The high-quality genome of Cryptotaenia japonica and comparative genomics analysis reveals anthocyanin biosynthesis in Apiaceae.

Cryptotaenia japonica, a traditional medicinal and edible vegetable crops, is well-known for its attractive flavors and health care functions. As a member of the Apiaceae family, the evolutionary trajectory and biological properties of C. japonica are not clearly understood. Here, we first reported a high-quality genome of C. japonica with a total length of 427 Mb and N50 length 50.76 Mb, was anchored into 10 chromosomes, which confirmed by chromosome (cytogenetic) analysis. Comparative genomic analysis revealed C. japonica exhibited low genetic redundancy, contained a higher percentage of single-cope gene families. The homoeologous blocks, Ks, and collinearity were analyzed among Apiaceae species contributed to the evidence that C. japonica lacked recent species-specific WGD. Through comparative genomic and transcriptomic analyses of Apiaceae species, we revealed the genetic basis of the production of anthocyanins. Several structural genes encoding enzymes and transcription factor genes of the anthocyanin biosynthesis pathway in different species were also identified. The CjANSa, CjDFRb, and CjF3H gene might be the target of Cjaponica_2.2062 (bHLH) and Cjaponica_1.3743 (MYB). Our findings provided a high-quality reference genome of C. japonica and offered new insights into Apiaceae evolution and biology.

Investigation of causal relationships between cortical structure and osteoporosis using two-sample Mendelian randomization.

The mutual interaction between bone characteristics and brain had been reported previously, yet whether the cortical structure has any relevance to osteoporosis is questionable. Therefore, we applied a two-sample bidirectional Mendelian randomization analysis to investigate this relationship. We utilized the bone mineral density measurements of femoral neck (n = 32,735) and lumbar spine (n = 28,498) and data on osteoporosis (7300 cases and 358,014 controls). The global surficial area and thickness and 34 specific functional regions of 51,665 patients were screened by magnetic resonance imaging. For the primary estimate, we utilized the inverse-variance weighted method. The Mendelian randomization-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis were conducted to assess heterogeneity and pleiotropy. We observed suggestive associations between decreased thickness in the precentral region (OR = 0.034, P = 0.003) and increased chance of having osteoporosis. The results also revealed suggestive causality of decreased bone mineral density in femoral neck to declined total cortical surface area (ß = 1400.230 mm2, P = 0.003), as well as the vulnerability to osteoporosis and reduced thickness in the Parstriangularis region (ß = -0.006 mm, P = 0.002). Our study supports that the brain and skeleton exhibit bidirectional crosstalk, indicating the presence of a mutual brain-bone interaction.

Neutrophils impaired by anti-galectin-3 antibodies elicit inflammation of endothelial cells to aggregate the development of lupus cutaneous vasculitis.

OBJECTIVES: To investigate whether the interplay of anti-galectin-3 antibodies (anti-Gal3 Abs) with neutrophils contributes to the development of lupus cutaneous vasculitis. METHODS: Enzyme-linked immunosorbent assay was used to determine the serum level of anti-Gal3 Abs in lupus patients. Flow cytometry, quantitative PCR and western blot were performed to investigate the expression of cell surface receptors, proinflammatory cytokines and signalling molecules in neutrophils stimulated by serum from lupus patients or healthy controls (HCs) or anti-Gal3 Ab, respectively. Immunofluorescence was performed to visualise the formation of neutrophil extracellular traps (NETs). Human umbilical vein endothelial cells were co-cultured with the supernatants from neutrophils stimulated by anti-Gal3 Ab, and cytokine production was measured at mRNA and protein levels. Immunohistochemistry was adopted to reveal the distribution of Gal3, cytokines and myeloperoxidase within lupus skin lesions. REULTS: Serum levels of anti-Gal3 Abs were negatively correlated with peripheral counts of neutrophils. Anti-Gal3 Abs positive sera from SLE patients accelerated neutrophil death, altered cell phenotype and promoted formation of NETs with the involvement of p38 MAPK pathway. Supernatants collected from neutrophils co-cultured with anti-Gal3 Ab provoked endothelial cells to produce cytokines such as IL-1, ICAM-1, SELE and particularly IL-6. Consistently, IL-6 was higher in SLE patients with anti-Gal3 Ab positive sera and enriched in the area of vascular inflammation together with enhanced expression of Gal3 protein and infiltration of neutrophils. CONCLUSIONS: Overall, these findings suggested that neutrophils were crucial mediators in anti-Gal3 Ab induced lupus cutaneous vasculitis.

