Potential effects and mechanism of flavonoids extract of Callicarpa nudiflora Hook on DSS-induced colitis in mice.

Callicarpa nudiflora Hook (C. nudiflora) is an anti-inflammatory, antimicrobial, antioxidant, and hemostatic ethnomedicine. To date, little has been reported regarding the activity of C. nudiflora against ulcerative colitis (UC). In this study, we investigated the effect of a flavonoid extract of C. nudiflora on Dextran Sulfate Sodium (DSS)-induced ulcerative colitis in mice. Mice in the treatment group (CNLF+DSS group) and drug-only (CNLF group) groups were administered 400 mg/kg of flavonoid extract of C. nudiflora leaf (CNLF), and drinking water containing 2.5 % DSS was given to the model and treatment groups. The symptoms of colitis were detected, relevant indicators were verified, intestinal barrier function was assessed, and the contents of the cecum were analyzed for intestinal microorganisms. The results showed that CNLF significantly alleviated the clinical symptoms and histological morphology of colitis in mice, inhibited the increase in pro-inflammatory factors (TNF-α, IL-6, IL-1ß, and IFN-γ), and increased the level of IL-10. The expression of NF-κB and MAPK inflammatory signal pathway-related proteins (p-p65, p-p38, p-ERK, p-JNK) was regulated. The expression of tight junction proteins (ZO-1, OCLDN, and CLDN1) was increased, while the content of D-LA, DAO, and LPS was decreased. In addition, 16S rRNA sequencing showed that CNLF restored the gut microbial composition, and increased the relative abundance of Prevotellaceae, Intestinimonas butyriciproducens, and Barnesiella_intestinihominis. In conclusion, CNLF alleviated colitis by suppressing inflammation levels, improving intestinal barrier integrity, and modulating the intestinal microbiota, and therefore has promising future applications in the treatment of UC.

Effect of the Pseudopleuronectes americanus-derived Pleurocidin on DSS-induced Ulcerative colitis in mice and its preliminary molecular mechanisms.

Pleurocidin is an antimicrobial peptide derived from the mucous membranes of the skin or intestinal secretions of Pseudopleuronectes americanus that has antimicrobial and immunomodulatory activities. Ulcerative colitis is recognized as a widespread human disease that may be influenced by environmental and genetic factors. Evidence emphasizes the critical role of the gut microbiota in UC. Synthetic Pleurocidin was analyzed by a combination of liquid chromatography and mass spectrometry. Pleurocidin pharmacological effects were evaluated by DAI score, colon histological score, cytokine levels, and tight junction protein expression in mice. The preliminary molecular mechanism was explored by the levels of key proteins in the NF-κB and MAPK inflammatory signaling pathways in colon tissues. The main analytical methods such as immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blot were used. We then used 16S rRNA gene sequences to characterize the gut microbiota. Firstly, our study demonstrated that rectal injection of Pleurocidin at 5 mg/kg body weight alleviated clinical symptoms and colonic histopathological changes in UC mice caused by DSS. Secondly, Pleurocidin altered the abnormal levels of inflammatory and immune-related cytokines in serum, modulated the significant down-regulation of tight junction proteins, and inhibited the expression of NF-κB and MAPK inflammatory signaling pathway-related proteins. Finally, Pleurocidin can regulate gut microbiota, increase the relative abundance of beneficial bacteria and reduce the relative abundance of harmful bacteria. In conclusion, Pleurocidin alleviates UC symptoms in mice, and its effects on the gut microbiome may be potential pathways. It is providing a promising therapeutic option for UC.

Oral administration of LfcinB alleviates DSS-induced colitis by improving the intestinal barrier and microbiota.

