Background
Artemisia annua is an important autumnal pollen allergen for seasonal allergic rhinitis (SAR) in northern China. To date, no study has investigated allergen immunotherapy with A annua. We ...aimed to investigate the efficacy and mechanisms underlying A annua‐sublingual immunotherapy (SLIT).
Methods
This was a randomized, double‐blind, placebo‐controlled phase III clinical trial involving 71 SAR patients, randomized to SLIT with A annua extract (n = 47) or placebo (n = 24) for 32 weeks. Total nasal symptom score (TNSS; primary clinical end point) was evaluated at baseline (peak pollen phase (PPP) in the previous year), initiation of A annua‐SLIT, 1st PPP during SLIT, end of SLIT and 2nd PPP during follow‐up. Blood samples and nasal secretions were collected at beginning and after SLIT for assessment of T cells and inflammatory mediators. Safety was assessed according to adverse events (AEs) reported.
Results
Artemisia annua‐SLIT significantly reduced TNSS to a greater level from baseline (from 9.45 ± 1.68 to 6.16 ± 2.27) than placebo (from 9.29 ± 2.09 to 9.05 ± 2.40) at the 1st PPP (P < .001) and sustained the improvement in symptoms throughout to the 2nd PPP. Preseasonal A annua‐SLIT for 16 weeks significantly decreased Th2 cells, increased nTreg and Tr1 cells in blood; and increased cystatin 1 (CST1) in nasal secretion after 16 and 32 weeks compared with pretreatment. Overall, 17/47 patients experienced mild local AEs and 2 patients mild systemic AEs, after A annua‐SLIT.
Conclusion
Artemisia annua‐SLIT is an efficacious and safe treatment in patients with A annua SAR.
This randomized, double‐blind, placebo‐controlled phase III clinical trial demonstrates the efficacy and favourable safety profile of the 32‐week SLIT with Artemisia annua in patients with seasonal allergic rhinitis. Artemisia annua‐SLIT significantly reduces total nasal symptom score at the 1st and 2nd PPP compared with placebo. Preseasonal Artemisia annua‐SLIT significantly decreases Th2 cells, increases nTreg and Tr1 cells in blood and increases CST1 in nasal secretion.
Osteosarcoma is a highly invasive and early metastatic tumor. At present, the toxic and side effects of chemotherapy affect the quality of life of cancer patients to varying degrees. Genipin is an ...extract of the natural medicine gardenia with various pharmacological activities.
The purpose of this study was to investigate the effect of Genipin on osteosarcoma and its potential mechanism of action.
Crystal violet staining, MTT assay and colony formation assay were used to detect the effect of genipin on the proliferation of osteosarcoma. The effects of vitexin on migration and invasion of osteosarcoma were detected by scratch healing assay and transwell assay. Hoechst staining and flow cytometry were used to detect the effect of genipin on apoptosis of osteosarcoma cells. The expression of related proteins was detected by Western blot. An orthotopic tumorigenic animal model was used to verify the effect of genipin on osteosarcoma in vivo.
The results of crystal violet staining, MTT method and colony formation method proved that genipin significantly inhibited the proliferation of osteosarcoma cells. The results of the scratch healing assay and transwell assay showed that gen significantly inhibited the migration and invasion of osteosarcoma cells. The results of Hoechst staining and flow cytometry showed that genipin significantly promoted the apoptosis of osteosarcoma cells. The results of animal experiments show that genipin has the same anti-tumor effect in vivo. Genipin may inhibit the growth of osteosarcoma through PI3K/AKT signaling.
Genipin can inhibit the growth of human osteosarcoma cells, and its mechanism may be related to the regulation of PI3K/AKT signaling pathway.
