A macrophage plasma membrane-coated and DNA structured nanomedicine targets to alleviate rheumatoid arthritis via dual inhibition to TNF-α and NF-κB.

High heterogenicity of rheumatoid arthritis (RA) leads to poor response in many patients. Combined therapies that simultaneously inhibit multiple proinflammatory targets may improve anti-RA efficacy. However, which monotherapies to combine and how to achieve the combination are critical issues. Here, we design a macrophage plasma membrane-coated and DNA structured nanomedicine to achieve a dual inhibitory therapy to Tumor necrosis factor alpha (TNF-α) and NF-κB. An anti-NF-κB decoy oligodeoxynucleotides (dODN) is first conjugated to a DNA cage with precise numbers and locations (Cage-dODN). Meanwhile, an anti-TNF-α siRNA is anchored to extracted macrophage plasma membrane (siRNA@M). Subsequently, siRNA@M is used to encapsulate Cage-dODN to fabricate siRNA@M(Cage-dODN) (siMCO). The size and zeta potential of siMCO are 63.1 ± 15.7 nm and -20.7 ± 3.8 mV respectively. siMCO shows increased intracellular uptake by inflamed macrophages and enhanced accumulation in inflamed mouse paws. siMCO also reduces pro-inflammatory factors at genetic and protein levels, alleviates arthritic symptoms, and shows no influence to major blood components. These results show that siMCO is a potential targeted, efficient, and safe dual inhibitory therapy for the treatment of inflammatory arthritis. The macrophage plasma membrane can be utilized to improve the targeting, stability, and efficacy of DNA structured nanomedicines.

Comparison of clinical effects of two surgical approaches in the treatment of acetabular fractures.

Objective: To determine the clinical effect of lateral rectus abdominis approach and modified Stoppa approach for the surgical treatment of acetabular fractures. Methods: A retrospective analysis was performed on the case data of 30 patients with acetabular fractures admitted to the Department of Orthopaedics of Hengshui City People's Hospital from June 2017 to June 2021. According to the surgical methods, the enrolled patients were divided into the lateral rectus abdominis approach group (observation group) and the modified Stoppa approach group (control group), with 15 patients in each group. Further comparison was made on the incision length, operation time, intraoperative blood loss, length of stay in the hospital, fracture reduction, hip joint function, neurological recovery, and postoperative complications between the two groups. Results: There was no significant difference between the two groups in the length of stay in the hospital, hip joint function score, fracture reduction quality, and excellent-to-good rate of hip joint function (p>0.05). There were significant differences in incision length, intraoperative blood loss, operation time, postoperative motor and touch function scores, and postoperative complication rate between the observation group and the control group (p<0.05). Conclusion: The clinical effect of the lateral rectus abdominis approach is close to that of the modified Stoppa approach for the surgical treatment of acetabular fracture patients. However, and importantly, surgery through the lateral rectus abdominis approach has less trauma, shorter operation time, lower surgical complications, and good postoperative functional recovery.

Facial changes in patients with skeletal class III deformity after bimaxillary surgery: an evaluation based on three-dimensional photographs registered with computed tomography.

The objective of this study was to evaluate facial soft and hard tissue changes, individually and relative to each other, in patients with skeletal class III deformity after bimaxillary surgery using three-dimensional (3D) photos obtained by white light scanning. Thirty patients with skeletal class III deformity who underwent bimaxillary surgery were selected. Each patient underwent white light scanning and spiral computed tomography (CT) within two weeks before (T0) and six months after surgery (T1). The 3D photos were registered with CT soft tissue models for T0 and T1, and the skeletal area unaffected by treatment (cranial base) was used to register T0 and T1. Then, the 3D colour-coded map was analysed to assess both skeletal and soft tissue changes between T0 and T1. Changes in the 3D coordinates of each anatomical landmark were analysed using the Student's t-test. Maxillary advancement by 2-3 mm and mandibular recession by 5-6 mm were observed; the mandible was shortened in the vertical direction. Compared with the preoperative values, the nasal columella was 0.51 mm shorter, the upper lip was 0.71 mm longer, the base of the alar cartilage was 1.38 mm wider, and the nasolabial angle became larger. The ratio of change in the position of soft tissue point Sn to hard tissue point A was 0.73:1, and that of soft tissue point Pg to hard tissue point Pog was 0.86:1. Images obtained by structured white light scanning registered with CT can be used as an alternative to study facial changes after orthognathic surgery.