[Abnormalities in signal transduction of Purkinje cells in spinocerebellar ataxias: a review].

Spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative diseases that have been currently identified with numerous subtypes exhibiting genetic heterogeneity and clinical variability. Purkinje neuronal degeneration and cerebellar atrophy are common pathological features among most SCA subtypes. The physiological functions of Purkinje cells are regulated by multiple factors, and their dysfunction in signal transduction may lead to abnormal cerebellar motor control. This review summarizes the abnormalities in voltage-gated ionic channels, intracellular calcium signaling, and glutamate signaling transduction of Purkinje cells in SCAs, aiming to provide a theoretical basis for further understanding the common pathogenesis of SCAs and developing specific treatments.

Distributed Dynamic Event-Triggered Control to Leader-Following Consensus of Nonlinear Multi-Agent Systems with Directed Graphs.

This paper investigates achieving leader-following consensus in a class of multi-agent systems with nonlinear dynamics. Initially, it introduces a dynamic event-triggered strategy designed to effectively alleviate the strain on the system's communication resources. Subsequently, a distributed control strategy is proposed and implemented in the nonlinear leader-follower system using the dynamic event-triggered mechanism, aiming to ensure synchronization across all nodes at an exponential convergence speed. Thirdly, the research shows that under the dynamic event-triggered strategy the minimum event interval of any two consecutive triggers guarantees the elimination of Zeno behavior. Lastly, the validity of the calculation results is verified by a simulation example.

Interaction between SlMAPK3 and SlASR4 regulates drought resistance in tomato (Solanum lycopersicum L.).

Tomato is a leading vegetable in modern agriculture, and with global warming, drought has become an important factor threatening tomato production. Mitogen-activated protein kinase 3 (MAPK3) plays an important role in plant disease and stress resistance. To clarify the downstream target proteins of SlMAPK3 and the mechanism of stress resistance in tomato, this study was conducted with the SlMAPK3-overexpressing lines OE-1 and OE-2 and the CRISPR/Cas9-mediated mutant lines slmapk3-1 and slmapk3-2 under PEG 6000-simulated drought. The results of yeast two-hybrid (Y2H), pull-down, and coimmunoprecipitation (Co-IP) assays confirmed that SlASR4 (NP_001269248.1) interacted with SlMAPK3. Analyses of the SlASR4 protein structure and SlASR4 expression under PEG 6000 and BTH stress revealed that SlASR4 has a highly conserved protein structural domain involved in the drought stress response under PEG 6000 treatment. The function of the SlASR4 and SlMAPK3 downstream target protein, in drought resistance in tomato plants, was identified by virus-induced gene silencing (VIGS). This study clarified that SlMAPK3 interacts with SlASR4 to positively regulate drought resistance in tomato plants.

Physical and psychosocial characteristics differ between individuals with knee pain and different knee osteoarthritis diagnostic criteria.

PURPOSE: Knee pain and osteoarthritis (OA) are common and often lead to disability among older adults. Existing published evidence, however, utilizes differing criteria to define studies' knee OA populations. We, therefore, aimed to determine whether differences exist in the characteristics of individuals with the presence of knee pain and different diagnostic criteria for knee OA. METHODS: The Promoting Independence in Seniors with Arthritis (PISA) study is a longitudinal observational study of individuals with and without knee pain and knee OA recruited from the orthopaedics clinic of the Universiti Malaya Medical Centre and the local hospital catchment. Patients were diagnosed with OA based on the American College of Rheumatology (ACR) criteria, the presence of knee pain, and a history of physician-diagnosed knee OA. Psychosocial parameters were measured using validated measures for social participation, independence, and ability to perform activities of daily living, and life satisfaction. RESULTS: Of the 230 included participants, mean age was 66.9 years (standard deviation: 7.2) and 166 (72.2%) were women. Kappa agreement between ACR criteria and knee pain was 0.525 and for ACR and physician-diagnosed OA it was 0.325. Binomial logistic regression analysis showed that weight, anxiety, and handgrip strength (HGS) were predictive of ACR OA. Knee pain was only predicted by HGS but not weight and anxiety. Physician-diagnosed OA was predicted by weight and HGS but not anxiety. HGS was predictive of ACR OA, knee pain, and physician-diagnosed OA. CONCLUSION: Our study showed that the characteristics of patients with OA are different, physically and psychosocially, depending on the criteria used. Poor agreement was observed between radiological diagnosis and the other diagnostic criteria. Our findings have important implications for the interpretation and comparison of published studies using different OA criteria.