Ulcerative colitis (UC) is a kind of inflammatory bowel disease (IBD) that often recurs and is difficult to cure, and no drugs with few side effects are available to treat this disease. LfcinB is a small molecular peptide obtained by the hydrolysis of bovine lactoferrin in the digestive tract of animals. It has strong antibacterial and anti-inflammatory activities. However, direct evidence that LfcinB improves the condition of colitis in mice is rarely reported. In this study, UC was induced in mice by adding 2.5% dextran sulfate (DSS) to drinking water and LfcinB was orally administered. The results showed that oral administration of LfcinB improved colonic tissue damage and inflammatory cell infiltration, increased the expression of tight junction proteins, and down-regulated the phosphorylation of proteins related to the NF-κB/MAPK inflammatory signalling pathway in mice. It also significantly suppressed the relative abundance of potentially pathogenic bacteria (Bacteroides, Barnesiella and Escherichia) in the intestinal flora. In conclusion, oral administration of LfcinB significantly alleviated DSS-induced UC. This may be related to the regulation of inflammatory signalling pathways and gut microbial composition by LfcinB.

The antimicrobial peptide Abaecin alleviates colitis in mice by regulating inflammatory signaling pathways and intestinal microbial composition.

Abaecin is a natural antimicrobial peptide (AMP) rich in proline from bees. It is an important part of the innate humoral immunity of bees and has broad-spectrum antibacterial ability. This study aimed to determine the effect of Abaecin on dextran sulfate sodium (DSS) -induced ulcerative colitis (UC) in mice and to explore its related mechanisms. Twenty-four mice with similar body weight were randomly divided into 4 groups. 2.5% DSS was added to drinking water to induce colitis in mice. Abaecin and PBS were administered rectally on the third, fifth, and seventh days of the experimental period. The results showed that Abaecin significantly alleviated histological damage and intestinal mucosal barrier damage caused by colitis in mice, reduced the concentration of pro-inflammatory cytokines IL-1ß, IL-6, TNF-α, IFN-γ, and the phosphorylation of NF-κB / MAPK inflammatory signaling pathway proteins, and improved the composition of intestinal microorganisms. These findings suggest that Abaecin may have potential prospects for the treatment of UC.

Porcine-derived antimicrobial peptide PR39 alleviates DSS-induced colitis via the NF-κB/MAPK pathway.

PR39 is an antimicrobial peptide (AMP) with a variety of biological functions, including antimicrobial, wound healing, leukocyte chemotaxis, angiogenesis, and immunomodulation; however, its therapeutic efficacy in colitis (IBD) has rarely been reported. For this reason, the present study aimed to investigate the therapeutic effect of PR39 on IBD and its underlying mechanisms. In this experiment, a mouse model of ulcerative colitis (UC) was induced with 3 % dextran sulfate (DSS) and administered by rectal injection of PR39. The results of the study showed that 5 mg/kg of PR39 was able to ameliorate the clinical manifestations of DSS-induced UC mice by improving the clinical symptoms, colonic tissue damage, up-regulating the expression of tight junction proteins, and alleviating the systemic inflammation in mice in various ways. The mechanism of action may involve inhibition of the phosphorylation level of proteins related to the NF-κB/MAPK signaling pathway and modulation of the relative abundance of potentially pathogenic (Bacteroides, Pseudoflavonifractor, Barnesiella, and Oscillibacter) and potentially beneficial bacteria (Candidatus_Saccharibacteria, Desulfovibrio, Saccharibacteria) in the intestinal flora. The results enriched the biological functions of PR-39 and also suggested that PR-39 may be able to be used as a novel drug for the treatment of IBD.

Regulation of the intestinal flora using polysaccharides from Callicarpa nudiflora Hook to alleviate ulcerative colitis and the molecular mechanisms involved.