Osteosarcoma (OS) is a highly aggressive malignant bone tumor that mainly occurs in adolescents. At present, chemotherapy is the most commonly used method in clinical practice to treat OS. However, ...due to drug resistance, toxicity and long-term side effects, chemotherapy can’t always provide sufficient benefits for OS patients, especially those with metastasis and recurrence. Natural products have long been an excellent source of anti-tumor drug development. In the current study, we evaluated the anti-OS activity of Echinatin (Ecn), a natural active component from the roots and rhizomes of licorice, and explored the possible mechanism. We found that Ecn inhibited the proliferation of human OS cells and blocked cell cycle at S phase. In addition, Ecn suppressed the migration and invasion, while induced the apoptosis of human OS cells. However, Ecn had less cytotoxicity against normal cells. Moreover, Ecn inhibited the xenograft tumor growth of OS cells in vivo. Mechanistically, Ecn inactivated Wnt/β-catenin signaling pathway while activated p38 signaling pathway. β-catenin over-expression and the p38 inhibitor SB203580 both attenuated the inhibitory effect of Ecn on OS cells. Notably, we demonstrated that Ecn exhibited synergistic inhibitory effect with cisplatin (DDP) on OS cells in vitro and in vivo. Therefore, our results suggest that Ecn may exert anti-OS effects at least partly through regulating Wnt/β-catenin and p38 signaling pathways. Most meaningfully, the results obtained suggest a potential strategy to improve the DDP-induced tumor-killing effect on OS cells by combining with Ecn.
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•We examined the associations between organic UV filters exposure and pubertal development.•Urinary concentrations of 12 organic UV filters and metabolites were analyzed.•Benzophenones, EHMC and ...OD-PABA were extensively detected in the urine of school-aged children.•EHMC and BP-3 were associated with later pubertal stages and onset in boys.•OD-PABA were associated with earlier pubertal stages, onset and accelerated progression in girls.
UV filters, widely used in personal care and industrial products, are being found in the environment and, in humans where with limited understanding on their potential health effects, especially during puberty.
To examine the association between UV filter exposure and pubertal development in a prospective follow-up study.
This study included 521 elementary and high school students from a suburban area of Shanghai. The initial study was done in October to November 2011; the follow-up study in April to May 2013. Twelve urinary organic UV filters were quantified, and the pubertal development was assessed at each study period by trained physicians using Tanner staging. We used (ordered) logistic regression model and multilevel mixed-effect (ordered) logistic regression model to assess cross-sectional and longitudinal effects between urinary concentration of five major UV filters and pubertal development of stages, onset and pace.
Ethylhexyl methoxycinnamate (EHMC) and its metabolite 4′-methoxyacetophenone (4′-MAP), two benzophenone derivatives (BP-2, BP-3) and Ethylhexyl dimethyl PABA (OD-PABA) were the most extensively detected UV filters in urine with geometric means (95% CI) in 2010 and 2012 as 1.77 (1.599, 1.956) and 2.28 (1.985, 2.622) ng/mL for EHMC; 4.55 (4.219, 4.907) and 5.26 (4.783, 5.775) ng/mL for 4′-MAP; 4.38 (4.011, 4.774) and 5.74 (5.023, 6.562) ng/mL for BP-2; 0.83 (0.760, 0.903) and 1.09 (0.967, 1.220) ng/mL for BP-3; 5.37 (4.949, 5.820) and 5.80 (5.193, 6.486) pg/mL for OD-PABA. Significant trend P-values (P < 0.05) include: EHMC and its metabolite were negatively correlated with stages of testicular volume and genital development; BP-3 was also negatively correlated with stages of testicular volume in boys, while OD-PABA positively correlated with stages of pubic hair and breast development in girls. Also, EHMC was associated with later pubertal onset of pubic hair and testicular volumes in boys, while OD-PABA correlated with earlier pubertal onset of breast development in girls. OD-PABA also significantly speeded up the progression of pubic hair and breast development in girls.
UV filters were extensively detected. Exposure to EHMC and BP-3 was significantly associated with later pubertal development in boys, and OD-PABA was associated with earlier pubertal development in girls. It demonstrates that the UV filters so widely used in personal care products and widely detected in environments are finding their way back into people where they are distorting endocrine function of adolescents.
