Effects of miR-29c on proliferation and adipogenic differentiation of porcine bone marrow mesenchymal stromal cells.

microRNAs (miRNAs), a subclass of noncoding short RNAs, direct cells fate decisions that are important for cell proliferation and cell lineage decisions. Adipogenic differentiation contributes greatly to the development of white adipose tissue, involving of highly organized regulation by miRNAs. In the present study, we screened and identified 78 differently expressed miRNAs of porcine BMSCs during adipogenic differentiation. Of which, the role of miR-29c in regulating the proliferation and adipogenic differentiation was proved and detailed. Specifically, over-expression miR-29c inhibits the proliferation and adipogenic differentiation of BMSCs, which were reversed upon miR-29c inhibitor. Interference of IGF1 inhibits the proliferation and adipogenic differentiation of BMSCs. Mechanistically, miR-29c regulates the proliferation and adipogenic differentiation of BMSCs by targeting IGF1 and further regulating the MAPK pathway and the PI3K-AKT-mTOR pathway, respectively. In conclusion, we highlight the important role of miR-29c in regulating proliferation and adipogenic differentiation of BMSCs.

The effectiveness of theory-based smoking cessation interventions in patients with chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: Smoking cessation can effectively reduce the risk of death, alleviate respiratory symptoms, and decrease the frequency of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). Effective smoking cessation strategies are crucial for the prevention and treatment of COPD. Currently, clinical interventions based on theoretical frameworks are being increasingly used to help patients quit smoking and have shown promising results. However, theory-guided smoking cessation interventions have not been systematically evaluated or meta-analyzed for their effectiveness in COPD patients. To improve smoking cessation rates, this study sought to examine the effects of theory-based smoking cessation interventions on COPD patients. METHODS: We adhered to the PRISMA guidelines for our systematic review and meta-analysis. The Cochrane Library, Web of Science, PubMed, Embase, Wanfang, CNKI, VIP Information Services Platform, and China Biomedical Literature Service System were searched from the establishment of the database to April 20, 2023. The study quality was assessed using the Cochrane Collaboration's risk assessment tool for bias. The revman5.4 software was used for meta-analysis. The I2 test was used for the heterogeneity test, the random effect model and fixed effect model were used for meta-analysis, and sensitivity analysis was performed by excluding individual studies. RESULTS: A total of 11 RCTs involving 3,830 patients were included in the meta-analysis. Results showed that theory-based smoking cessation interventions improved smoking cessation rates, quality of life, and lung function in COPD patients compared to conventional nursing. However, these interventions did not significantly affect the level of nicotine dependence in patients. CONCLUSION: Theory-based smoking cessation intervention as a non-pharmacologically assisted smoking cessation strategy has a positive impact on motivating COPD patients to quit smoking and improving their lung function and quality of life. TRIAL REGISTRATION: PROSPERO registration Number: CRD42023434357.

Elucidating the Geometric Active Sites for Oxygen Evolution Reaction on Crystalline Iron-Substituted Cobalt Hydroxide Nanoplates.

Transition-metal (oxy)hydroxides are among the most active and studied catalysts for the oxygen evolution reaction in alkaline electrolytes. However, the geometric distribution of active sites is still elusive. Here, using the well-defined crystalline iron-substituted cobalt hydroxide as a model catalyst, we reported the scanning electrochemical cell microscopy (SECCM) study of single-crystalline nanoplates, where the oxygen evolution reaction at individual nanoplates was isolated and evaluated independently. With integrated prior- and post-SECCM scanning electron microscopy of the catalyst morphology, correlated structure-activity information of individual electrocatalysts was obtained. Our result reveals that while the active sites are largely located at the edges of the pristine Co(OH)2 nanoplates, the Fe lattice incorporation significantly promotes the basal plane activities. Our approach of correlative imaging provides new insights into the effect of iron incorporation on active site distribution across nano-electrocatalysts.

A pH-sensitive intelligent packaging film harnessing Dioscorea zingiberensis starch and anthocyanin for meat freshness monitoring.