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that cannot be completely cured by current treatments. C. nudiflora Hook has antibacterial, anti-inflammatory, and hemostatic biological functions; however, the therapeutic role of C. nudiflora Hook or its extracts in IBD remains poorly understood. In this study, we extracted and purified three fractions of C. nudiflora Hook polysaccharides by hydroalcohol precipitation method, which were named as CNLP-1, CNLP-2 and CNLP-3, respectively. CNLP-2, the main component of the polysaccharides of C. nudiflora Hook is an pyranose type acidic polysaccharide composed of Fuc, Rha, Ara, Gal, Glc, Xyl, Man, Gal-UA and Glc-UA, with an Mn of 15.624 kDa; Mw of 31.375 kDa. CNLP-2 was found to have a smooth lamellar structure as observed by scanning electron microscopy. To investigate the effect of CNLP-2 (abbreviated to CNLP) on dextran sodium sulfate (DSS)-induced UC mice and its mechanism of action, we treated DSS-induced UC mice by administering CNLP at a dose of 100 mg/kg every other day. The results of the study showed that CNLP alleviated the clinical symptoms such as body weight (BW) loss, pathological damage, and systemic inflammation. The mechanism may be through the regulation of intestinal flora and its metabolism, which in turn affects the expression of NF-κB/MAPK pathway-related proteins through the metabolites of intestinal flora to further alleviate inflammation and ultimately improve the intestinal barrier function in UC mice. In conclusion, CNLP has great potential for the treatment of IBD.

Effect of purple sweet potato-derived anthocyanins on heat stress response in Wenchang chickens and preliminary mechanism study.

This study was conducted to investigate the beneficial effect of purple sweet potato anthocyanins (PSPA) on growth performance, oxidative status, immune response, intestinal morphology, and intestinal flora homeostasis in heat-stressed Wenchang chickens. A total of 100 Wenchang chickens (50-day-old) were randomly assigned to 5 groups, including the thermoneutral environment (TN) group (26°C); high-temperature stressed (HS) group (33°C ± 1°C); low-dose PSPA treatment (L_HS) group (8 mg/kg body weight, 33°C ± 1°C); medium-dose PSPA treatment (M_HS) group and high-dose PSPA treatment (H_HS) group (16 mg/kg and 32 mg/kg body weight, respectively, 33°C ± 1°C). The results showed that PSPA reversed the adverse effects of heat stress on growth performance, meat quality, and carcass characteristics. And the effect was associated with the concentration of PSPA partially. Heat stress increased the serum lipids of Wenchang chickens. LDL-C, TG, TC, and FFA in the serum were significantly decreased, and HDL-C and LPS in the serum were increased by PSPA treatment. The digestive enzymes in duodenal chyme were significantly (P < 0.05) increased by PSPA treatment. And PSPA treatment significantly (P < 0.05) enhanced the redox status by improving antioxidant parameters (GSH-Px and SOD) and decreasing the MDA level in the serum and liver. Moreover, the level of inflammatory cytokines was significantly (P < 0.05) regulated by PSPA treatment compared to the HS group. The villus length and goblet cell numbers after PSPA treatment were significantly higher than HS group. Furthermore, PSPA also played protection on the intestine structure by decreasing the level of D-LA and DAO. 16S rRNA sequencing revealed the microbial composition was altered by PSPA, and Acetanaerobacterium and Oscillibacter were dominant in the H_HS group. Microbial functional prediction indicated that function pathways based on KEGG and metacyc database were regulated by PSPA, and intestinal flora correlated with metabolic function significantly. The spearman correlation analysis showed that Saccharibacteria and Clostridium_IV correlated with the serum lipids, antioxidant, and inflammatory cytokines. Collectively, these findings suggest that PSPA has a positive effect against heat stress in poultry.

Effects of the Vitamin D3 on Alleviating the Oxidative Stress Induced by Diquat in Wenchang Chickens.