TNF-α promotes CXCL-1/8 production in keratinocytes by downregulating galectin-3 through NF-κB and hsa-miR-27a-3p pathway to contribute psoriasis development.

OBJECTIVE: Treatment with TNF-α inhibitors improve psoriasis with minimize/minor neutrophils infiltration and CXCL-1/8 expression in psoriatic lesions. However, the fine mechanism of TNF-α initiating psoriatic inflammation by tuning keratinocytes is unclear. Our previous research identified the deficiency of intracellular galectin-3 was sufficient to promote psoriasis inflammation characterized by neutrophil accumulation. This study aims to investigate whether TNF-α participated in psoriasis development through dysregulating galectin-3 expression. METHODS: mRNA levels were assessed through quantitative real-time PCR. Flow cytometry was used to detect cell cycle/apoptosis. Western blot was used to evaluate the activation of the NF-κB signaling pathway. HE staining and immunochemistry were used to detect epidermal thickness and MPO expression, respectively. Specific small interfering RNA (siRNA) was used to knock down hsa-miR-27a-3p while plasmids transfection was used to overexpress galectin-3. Further, the multiMiR R package was utilized to predict microRNA-target interaction. RESULTS AND DISCUSSION: We found that TNF-α stimulation altered cell proliferation and differentiation and promoted the production of psoriasis-related inflammatory mediators along with the inhibition of galectin-3 expression in keratinocytes. Supplement of galectin-3 could counteract the rise of CXCL-1/8 but not the other phenotypes of keratinocytes induced by TNF-α. Mechanistically, inhibition of the NF-κB signaling pathway could counteract the decrease of galectin-3 and the increase of hsa-miR-27a-3p expression whereas silence of hsa-miR-27a-3p could counteract the decrease of galectin-3 expression induced by TNF-α treatment in keratinocytes. Intradermal injection of murine anti-CXCL-2 antibody greatly alleviated imiquimod-induced psoriasis-like dermatitis. CONCLUSION: TNF-α initiates psoriatic inflammation by increasing CXCL-1/8 in keratinocytes mediated by the axis of NF-κB-hsa-miR-27a-3p-galectin-3 pathway.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Etanercept treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs with considerable morbidity and mortality. Immunomodulators for SJS/TEN including systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice. Emerging evidence suggested the therapeutic effects of tumor necrosis factor-α antagonists on SJS/TEN. OBJECTIVE: To compare the efficacy and safety of IVIG and systemic steroids in conjunction with or without etanercept, a tumor necrosis factor-α inhibitor, for patients with SJS/TEN. METHODS: We undertook a retrospective review of 41 patients with SJS/TEN admitted to our institution from 2015 to February 2021. A total of 25 patients with integrated data were involved in this study, of which 14 patients were treated with IVIG and corticosteroids and 11 were in addition given etanercept. The clinical characteristics, duration of hospitalization, exposure time to high-dose steroids, and the total amount of systemic steroids were analyzed. RESULTS: In comparison to conventional therapy, conjunction with etanercept reduced the duration of hospitalization (13.5 vs 19.0 days; P = .01), the exposure time of high-dose steroids (7.1 vs 14.9 days; P = .01), and the overall amount of systemic steroid (925 mg vs 1412.5 mg; P = .03) in patients with SJS/TEN. No pronounced adverse effects were observed within 6 months of follow-up after the treatment. CONCLUSION: The add-in of etanercept at the time of initiating conventional therapy could be a superior option to accelerate disease recovery and reduce the high dose and total amount of systemic steroids without pronounced adverse events in patients with SJS/TEN.

Phase transitions induced by exchange coupling, magnetic field, and temperature in a strongly correlated molecular trimer with a triangular topology.

Regulating the physical properties such as the quantum phase and the Kondo effect of molecular electronic devices near critical points may play a key role in increasing the robustness of quantum memory, which is a crucial component in quantum information processing. Molecules with a triangular topology are ideal prototypes to reveal the competition among magnetic frustration, Kondo screening, and local inter-molecule exchange interactions. Herein, motivated by a recent work investigating the single-electron tunneling through a redox-active edge-fused porphyrin trimer by using a Hubbard dimer model [J. O. Thomas, J. K. Sowa, B. Limburg, X. Bian, C. Evangeli, J. L. Swett, S. Tewari, J. Baugh, G. C. Schatz, G. A. D. Briggs, H. L. Anderson and J. A. Mol, Chem. Sci., 2021, 12, 11121], we studied the phase transition, the electronic transport, and the thermodynamical properties of a real molecular trimer structure organized in a triangular topology, with and without an external magnetic field, and at zero and non-zero temperatures. Both the Hubbard electron-electron interaction and the Heisenberg exchange interaction are fully taken into account, with the aid of the state-of-the-art numerical renormalization group method. Various kinds of Kondo behaviors and quantum phase transitions are demonstrated, due to the competition among the Ruderman-Kittel-Kasuya-Yosida interaction, the direct exchange coupling, and the Zeeman effect. Our findings may offer deep insights into the manipulation of the quantum phase and the Kondo behavior in a molecular trimer with a triangular topology.

