Mortality outcomes in diabetic metabolic dysfunction-associated fatty liver disease: non-obese versus obese individuals.

The difference in the survival of obese patients and normal-weight/lean patients with diabetic MAFLD remains unclear. Therefore, we aimed to describe the long-term survival of individuals with diabetic MAFLD and overweight/obesity (OT2M), diabetic MAFLD with lean/normal weight (LT2M), MAFLD with overweight/obesity and without T2DM (OM), and MAFLD with lean/normal weight and without T2DM (LM). Using the NHANESIII database, participants with MAFLD were divided into four groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD)-related, and cancer-related mortalities for different MAFLD subtypes were evaluated using Cox proportional hazards models. Of the 3539 participants, 1618 participants (42.61%) died during a mean follow-up period of 274.41 ± 2.35 months. LT2M and OT2M had higher risks of all-cause mortality (adjusted HR, 2.14; 95% CI 1.82-2.51; p < 0.0001; adjusted HR, 2.24; 95% CI 1.32-3.81; p = 0.003) and CVD-related mortality (adjusted HR, 3.25; 95% CI 1.72-6.14; p < 0.0001; adjusted HR, 3.36; 95% CI 2.52-4.47; p < 0.0001) than did OM. All-cause and CVD mortality rates in LT2M and OT2M patients were higher than those in OM patients. Patients with concurrent T2DM and MAFLD should be screened, regardless of the presence of obesity.

Bioinspired Superhydrophobic All-In-One Coating for Adaptive Thermoregulation.

The development of scalable and passive coatings that can adapt to seasonal temperature changes while maintaining superhydrophobic self-cleaning functions is crucial for their practical applications. However, the incorporation of passive cooling and heating functions with conflicting optical properties in a superhydrophobic coating is still challenging. Herein, an all-in-one coating inspired by the hierarchical structure of a lotus leaf that combines surface wettability, optical structure, and temperature self-adaptation is obtained through a simple one-step phase separation process. This coating exhibits an asymmetrical gradient structure with surface-embedded hydrophobic SiO2 particles and subsurface thermochromic microcapsules within vertically distributed hierarchical porous structures. Moreover, the coating imparts superhydrophobicity, high infrared emission, and thermo-switchable sunlight reflectivity, enabling autonomous transitions between radiative cooling and solar warming. The all-in-one coating prevents contamination and over-cooling caused by traditional radiative cooling materials, opening up new prospects for the large-scale manufacturing of intelligent thermoregulatory coatings.

Forced capillary wetting of viscoelastic fluids.

HYPOTHESIS: Achieving rapid capillary wetting is highly desirable in nature and industries. Previous endeavors have primarily concentrated on passive wetting strategies through surface engineering. However, these approaches are inadequate for high-viscosity fluids due to the significant viscous resistance, especially for non-Newtonian fluids. In contrast, forced wetting emerges as a promising method to address the challenges associated with achieving rapid wetting of non-Newtonian fluids in capillaries. EXPERIMENTS: To investigate the forced wetting behavior of viscoelastic fluids in capillaries, we employ Xanthan Gum (XG) aqueous solutions as target fluids with the storage modulus significantly exceeding the loss modulus. We utilize smooth glass capillaries connected to a syringe pump to achieve high moving speeds of up to 1 m/s. FINDINGS: Our experiments reveal a significant distinction in the power-law exponent that governs the scaling relationship between the dynamic contact angle and velocity for viscoelastic fluids compared to Newtonian fluids. This exponent is considerably smaller and varies based on the concentration of viscoelastic fluids and the diameter of the capillaries. We suggest that the viscosity dominates the wetting dynamics of viscoelastic fluids, manifested by the contact line morphology-dependent behavior. This insight has significant implications for microfluidics and drug injectability.

Lung imaging characteristics in a patient infected with Elizabethkingia miricola following cerebral hemorrhage surgery: A case report.