Vitamin D3 (VD3) is an indispensable micronutrient in livestock and poultry feed. Its function in antioxidant stress has been reported. We investigate whether the addition of different concentrations of VD3 to the diet affects the production performance, slaughter performance, meat quality, organ index, and gut injury on the diquat (DQ)-induced model of oxidative stress in Wenchang chickens. Four hundred and eighty one-day-old chickens were randomly divided into six groups: control (basal diet), 4000 VD (basal diet + VD3 4000 IU per kg feed intake), 1000 VD+DI (DQ, basal diet + VD3 1000 IU per kg feed intake), 2000 VD+DI (DQ, basal diet + VD3 2000 IU per kg feed intake), and 4000 VD+DI (DQ, basal diet + VD3 4000 IU per kg feed intake). The results showed that the addition of VD3 to the diet promoted DQ-induced weight loss and reduced ADFI, slaughter rate, splenic index, and pH after 1 h and 24 h in the leg muscles. VD3 decreased the increase in content of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) among proinflammatory cytokines (p < 0.05) and increased the reduction in anti-inflammatory cytokines content of interleukin-10 (IL-10) (p < 0.05) induced by DQ. In addition, liver and kidney injury biomarkers and the intestinal permeability index in serum were disordered after treatment with DQ (p < 0.05). VD3 perfected the increase of D-lactic acid (D-LA), diamine oxidase (DAO), total cholesterol (T-CHO), creatinine (CR), blood urea nitrogen (BUN), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) content, aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) activity (p < 0.05); it increased the decrease of albumin (ALB) content (p < 0.05). Meanwhile, VD3 regulated the intestinal morphology and intestinal barrier. Moreover, DQ induced a decrease in total antioxidant capacity and antioxidant enzyme activity in the serum, liver, and jejunum (p < 0.05), and an increase in malonaldehyde (MDA) content (p < 0.05). However, the addition of different levels of VD3 could alleviate the above phenomenon of oxidative stress in Wenchang chickens to different degrees. Thus, this research suggested that the addition of VD3 can relieve the DQ-induced oxidative stress of Wenchang chickens, and the level of VD3 acquisition is positively correlated with the remission effect.

[Clinical application of nose ring drain technique combined with Ilizarov circular external fixation for Gustilo â ¢A Pilon fractures].

OBJECTIVE: To investigate the effectiveness of the nose ring drain (NRD) technique combined with Ilizarov circular external fixation in treatment of Gustilo ⅢA Pilon fracture. METHODS: Between March 2017 and December 2019, 17 patients with Gustilo ⅢA Pilon fractures were admitted and treated with NRD technique combined with Ilizarov circular external fixation. Among them, there were 11 males and 6 females; the age ranged from 24 to 63 years, with an average of 38.2 years. There were 3 cases of traffic accident injury, 13 cases of falling injury, and 1 case of penetrating injury. There were 13 cases of emergency admittance and 4 cases of wound infection after surgical treatment. Furthermore, there were 2 cases of fibula fractures and 3 cases of lateral malleolus fractures. RESULTS: All patients were followed up 8-12 months, with an average of 9.9 months. All wounds healed by first intention, and 4 patients with preoperative infection had no recurrence during the follow-up. The external fixator was removed after fracture healing in 17 patients at 3-7 months after operation (mean, 4.5 months). At last follow-up, the pain score of the ankle joint Kofoe score was 40-50, with an average of 44; the functional score was 17-27, with an average of 25; the mobility score was 8-18, with an average of 14; and the effectiveness was rated as excellent in 8 cases, good in 7 cases, and poor in 1 case. CONCLUSION: For Gustilo ⅢA Pilon fractures, the NRD technique combined with Ilizarov circular external fixation has advantages of good fracture fixation and drainage effects, which greatly reduces the complications of traditional treatment options and the number of operations.

Removal, seasonal variation, and environmental impact of parabens in a municipal wastewater treatment facility in Guangzhou, China.