Abundant starch was isolated from Dioscorea zingiberensis C.H. Wright, a novel and underutilized industrial crop resource. In this study, an intelligent packaging film able to indicate food freshness was developed and characterized. D. zingiberensis starch (DZS) was bleached first, and its particle size, total starch content, amylose content, and gelatinization temperature were then measured. Butterfly pea (Clitoria ternatea Linn.) flowers were selected as the source of polyphenols, which rendered the prepared film intelligent and progressively blue-violet. SEM and FT-IR analyses showed the homogeneous dispersion of butterfly pea flower extract (BPE) in the film. The BPE-loaded film showed improved flexibility and resistance to UV and oxidation while maintaining sufficient mechanical strength and physical properties. Moreover, the film underwent a distinguishable color change from red to blue-violet and finally to green-yellow with increasing pH from 2 to 13. Similar color alteration also occurred when the film was exposed to ammonia. When the film was used to monitor the freshness of chicken stored at room temperature, it exhibited an obvious color change, implying its deterioration. Therefore, the newly developed BPE-DZS film, which was produced from readily accessible natural substances, can serve as an intelligent packaging material, indicating food freshness and prolonging shelf life.

Single-Entity Electrochemistry of Nano- and Microbubbles in Electrolytic Gas Evolution.

Gas bubbles are found in diverse electrochemical processes, ranging from electrolytic water splitting to chlor-alkali electrolysis, as well as photoelectrochemical processes. Understanding the intricate influence of bubble evolution on the electrode processes and mass transport is key to the rational design of efficient devices for electrolytic energy conversion and thus requires precise measurement and analysis of individual gas bubbles. In this Perspective, we review the latest advances in single-entity measurement of gas bubbles on electrodes, covering the approaches of voltammetric and galvanostatic studies based on nanoelectrodes, probing bubble evolution using scanning probe electrochemistry with spatial information, and monitoring the transient nature of nanobubble formation and dynamics with opto-electrochemical imaging. We emphasize the intrinsic and quantitative physicochemical interpretation of single gas bubbles from electrochemical data, highlighting the fundamental understanding of the heterogeneous nucleation, dynamic state of the three-phase boundary, and the correlation between electrolytic bubble dynamics and nanocatalyst activities. In addition, a brief discussion of future perspectives is presented.

Essential Oil Compositions, Antioxidant Activities, and Procollagen Synthesis Abilities of Four Lavandula angustifolia Varieties.

BACKGROUND: Lavender is an essential commercial crop with multiple varieties grown in the Ili River valley. The lavender essential oils (LEOs) produced from various vary in quality. METHODS: This study evaluated the biological activity of LEOs from the four commonly planted Lavandula angustifolia cultivars (L.Angustifolia 'Xinxun-1'-'Xinxun-4') in Ili. The chemical composition, antioxidant activity, and effect on human skin fibroblasts were analyzed. RESULTS: Gas chromatography results, coupled with flame ionization detection and mass spectrometry of the LEOs, indicated the presence of linalool, linalyl acetate, geranyl acetate, and trans-ß-ocimene as the significant components of the essential oils. All LEOs exhibited significant antioxidant activity, with Xinxun3 oil exhibiting the most vigorous activity. Xinxun2 showed the highest ferrous ion chelating activity and reducing power, displaying the most increased collagen regeneration activity. CONCLUSION: To our knowledge, this is the first report on the collagen regeneration ability of LEO from the Ili river valley and reveals Xinxun2 as a potential collagen regeneration promoter.

A Theranostic Nanocomplex Combining with Magnetic Hyperthermia for Enhanced Accumulation and Efficacy of pH-Triggering Polymeric Cisplatin(IV) Prodrugs.

Although polymeric platinum(IV) (Pt(IV)) prodrugs can reduce the side effects of cisplatin, the efficacy of the prodrug is still limited by its non-targeted distribution, poor penetration in deep tumor tissue, and low cytotoxicity in tumor cells. To improve the clinical potential of polymeric prodrug micelle, we synthesized amphiphilic polymeric Pt(IV) with high Pt content (22.5%), then developed a theranostic nanocomplex by integrating polymeric Pt(IV) with superparamagnetic Mn0.6Zn0.4Fe2O4 via simple self-assembly. Due to the high content of Mn0.6Zn0.4Fe2O4 (41.7% w/w), the theranostic nanocomplex showed high saturation magnetization (103.1 emu g-1) and excellent magnetocaloric effect (404 W g-1), both of them indicating its advantages in efficient magnetic targeting (MT), magnetic hyperthermia (MH), and magnetic resonance imaging (MRI). In vitro, in combination with MH, the theranostic nanocomplex showed as high cytotoxicity as cisplatin because of a significant increase in platinum of cellular uptake. In vivo, the accumulation of theranostic nanocomplex in tumors was increased by MT and confirmed by MRI. Furthermore, MH improved penetration of theranostic nanocomplex in tumors as expanding blackened area in tumors was observed by MRI. Based on these properties, the theranostic nanocomplex, under the assistance of MT and MH, showed the highest tumor growth inhibition rate (88.38%) after different treatments, while the body weight of mice increased slightly, indicating low side effects compared to those of cisplatin. The study provided an advanced theranostic nanocomplex with low toxicity and high efficacy, indicating a great clinical potential of polymeric Pt(IV).

