Emotions, COVID-19 related thoughts and satisfaction with life during the critical period from control to relaxation.

Introduction: In the context of declining mortality rates and increasing infectivity, it has become unavoidable for the majority of individuals to experience a COVID-19 infection at some point. This study aimed to investigate the psychological well-being of the general population during China's transition period from strict control measures to relaxed policies in COVID-19 prevention and control, as well as the impact of COVID-19 related thoughts on emotion and life satisfaction during widespread infections. Methods: A cross-sectional study was conducted involving a sample size of 1578 participants. Participants completed self-report questionnaires assessing positive and negative emotions, thoughts about COVID-19, and satisfaction with life. Demographic characteristics such as sex, age, and education level were controlled for in the analysis. Results: The findings revealed that individuals who had been infected with COVID-19 (specifically the Omicron variant BA.5.2 or BF.7) reported lower levels of positive emotions compared to those who were uninfected or had recovered from the infection. There was a significant relationship between COVID-19-related thoughts, emotions, and life satisfaction. Positive COVID-19 related thoughts were found to mediate the relationship between negative emotions and satisfaction with life. Discussion: This study represents a comprehensive examination conducted in China, focusing on assessing the impact of the COVID-19 pandemic on the general population during the critical transition period from control to relaxation. Throughout this period, the number of infections experienced fluctuations, initially rising but eventually declining over a one-month span. In such a momentous historical period, maintaining a positive perspective on COVID-19 and its management becomes paramount in enhancing the emotional well-being, life satisfaction and overall well-being of individuals.

Interleukin-37b Suppressed ILC2s in Children with Allergic Rhinitis.

Background: Interleukin-37b is a fundamental inhibitor of innate and acquired immunity. Type 2 innate lymphoid cells (ILC2s) can secret type 2 cytokines and regulate allergic rhinitis (AR). However, the role of IL-37b in ILC2s in children with AR was not clear. Methods: We recruited 15 AR children and controls. The serum IL-37b levels and its relation with the frequency and functional phenotype of ILC2s. The regulation of IL-37b on ILC2s proliferation and function was confirmed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-1R8, IL-18Rα, and ICOSL was examined using RCR. The change of IL-37b protein level in serum during subcutaneous allergen immunotherapy (SCIT) was determined by ELISA. Results: We have demonstrated that both of the frequencies of blood ILC2s, IL-5+ILC2s, and IL-13+ILC2s in AR children were elevated compared with controls. The serum protein level of IL-37b was downregulated in AR, and it was negatively related to the frequency of ILC2s, IL-5+ILC2s, and IL-13+ILC2s. IL-37b increased the mRNA levels of IL-1R8, IL-18Rα, and ICOSL expressed by ILC2s. IL-37b suppressed the proliferation of ILC2s and the secretion of IL-5 and IL-13 from ILC2s. Finally, we found that IL-37b was increased in AR children after 3 years' SLIT, especially in the good response group. Conclusion: Our findings highlight the role of IL-37b in the suppression of ILC2s and establish a new therapeutic target in AR.

Inhibited interleukin 35 expression and interleukin 35-induced regulatory T cells promote type II innate lymphoid cell response in allergic rhinitis.

BACKGROUND: Interleukin (IL)-35 and IL-35-producing regulatory T cells (iTr35) have been reported to inhibit TH2 response in allergic rhinitis (AR). However, its effects on type II innate lymphoid cells (ILC2) are not well characterized. OBJECTIVE: To investigate the effect of IL-35 on ILC2 in AR. METHODS: A total of 25 patients with AR and 20 controls were recruited. The expression and regulation of IL-35 receptor in ILC2 were analyzed by real-time polymerase chain reaction. The effect of IL-35 on ILC2 differentiation and cytokine production was analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, iTr35 were cocultured with ILC2 to explore the effect of iTr35 on ILC2. The AR mice models were also established to confirm the role of IL-35 in vivo. RESULTS: The patients with AR had decreased IL-35 expression and iTr35 proportion and increased ILC2 and type II cytokines compared with the controls. Notably, IL-35 inhibited ILC2 differentiation and type II cytokine production by regulating IL-12Rß2 and gp130. IL-35 promoted the inducible costimulatory molecule expression by iTr35 and the inducible costimulatory molecule ligand expression by ILC2. IL-35-treated mice with AR presented decreased frequency and function of nasal ILC2. CONCLUSION: IL-35 inhibited ILC2 responses directly or through mutual contact between iTr35 and ILC2 in AR, suggesting that IL-35 may be used as a potential treatment target in AR.