Down-regulation of EGFL8 regulates migration, invasion and apoptosis of hepatocellular carcinoma through activating Notch signaling pathway.

BACKGROUND: Our previous studies have reported the down-regulation of EGFL8 correlates to the development and prognosis of colorectal and gastric cancer. The present study is carried out to explore the expression pattern and role of EGFL8 in hepatocellular carcinoma (HCC). METHODS AND MATERIALS: EGFL8 expression in 102 cases of HCC tissues matched with adjacent non-tumorous liver tissues, a normal liver cell line and three liver cancer cell lines with different metastatic capacity was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Moreover, the clinicopathological features and prognosis of HCC patients were correlated with expression of EGFL8. Subsequently, the gain-and loss-of-function experiments were carried out to investigate the biological function of EGFL8 in HCC. We also used N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-(S)- phenylglycine t-butyl ester (DAPT), an inhibitor for Notch signaling pathway, in these experiments to verify the involvement of Notch signaling pathway in the effects of EGFL8. Additionally, a mouse model was established to investigate the effect of EGFL8 on metastasis of HCC cells. The expression of Notch signaling pathway in HCC cells and xenograft mouse tumors were detected by Western blot and immunohistochemistory. RESULTS: The expression of EGFL8 was significantly decreased in HCC tissues and cell lines and EGFL8 down-regulation correlated to multiple nodules, vein invasion, high TNM stage and poor prognosis of HCC. Interestingly, the expression levels of EGFL8 in three liver cancer cell lines were negatively associated with their metastatic capacity. In vitro and in vivo experiments indicated that EGFL8 obviously suppressed metastasis and invasion of HCC cells but slightly promoted apoptosis. Meanwhile, the expression of Notch signaling pathway was obviously suppressed in EGFL8 overexpressed HCCLM3 cells and xenograft mouse tumors generated from these cells but markedly elevated in EGFL8 depleted Hep3B cells. Furthermore, the up-regulated expression of Notch signaling pathway and effects induced by EGFL8 knockdown in Hep3B cells could be counteracted by DAPT treatment. CONCLUSION: The down-regulation of EGFL8 was correlated to progression and poor prognosis of HCC and regulates HCC cell migration, invasion and apoptosis through activating the Notch signaling pathway, suggesting EGFL8 as a novel therapeutic target and a potential prognostic marker for HCC.

Characterization of autoantibodies and cytokines related to cutaneous lupus erythematosus.

OBJECTIVE: To investigate the profiles of anti-RPLP0, anti-galectin3 antibodies, interferon-α (IFN-α), interferon-λ1(IFN-λ1) and interleukin-17A/F(IL-17A/F) in the subtypes of cutaneous lupus erythematosus (CLE) including acute CLE (ACLE), subacute CLE (SCLE) and discoid lupus erythematosus (DLE). METHODS: Serum levels of autoantibodies and cytokines were determined by enzyme-linked immunoabsorbent assay (ELISA). Lupus lesions were evaluated by cutaneous lupus erythematosus disease area and severity index (CLASI). RESULTS: Serum anti-RPLP0, anti-galectin3 antibodies and IFN-λ1 were higher in systemic lupus erythematosus (SLE) patients with skin lesions than those without skin lesions, compared to healthy controls. IFN-α, IL-17A and IL-17F was elevated in all patients regardless of skin lesions. The two antibodies, IFN-α and IL-17A were positively correlated with the CLASI score in all patients with CLE. In addition, serum IL-17A was positively correlated to the CLASI score of ACLE, SCLE and DLE, while anti-RPLP0 and anti-galectin3 antibodies were only correlated to the score of SCLE and IL-17F to DLE. CONCLUSION: Serum anti-RPLP0, anti-galectin3 antibodies, IFN-α, IFN-λ1 and IL-17A/F are associated with the occurrence of lupus skin lesions regardless of the systemic complications, whereas the profiles of these inflammatory mediators vary with the subtypes of lupus skin lesions.

