The Role of Neuro-Immune Interactions in the Pathology and Pathogenesis of Allergic Rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a non-infectious inflammatory disease of the nasal mucosa mediated by IgE and involving a variety of immune cells such as mast cells. In previous studies, AR was considered as an isolated disease of the immune system. However, recent studies have found that the nervous system is closely related to the development of AR. Bidirectional communication between the nervous and immune systems plays an important role in AR. SUMMARY: The nervous system and immune system depend on the anatomical relationship between nerve fibers and immune cells, as well as various neurotransmitters, cytokines, inflammatory mediators, etc. to produce bidirectional connections, which affect the development of AR. KEY MESSAGES: This article reviews the impact of neuro-immune interactions in AR on the development of AR, including neuro-immune cell units.

LncRNA PWRN2 promotes polycystic ovary syndrome progression via epigenetically reducing ATRX by recruiting LSD1.

Long non-coding RNA has been shown to mediate the progression of polycystic ovary syndrome (PCOS). However, the role and mechanism of Prader-Willi region nonprotein coding RNA 2 (PWRN2) in PCOS progression remain unclear. In our study, Sprague-Dawley rat was injected with dehydroepiandrosterone to mimic PCOS rat models. HE staining was used to assess the number of benign granular cells, and serum insulin and hormone levels were detected by ELISA kit. The expression of PWRN2 was examined by qRT-PCR. Ovarian granulosa cells (GCs) proliferation and apoptosis were examined by CCK-8 assay and flow cytometry. The protein levels of apoptosis markers and Alpha thalassemia retardation syndrome X-linked (ATRX) were determined by western blot. The interaction between lysine-specific demethylase 1 (LSD1) and PWRN2 or ATRX was confirmed by RIP and ChIP assay. Our data showed that PWRN2 was upregulated and ATRX was downregulated in the ovarium tissues and serum of PCOS rat. PWRN2 knockdown promoted GCs proliferation and inhibited apoptosis. In the mechanism, PWRN2 inhibited ATRX transcription by binding with LSD1. In addition, downregulation of ATRX also eliminated the effect of sh-PWRN2 on GCs growth. In conclusion, our data suggested that PWRN2 might restrain GCs growth to promote PCOS progression, which was achieved by binding with LSD1 to inhibit ATRX transcription.

Establishment and optimization of an in vitro guinea pig oocyte maturation system.

Guinea pigs are a valuable animal model for studying various diseases, including reproductive diseases. However, techniques for generating embryos via embryo engineering in guinea pigs are limited; for instance, in vitro maturation (IVM) technique is preliminary for guinea pig oocytes. In this study, we aimed to establish and optimize an IVM method for guinea pig oocytes by investigating various factors, such as superovulation induced by different hormones, culture supplementation (e.g., amino acids, hormone, and inhibitors), culture conditions (e.g., oocyte type, culture medium type, and treatment time), and in vivo hCG stimulation. We found that oocytes collected from guinea pigs with superovulation induced by hMG have a higher IVM rate compared to those collected from natural cycling individuals. Moreover, we found that addition of L-cysteine, cystine, and ROS in the culture medium can increase the IVM rate. In addition, we demonstrated that in vivo stimulation with hCG for 3-8 h can further increase the IVM rate. As a result, the overall IVM rate of guinea pig oocytes under our optimized conditions can reach ~69%, and the mature oocytes have high GSH levels and normal morphology. In summary, we established an effective IVM method for guinea pig oocytes by optimizing various factors and conditions, which provides a basis for embryo engineering using guinea pigs as a model.

Gene therapy for cystic fibrosis: Challenges and prospects.

Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects.

Immunotherapy of targeting MDSCs in tumor microenvironment.

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells which are abnormally accumulated during the differentiation of myeloid cells. Immunosuppression is the main functional feature of MDSCs, which inhibit T cell activity in the tumor microenvironment (TME) and promote tumoral immune escape. The main principle for immunotherapy is to modulate, restore, and remodel the plasticity and potential of immune system to have an effective anti-tumor response. In the TME, MDSCs are major obstacles to cancer immunotherapy through reducing the anti-tumor efficacy and making tumor cells more resistant to immunotherapy. Therefore, targeting MDSCs treatment becomes the priority of relevant studies and provides new immunotherapeutic strategy for cancer treatment. In this review, we mainly discuss the functions and mechanisms of MDSCs as well as their functional changes in the TME. Further, we review therapeutic effects of immunotherapy against MDSCs and potential breakthroughs regarding immunotherapy targeting MDSCs and immune checkpoint blockade (ICB) immunotherapy.

MicroRNAs/LncRNAs Modulate MDSCs in Tumor Microenvironment.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature cells derived from bone marrow that play critical immunosuppressive functions in the tumor microenvironment (TME), promoting cancer progression. According to base length, Non-coding RNAs (ncRNAs) are mainly divided into: microRNAs (miRNAs), lncRNAs, snRNAs and CircRNAs. Both miRNA and lncRNA are transcribed by RNA polymerase II, and they play an important role in gene expression under both physiological and pathological conditions. The increasing data have shown that MiRNAs/LncRNAs regulate MDSCs within TME, becoming one of potential breakthrough points at the investigation and treatment of cancer. Therefore, we summarize how miRNAs/lncRNAs mediate the differentiation, expansion and immunosuppressive function of tumor MDSCs in TME. We will then focus on the regulatory mechanisms of exosomal MicroRNAs/LncRNAs on tumor MDSCs. Finally, we will discuss how the interaction of miRNAs/lncRNAs modulates tumor MDSCs.

Follicular development in livestock: Influencing factors and underlying mechanisms.