The efficacy of function-preservation in treating paranasal sinus and nasal cavity neoplasms.

Background: Craniofacial resection (CFR) has been regarded as the gold standard for paranasal sinus and nasal cavity (PNSNC) neoplasms. The improvement of surgical procedures has been ongoing in recent years. We analyzed the clinical curative effects of the function-preservation therapy that was mainly using nasal endoscopic surgery along with appropriate radiotherapy and chemotherapy as applicable. Methods: We performed a retrospective analysis of factors that influence the survival time of the 28 patients with PNSNC neoplasms who underwent nasal endoscopic surgery. All patients with tumor lesions underwent a complete resection in en bloc or piecemeal resection. Five cases did not undergo radiotherapy or chemotherapy; the remaining 23 patients had multimodality therapy. Results: The median follow-up time was 41.5 (range = 14-97) months. The overall 3-year survival rate was 78.57% for T3 cancer and 50% for those with T4. T classification (P = 0.031) and multimodality therapy (P = 0.038) were independent prognostic factors for postoperative 3-year survival rate of patients with PNSNC neoplasms. Conclusion: Function-preservation therapy based on the minimally invasive endoscopic resection (MIER) with appropriate adjuvant therapy not only prolonged the overall survival time but also provided an opportunity to preserve organ function at the same time, which helped to improve the patients' quality of life.

Circ-PITX1 Promotes the Progression of Non-Small Cell Lung Cancer Through Regulating the miR-1248/CCND2 Axis.

BACKGROUND: Circular RNA (circRNA) is a key regulator of cancer, and it has been proved to be involved in the regulation of cancer progression including non-small cell lung cancer (NSCLC). Circ-PITX1 was found to be a significantly upregulated circRNA in NSCLC, and its role and potential mechanism in NSCLC progression deserve further investigation. METHODS: The expression levels of circ-PITX1, microRNA (miR)-1248 and cyclin D2 (CCND2) were examined by quantitative real-time PCR (qRT-PCR). Cell proliferation, apoptosis, cell cycle process, migration and invasion were determined using cell counting kit 8 (CCK8) assay, colony formation assay, flow cytometry, wound healing assay and transwell assay. Xenograft models were built to explore the role of circ-PITX1 in NSCLC tumor growth in vivo. The glycolysis and glutamine metabolism of cells were assessed by detecting the consumptions of glucose and glutamine, cell extracellular acidification rate (ECAR), and the productions of lactate, α-ketoglutaric acid (α-KG) and ATP. The protein levels of hexokinase 2 (HK-2), glutaminase 1 (GLS1) and CCND2 were tested by Western blot (WB) analysis. Dual-luciferase reporter assay and RIP assay were employed to verify the interaction between miR-1248 and circ-PITX1 or CCND2. RESULTS: Circ-PITX1 was upregulated in NSCLC and its silencing could inhibit the proliferation, migration, invasion, cell cycle process, glycolysis, glutamine metabolism, and promote the apoptosis of NSCLC cells in vitro, as well as reduced tumor growth in vivo. In the terms of mechanism, we found that circ-PITX1 could act as a sponge of miR-1248, and miR-1248 could target CCND2. In addition, miR-1248 inhibitor reversed the inhibitory effect of circ-PITX1 knockdown on NSCLC progression. Similarly, CCND2 overexpression also reversed the suppressive effect of miR-1248 on NSCLC progression. Moreover, circ-PITX1 positively regulated CCND2 expression by sponging miR-1248. CONCLUSION: Circ-PITX1 served as a sponge of miR-1248 to promote NSCLC progression by upregulating CCND2.

