Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.
Adult ; Asthenozoospermia/virology* ; COVID-19/physiopathology* ; China ; Gonadal Steroid Hormones/blood* ; Humans ; Male ; Progesterone/blood* ; Prolactin/blood* ; SARS-CoV-2 ; Semen/physiology* ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa/physiology* ; Time Factors

Pneumonia caused by SARS-CoV-2 has seriously threatened human life and health worldwide and caused a large number of deaths. Viral infection and acute inflammation are important causes of death, so it is particularly important to combine antiviral therapy with anti-inflammatory therapy. Glycyrrhizic acid, the main component of the glycyrrhizic root extract, has a wide range of pharmacological effects as well as high efficiency and low toxicity, its preparation has been widely used in the treatment of chronic hepatitis and other diseases. Glycyrrhizic acid can regulate the expression and release of a variety of cytokines and play a significant anti-inflammatory effect. At the same time, glycyrrhizic acid also showed significant inhibition towards a variety types of viruses. Therefore, the potential application of glycyrrhizic acid as COVID-19 treatment should be explored.

OBJECTIVE: To investigate the risk factors for cow's milk protein allergy (CMPA) among infants through a multicenter clinical study. METHODS: A total of 1 829 infants, aged 1-12 months, who attended the outpatient service of the pediatric department in six hospitals in Shenzhen, China from June 2016 to May 2017 were enrolled as subjects. A questionnaire survey was performed to screen out suspected cases of CMPA. Food avoidance and oral food challenge tests were used to make a confirmed diagnosis of CMPA CMPA. A multivariate logistic regression analysis was used to investigate the risk factors for CMPA. RESULTS: Among the 1 829 infants, 82 (4.48%) were diagnosed with CMPA. The multivariate logistic regression analysis showed that maternal food allergy (OR=4.91, 95%CI: 2.24-10.76, P<0.05), antibiotic exposure during pregnancy (OR=3.18, 95%CI: 1.32-7.65, P<0.05), and the introduction of complementary food at an age of <4 months (OR=3.55, 95%CI: 1.52-8.27, P<0.05) were risk factors for CMPA, while exclusive breastfeeding (OR=0.21, 95%CI: 0.08-0.58, P<0.05) and the introduction of complementary food at an age of >6 months (OR=0.38, 95%CI: 0.17-0.86, P<0.05) were protective factors. CONCLUSIONS The introduction of complementary food at an age of <4 months, maternal food allergy, and antibiotic exposure during pregnancy are risk factors for CMPA in infants.
Animals ; Cattle ; China ; Female ; Humans ; Infant ; Milk Hypersensitivity ; Milk Proteins ; Pregnancy ; Risk Factors ; Surveys and Questionnaires

Bupleurum polysaccharides (BPs) is isolated from Bupleurum smithii var. parvifolium, a key traditional Chinese medicine. The study was to investigate the effects of BPs on diabetic kidney injury. After two intraperitoneal injections of streptozotozin (STZ) 100 mg·kg, renal injury in diabetic mice was induced and BPs was orally administrated at dosages of 30 and 60 mg·kg·d. The STZ injected mice developed renal function damage, renal inflammation and fibrosis known as diabetic kidney disease (DKD). BPs significantly reduced serum creatinine level and urinary albumin excretion rate, with the attenuated swelling of kidneys. BPs treatment obviously alleviated the pathological damage of renal tissue. The progression of renal injury in BPs treated mice was inhibited with less expression of type IV collagen (Col IV), fibronectin (FN) and α-smooth muscle actin (α-SMA). The inhibition of inflammation in kidney was associated with the reduced level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). BPs administration suppressed the over-expression of toll like receptor 4 (TLR4) and high-mobility group box 1 (HMGB1) with lowered activity of nuclear factor kappa B (NF-κB) in renal tissue of diabetic mice. Oral administration of BPs effectively prevented the development ofrenal injury in diabetic mice. This study suggested that the protection provided by BPs might affect through the interruption of HMGB1-TLR4 pathway, leading to the inhibition of renal inflammation and fibrotic process.

Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg(d. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.
Animals ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; Houttuynia ; chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Inflammation ; drug therapy ; pathology ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Intestinal Mucosa ; drug effects ; metabolism ; microbiology ; pathology ; Lung ; drug effects ; metabolism ; pathology ; Male ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; pathology ; physiopathology ; Plant Extracts ; chemistry ; Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Toll-Like Receptors ; metabolism ; Zonula Occludens-1 Protein ; metabolism

Objective To observe the effects of Xingbi Wenmin Gel on serum levels of IL-4, TGF-β1 and nasal mucosa eosinophils (EOS) in allergic rhinitis (AR) rats; To discuss its mechanism of action. Methods Intraperitoneal injection of egg albumin and aluminum hydroxide based sensitized to ovalbumin challenge 2％ local AR model was established successfully. The experimental rats were randomly divided into normal group, model group, positive control group, and Xingbi Gel low-, medium-, and high-dosage groups. Each medication group was given relevant medicine for intervention. The rat symptom scores in each group were compared, and serum IL-4, TGF-β1, and nasal mucosa EOS counts were detected. Results Compared with the normal group, the serum levels of IL-4 and TGF-β1 in model group increased significantly (P<0.01), and the nasal mucosa EOS counts increased significantly (P<0.05). Compared with model group, the serum levels of IL-4 and TGF-β1 in Xingbi Gel medium-dosage group and positive control group decreased significantly (P<0.01), and the nasal mucosa EOS counts decreased significantly (P<0.05). Conclusion Xingbi Wenmin Gel may be effective through down-regulation of IL-4, TGF-β1 levels of inflammatory factors, and reduction of EOS infiltration in nasal mucosa.

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.
Albumins ; Animals ; Blood Glucose ; metabolism ; Creatinine ; blood ; Diabetic Nephropathies ; blood ; drug therapy ; genetics ; urine ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Smad Proteins ; genetics ; metabolism ; Taxus ; chemistry ; Transforming Growth Factor beta1 ; metabolism

Objective:To comprehensively investigate the environmental factors influencing maternal and neonatal telomere length at birth,and to provide evidences for exploring the role of telomere in pathogenesis and development of diseases.Methods:From March 2015 to February 2016,444 newborns and their mothers in Nanjing Drum Tower Hospital were enrolled.Questionnaire surveys,physical examinations and clinical assessments were conducted in pregnant women,and the maternal peripheral blood samples as well as their matching umbilical venous blood samples were collected.The relative telomere length was measured by quantitative PCR method.The maternal telomere length and neonatal telomere length were compared by paired t test.The telomere length between different subgroups was compared by variance analysis and t test.The correlation between maternal telomere length and neonatal telomere length as well as the correlations of telomere length with other continuous variables were analyzed by using general linear model.Results:The overall telomere length of cord blood was significantly longer than that of maternal blood (0.358 vs 0.309,P＜0.001),but there was no significant correlation between telomere length of maternal blood and telomere length of cord blood (r2 =0.004,P=0.174).There was a significant positive correlation between maternal education level and the telomere length of cord blood (P =0.022).There were no obvious correlations of maternal and neonatal telomere length with gestational age,delivery mode,newborn sex and birth weight.The more dairy intake during pregnancy,the shorter maternal telomere length (P=0.048).There were no significant differences of maternal and neonatal telomere length among different subgroups intaking fruits,vegetables,meat,animal offal,fish,shrimp,bean products,baked and preserved food,folic acid and vitamins.Coffee drinking during pregnancy was significantly associated with shorter neonatal telomere length (P=0.011).Second hand smoke exposure,alcohol consumption and tea drinking during pregnancy were not significantly associated with maternal and neonatal telomere lengths.Longer maternal telomere length was observed in those taking physical exercise during pregnancy (P=0.01),but no significant difference was observed in neonatal telomere length (P=0.187).Conclusions:Various environment exposures such as education level,intake of dairy products,coffee drinking and physical exercise during pregnancy have significant effects on maternal and neonatal telomere length.This study provides valuable clues for further revealing the role of telomere in diseases.