Leptin Promoted IL-17 Production from ILC2s in Allergic Rhinitis.

BACKGROUND: Interleukin-17 plays important roles in allergic diseases. Several studies proved that leptin promoted Th17 immune responses by inducing RORγt transcription. ILC2 is an important member of the early stage of immune response. Therefore, we aimed to explore the effect of leptin on the IL-17 production by ILC2 in AR in this study. METHODS: Fifteen AR patients and fifteen healthy controls were enrolled. Serum leptin levels were measured, and their correlation with the frequency of IL-17+ ILC2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. ILC2 was stimulated by leptin, and the expression of IL-17, IL-5, and IL-13 was detected by ELISA. The correlated pathways were confirmed by real-time PCR. RESULTS: We found that serum leptin and the frequency of IL-17-producing ILC2s in AR were significantly higher compared with those in controls. After being incubated with leptin, the frequency of IL-17+ ILC2 cells and IL-17 production from ILC2 was upregulated compared with that in controls. We also found that leptin induced RORγt and Ahr expression by ILC2. Moreover, leptin-induced IL-17-producing ILC2 concomitantly expressed IL-5 and IL-13. CONCLUSIONS: Our data provide preliminary evidence that leptin-induced IL-17 production from ILC2 cells is dependent on RORγt and Ahr expression and the blockade of leptin may be a promising target for the treatment of AR.

Role of leptin in allergic rhinitis during sublingual immunotherapy.

OBJECTIVE: Increasing evidence suggests that leptin is upregulated during allergic reactions in the airway and related to the severity of disease in allergic rhinitis (AR). In this study, we aimed to investigate the expression of leptin during sublingual immunotherapy (SLIT) in AR patients. METHODS: Forty AR patients without obesity were recruited in this study. Twenty patients received house dust mite (HDM) allergen extract for SLIT and twenty patients received placebo randomly. Protein expression of leptin in serum and nasal lavage was tested by enzyme-linked immuno sorbent assay (ELISA) 1 and 2 years after SLIT treatment, respectively. Peripheral blood mononuclear cells (PBMCs) and human nasal epithelial cell were prepared and stimulated by recombinant leptin after 24 months' SLIT treatment and the induction of Th2 cytokines (IL-4/IL-5/IL-13) were detected by ELISA. RESULTS: SLIT treatment decreased the expression of leptin protein in serum and nasal lavage significantly compared with placebo group 1 and 2 years after SLIT treatment. Nasal leptin level was correlated to decreased Th2 response (IL-4/IL-5/IL-13) and enhanced Treg (IL-10/TGF-beat) response after 2 years' SLIT. We also found that SLIT decreased the ability of leptin in promoting Th2 cytokines expression by PBMCs and human nasal epithelial cell after 2 years' SLIT treatment. CONCLUSION: Changes of leptin expression in serum and nasal lavage may be correlated with Th2/Treg regulation during SLIT. Our results suggested that leptin served as an important biomarker during SLIT.

Niclosamide acts as a new inhibitor of vasculogenic mimicry in oral cancer through upregulation of miR-124 and downregulation of STAT3.