Effects of Betulinic Acid Derivative on Lung Inflammation in a Mouse Model of Chronic Obstructive Pulmonary Disease Induced by Particulate Matter 2.5.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is mainly induced by the increased content of particulate matter 2.5 (PM2.5) in the atmosphere. This study aimed to evaluate the effects of betulinic acid derivative on lung inflammation in a mouse model of chronic obstructive pulmonary disease induced by particulate matter 2.5. MATERIAL AND METHODS The mice were given a PM2.5 (25 µl) suspension for 7 days by the intranasal route to establish a COPD model. The content of TNF-alpha and IL-6 in the BALF samples was measured by commercially available ELISA kits. RESULTS The PM2.5-induced higher LDH and ACP levels were significantly alleviated in mouse lung tissues by treatment with betulinic acid derivative. Treatment with betulinic acid derivative also suppressed PM2.5-induced increase in AKP and ALB levels in mouse lung tissues. Betulinic acid derivative reversed PM2.5-mediated suppression of SOD activity and elevation of NOS level in mouse BALF. Moreover, the PM2.5-induced excessive NO and MDA levels in mouse BALF were significantly reduced (P.

Analysis of the Effect of Intraocular Lens Implantation on Retinal Nerve and Postoperative Nursing Outcome Based on Ultrasound Imaging.

Traumatic cataract is a common complication of ocular contusion. Caused by various forms of trauma, the course and prognosis of traumatic cataract are also different. Intraocular lens (IOL) implantation is the most effective treatment at the present time and can provide good visual quality and near, medium, and far vision. In this study, an adaptive medical ultrasound image denoising algorithm was constructed based on the biological vision mechanism and was applied to observe IOL implantation and postoperative care of 30 patients with traumatic cataract. Results showed that eyesight could be restored to the original healthy state after IOL implantation, and eyesight was close to normal 3 months after surgery. The corresponding noise pixel block of the noise reduction algorithm was obviously the lowest. A total of 30 patients (9 patients with contusion, 13 patients with intraocular foreign body, and 8 patients with perforation) were treated with aspheric and multifocal IOL to achieve the expected outcome. The noise reduction algorithm constructed in this study effectively reduced the speckle noise of ultrasound images, improved the clarity of ultrasound images, and achieved the effective observation of medical nursing outcome after traumatic cataract IOL implantation. After IOL implantation, the retinal nerves of patients with traumatic cataract were affected to different degrees.

Prognostic Value of a Ten-Gene Signature in HNSCC Patients Based on Tumor-Associated Macrophages Expression Profiling.

Tumor-associated macrophages (TAMs) are regarded as the most abundantly infiltrating immune cells around the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC), which plays an essential role in immunosuppression and tumorigenesis. In the TCGA HNSCC cohort, 500 patients with clinical-pathological information and RNA sequence expression were randomly assigned to training for lasso regression and validation for verification, respectively. A TAM-based ten-gene signature (TBGs) was constructed, which divided the patients into high-risk and low-risk groups, could predict overall survival (OS) of HNSCC patients in the training dataset (p = 3.527e-05) and validation dataset (p = 3.785e-02). The result of Cox univariate and multivariate regression analyses showed that the risk score of TBGs could be an independent prognostic factor in HNSCC. ROC curve confirmed that the risk score of TBGs has good sensitivity and specificity for prognosis prediction (AUC = 0.659) and was also verified by the validation dataset (AUC = 0.621). We obtained key risk transcription factors (TFs)-EHF and SNAI2-by correlation analysis with TBGs. Moreover, we ran a gene set enrichment analysis (GSEA) to speculate that TBGs act on interstitial remodeling, tumor killing, metabolic reprogramming, and tumor immune-related pathways. Finally, we combined clinical-pathological features and risk score of TBGs to establish clinical nomograms, and calibration curves verified the accuracy of long-term clinical prognosis in the two datasets (C-index of 5-year OS = 0.721 and 0.716). In general, the TBGs we obtained may accurately predict the prognosis of HNSCC patients to provide personalized treatment.

Dihydroartemisinin Inhibits the Proliferation, Colony Formation and Induces Ferroptosis of Lung Cancer Cells by Inhibiting PRIM2/SLC7A11 Axis.