The occurrence, seasonal variation, and environmental impact of five widely used parabens, methyl-(MeP), ethyl-(EtP), n-propyl-(n-PrP), n-butyl-(n-BuP), and benzyl-(BzP) parabens, were investigated in a municipal wastewater treatment plant (WWTP) located in Guangzhou, China, for 1 year. The concentrations of ∑5parabens in the influent and the effluent were 94.2-957 and 0.89-14.7 ng L-1, respectively. The influent paraben concentrations in autumn were significantly lower than in winter, spring, and summer, and the concentrations were generally higher in spring. The removal efficiencies of ∑5parabens in the dissolved phase were over 96%, with high efficiencies in MeP, EtP, and n-PrP. Risk assessment indicated that parabens in the effluent were not likely to pose an environmental risk to aquatic ecosystems. The present study indicates that the treatment processes employed in full-scale WWTPs are effective at removing parabens and highlights the possibility of utilizing WWTPs for restoring water quality in riverine and coastal regions heavily impacted by paraben contamination.

Occurrence, seasonal variation and environmental impact of phosphorus flame retardants in a large scale wastewater treatment plant.

The occurrence, seasonal variation and emission of nine widely used phosphorus flame retardants (PFRs) were investigated in a wastewater treatment plant (WWTP) located in Guangzhou, China, over 1 year. Results showed that PFRs were widely detected in wastewater and sewage sludge. Tris(2-chloroisopropyl) phosphate (TCIPP) was the most dominant PFRs in influent, effluent, and sludge. Significant seasonal variation of total PFRs in the influent was observed (p < 0.05). However, no significant seasonal variation found in chlorinated and alkyl PFRs. The emission of PFRs was comparable with the previously reported values of decabromodiphenyl ether in WWTPs. Risk quotient for PFRs showed low eco-toxicity risk in effluent for aquatic organisms. Since the removal efficiency of total PFRs was less than 30% and the use of PFRs had been increasing, continuous monitoring of the environmental impact on the receiving water is still needed.

Assessing pollution and risk of polycyclic aromatic hydrocarbons in sewage sludge from wastewater treatment plants in China's top coal-producing region.

Managing and disposing of sewage sludge have been a severe environmental challenge around the world. China produces hundreds of million tons of sewage sludge annually, and a better understanding of the extent and risk of the associated pollution is of critical importance for implementing environmentally safe regulations and practices. The present study examined the quantity, composition, source, and risk of polycyclic aromatic hydrocarbons (PAHs) in sewage sludge from 18 wastewater treatment plants (WWTPs) in Shaanxi, one of China's top coal-producing provinces. The total concentrations of 16 PAHs varied from 778 to 3264 ng/g dry weight, which is below the upper safety limit (5000 ng/g dry weight) set for the disposal of sludge from municipal wastewater treatment plants for agricultural use in China. However, the concentration of individual PAH compound exceeded the acceptable level prescribed by the Netherland Soil Standard. Three-ring PAHs were the most abundant constituent (50% of total PAHs on average), followed by four-ring PAHs averaging 25%. Relative to sludge PAHs in the same region a decade ago, the total concentrations decreased by more than 27% and the composition shifted to a more pronounced dominance by low molecular weight compounds. This compositional shift suggests higher contributions of petrogenic sources, which may reflect China's increasing consumption of petroleum products over the past decade. The flux of sludge PAHs from each WWTP was positively correlated with the corresponding city's GDP and population, and the total flux amounted to over 100 kg each year for WWTPs in the Xi'an city. The mean toxicity equivalent quantity (TEQ) value was more than twice higher than the value recommended by the Netherlands Soil Standard, and seven carcinogenic PAHs were the primary contributor (i.e., 89-99%) of the TEQ. Collectively, our findings demonstrate that sewage sludge PAHs in Shaanxi constitute a significant source of environmental pollution and toxicity, which cautions against the direct discharge and reuse of sewage sludge and further highlights challenges in managing and disposing of the vast quantities of sewage sludge in China.

Organophosphorus flame retardants and heavy metals in municipal landfill leachate treatment system in Guangzhou, China.