Self-Assembling Anchorage of Hyaluronic Acid on the Nanoparticle Surface Confers Superiority of Triple Negative Breast Cancer Treatment.

Triple-negative breast cancer (TNBC) has been listed as one of the most fatal diseases, and no effective targeting treatment is clinically available. Although CD44-targeting hyaluronic acid (HA) has been utilized as targeting ligands in many studies, no facile ways have been developed through HA self-assembly at the nanoparticle surface. Herein, we reported N-isopropylacrylamide-grafted chitosan-based nanoparticles self-assembling with HA (HA-NPs) through electrostatic forces and loaded with curcumin (CUR). The HA-NPs displayed pH-responsive properties due to the chemical modification of chitosan, and the preparation process was optimized by central composite design-response surface methodology. HA anchorage confers the vehicle with tumor-targeting capability. HA-NPs displayed more robust effects of inhibiting TNBC primary tumor growth than free CUR and a plain counterpart but without increased systemic cytotoxicity. In addition, in vivo pharmacokinetic studies showed that HA-NPs significantly increased the in vivo residence time of free CUR and improved the bioavailability of CUR. These findings suggested that chitosan-based HA-NPs may provide a feasible and unique strategy to achieve CD44 targeting and enhance its efficacy in vivo for the treatment of advanced TNBC.

Network pharmacology analysis on mechanism of Jian Pi Qing Gan Yin decoction ameliorating high fat diet-induced non-alcoholic fatty liver disease and validated in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Jian Pi Qing Gan Yin (JPQGY) has been used clinically to relieve non-alcoholic fatty liver disease (NAFLD) in China for decades; however, the underlying mechanisms of JPQGY remain unclear. AIM OF THE STUDY: We evaluated the effects and mechanisms of JPQGY and hepatic steatosis caused by the middle stage of 13-week-high-fat-diet-induced NAFLD in mice. MATERIALS AND METHODS: Different dosages of JPQGY (5.5, 11, and 22 g/kg/day) were administered to NAFLD mice simultaneously. Body weight, body mass index (BMI), and liver lipid- and inflammation-related serum indicators were measured enzymatically. Liver samples were stained with Oil Red O and hematoxylin and eosin (H&E). Next, we performed a network pharmacology analysis and verified eight target genes mapping to NAFLD-related lipid metabolism pathways. The mRNA/protein expression was analyzed by real-time polymerase chain reaction (PCR) and western blotting. RESULTS: JPQGY significantly relieved histological damage (steatosis-inflammation-fibrosis), prevented the downregulation of AMPK and Pparα, and upregulated LXRα, Srebp-1c, F4/80, Nf-κb, and Cyp2e1 in the HFD-induced NAFLD mouse model. CONCLUSIONS: The present results suggest that chronic treatment with JPQGY ameliorated HFD-induced NAFLD in mice by targeting the first and second phases of hepatic steatosis by stimulating the AMPK/PPARα pathway and inhibiting the LXRα/Srebp1/Nf-κb pathway. Our findings provide evidence that supports the clinical use of this formula for high-fat diet-induced fatty liver disease.

Minimally Invasive Percutaneous Plate Osteosynthesis technique combined with locking compression plates guided by C-Arm X-Ray machine in treatment of tibial metaphyseal fractures: Curative effect and postoperative complications.