OBJECTIVE: Lung cancer is the first leading cause of cancer-related deaths both worldwide and in China and threatens human health and quality of life. New drugs and therapeutic methods are urgently needed. Our study evaluated the roles of dihydroartemisinin (DHA) in lung cancer and further explored its underlying mechanisms. METHODS: CCK-8, colony formation and trypan blue exclusion assays were used to detect the cell viability, colony formation ability and cell death. qRT-PCR and Western blotting assays were applied to analyze the expressions of key molecules. RESULTS: DHA inhibited the proliferation and colony formation abilities and enhanced the cell death and induced ferroptosis of lung NCI-H23 and XWLC-05 cancer cells. DHA reduced PRIM2 expression and silencing PRIM2 mimicked the inhibitory roles on proliferation and colony formation and promotive roles on cell death and ferroptosis of DHA in lung NCI-H23 and XWLC-05 cancer cells. We further found that DHA treatment and loss of PRIM2 reduced the GSH level and increased the cellular lipid ROS and mitochondrial MDA levels, and further downregulated the expressions of SLC7A11 and ß-catenin in lung cancer cells, respectively. Exogenetic overexpression of PRIM2 recovered the inhibitory effects of DHA on proliferation and colony formation in lung NCI-H23 cancer cells, meanwhile loss of PRIM2 sensitizes NCI-H23 cells to DHA therapy. In vivo experiment further showed that DHA treatment significantly suppressed the tumor growth and downregulated PRIM2 and SLC7A11. CONCLUSION: Our study suggested that DHA inhibited the proliferation, colony formation and enhanced cell death and induced ferroptosis of lung cancer cells by inactivating PRIM2/SLC7A11 axis. Loss of PRIM2 induced ferroptosis might developed to be a novel therapeutic method in lung cancer therapy.

Change of serum B-cell activating factor level in patients with positive antiphospholipid antibodies and previous adverse pregnancy outcomes and its significance.

BACKGROUND: B-cell activating factor (BAFF) is vital for B cell survival. Serum BAFF levels are elevated in thrombotic antiphospholipid syndrome, but little is known about levels in patients with positive antiphospholipid antibodies (aPLs) and previous adverse pregnancy outcomes (APOs). We aimed to analyze serum BAFF concentrations of these patients in early pregnancy along with different pregnancy outcomes. METHODS: Thirty-six pregnant patients positive for aPLs and previous APOs (patient group), 25 healthy pregnant females (HP group) and 35 healthy non-pregnant females (HNP group) from the Peking University Third Hospital, between October 2018 and March 2019, were enrolled in this study. Serum of HNP and serum of patients as well as HP in the first gestational trimester were collected. Enzyme-linked immunosorbent assay kits were used to measure serum BAFF and interferon-alpha (IFN-α) concentrations. Cytometric bead array analysis was used to measure serum concentrations of cytokines. The patient group was further divided into APOs and non-APOs (NAPOs) group, fetal loss and live birth group according to pregnancy outcomes. The Mann-Whitney U-test was used to assess significance between and within groups. Spearman rank-order was used to evaluate correlation coefficients between BAFF and related cytokines. RESULTS: The serum BAFF level in HP group was significantly lower than HNP group (245.24 [218.80, 265.90] vs. 326.94 [267.31, 414.80] pg/mL, Z = -3.966, P < 0.001). The BAFF level was obviously elevated in patient group compared to that in HP group (307.77 [219.86, 415.65] vs. 245.24 [218.80, 265.90] pg/mL, Z = -2.464, P = 0.013). BAFF levels in APOs group tended to be higher than that in NAPOs group (416.52 [307.07, 511.12] vs. 259.37 [203.59, 375.81] pg/mL, Z = -2.718, P = 0.006). Compared to HP group, concentrations of IFN-α, interleukin (IL-6) and tumor necrosis factor were higher in patient group (33.37 [18.85, 48.12] vs. 13.10 [6.85, 25.47] pg/mL, Z = -2.023, P = 0.043; 39.16 [4.41, 195.87] vs. 3.37 [2.92, 3.90] pg/mL, Z = -3.650, P < 0.001; 8.23 [2.27, 64.46] vs. 1.53 [1.25, 2.31] pg/mL, Z = -3.604, P < 0.001, respectively). Serum BAFF levels had a positive correlation with the concentrations of both IL-6 and IL-10 (IL-6: r = 0.525, P = 0.002; IL-10: r = 0.438, P = 0.012). CONCLUSIONS: Serum BAFF levels are increased in patients with positive aPLs and previous APOs as compared to healthy pregnant females and tend to be higher in individuals with current APOs. The BAFF levels have a positive correlation with serum IL-6 and IL-10.

Clinical Significance of an m6A Reader Gene, IGF2BP2, in Head and Neck Squamous Cell Carcinoma.

