It is found the PGE content in the gastric mucosa and plasma is increased in all patients with gastric cancer, especially with signet ring cell carcinoma. It is higher in the regional lymph node metastasis than in the early cancer, extensive metastases and normal subjects. The PGE content in the plasma is reduced obviously 7-10 days after operation but is increased markedly in recurrent patients. There is no significant difference in extensive metastases, relapse free and normal subjects. The PGE content in the plasma is significantly higher in gastric carcinoma than in chronic atrophic gastritis, but no difference is present between chronic atrophic gastritis and normal subjects.