Objectives: To explore the curative effect of minimally invasive percutaneous plate osteosynthesis (MIPPO) technology combined with locking compression plates (LCP) guided by C-arm X-ray machine in the treatment of tibial metaphyseal fracture and its impact on the surgical indexes and postoperative complications. Methods: The present study was a retrospective analysis focusing on the clinical data of 104 cases of tibial metaphyseal fracture who were treated surgically in our hospital from February 2019 to February 2021. According to different surgical methods, patients who were treated by using MIPPO technology combined with LCP guided by C-arm X-ray machine were divided into the observation group (n=54), while those who underwent traditional open reduction and internal fixation were classified into the control group (n=50). Further comparison was made on the differences of the curative effect, surgical index (operation time, intraoperative blood loss, incision length, and healing time) and postoperative complications between the two groups. In addition, the differences in ankle function, knee function and quality of life [Medical Outcomes Study 36-item Short-Form Health Survey (MOS SF-36)] were evaluated between the two groups before treatment and 6 months after treatment. Results: The clinical curative effect and total efficacy of the observation group were better than those of the control group (All p<0.05). The operation time, intraoperative blood loss, incision length, and healing time were lower in the observation group when compared to those of the control group (All p<0.05). The total incidence of postoperative complications was also lower in the observation group than that in the control group (p<0.05). In addition, the scores of ankle function, knee function and MOS SF-36 in both groups were higher after 6 months of treatment than those before treatment; besides, the inter-group comparison showed that the scores of ankle function, knee function and MOS SF-36 in the observation group were higher than those in the control group (All p<0.05). Conclusion: MIPPO technology combined with LCP guided by C-arm X-ray machine has a significant curative effect on the treatment of tibial metaphyseal fracture. It can significantly improve the surgical index, reduce postoperative complications, and have an obvious effect on postoperative recovery of ankle function, knee joint function and quality of life.

Study on the Grading Model of Hepatic Steatosis Based on Improved DenseNet.

To achieve intelligent grading of hepatic steatosis, a deep learning-based method for grading hepatic steatosis was proposed by introducing migration learning in the DenseNet model, and the effectiveness of the method was verified by applying it to the practice of grading hepatic steatosis. The results show that the proposed method can significantly reduce the number of model iterations and improve the model convergence speed and prediction accuracy by introducing migration learning in the deep learning DenseNet model, with an accuracy of more than 85%, sensitivity of more than 94%, specificity of about 80%, and good prediction performance on the training and test sets. It can also detect hepatic steatosis grade 1 more accurately and reliably, and achieve automated and more accurate grading, which has some practical application value.

Recent advances on transdermal delivery systems for the treatment of arthritic injuries: From classical treatment to nanomedicines.

Arthritic injuries happen frequently during a lifetime due to accidents, sports, aging, diseases, etc. Such injuries can be cartilage/bone injuries, tendon injuries, ligament injuries, inflammation, pain, and/or synovitis. Oral and injective administration of therapeutics are typically used but cause many side effects. Transdermal administration is an alternative route for safe and efficient delivery. Transdermal formulations of non-steroidal anti-inflammatory drugs have been available on market for years and show promising efficacy in pain relieving, inflammation alleviation, infection control, and so on. Innovative transdermal patches, gels/films, and microneedles have also been widely explored as formulations to deliver therapeutics to combat arthritic injuries. However, transdermal formulations that halt disease progression and promote damage repair are translated slowly from lab bench to clinical applications. One major reason is that the skin barrier and synovial capsule barrier limit the efficacy of transdermal delivery. Recently, many nanocarriers, such as nanoparticles, nanolipids, nanoemulsions, nanocrystals, exosomes, etc., have been incorporated into transdermal formulations to advance drug delivery. The combined transdermal formulations show promising safety and efficacy. Therefore, this review will focus on stating the current development of nanomedicine-based transdermal formulations for the treatment of arthritic injuries. The advances, limitations, and future perspectives in this field will also be provided to inspire future studies and accelerate clinical translational studies. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Biology-Inspired Nanomaterials > Lipid-Based Structures.

Effects of probiotics on nonalcoholic fatty liver disease: a systematic review and meta-analysis.