Osteosarcoma(OS) is a common primary malignant bone tumor, which mostly occurs in children and adolescents. Currently, chemotherapy drugs for the clinical treatment of OS have high side effects and ...patients are prone to chemotherapy resistance, which reduces the therapeutic effect. Therefore, the development of new therapeutic drugs is very important to reduce the toxicity and adverse reactions of drugs and improve the survival rate of patients. At present, the antitumor activity of traditional Chinese medicine monomers has received extensive attention because of its safety and efficacy. Asiatic acid (AA) is a naturally pentacyclic triterpenoids extracted from Centella asiatica. The aim of this study was to evaluate the effect and mechanism of AA on OS cells in vitro and in vivo. In vitro results showed that AA inhibited the proliferation, migration and invasion of OS cells and was able to induce apoptosis and cycle arrest. In vivo results showed that AA inhibited the growth of OS and the size of lung metastasis in nude mice. Network pharmacology, molecular docking and in vitro experiments prove that AA may play a role in the treatment of OS by inhibiting PI3K/AKT and NF-κB signaling pathways. Our study shows that AA can act on multiple targets of OS and regulate multiple pathways to intervene in the occurrence and development of OS, which may provide reference for the clinical application and development of AA.
The gas adsorption of shale is one of the most important factors influencing shale gas accumulation and production. Different from other shale gas fields, the shale in Northwestern Hunan province ...with strong structural deformation has especially high portion of adsorbed gas. The adsorption abilities of shale reservoir play a significant role in the success of exploration and production of shale gas in Northwestern Hunan. Therefore, based on many experiments including field emission scanning electron microscopy, N₂/CO₂ adsorption, excess CH₄ adsorption with constant temperature and others, this paper found that: (1) the shale pores were identified with mineral matrix pores, organic-matter pores and fracture pores, and the pores can be further classified according to their shape features and forming mechanism; (2) after analyses of the distribution of the pore size, mesoporous is the largest contributor and widely distributed, and micropores provide more contribution on surface area but limited contribution to pore volume. Meanwhile, depth has little effect on the properties of shale reservoirs; (3) based on the fractal geometry theory, surface roughness is positively correlated to microstructure irregularity, which means the effects between the gas adsorption by Van der Waals force and by multilayer or capillary condensation in single pore system are consistent during the N₂ adsorption process. (4) The abilities of gas storage are apparently sensitive to the surface roughness of shale pores and nonsensitive to microstructure irregularity. Total organic carbon has strong positive correlation with the surface roughness, specific surface area, total pore volume, and Langmuir volume, which means TOC can improve the adsorption of shale reservoir in many ways. Pyrite can offer much contribution to the ability of gas adsorption.
Melanoma is a highly invasive and metastatic malignant tumor originating from melanocytes and is associated with a poor prognosis. Surgical resection and chemotherapy are currently the main ...therapeutic options for malignant melanoma; however, their efficacy is poor, highlighting the need for the development of new, safe, and effective drugs for the treatment of this cancer.
To investigate the effects of alantolactone (ALT) on the proliferative, migratory, invasive, and apoptotic ability of malignant melanoma cells and explore its potential anticancer mechanism.
Melanoma cells (A375 and B16) were treated with different concentrations (4, 6, 8, and 10 μmol/L) of ALT, with DMSO and no treatment serving as controls. The effects of the different concentrations of the drug on cell proliferation were assessed by crystal violet staining and CCK-8 assay. The effects on cell migration and invasion were detected by wound healing and Transwell assays, respectively. Flow cytometry was used to evaluate the effects of the drug on apoptosis and the cell cycle. ALT target genes in melanoma were screened using network pharmacology. Western blotting was used to measure the expression levels of the proliferation-related protein PCNA; the apoptosisrelated proteins Bax, Bcl-2, and caspase-3; the invasion and metastasis-related proteins MMP-2, MMP-7, MMP-9, vimentin, E-cadherin, and N-cadherin; and the canonical Wnt signaling pathway-related proteins β-catenin, c-Myc, and p-GSK3β. In addition, an l model of melanoma was established by the subcutaneous injection of A375 melanoma cells into nude mice, following which the effects of ALT treatment on malignant melanoma were determined in vivo.