Tumors require nutrients and oxygen for growth and metastasis. Vasculogenic mimicry (VM) has been found as a new manner of blood supply, which is characterized as the formation of tumor cell-lined vessels instead of endothelial vessels. This is why angiogenesis agents targeted to endothelial cells show a limited efficacy. Up to this point, there is no effective drug reported for inhibiting VM formation. Niclosamide is an oral anti-helminthic drug used to treat human tapeworms. Recent studies have indicated that niclosamide has broad applications for cancer and other diseases. In this study, we found that niclosamide could not only inhibit proliferation and promote apoptosis of oral cancer cells, but also inhibited VM formation in vitro and in vivo through downregulation of the expression of VM-related genes VEGFA, MMP2, ROCK1 and Cdc42. In addition, niclosamide upregulated miR-124 and downregulate phosphorylated (p)-STAT3 expression. Further studies showed that, the stable highly expressing miR-124 cell line HN6-miR-124, such as niclosamide, could downregulate p-STAT3 expression. Moreover, HN6-miR­124 showed lower mobility, invasiveness and VM formation ability than control cells. Taken together, our study suggests that niclosamide functions as a new inhibitor of VM in oral cancer through upregulation of miR-124 and downregulation of STAT3, providing a new and safe potential drug candidate for anti-VM therapy.

Inhibition of CYFIP2 promotes gastric cancer cell proliferation and chemoresistance to 5-fluorouracil through activation of the Akt signaling pathway.

Gastric cancer is a common gastrointestinal malignancy that accounts for a notable proportion of cancer-associated mortalities worldwide. Cytoplasmic fragile X mental retardation 1-interacting protein 2 (CYFIP2) is a novel p53-mediated pro-apoptotic protein whose expression is decreased in gastric cancer. However, whether decreased expression of CYFIP2 contributes to gastric carcinogenesis remains unclear. In order to mimic in vivo gastric tumor CYFIP2 expression levels, the present study used short hairpin RNA targeting CYFIP2 mRNA to silence CYFIP2 expression in MGC803 and SGC7901 gastric cancer cells. Gastric cancer cells with constitutively decreased CYFIP2 expression levels were successfully established. It was observed that CYFIP2 knockdown promoted proliferation and colony formation, and inhibited apoptosis in these cells. Furthermore, 5-fluorouracil (5-FU)-induced apoptosis was decreased following inhibition of CYFIP2 expression. In SGC7901 cells, protein expression of active caspase-3 and cleaved poly (ADP-ribose) polymerase was increased following treatment with 5-FU, while phosphorylated Akt serine/threonine kinase 1 (Akt) levels were decreased. These 5-FU-induced effects were reduced following CYFIP2 knockdown. In addition, inhibition of the Akt signaling pathway using the Akt inhibitor LY294002 restored CYFIP2-knockdown SGC7901 cell chemosensitivity to 5-FU. The results of the present study demonstrate that decreased CYFIP2 expression is associated with increased gastric tumor growth in vitro and that CYFIP2 knockdown-induced activation of the Akt pro-survival signaling pathway confers resistance to 5-FU-based chemotherapy in gastric cancer cells. Therefore, combined treatment with an Akt inhibitor and chemotherapeutic drugs may improve the efficacy of gastric cancer therapy in patients with low CYFIP2 expression.

Clinical study on Kangquan Recipe (康泉方) for benign prostatic hyperplasia patients: a randomized controlled trial.

OBJECTIVE: To observe the effectiveness and safety of Kangquan Recipe (康泉方, KQR) for benign prostatic hyperplasia (BPH) patients. METHODS: One hundred and six BPH patients were randomly assigned to the treatment group (53 cases) and the control group (53 cases) according to a random number table. The treatment group was given KQR orally; the control group was given cernilton orally. After 24-week treatment, the clinical effect and safety were evaluated using the International Prostatic Symptom Score (I-PSS), quality of life (QOL), maximum flow rate (Qmax), average flow rate (Qave), residual urine volume (RUV), total prostatic volume (TPV), etc. RESULTS: After treatment, the score of I-PSS was decreased from 16.9±5.6 to 12.5±4.6 in the treatment group, significantly lower compared with the control group; the levels of Qmax and Qave were from 10.9±3.5 to 15.6±4.5 and 5.4±2.1 to 7.3±2.5 (mL/s) in the treatment group, significantly higher compared with the control group; the levels of RUV and TPV were from 70.8±28.2 to 35.2±21.8 and 37.2±16.9 to 30.1±10.8 (mL) in the treatment group, significantly lower compared with the control group (all P<0.05). The incidence rate of adverse reaction was similar between the two groups (P>0.05). CONCLUSION: KQR is effective and safe for the treatment of BPH.