The importance of N6-methyladenosine (m6A) in tumor recurrence and prognosis has been recognized in recent years. The role of m6A readers, such as insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), in regulating head and neck squamous cell carcinoma (HNSCC) remains unclear. We, therefore, assessed the prognostic role of IGF2BP2 in HNSCC using openly available data from The Cancer Genome Atlas (TCGA) in conjunction with HNSCC patient sample immunohistochemistry (n = 36). The correlation between IGF2BP2 expression and clinical characteristics was then examined. The role of IGF2BP2 in prognosis was assessed by Kaplan-Meier curves and Cox analysis. Finally, TCGA data was used to explore possible carcinogenic mechanisms with multi-GSEA (gene set enrichment analysis). Analysis of TCGA data and IHC results revealed that IGF2BP2 was upregulated in HNSCC tumor tissues, and the expression level was related to the T stage. Simultaneously, Kaplan-Meier curves and Cox analysis indicated that highly expressed IGF2BP2 correlated with poor prognosis and that IGF2BP2 was a potential prognostic factor for HNSCC. Gene set enrichment analysis revealed that scavenging and degradation, synthesis and metabolism, cell growth, death and motility, and cancer pathways were differentially enriched in patients with high IGF2BP2 expression. Our results demonstrate that IGF2BP2 plays an important role in tumor progression and may serve as an important biological prognostic factor for HNSCC.

Chemokine-like factor-like MARVEL transmembrane domain-containing family in autoimmune diseases.

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is widely expressed in the immune system. Abnormal expression of CMTM is associated with the development of various diseases. This article summarizes the relevant research on the role of the CMTM family in immune disorders. This information will increase our understanding of pathogenesis and identify promising targets for the diagnosis and treatment of autoimmune diseases. The CMTM family is highly expressed in peripheral blood mononuclear cells. CKLF1 may be involved in the development of arthritis through its interaction with C-C chemokine receptor 4. CKLF1 is associated with the pathogenesis of lupus nephritis and psoriasis. Both CMTM4 and CMTM5 are associated with the pathogenesis of systemic lupus erythematosus. CMTM1, CMTM2, CMTM3, and CMTM6 play a role in rheumatoid arthritis, systemic sclerosis, Sjögren syndrome, and anti-phospholipid syndrome, respectively. The CMTM family has been implicated in various autoimmune diseases. Further research on the mechanism of the action of CMTM family members may lead to the development of new treatment strategies for autoimmune diseases.

CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2/STAT3 and p38/MAPK signaling pathway.

OBJECTIVE: To explore the influence of chemokine, CXCL16, on the expression of the receptor activator nuclear factor κB ligand (RANKL) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS). METHODS: The expression of CXCL16/CXCR6 and RANKL in RA or osteoarthritis (OA) patient synovia was examined by Western blot and immunohistochemistry. The serum concentration of CXCL16 and RANKL was measured by enzyme-linked immunosorbent assay (ELISA). RA-FLS were treated with recombinant CXCL16, and RANKL mRNA and protein were measured using PCR, Western blot and ELISA. RESULTS: The synovial expression of CXCL16, CXCR6, and RANKL was higher in RA patients than in patients with OA. The serum CXCL16 and RANKL levels were higher in RA patients compared with OA patients and healthy controls. CXCL16 correlated with erythrocyte sedimentation rate, C reactive protein, disease activity, serum rheumatoid factor, and RANKL. RA-FLS treated with CXCL16 showed markedly increased expression of RANKL. When STAT3 or p38 activation was blocked by an inhibitor, CXCL16 failed to upregulate RANKL expression. In contrast, inhibiting the Akt or Erk pathway did not achieve the same effect. CONCLUSIONS: CXCL16 upregulates RANKL expression in RA-FLS and these effects are mainly mediated by the JAK2/STAT3 and p38/MAPK signaling pathways.

Efficacy of low-dose 90Sr-90Y therapy combined with topical application of 0.5% timolol maleate solution for the treatment of superficial infantile hemangiomas.