Compared with the controls, the proliferative, migratory, and invasive capacity of ALT-treated melanoma cells was significantly inhibited, whereas apoptosis was enhanced (P<0.01), showing effects that were exerted in a dose-dependent manner. The expression levels of the pro-apoptotic proteins Bax and caspase-3, as well as those of the interstitial marker E-cadherin, were upregulated in melanoma cells irrespective of the ALT concentration (P<0.05). In contrast, the expression levels of the anti-apoptotic protein Bcl-2, the proliferation-related protein PCNA, and the invasion and metastasis-related proteins MMP-2, MMP-7, MMP-9, N-cadherin, and vimentin were downregulated (P<0.05). The network pharmacology results indicated that GSK3β may be a key ALT target in melanoma. Meanwhile, western blotting assays showed that ALT treatment markedly suppressed the expression of β-catenin as well as that of its downstream effector c-Myc, and could also inhibit GSK3β phosphorylation.
ALT can effectively inhibit the culture viability, migration, and invasion of A375 and B16 melanoma cells while also promoting their apoptosis. ALT may exert its anti-melanoma effects by inhibiting the Wnt/β-catenin signaling pathway. Combined, our data indicate that ALT has the potential as an effective and safe therapeutic drug for the treatment of melanoma.
Introduction
This study used systematic review and meta-analysis to evaluate the association between
Helicobacter pylori
infection and osteoporosis.
Materials and methods
PubMed, Ovid and Web of ...Science were searched to include observational studies published in English comparing bone mineral density changes between
Helicobacter pylori
-positive and -negative participants. The quality of the included literature was assessed using the Newcastle–Ottawa Quality Assessment Scale (NOS). R software was used for meta-analysis, and odds ratio (OR) and 95% confidence interval (CI) were calculated to evaluate the relationship between
Helicobacter pylori
infection and osteoporosis.
Results
Twenty-two studies involving 24,176 participants were included in the study. Our meta-analysis showed that
Helicobacter pylori
infection was significantly associated with the risk of osteoporosis (OR: 1.12, 95%CI: 1.03, 1.22). Participants infected with the CagA-positive
Helicobacter pylori
strain were more likely to develop osteoporosis (OR = 1.42, 95%CI: 1.09; 1.85).
Conclusion
Infection with
Helicobacter pylori
, particularly the CagA-positive strain, has been associated with an increased risk of osteoporosis. The bone health of
Helicobacter pylori
-positive patients deserves more attention.
Regulating macrophage activation precisely is crucial in treating chronic inflammation in osteoarthritis (OA). However, the stable pro-inflammatory state and deep distribution of macrophages in vivo ...pose a great challenge to treatment. In this study, inspired by the innate immune, immune cell mobilized hydrogel microspheres were constructed by microfluidic methods and load chemokines, macrophage antibodies and engineered cell membrane vesicles (sEVs) via covalent and non-covalent junctions. The immune cell mobilized hydrogel microspheres, based on a mixture of streptavidin grafted hyaluronic acid methacrylate (HAMA-SA) and Chondroitin sulfate methacrylate (ChSMA) microspheres (HCM), can recruit, capture and reprogram proinflammatory macrophages in the joint cavity to improve the joint inflammatory microenvironment. In vitro experiments demonstrated that immune cell mobilized hydrogel microspheres had excellent macrophage recruitment, capture, and reprogramming abilities. Pro-inflammatory macrophages can be transformed into anti-inflammatory macrophages with an efficiency of 88.5 %. Animal experiments also revealed significant reduction in synovial inflammation and cartilage matrix degradation of OA. Therefore, the immune cell mobilized hydrogel microspheres may be an effective treatment of OA inflammation for the future.
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