OBJECTIVES: Several studies have suggested that the gut-liver axis is closely related to nonalcoholic fatty liver disease (NAFLD). This study was designed to conduct a meta-analysis based on a randomized controlled trial (RCT) to systematically evaluate the efficacy of probiotics in the treatment of NAFLD. METHODS: This study carried out a literature search of published scientific data (up to April 2021) on probiotic therapies of NAFLD. The quality of the included literature was evaluated, and the corresponding data were extracted using the RevMan5.4 software. RESULTS: A total of 9 randomized clinical trials involving 352 patients with NAFLD were included in this study. Results of the meta-analysisstudy showed that probiotic therapy group have significant reduction in the levels of serum indices: alanine aminotransferase (ALT), aspartate transaminase (AST) and total cholesterol (TC) in comparison with the control group. Probiotic therapy was not associated with changes in body mass index (BMI) homeostasis model assessment of insulin resistance (HOMA-IR) and tumor necrosis factor (TNF) Subgroup analyses of BMI indicated that three or more composite probiotics or probiotic treatment for more than three months can significantly reduce the BMI level. CONCLUSION: This systematic review and meta-analysis demonstrated that modulating gut microbiota may be utilized as an effective method to improve liver function and reduce blood lipid levels in patients with NAFLD.

Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics.

Patients with ulcerative colitis (UC) have a high prevalence of mental disorders, such as depression and anxiety. Gut microbiota imbalance and disturbed metabolism have been suggested to play an important role in either UC or mental disorders. However, little is known about their detailed multi-omics characteristics in patients with UC and depression/anxiety. In this prospective observational study, 240 Chinese patients were enrolled, including 129 patients with active UC (69 in Phase 1 and 60 in Phase 2; divided into depression/non-depression or anxiety/non-anxiety groups), 49 patients with depression and anxiety (non-UC), and 62 healthy people. The gut microbiota of all subjects was analyzed using 16S rRNA sequencing. The serum metabolome and proteome of patients with UC in Phase 2 were analyzed using liquid chromatography/mass spectrometry. Associations between multi-omics were evaluated by correlation analysis. The prophylactic effect of candidate metabolites on the depressive-like behavior of mice with colitis was investigated. In total, 58% of patients with active UC had depression, while 50% had anxiety. Compared to patients with UC without depression/anxiety, patients with UC and depression/anxiety had lower fecal microbial community richness and diversity, with more Lactobacillales, Sellimonas, Streptococcus, and Enterococcus but less Prevotella_9 and Lachnospira. Most metabolites (e.g., glycochenodeoxycholate) were increased in the serum, while few metabolites, including 2'-deoxy-D-ribose and L-pipecolic acid, were decreased, accompanied by a general reduction in immunoglobulin proteins. These related bacteria, metabolites, and proteins were highly connected. A prophylactic administration of 2'-deoxy-D-ribose and L-pipecolic acid significantly reduced the depressive-like behaviors in mice with colitis and alleviated the inflammatory cytokine levels in their colon, blood and brain. This study has identified a comprehensive multi-omics network related to depression and anxiety in active UC. It is composed of a certain set of gut microbiota, metabolites, and proteins, which are potential targets for clinical intervention for patients with UC and depression/anxiety.

From traditional to novel treatment of arthritis: a review of recent advances in nanotechnology-based thermal therapy.

Arthritis has been a heavy burden on the economy and society at large. Recently, nanomaterials that can convert near-infrared light into localized heat have demonstrated better targeting to arthritic joints, fewer side effects, ease of combined application with current therapeutics and enhanced efficacy for arthritis treatment. In this review, the authors summarize traditional thermal therapies for arthritis treatment and their molecular mechanisms and discuss the advantages and applications of nanotechnology-based thermal therapies for arthritis treatment. In conclusion, nanotechnology-based thermal therapies are effective alternatives or adjuvant strategies to the current pharmacological treatment of arthritis. Future clinical translation of thermal therapies could benefit from research elucidating their mechanisms and standardizing their parameters to optimize efficacy.