BACKGROUND: Elizabethkingia miricola is a non-fermenting gram-negative bacterium, which was first isolated from the condensate of the Russian peace space station in 2003. Most studies on this bacterium have been carried out in the laboratory, and clinical case studies are rare. To date, a total of 6 clinical cases have been reported worldwide. CASE SUMMARY: We present the first case of postoperative pulmonary infection in a patient with intracerebral hemorrhage due to Elizabethkingia miricola. The imaging characteristics of pulmonary infection were identified and the formulation and selection of the clinical treatment plan for this patient are discussed. CONCLUSION: Elizabethkingia miricola infection is rare. When pulmonary infection occurs, computed tomography imaging may show diffuse distribution of a ground glass density shadow in both lungs, the air containing bronchial sign in local areas, thickening of bronchial vascular bundle, and pleural effusion.

Developing a hypertension visualization risk prediction system utilizing machine learning and health check-up data.

As an important risk factor for many cardiovascular diseases, hypertension requires convenient and reliable methods for prevention and intervention. This study designed a visualization risk prediction system based on Machine Learning and SHAP as an auxiliary tool for personalized health management of hypertension. We used ten Machine Learning algorithms such as random forests and 1617 anonymized health check data to build ten hypertension risk prediction models. The model performance was evaluated through indicators such as accuracy, F1-score, and ROC curve. We used the best-performing model combined with the SHAP algorithm for feature importance analysis and built a visualization risk prediction system on the web page. The LightGMB model exhibited the best predictive performance, and age, alkaline phosphatase, and triglycerides were important features for predicting the risk of hypertension. Users can obtain their risk probability of hypertension and determine the focus of intervention through the visualization system built on the web page. Our research helps doctors and patients to develop personalized prevention and intervention programs for hypertension based on health check data, which has significant clinical and public health significance.

Hierarchically structured passive radiative cooling ceramic with high solar reflectivity.

Passive radiative cooling using nanophotonic structures is limited by its high cost and poor compatibility with existing end uses, whereas polymeric photonic alternatives lack weather resistance and effective solar reflection. We developed a cellular ceramic that can achieve highly efficient light scattering and a near-perfect solar reflectivity of 99.6%. These qualities, coupled with high thermal emissivity, allow the ceramic to provide continuous subambient cooling in an outdoor setting with a cooling power of >130 watts per square meter at noon, demonstrating energy-saving potential on a worldwide scale. The color, weather resistance, mechanical robustness, and ability to depress the Leidenfrost effect are key features ensuring the durable and versatile nature of the cooling ceramic, thereby facilitating its commercialization in various applications, particularly building construction.

Protective effects of brain and muscle ARNT-like gene 1 on oxidized low-density lipoprotein-induced human brain microvascular endothelial cell injury by alleviating ferroptosis.

Ferroptosis plays an important role in atherosclerotic cerebrovascular diseases. The brain and muscle ARNT-like gene 1 (BMAL1) is an important mediator in the progression of cerebrovascular diseases. However, whether BMAL1 regulates ferroptosis in atherosclerotic cerebrovascular diseases remains obscure. Here, human brain microvascular endothelial cells (HBMECs) were exposed to oxidized low-density lipoprotein (ox-LDL) to imitate cerebrovascular atherosclerosis. It was found that ox-LDL treatment induced ferroptosis events and reduced BMAL1 expression in HBMECs, which could be reversed by ferroptosis inhibitor ferrostatin-1. Furthermore, BMAL1 overexpression markedly mitigated ox-LDL-induced ferroptosis events and cell damage. Moreover, BMAL1 overexpression significantly promoted nuclear factor erythroid 2-related factor 2 (Nrf2) expression in HBMECs under ox-LDL conditions. And, Nrf2 silencing attenuated the protective effects of BMAL1 on ox-LDL-stimulated HBMEC damage and ferroptosis. Altogether, our findings delineate the cerebrovascular protective role of BMAL1/Nrf2 by antagonizing ferroptosis in response to ox-LDL stimulation and provide novel perspectives for therapeutic strategies for atherosclerotic cerebrovascular diseases.

Urine miR-93-5p is a promising biomarker for early detection of HBV-related hepatocellular carcinoma.