The aim of the present study was to investigate the clinical efficacy and safety of low-dose 90Sr-90Y therapy combined with the topical application of 0.5% timolol maleate solution for the treatment of superficial infantile hemangiomas (IHs). A total of 72 infants with hemangiomas were allocated at random into the observation group (17 cases aged ≤3 months, 20 cases aged >3 months) or the control group (15 cases aged ≤3 months, 20 cases aged >3 months). The observation group was treated with low-dose 90Sr-90Y combined with timolol, while the control group received an identical dose of 90Sr-90Y with physiological saline. Data were collected for statistical analysis, and treatment efficacy was compared between the two groups. In the observation group, 100% (37/37) of subjects exhibited an 'excellent' response to the treatment, while 94.1% (16/17) of patients aged ≤3 months and 85.0% (17/20) aged >3 months were classed as being cured. In the control group, the treatment was classed as 'effective' in 100% (35/35) of the subjects, while the excellent response rate was 86.7% (13/15) among the infants aged ≤3 months and 75.0% (15/20) among the infants aged >3 months. The 'cure' rates in the control group were 66.7% (10/15) and 60.0% (12/20) for the ≤3-month- and >3-month-old subjects, respectively. The excellent response and cure rates were notably higher in the observation group than those in the control group. Comparison between the two groups revealed a χ2 value of 13.90 (P<0.01) for excellent responses in subjects aged ≤3 months, while for patients aged >3 months the χ2 value was 28.57 (P<0.01). Analysis of the cure responses gave similar results [≤3 months, χ2=23.22 (P<0.01); >3 months, χ2=15.67 (P<0.01)]. At 3-4 months after the first course of treatment, the cure rate was 33.3% (11/33) in the observation group, which was significantly higher than the rate of 18.32% (4/22) in the control group (χ2=5.92, P<0.05). No serious adverse reactions were observed in either group. In summary, low-dose 90Sr-90Y therapy combined with the topical application of 0.5% timolol maleate induces a rapid response in superficial IH, with excellent efficacy and no obvious adverse reactions, and may represent a clinically applicable intervention.

AG490 inhibits NFATc1 expression and STAT3 activation during RANKL induced osteoclastogenesis.

Commonly, JAK/STAT relays cytokine signals for cell activation and proliferation, and recent studies have shown that the elevated expression of JAK/STAT is associated with the immune rejection of allografts and the inflammatory processes of autoimmune disease. However, the role which JAK2/STAT3 signaling plays in the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis is unknown. In this study, we investigated the effects of AG490, specific JAK2 inhibitor, on osteoclast differentiation in vitro. AG490 significantly inhibited osteoclastogenesis in murine osteoclast precursor cell line RAW264.7 induced by RANKL. AG490 suppressed cell proliferation and delayed the G1 to S cell cycle transition. Furthermore, AG490 also suppressed the expression of nuclear factor of activated T cells (NFAT) c1 but not c-Fos in RAW264.7. Subsequently, we investigated various intracellular signaling components associated with osteoclastogenesis. AG490 had no effects on RANKL-induced activation of Akt, ERK1/2. Interestingly, AG490 partly inhibited RANKL-induced phosphorylation of Ser(727) in STAT3. Additionally, down-regulation of STAT3 using siRNA resulted in suppression of TRAP, RANK and NFATc1 expression. In conclusion, we demonstrated that AG490 inhibited RANKL-induced osteoclastogenesis by suppressing NFATc1 production and cell proliferation via the STAT3 pathway. These results suggest that inhibition of JAK2 may be useful for the treatment of bone diseases characterized by excessive osteoclastogenesis.

Preparation, characterization and application of N-2-Pyridylsuccinamic acid-functionalized halloysite nanotubes for solid-phase extraction of Pb(II).

Halloysite nanotubes (HNTs) were chemically modified with N-2-Pyridylsuccinamic acid (PSA) to produce a new nano-adsorbent (HNTs-PSA) for selective solid-phase extraction of Pb(II). The new adsorbent was characterized by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscope (TEM), thermogravimetric analysis (TGA), and elemental analysis to evaluate the surface modification. Under the optimized conditions (pH 5, flow rate 1.5 mL min(-1)), Pb(II) was retained on the column packed with HNTs-PSA, and then was quantitatively eluted by 1.5 mL 0.5 mol L(-1) HCl and determined by inductively coupled plasma-optical emission spectrometry. An enrichment factor of 67 was obtained using 30 mg of HNTs-PSA. The maximum adsorption capacity for Pb(II) was found to be 23.58 mg g(-1). The detection limits of this method for Pb(II) was 0.32 µg L(-1). The relative standard deviation under optimum conditions was 3.4% (n = 11). The developed method was validated by analyzing a certified reference material, and then successfully applied to the determination of Pb(II) in actual samples.