[Effect of electroacupuncture on serum melatonin and dopamine in aged insomnia].

OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism. METHODS: A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected. RESULTS: After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment (P<0.01, P<0.05), among them, the sub-item scores of sleep quality, time to fall asleep, sleep time and sleep efficiency, daytime dysfunction and total score were all lower than those in the sham EA group (P<0.01, P<0.05). After treatment, the MoCA score and serum MT and DA levels in the EA group were higher than those before treatment (P<0.01), and the MoCA score and serum MT level in the EA group were higher than the sham EA group (P<0.01, P<0.05). CONCLUSION: Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.

Experimental Study on the Bone Morphogenetic Protein 1-Modified Bone Marrow Mesenchymal Stem Cell Sheets to Promote Mandibular Distraction Osteogenesis.

OBJECTIVE: The present study aims to increase the concentration of genetically modified bone marrow mesenchymal stem cells (BMSCs) in the distraction osteogenesis (DO) interstitial space and induce the conversion of BMSCs to osteoblasts to improve the osteogenic efficiency in DO and shorten the treatment period. METHODS: Bone morphogenetic protein 1 (BMP-1) and green fluorescent protein (GFP) gene-modified cell sheets of BMSCs were constructed by tissue engineering. Thirty-six New Zealand white rabbits were randomly divided into three groups: group A (the blank control group), group B (the GFP group) with the injection of GFP gene-modified BMSC sheets into the DO gap, and group C (the BMP-1 group) with the injection of BMP-1 gene-modified BMSC sheets into the DO gap. Rabbits in all three groups were distracted for 5 days at a distraction rate of 2.0 mm/d, once/day. After distraction, the above-mentioned cell sheet suspension was injected into the distraction gap to observe osteogenesis, which was observed by gross specimen observation, micro-computed tomography (Micro-CT) scanning, and histomorphology. RESULTS: The gross specimen observation showed that all animals had smooth and continuous bone cortex in the distraction region with relatively high hardness. The osteogenesis quality or hardness was ranked from the highest to the lowest, as Group C > Group B > Group A. Micro-CT and histomorphological observation revealed that group C had better maturation and bone volume of the new bone in the DO region at weeks 3 and 6 than groups B and A. CONCLUSION: BMP-1 gene-modified BMSC sheets could effectively promote the formation of new bone during rapid DO in the mandible, compensating for the poor osteogenesis caused by rapid distraction and providing a new approach to shorten the DO treatment period in clinical practice.

The Possible Anti-Inflammatory Effect of Dehydrocostus Lactone on DSS-Induced Colitis in Mice.

BACKGROUND: Dehydrocostus lactone (DL), one of the main active constituents in Aucklandia lappa Decne. (Muxiang), reported to have anti-inflammatory, antiulcer, and immunomodulatory properties. However, the effect of DL on ulcerative colitis (UC) has not been reported. To analyze the anti-inflammatory potential role of DL in UC, we provide a mechanism for the pharmacological action of DL. METHODS: The experimental model of UC was induced by using oral administration of 2% dextran sulfate sodium (DSS) with drinking water in BALB/c mice. Mesalazine (Mes, 0.52 g/kg/d), DL-high doses (DL-H, 20 mg/kg/d), DL-middle doses (DL-M, 15 mg/kg/d), DL-low doses (DL-L, 10 mg/kg/d) were gavaged once a day from day 4 to day 17. Disease activity index (DAI) was calculated daily. On day 18, mice were rapidly dissected and the colorectal tissues were used to detect the levels of UC-related inflammatory cytokines (TNF-α, IL-1ß, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α, IL-1. RESULTS: DL reduced the colorectal inflammation histological assessment, decreased UC-related inflammatory cytokines (TNF-α, IL-1ß, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α, IL-1. CONCLUSIONS: DL possessed the potential of anti-inflammatory effect to treated colitis. The protective mechanism of DL may involve in reducing inflammation and improving colorectal barrier function via downregulating the IL-6/STAT3 signaling.