INTRODUCTION: The mortality rate of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)continues to increase because sensitive, early and readily available diagnostic tools are lacking. To address this problem, we aimed to identify diagnosticbio markers to be used for early detection of HCC. MATERIALS AND METHODS: miR-93-5p was selected as a candidate biomarker based on the analyses of relevant Gene Expression Omnibus (GEO) datasets; it was validated using qPCR to quantify its expression levels in tissue, plasma and saliva sample sets. RESULTS: miR-93-5p was significantly upregulated in HBV-related HCC tissue. Notably, miR-93-5p in plasma and urine was also significantly increased in patients with early HBV-related HCC. The expression of miR-93-5p was significantly and positively correlated in pairwise comparisons of samples (tissue vs. plasma, tissue vs. urine, plasma vs. urine). Moreover, after curative hepatectomy,miR-93-5p in plasma and urine decreased significantly over one month after the curative hepatectomy and returned to normal levels. Furthermore, receiver operating characteristic (ROC) analysis indicated that both plasma and urine miR-39-5p could detect be used to early, advanced and overall HBV-related HCC cases with more than 85% sensitivities and 93% of specificities. Finally, urine miR-93-5p could be used to predict progress-free survival for early HCC patients who received curative hepatectomy and overall survival for advanced HCC patients without curative treatments. CONCLUSIONS: Plasma and urine miR-93-5p show great promise as potential novel biomarkers for early detection of HBV-related HCC. Moreover, urine miR-93-5p could be used to predict the prognosis of patients with HBV-related HCC.

A Review of Foreign Language Enjoyment and Engagement.

The introduction of positive psychology into foreign/second language learning has led to a multitude of novel theoretical and empirical studies. Foreign language enjoyment (FLE) is regarded as a response to the widely examined concept of classroom anxiety. The majority of these studies have investigated the effect of learners' and teachers' characteristics (Xie and Derakhshan, 2021) pertaining to FLE on learners' academic achievement and their engagement in classroom tasks. Following a seminal study by Dewaele and MacIntyre (2014) and the development of the primary FLE scale, some researchers evaluated the extent of learners' enjoyment in the language learning environment; these studies approved the effectiveness and prominence of FLE throughout the learning process. The present review is an attempt to review studies on FLE during the past two decades. The related literature confirms the significance and efficiency of promoting FLE in the classroom because it brings about higher levels of motivation and engagement among language learners and leads to prolonged success and achievement. A summary of the major efforts regarding this area of research is presented in this study.

Culprit vascular patterns and surgical outcomes of hemifacial spasm caused by an AICA segment passing between cranial nerve VII and VIII: A series of 25 cases.

OBJECTIVE: To report the vascular anatomic characteristics and surgical outcomes of hemifacial spasm (HFS) caused by an anterior inferior cerebellar artery (AICA) segment passing between cranial nerve VII (CN VII) and cranial nerve VIII (CN VIII). PATIENTS AND METHODS: This case series study retrospectively reviewed records of 1040 consecutive patients treated with MVD for HFS in our hospital in 10 years. 25 patients had the culprit vessel recorded as an AICA segment passing between CN VII and CN VIII. Vascular anatomic characteristics were reviewed from intraoperative microscopic videos. The clinical outcomes were followed up at 3-month and 1-year time points. RESULTS: The culprit AICA segments feature 3 discrete anatomic patterns. The patterns denoted as pattern A, B, and C were identified in 19(76%), 3(12%), and 3 (12%) of the 25 patients respectively. Postoperative spasm relief were achieved in 19(76%), 22(88%), and 23 (92%) of the patients at immediately after surgery, 3-month, and 1-year follow-up respectively. 3(12%) of them have permanent postoperative cranial nerve deficits, including one patient with hearing loss and 2 patients with vocal cord palsy. CONCLUSIONS: Though an AICA segment passing between CN VII and CN VIII is common, very rarely it was deemed the culprit for HFS in our patients. We used fREZ centered definition and operation. We found the culprit AICA segments feature 3 discrete anatomic patterns. We observed good spasm relief outcome and relatively fewer complications with CN VII and CN VIII. Identifying the 3 anatomic patterns may help with a smooth decision-making when vascular compression by an AICA segment passing between CN VII and CN VIII is suspected.