Kondo effect and RKKY interaction assisted by magnetic anisotropy in a frustrated magnetic molecular device at zero and finite temperature.

Molecular magnetic compounds, which combine the advantages of nanoscale behaviors with the properties of bulk magnetic materials, are particularly attractive in the fields of high-density information storage and quantum computing. Before molecular electronic devices can be fabricated, a crucial task is the measurement and understanding of the transport behaviors. Herein, we consider a magnetic molecular trimer sandwiched between two metal electrodes, and, with the aid of the sophisticated full density matrix numerical renormalization group (FDM-NRG) technique, we study the effect of magnetic anisotropy on the charge transport properties, illustrated by the local density of states (LDOS, which is proportional to the differential conductance), the Kondo effect, and the temperature and inter-monomer hopping robustness. Three kinds of energy peaks are clarified in the LDOS: the Coulomb, the Kondo and the Ruderman-Kittel-Kasuya-Yosida (RKKY) peaks. The local magnetic moment and entropy go through four different regimes as the temperature decreases. The Kondo temperature TK could be described by a generalized Haldane's formula, revealing in detail the process where the local moment is partially screened by the itinerant electrons. A relationship between the width of the Kondo resonant peak WK and TK is built, ensuring the extraction of TK from WK in an efficient way. As the inter-monomer hopping integral varies, the ground state of the trimer changes from a spin quadruplet to a magnetically frustrated phase, then to an orbital spin singlet through two first order quantum phase transitions. In the first two phases, the Kondo peak in the transmission coefficient reaches its unitary limit, while in the orbital spin singlet, it is totally suppressed. We demonstrate that magnetic anisotropy may also induce the Kondo effect, even without Coulomb repulsion, hence it is replaceable in the many-body behaviours at low temperature.

Iatrogenic Arsenism Characterized by Palmoplantar Hyperkeratosis and Diffused Skin Cancers for Over Decades.

ABSTRACT: Chronic arsenism usually occurs after a long-term unawareness of arsenic exposure from environment, occupation, food, and water. We here reported 3 cases with diffused arsenic keratosis and skin cancers derived from long-term arsenic medication ingestion. In these cases, hyperkeratotic skin lesions were initially found on palms and soles, slowly progressed to every part of the skin and lasted maximally for over 30 years. Skin cancers were diagnosed and removed intermittently within decades, but with no malignancies in other organs. Oral retinoids combing with topical 5- fluorouracil and photodynamic treatment yielded a desirable outcome.

AgNAC1, a celery transcription factor, related to regulation on lignin biosynthesis and salt tolerance.

The NAC transcription factor participates in various biotic and abiotic stress responses and plays a critical role in plant development. Lignin is a water-insoluble dietary fiber, but it is second only to cellulose in abundance. Celery is the main source of dietary fiber, but its quality and production are limited by various abiotic stresses. Here, AgNAC1 containing the NAM domain was identified from celery. AgNAC1 was found to be a nuclear protein. Transgenic Arabidopsis thaliana plants hosting AgNAC1 have longer root lengths and stomatal axis lengths than the wide type (WT). The evidence from lignin determination and expression levels of lignin-related genes indicated that AgNAC1 plays a vital role in lignin biosynthesis. Furthermore, the results of the physiological characterization and the drought and salt treatments indicate that AgNAC1-overexpressing plants are significantly resistive to salt stress. Under drought and salt treatments, the AgNAC1 transgenic Arabidopsis thaliana plants presented increased superoxide dismutase (SOD) and peroxidase (POD) activities and decreased malondialdehyde (MDA) content and size of stomatal apertures relatively to the WT plants. The AgNAC1 served as a positive regulator in inducing the expression of stress-responsive genes. Overall, the overexpressing AgNAC1 enhanced the plants' resistance to salt stress and played a regulatory role in lignin accumulation.

The prognostic value of serum amyloid A in solid tumors: a meta-analysis.