Overexpression of Bone Morphogenetic Protein-1 Promotes Osteogenesis of Bone Marrow Mesenchymal Stem Cells In Vitro.

BACKGROUND Osteogenesis of bone marrow mesenchymal stem cells (BMSCs) is an important research topic in the application of bone tissue engineering. Bone morphogenetic protein-1 (BMP-1) is important in bone formation and stability, but its effects on the osteogenesis of BMSCs are unclear. This study aimed to investigate the association of BMP-1 with the osteogenic capacity of BMSCs. MATERIAL AND METHODS Primary rabbit BMSCs were cultured and divided into a BMP-1-overexpressing group, a Green Fluorescent Protein-expressing (GFP) group, and a Control group. The transfection efficiency of BMP-1 was tested by Western blotting. Cell viabilities, alkaline phosphatase (ALP) activities, Ca2+ concentrations, and gross examinations of BMSC sheets were examined at different times. The osteogenic marker collagen I was assessed by immunohistochemical analysis. RESULTS The cell viability, ALP activity, and Ca2+ content of the BMP1-overexpressed group were significantly enhanced compared with the GFP group and Control group. Immunohistochemistry staining results showed that BMP-1 promoted the expression of type I collagen in BMSCs sheets. CONCLUSIONS Our results suggest that the overexpression of BMP-1 can promote the osteogenesis of BMSCs and provides an improved method of cell-based tissue engineering.

A high-throughput and untargeted lipidomics approach reveals new mechanistic insight and the effects of salvianolic acid B on the metabolic profiles in coronary heart disease rats using ultra-performance liquid chromatography with mass spectrometry.

High-throughput lipidomics provides the possibility for the development of new therapeutic drugs. Accordingly, herein, we reveal the protective role of salvianolic acid B (Sal B) in rats with coronary heart disease (CHD) and propose a new mechanism for its action through a high-throughput and non-targeted lipidomics strategy. A CHD animal model was induced by consecutive high-fat diet feeding with vitamin D3 injection. At the end of the 8th week, the serum sample was analyzed to explore the metabolic biomarker and pathway changes using untargeted lipidomics based on ultra-performance liquid chromatography with mass spectrometry (UPLC/MS). In addition, blood and heart tissue samples were collected and processed for the detection of biochemical indicators and liver histological observation. After salvianolic acid B treatment, the levels of LDH, CK, CK-MB, MYO, CTn1, TG, TC, LDL-c, and Apo(b) were significantly lower than that in the model group, while the levels of HDL-c and Apo(a1) were significantly higher than that in the model group. Furthermore, the histological features of fibrosis and steatosis were also evidently relieved in the model group. A total of twenty-six potential biomarkers were identified to express the lipid metabolic turbulence in the CHD animal models, of which twenty-two were regulated by salvianolic acid B trending to the normal state, including TG(20:0/20:4/o-18:0), PC(20:4/18:1(9Z)), PC(18:3/20:2), PA(18:0/18:2), LysoPE(18:2/0:0), SM(d18:0/22:1), PE(22:6/0:0), LysoPE (20:4/0:0), sphinganine, Cer(d18:0/18:0), PS(14:0/14:1), PC (18:0/16:0), LysoPC(17:0), PE(22:2/20:1), PC(20:3/20:4), PE(20:4/P-16:0), PS(20:3/18:0), cholesterol sulfate, TG(15:0/22:6/18:1), prostaglandin E2, arachidonic acid and sphingosine-1-phosphate. According to the metabolite enrichment and pathway analyses, the pharmacological activity of salvianolic acid B on CHD is mainly involved in three vital metabolic pathways including glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism. Thus, based on the lipidomics-guided biochemical analysis of the lipid biomarkers and pathways, Sal B protects against CHD with good therapeutic effect by regulating glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism, inhibiting oxidative stress damage and lipid peroxidation.