The Preparation, Determination of a Flexible Complex Liposome Co-Loaded with Cabazitaxel and ß-Elemene, and Animal Pharmacodynamics on Paclitaxel-Resistant Lung Adenocarcinoma.

Paclitaxel is highly effective at killing many malignant tumors; however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and ß-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, ß-elemene liposome and cabazitaxel-ß-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and ß-elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and ß-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and ß-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and ß-elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that ß-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.

Drug delivery systems for elemene, its main active ingredient ß-elemene, and its derivatives in cancer therapy.

ß-elemene is a noncytotoxic Class II antitumor drug extracted from the traditional Chinese medicine Curcuma wenyujin Y. H. Chen et C. Ling. ß-elemene exerts its effects by inhibiting cell proliferation, arresting the cell cycle, inducing cell apoptosis, exerting antiangiogenesis and antimetastasis effects, reversing multiple-drug resistance (MDR), and enhancing the immune system. Elemene injection and oral emulsion have been used to treat various tumors, including cancer of the lung, liver, brain, breast, ovary, gastric, prostate, and other tissues, for >20 years. The safety of both elemene injection and oral emulsion in the clinic has been discussed. Recently, the secondary development of ß-elemene has attracted the attention of researchers and made great progress. On the one hand, studies have been carried out on liposome-based systems (including solid lipid nanoparticles [SLNs], nanostructured lipid carriers [NLCs], long-circulating liposomes, active targeting liposomes, and multidrug-loaded liposomes) and emulsion systems (including microemulsions, self-emulsion drug delivery systems [SEDDSs], and active targeting microemulsion) to solve the issues of poor solubility in water, low bioavailability, and severe phlebitis, as well as to improve antitumor efficacy. The pharmacokinetics of different drug delivery systems of ß-elemene are also summarized. On the other hand, a number of highly active anticancer ß-elemene derivatives have been obtained through modification of the structure of ß-elemene. This review focuses on the two drug delivery systems and derivatives of ß-elemene for cancer therapy.

The PPARγ agonist rosiglitazone sensitizes the BH3 mimetic (-)-gossypol to induce apoptosis in cancer cells with high level of Bcl-2.

The BH3 mimetic (-)-gossypol (-)-G has shown promising efficacy to kill several kinds of cancer cells or potentiate current chemotherapeutics. But it induces limited apoptosis in cancer cells with high level of Bcl-2. The nuclear receptor PPARγ and its agonist rosiglitazone can suppress various malignancies. More importantly, rosiglitazone is able to enhance the anti-tumor effects of chemotherapy drugs such as carboplatin and tyrosine kinase inhibitors. In this study, we for the first time demonstrated that rosiglitazone could sensitize (-)-G to induce apoptosis in cancer cells with high level of Bcl-2. Furthermore, we found that (-)-G increased the mRNA level and protein stability of Mcl-1, which weakened the pro-apoptotic effect of (-)-G. Rosiglitazone attenuated the (-)-G-induced Mcl-1 stability through decreasing JNK phosphorylation. Additionally, rosiglitazone upregulated dual-specificity phosphatase 16 (DUSP16), leading to a reduction of (-)-G-triggered JNK phosphorylation. Animal experiments showed that rosiglitazone could sensitize (-)-G to repress the growth of cancer cells with high level of Bcl-2 in vivo. Taken together, our results suggest that the PPARγ agonists may enhance the therapeutic effect of BH3 mimetics in cancers with high level of Bcl-2 through regulating the DUSP16/JNK/Mcl-1 singling pathway. This study may provide novel insights into the cancer therapeutics based on the combination of PPARγ agonists and BH3 mimetics.

Neuroprotective effects of p53/microRNA­22 regulate inflammation and apoptosis in subarachnoid hemorrhage.