The occurrence, distribution and removal efficiencies of organophosphorus flame retardants (OPFRs) and metals were examined in a municipal landfill leachate treatment system in Guangzhou, China. Five OPFRs and thirty-five metals were detected in wastewater samples collected at different treatment stages. ∑OPFRs was reduced from 4807.02 ng L-1 to 103.91 ng L-1 through the treatment system, with close to 98% removed from the dissolved phase. Tris(clorisopropyl) phosphates (TCPPs) dominated through the treatment process and accounted for over 80% and 50% of ∑OPFRs at the influent and the effluent, respectively. TCPPs were most efficiently removed (98.6%) followed by tris(2-chloroethyl) phosphate (TCEP) (96.6%) and triphenyl phosphate (TPP) (88.5%). For metals, Fe, Cr, and Rb were dominant in the raw leachate, detected at 7.55, 2.82, and 4.50 mg L-1, respectively. Thirteen regulated heavy metals - including eight major pollutants (i.e., As. Cd, Cr, Cu, Hg, Ni, Pb, and Zn) - have been detected in all wastewater samples at sub-mg L-1 levels. Over 99.5% removal was achieved for Cr, Ni, and Fe, and close to 95% removal efficiency was observed for Rb. For the eight major heavy metals, over 99% removal was observed; the only exception was Cu, which was removed at 89%. It was found that microfiltration/reverse osmosis was critical for the removal of OPFRs and heavy metals while the core biological treatment played a minor role towards their removal. Remobilization of Co, Cu, Fe, Hg, Mn, Ni, Sb, and Sr from the returned sludge occurred during the second denitrification, indicating the need for additional post-biological process for effective removal of both contaminants. This study highlights the critical need to develop cheap, effective treatment technologies for contaminants-laden leachate generated from open dumps and under-designed landfills.

Removal Efficiency and Risk Assessment of Polycyclic Aromatic Hydrocarbons in a Typical Municipal Wastewater Treatment Facility in Guangzhou, China.

The loading and removal efficiency of 16 US EPA polycyclic aromatic hydrocarbons (PAHs) were examined in an inverted A²/O wastewater treatment plant (WWTP) located in an urban area in China. The total PAH concentrations were 554.3 to 723.2 ng/L in the influent and 189.6 to 262.7 ng/L in the effluent. The removal efficiencies of ∑PAHs in the dissolved phase ranged from 63 to 69%, with the highest observed in naphthalene (80% removal). Concentration and distribution of PAHs revealed that the higher molecular weight PAHs became more concentrated with treatment in both the dissolved phase and the dewatered sludge. The sharpest reduction was observed during the pretreatment and the biological phase. Noncarcinogenic risk, carcinogenic risk, and total health risk of PAHs found in the effluent and sewage sludge were also assessed. The effluent BaP toxic equivalent quantities (TEQBaP) were above, or far above, standards in countries. The potential toxicities of PAHs in sewage effluent were approximately 10 to 15 times higher than the acceptable risk level in China. The health risk associated with the sewage sludge also exceeded international recommended levels and was mainly contributed from seven carcinogenic PAHs. Given that WWTP effluent is a major PAH contributor to surface water bodies in China and better reduction efficiencies are achievable, the present study highlights the possibility of utilizing WWTPs for restoring water quality in riverine and coastal regions heavily impacted by PAHs contamination.

Occurrence of PBDEs and alternative halogenated flame retardants in sewage sludge from the industrial city of Guangzhou, China.