Polymeric Micelles for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) affects around 1% of the world's population and places heavy burdens on patients and society. RA pathogenesis has been studied for centuries, and findings suggest that it is activated by varied factors such as infection, genetic activation, and environmental changes, and travels differential pathways in patients, which increases the difficulty of treatment. There is currently no cure for RA. Current treatments inhibit inflammation, protect joints, and suppress immune cells like macrophages and T-lymphocytes. However, these therapies usually have issues of ineffectiveness, drug resistance, and many side effects. The reason is that therapies like methotrexate (MTX), dexamethasone (Dex), and cyclosporine A (CsA) are very lipophilic and have broad distribution in vivo. Micelles are ideal carriers to increase the solubility, bioavailability, half-life, and targeting of these hydrophobic drugs, and thus can be used for RA treatment. In the past decade, micelle-based therapies have become an attractive new strategy for RA treatment. This review summarizes the merits of micelles for RA, the therapeutic targets for RA, and studies that show the recent progress of developed micelles for RA. We compare the composition, performance, potential merits, and limitations of current therapies, and discusses the future directions of advanced and smart micelles for RA.

Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. METHODS: In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn's disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. FINDINGS: We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. CONCLUSION: In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.

Human Indoor Exposome of Chemicals in Dust and Risk Prioritization Using EPA's ToxCast Database.

Humans spend most of their time indoors and thus have long-term exposure to chemicals. Dust is a sink for most indoor chemicals, and its ingestion is an important pathway for chemical uptake. Therefore, the chemical atlas from dust is an ideal environmental sample to investigate the indoor exposome and associated risk. In this study, we aimed to establish an indoor exposome database through comprehensive data mining on the occurrence of identified compounds in dust, and we prioritize chemicals of health concern. Through an extensive literature review (2849 articles), 355 chemicals and their concentrations were documented and analyzed for human exposure. Together with 81 compounds without concentration and 75 volatile organic compounds, we have established an indoor exposome database with 511 chemicals. Sixteen toxicological end points were selected for toxicity prioritization. Toxic equivalency factor (TEF)-based toxicity, calculated from EPA's ToxCast database, revealed a comprehensive atlas of the chemicals that had a primary contribution. Many of the prioritized compounds are currently neglected or are not actively studied. Overall, this investigation provides one of the most comprehensive analyses on chemical occurrence in indoor dust and prioritizes their chemical toxicity. Our findings can be used as a database for future exposome studies of the indoor environment and provide guidance for indoor risk assessments.

Exposure and risk assessment of volatile organic compounds and airborne phthalates in Singapore's Child Care Centers.

Infants and children under 6 years old spend most of daily time in Child Care Centers (CCCs), especially in the tropical regions like Singapore. Environmental exposure and associated risk during this early critical developmental stage is of great public concern. In this study, seven representative volatile organic compounds (VOCs) and five typical phthalates were analyzed in the indoor and outdoor air samples collected from 32 Singapore CCCs. The median of total VOC and phthalate concentration in indoor air was 19.03 and 5.41 µg m-3; respectively. For both indoors and outdoors environment, benzene, toluene and xylene were the dominant VOC contributors (more than 68%). For indoor air phthalates, di(2-ethylhexyl) phthalate and di-butyl phthalate (DBP) accounts for 60-76%. The level of both VOCs and phthalates in indoor environment was significantly higher than that in outdoor, with an average indoor/outdoor ratio of 1.24 and 1.45; respectively. A strong correlation (r > 0.50, p < 0.05) was observed between indoor and outdoor air compounds. VOC and phthalate levels have no significant difference between CCCs with split-unit and centrally ventilated air conditioners. Monte Carlo simulation was used to estimate exposure uncertainty and variability for the risk assessment. Overall, the concentrations of VOC were below the healthy reference values from either EPA Integrated Risk Information System (IRIS) or Singapore guideline. However, similar to other countries' report, benzene, DBP, ethylbenzene and naphthalene were at levels that could exceed the stringent standards such as Office of Environmental Health Hazard Assessment (OEHHA) cancer and reproductive health-based benchmarks.