The present study aimed to investigate whether the neuroprotective effects of p53/microRNA­22 regulate inflammation and apoptosis in subarachnoid hemorrhage (SAH). In a mouse model of SAH, microRNA­22 expression was upregulated. In addition, downregulation of microRNA­22 in HEB cells increased the mRNA expression levels of interleukin (IL)­6, induced cysteine rich angiogenic inducer 61 (Cyr61) expression, and suppressed the protein expression levels of B­cell lymphoma 2­associated X protein (Bax) and caspase­3 activity. Treatment with the p53 inhibitor, pifithrin­α, suppressed p53 protein expression, increased IL­6 mRNA expression, decreased microRNA­22 expression, Bax protein expression and caspase­3 activity, and induced Cyr61 expression in mice with SAH. Furthermore, p53 expression was knocked down using p53 small interfering RNA, which suppressed microRNA­22 expression and increased IL­6 mRNA expression, inhibited Bax protein expression and caspase­3 activity, and induced Cyr61 expression in HEB cells. The present study demonstrated that the neuroprotective effects of p53/microRNA­22 may regulate inflammation and apoptosis in SAH. Reverse transcription quantitative polymerase chain reaction (qPCR) was used to analyze the expression of microRNA-22, western blot analysis was used to analyze the protein expression of Bax and Cyr61.

Induction of SOCS3 by liver X receptor suppresses the proliferation of hepatocellular carcinoma cells.

Liver X receptor (LXR), a member of nuclear receptor superfamily, is involved in the regulation of glucose, lipid and cholesterol metabolism. Recently, it has been reported that LXR suppress different kinds of cancers including hepatocellular carcinoma (HCC). However, the corresponding mechanism is still not well elucidated. In the present study, we found that activation of LXR downregulated cyclin D1 while upregulated p21 and p27 by elevating the level of suppressor of cytokine signaling 3 (SOCS3), leading to the cell cycle arrest at G1/S phase and growth inhibition of HCC cells. Moreover, we demonstrated that LXRα (not LXRß) mediated the induction of SOCS3 in HCC cells. Subsequently, we showed that LXR activation enhanced the mRNA stability of SOCS3, but had no significant influence on the transcriptional activity of SOCS3 gene promoter. The experiments in nude mice revealed that LXR agonist inhibited the growth of xenograft tumors and enhanced SOCS3 expression in vivo. These results indicate that "LXRα-SOCS3-cyclin D1/p21/p27" is a novel pathway by which LXR exerts its anti-HCC effects, suggesting that the pathway may be a new potential therapeutic target for HCC treatment.

Inhibition of COX2 enhances the chemosensitivity of dichloroacetate in cervical cancer cells.

Dichloroacetate (DCA), a traditional mitochondria-targeting agent, has shown promising prospect as a sensitizer in fighting against malignancies including cervical cancer. But it is unclear about the effect of DCA alone on cervical tumor. Moreover, previous reports have demonstrated that the increased cyclooxygenase-2 (COX2) expression is associated with chemoresistance and poor prognosis of cervical cancer. However, it is still unknown whether COX2 can affect the sensitivity of DCA in cervical cancer cells. In this study, we found that cervical cancer cells were insensitive to DCA. Furthermore, we for the first time revealed that DCA could upregulate COX2 which impeded the chemosensitivity of DCA in cervical cancer cells. Mechanistic study showed that DCA reduced the level of RNA binding protein quaking (QKI), leading to the decay suppression of COX2 mRNA and the subsequent elevation of COX2 protein. Inhibition of COX2 using celecoxib could sensitize DCA in repressing the growth of cervical cancer cells both in vitro and in vivo. These results indicate that COX2 is a novel resistance factor of DCA, and combination of celecoxib with DCA may be beneficial to the treatment of cervical cancer.

HSF1 upregulates ATG4B expression and enhances epirubicin-induced protective autophagy in hepatocellular carcinoma cells.

Considerable evidences have shown that both heat shock transcription factor 1 (HSF1) and autophagy can attenuate the sensitivity of hepatocellular carcinoma (HCC) cells to chemotherapeutic reagents. However, it is still little known whether HSF1 is associated with autophagy in regulating the chemosensitivity of HCC cells. In this study, we for the first time demonstrated that HSF1 markedly attenuated the killing effect of epirubicin (EPI) to HCC cells via enhancing the EPI-induced protective autophagy. Mechanistically, HSF1 upregulated autophagy related 4B (ATG4B) in HCC cells, which enhanced the EPI-triggered protective autophagy. Reporter assay showed that HSF1 increased the transcriptional activity of ATG4B gene promoter, and chromatin immunoprecipitation assay verified that HSF1 bound to the site (-1429 to -1417) in ATG4B gene promoter region. The experiments in nude mice showed that knockdown of HSF1 or ATG4B strengthened the anti-HCC effect of EPI in vivo. Collectively, these results revealed that HSF1 elevates ATG4B via promoting its transcription, which alleviates the sensitivity of EPI in HCC cells through enhancing protective autophagy, suggesting that the "HSF1/ATG4B/protective autophagy" pathway may be a novel target for developing sensitizing strategy to HCC chemotherapy.