Livestock farming development has become increasingly important in recent years. It not only provides us with meat nutrition and pet feeding but also increases the economic value by providing numerous employment opportunities, which improves our life quality. The livestock farming development depends on successful animal reproduction. As a vital process in animal reproduction, folliculogenesis and its influencing factors as well as their underlying mechanisms need to be understood thoroughly. This review is aimed at summarizing the factors such as cellular processes, gene regulation, noncoding RNAs and other endocrine or paracrine regulatory factors that affect follicular development, and their underlying mechanisms of action in livestock in order to provide novel insights for future studies. The above factors were found as significant determinants influencing the follicular development in livestock through various signaling pathways.

Relationship between chromatin configuration and in vitro maturation ability in guinea pig oocytes.

BACKGROUND: Germinal vesicle (GV) chromatin configurations of oocytes are proposed to be related to oocyte competence and may reflect the quality of oocyte. Currently, a limited number of published studies investigated the GV chromatin configurations of guinea pig oocytes. OBJECTIVE: In this study on the in vitro maturation (IVM) of guinea pig oocytes, we examined the changes in their GV chromatin configurations during meiotic progression. METHODS: Based on the degree of chromatin compaction, the GV chromatin configurations of guinea pig oocytes could be divided into three categories depending on whether the nucleolus-like body (NLB) was surrounded or partly surrounded by compacted chromatin, namely the uncondensed (NSN), the intermediate type (SN-1) and the compacted type (SN-2). RESULTS: The percentage of cells displaying the SN-2 configuration increased with the growth of guinea pig oocytes, suggesting that this configuration presents the potential for maturation in oocytes. Oocytes derived from larger follicle exhibited increased meiotic potential. Serum starvation affected the GV chromatin configurations of guinea pig oocytes. CONCLUSIONS: Collectively, these results suggest that the SN-2 type might be a more mature form of configuration in guinea pig oocyte, whose proportion was associated with the follicle size and susceptible to the environment (e.g. serum concentration).

[Clinical study on prevention of recurrence of asthma in children by Xiaochuangao acupoint paste: treating winter diseases in summer].

OBJECTIVE: To verify the clinical efficacy of Xiaochuangao acupoint paste (XAP) in treating asthma in children. METHOD: Ninety children patients with asthma were randomly assigned to three groups with 30 patients each, being treated with XAP, hormone and XAP combined with hormone, respectively. The changes of the lung function and the recurrence times during one-year follow-up were observed. RESULT: Group II (Hormone group) saw higher total effective rate (69.2%) than Group I (XAP group) (63.3%) , but with no statistic difference between these two groups. Group llI (XAP and Hormone) saw the highest total effective rate (93.1%), with significant statistic difference from the other two groups (P < 0.05). All three groups saw the significant increase of the levels of FEV1, FEV11/FVC and PEF after the treatments (P < 0.05), while no statistical difference of FEV1, FEV1/FVC, PEF were observed in the three groups before the treatments. After the treatments, statistic differences of FEV1, FEV1/FVC, PEF between Group Ill and Group II were observed (P < 0.05). CONCLUSION: XAP played a role in preventing the recurrence of asthma in children. Combined with hormone, XAP showed better effects.

[Clinical observation of effects of Modified Sijunzi Decoction on the intestinal mucosal barrier of giant colon children patients].

OBJECTIVE: To study whether Modified Sijunzi Decoction (MSD) has protective effects on the intestinal mucosal barrier function of giant colon children. METHODS: Thirty-two giant colon children patients were randomly assigned to two groups. Patients in the treatment group (16 cases) took MDS after cleaning edema, while cleaning enema was given to those in the control group 10 days before operation. The affected colon tissues were cut out during the radical correction and made into slices. The secreted immunoglobulin A (SIgA) level of colonic mucosal lamina propria plasma cells ws detected using immunohistochemical assay. The colonic mucosal gland density was detected under the light microscope. The tight junction between the colon epitheliums, the epithelium microvilli, the morphologies of organelles such as mitochondria, and endoplasmic reticulum, etc. were observed under the electron microscope. RESULTS: The average number of colonic mucosal glands and the SigA value of submucosal lamina propria plasma cells were higher in the treatment group than in the control group under the high power field. Compared with the control group, more intact morphologies of organelles were observed under the electron microscope. CONCLUSION: MSD could strengthen the intestinal mucosal barrier function of giant colon children and play certain roles in protecting its functions through improving the proliferation of the intestinal mucosa cells and maintaining the integrity of the bowel mucosa, as well as enhancing the local intestinal immunity.

Prevention of anastomotic stricture with a purse-string suture technique on the gastric side during esophageal carcinoma operations: retrospective study of 463 consecutive cases.

OBJECTIVE: The objective of this study was to investigate the effect of a gastric side purse-string technique on anastomotic strictures during esophageal carcinoma operations. METHODS: From 1996 to 2005, esophageal carcinoma operations were performed on 1128 consecutive patients. Among them, 463 underwent esophagogastric anastomosis with purse-string sutures on the gastric side (purse group) and the other 665 did not (nonpurse group). Anastomotic strictures, reflux, and leakage were analyzed and compared between the two groups after the operations. RESULTS: Complete follow-up was conducted on all 1128 patients within 6 months after the operation. In contrast to the nonpurse group with a postoperative anastomotic stricture rate of 5.4% (36/665), the purse group demonstrated a significantly lower rate (0.2%, 1/463). The occurrence rates of anastomotic leakage in the nonpurse and purse groups were 0.9% (6/665) and 0.4% (2/463), respectively. Of the 17 cases of gastroesophageal reflux, 15 (15/665, 1.8%) were found in the nonpurse group and 2 (2/463, 1.1%) in the purse group. CONCLUSIONS: Thus, a purse-string suture technique on the gastric side might be an effective method for preventing the occurrence of anastomotic strictures after esophageal resection.