This study investigated the prevalence and abundance of halogenated flame retardants (HFRs) in sludge samples from 5 sewage treatment plants in Guangzhou, China. Detection of 18 polybrominated diphenyl ethers (PBDEs), 9 alternative HFRs including Dechlorane Plus (DP), brominated alkylbenzenes, and polybrominated biphenyls, and 2 related degradation products was conducted. Decabromodiphenyl ether (BDE 209) and decabromodiphenyl ethane (DBDPE) were the dominant HFRs, with concentrations ranging from 200 to 2150 ng/g and 680-27,400 ng/g, respectively. The DBDPE detected was the highest level reported so far, exceeding those previously reported by 10-100 times. PBDEs were surpassed as the dominant HFRs in sewage sludge, with mean DBDPE/BDE 209 ratio exceeding 2 in all samples. The review of earlier surveys reveals that DBDPE level was surging while BDE 209 was declining. Annual emissions of BDE 209, DP, and DBDPE were estimated to be 227.9, 10.5, and 979.3 kg/yr, respectively. Although ecological risks assessment suggested low risks for the examined sludge, the key environmental properties and transformation pathways of alternative HFRs remain largely unknown. These findings prompt for further investigations on alternative HFR and sustainable management practices for HFR-laden biosolids. The HFR emission pattern revealed in this study is likely representative of other similarly industrialized regions in the post-PBDE era.

Low long non-coding RNA HOTAIR expression is associated with down-regulation of Nrf2 in the spermatozoa of patients with asthenozoospermia or oligoasthenozoospermia.

HOTAIR, a long noncoding RNA, regulates development and progression of tumor cells and function of normal stem cells. However, the role and the molecular mechanism of HOTAIR in the spermatozoa of patients with asthenozoospermia and oligoasthenozoospermia are still unclear. Herein, 45 healthy control, 45 asthenozoospermic patients and 45 oligoasthenozoospermic patients were enrolled. Initially, through analyzing HOTAIR expression, we observed a decreased level of HOTAIR expression in patients. Subsequently, we found that there was a positive correlation between HOTAIR expression and Nrf2 expression in patients. The low expression of HOTAIR was also observed to be associated with specific sperm function parameters, including motility and vitality. In the ejaculated spermatozoa from patients, low level of histone H4 acetylation of the Nrf2 gene promoter was observed. Finally, we found that downregulation of HOTAIR expression reduced histone H4 acetylation in Nrf2 promoter and Nrf2 expression. Therefore, this study demonstrated that HOTAIR expression was low in the spermatozoa of patients with asthenozoospermia and oligoasthenozoospermia, which resulted in down-regulation of Nrf2 expression. Our data suggested the decrease of HOTAIR expression led to ROS related defects in sperm function.

Artesunate exerts an anti-immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression.

Artesunate (ART), derived from a common traditional Chinese medicine, has beeen used an antimalarial for several years. In this study, the effect and mechanism of ART on anti-human cervical cancer cells was examined. The level of prostaglandin E2 (PGE2 ) and the population of CD4+CD25+Foxp3 regulatory T cells (Treg) in peripheral blood were detected by flow cytometry. In vivo antitumor activity was investigated in mice with cervical cancer by the subcutaneous injection of various concentrations of ART. The concentrations of PGE2 in the supernatants of CaSki cells were measured using an ELISA kit. Cyclooxygenase-2 (COX-2) and Foxp3 expression were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The effect of ART on the viability of CaSki and Hela cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It was identified that the level of PGE2 and the population of CD4+CD25+Foxp3 Treg cells in the peripheral blood were significantly higher in cervical cancer patients and mice with cervical cancer. ART was capable of inhibiting orthotopic tumor growth, which correlated with a decrease in the level of PGE2 and the percentage of Treg cells in mice with cervical cancer. Furthermore, ART decreased COX-2 expression and the production of PGE2 in CaSki and Hela cells. Notably, the supernatants of CaSki cells treated with ART lowered the expression of Foxp3 in Jurkat T cells, which was capable of being reversed by exogenous PGE2 . Our data revealed that ART may elicit an anti-tumor effect against cervical cancer by inhibition of PGE2 production in CaSki and Hela cells, which resulted in the decrease of Foxp3 expression in T cells. Therefore, ART may be an effective drug for immunotherapy of cervical cancer.