lncRNA HULC promotes the growth of hepatocellular carcinoma cells via stabilizing COX-2 protein.

Highly upregulated in liver cancer (HULC), a lncRNA overexpressed in hepatocellular carcinoma (HCC), has been demonstrated to be involved in the carcinogenesis and progression of HCC. However, the mechanisms of HULC promoting the abnormal growth of HCC cells are still not well elucidated. In the present study, we for the first time demonstrated that HULC promoted the growth of HCC cells through elevating COX-2 protein. Moreover, the study of the corresponding mechanism by which HULC upregulated COX-2 showed that HULC enhanced the level of ubiquitin-specific peptidase 22 (USP22), which decreased ubiquitin-mediated degradation of COX-2 protein by removing the conjugated polyubiquitin chains from COX-2 and finally stabilized COX2 protein. In addition, knockdown of USP22 or COX-2 attenuated HULC-mediated abnormal growth of HCC cells. In conclusion, our results demonstrated that "USP22/COX-2" axis played an important role in HULC promoting growth of HCC cells. The identification of this novel pathway may pave a road for developing new potential anti-HCC strategies.

Metformin Synergizes with BCL-XL/BCL-2 Inhibitor ABT-263 to Induce Apoptosis Specifically in p53-Defective Cancer Cells.

p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the proapoptotic machineries in various p53-defective cancer cells. Mechanistic studies revealed that metformin sensitized ABT-263 via attenuating mTORC1-mediated cap-dependent translation of MCL-1 and survivin and weakening internal ribosome entry site (IRES)-dependent translation of XIAP Meanwhile, ABT-263 sensitized metformin through disrupting the BCL-XL/BIM complex. However, metformin and ABT-263 had no synergistic killing effect in p53 wild-type (p53-WT) cancer cells because the cotreatment dramatically induced the senescence-associated secretory phenotype (SASP) in the presence of wild type p53, and SASP could aberrantly activate the AKT/ERK-mTORC1-4EBP1-MCL-1/survivin signaling axis. Blocking the axis using corresponding kinase inhibitors or neutralizing antibodies against different SASP components sensitized the cotreatment effect of metformin and ABT-263 in p53-WT cancer cells. The in vivo experiments showed that metformin and ABT-263 synergistically inhibited the growth of p53-defective (but not p53-WT) cancer cells in tumor xenograft nude mice. These results suggest that the combination of metformin and ABT-263 may be a novel targeted therapeutic strategy for p53-defective cancers. Mol Cancer Ther; 16(9); 1806-18. ©2017 AACR.

Chicoric acid suppresses BAFF expression in B lymphocytes by inhibiting NF-κB activity.

B cell activating factor belonging to the TNF family (BAFF) plays a critical role in the pathogenesis of autoimmune diseases. The inhibition of BAFF expression is an emerging therapeutic approach for these disorders. Chicoric acid (CA), a bioactive phytochemical found in several widely used traditional medicinal plants, has significant anti-inflammatory activity and anti-arthritic effects. However, the role of CA in modulation of BAFF expression remains unknown. In this study, we demonstrated that CA reduced BAFF expression in human B lymphocyte cell lines and decreased the DNA-binding activity of nuclear factor-κB (NF-κB) in the BAFF promoter region. Furthermore, CA inhibited both the nuclear translocation of p65 (the subunit of NF-κB) and the phosphorylation of IκBα (inhibitor of NF-κB). These results suggest that CA suppresses BAFF expression by inhibiting NF-κB activity, and CA may serve as a novel therapeutic agent to down-regulate excessive BAFF expression in autoimmune diseases.