BACKGROUND: Previous studies have demonstrated that serum amyloid A (SAA) levels are correlated with the clinical outcomes of solid tumors. However, the available data have not been systematically evaluated. The objective of the present meta-analysis was to explore the prognostic value of SAA levels in solid tumors. METHODS: Eligible studies were identified from the PubMed, EMBASE and Science Citation Index electronic databases. The clinical characteristics, disease/progression-free survival (DFS/PFS) and overall survival (OS) were extracted from the eligible studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Stata 12.0 software. We also performed subgroup, meta-regression and sensitivity analyses. RESULTS: In total, 12 eligible studies including 2749 patients were enrolled in the present meta-analysis. The pooled HRs with 95% CIs showed that elevated levels of SAA were significantly associated with poor OS (HR = 3.01, 95% CI 1.96-4.63) and DFS/PFS (HR = 1.67, 95% CI 1.31-2.12) in patients with solid tumors. Although publication bias was seem found in the studies with regard to OS, a further trim and fill analysis revealed that the adjusted HR was 3.02 (95% CI 1.96-4.63), which was close to the original HR. Subgroup analysis confirmed an elevated level of SAA as a strong prognostic marker in patients with solid tumors, regardless of tumor type, detection method, cut-off value, sample size, area and variance analyses. CONCLUSION: Our meta-analysis indicated that elevated levels of SAA might be an unfavorable prognostic marker for OS in patients with solid tumors.

Bioactive glass functionalized chondroitin sulfate hydrogel with proangiogenic properties.

Blood vessels play an important role in bone defect repair and growth, and a critical challenge of bone defect repair is the promotion of blood vessel formation. Most of the current methods promote vascularization by adding specific growth factors, which are costly and easy to inactivate. In this study, we developed a covalently cross-linked aminated bioactive glass nanoparticle-chondroitin sulfate methacrylate (ABGN-CSMA) organic-inorganic composite hydrogel with angiogenic properties. The amino groups of the ABGNs form covalent bonds with the carboxyl groups on CSMA. Surface amination modification of BGNs not only improved the dispersion of BGNs in CSMA but also significantly improved the mechanical properties of the composite hydrogel. The largest storage modulus (1200 Pa), the largest loss modulus (560 Pa) and the strongest resistance to deformation of the hydrogel are seen at 10% concentration of ABGNs. Simultaneously, the local pH stability and sustained ion release of the composite hydrogel are conducive to cell adhesion, proliferation, and angiogenesis. This work provides evidence for the development of covalently cross-linked organic-inorganic composite hydrogels with angiogenic properties.

Nordihydroguaiaretic acid can suppress progression of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a poorly understood disease mechanistically. MOG35-55 peptide induced experimental autoimmune encephalomyelitis (EAE) is a broadly used model to study MS. Using this model we have earlier shown that the antioxidant tempol or the small molecule inhibitor of p38 SB203580 can effectively prevent EAE progression. This effect was mediated by means of regulating immune inflammation, signaling by the p38MAPK-SGK1 pathway, and oxidative stress. However, there is a need to test drugs that can be used in pharmacological intervention of EAE. Given that nordihydroguaiaretic Acid (NDGA) has been shown to possess anti-oxidant activity and capacity of antagonizing autoimmune inflammation, we tested the effect of NDGA in ameliorating EAE in the current study. NDGA showed significant beneficial effect against EAE with both anti-inflammation and antioxidant activity. NDGA could weaken the immune inflammation at least partly by inhibiting the oxidant stress-p38MAPK-SGK1 pathway representing a target for putative pharmacological intervention. © 2018 IUBMB Life, 70(5):432-436, 2018.

Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis.

Psoriasis-specific proteins dysregulated in keratinocytes and involved in the pathophysiological process of psoriasis remains elusive. We report here that epidermal galectin-3 expression is significantly downregulated in lesional skin, but not in non-lesional skin in psoriasis patients, nor in a group of diseases known as psoriasiform dermatitis clinically and histologically similar to psoriasis. The deficiency of epidermal galectin-3 is sufficient to promote development of psoriatic lesions, as evidenced by more severe skin inflammation in galectin-3 knockout (gal3-/-) mice, compared to wild-type mice, after imiquimod treatment, and in skin from gal3-/- mice grafted onto wildtype mice. The development of psoriatic-like lesions is attributable to 1) the spontaneously tuning up of psoriasis signatures in keratinocytes through JNK pathway; and 2) neutrophil accumulation caused by the enhanced leukocyte-recruiting capacity associated with overexpression of S100A7-9 and CXCL-1, 8 in keratinocytes with impaired galectin-3 expression. Psoriasis-like skin inflammation is significantly improved in gal-3-/- mice both by inhibition of neutrophils accumulation with a selective CXCR2 antagonist of SB225002, and by intracutaneous injection of recombinant galectin-3. Overall, these findings offer promising galectin-3-related diagnostic and therapeutic resolutions of psoriasis.