Association of homocysteine with ankylosing spondylitis: a systematic review and meta-analysis

Abstract Background: Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. Methods: Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. Results: Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. Conclusion: This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. Trial registration: This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.(AU)

Prognostic value of long non-coding RNA TP73-AS1 expression in different types of cancer: a systematic review and meta-analysis

Background: TP73 antisense RNA 1 (TP73-AS1), a newly discovered long non-coding RNA (lncRNA), has been reported to be upregulated in various kinds of tumors, and shows a variable influence on living quality and prognosis of patients. Thus, we conducted a meta-analysis to evaluate the overall prognostic value of the lncRNA TP73-AS1 in cancer patients. Results: A systematic literature retrieval was carried out using the PubMed, Cochrane Library, EMBASE, and Web of Science databases. We calculated the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs) to evaluate the association of TP73-AS1 expression with prognostic and clinicopathological parameters. A total of 15 studies including 1057 cancer patients were finally selected for the meta-analysis. The results demonstrated that high TP73-AS1 expression was significantly associated with shorter overall survival (OS) (HR = 1.97, 95% CI: 1.68­2.31, P b 0.001). According to a fixed-effects or random-effects model, elevated TP73-AS1 expression markedly predicted advanced clinical stage (OR = 3.30, 95% CI: 2.35­4.64, P b 0.001), larger tumor size (OR = 2.37, 95% CI: 1.75­3.22, P b 0.001), earlier lymph node metastasis (OR = 3.28, 95% CI: 1.59­6.76, P = 0.001), and distant metastasis (OR = 4.94, 95% CI: 2.61­9.37, P b 0.001). Conclusions: High lncRNA TP73-AS1 expression appears to be predictive of a worse OS and clinicopathologic features for patients with various types of malignant tumors. These results provide a basis for utilizing TP73- AS1 expression as an unfavorable indicator to predict survival outcomes.

Brazilin induces FOXO3A-dependent autophagic cell death by disturbing calcium homeostasis in osteosarcoma cells.

PURPOSE: Osteosarcoma is a common primary malignant bone tumour, and its cure rate has stagnated over the past 25-30 years. Brazilin, a purified natural product from sappan wood (Caesalpinia sappan L.), has been proved to possess potent anti-cancer effects. In this study, we investigated the anti-cancer effect of brazilin on human osteosarcoma and elucidated the underlying mechanisms. METHODS: We exposed MG-63 cells to different concentrations of brazilin (5, 10 and 20 µM) for 24 h. Western blotting, immunocytofluorescence, luciferase reporter assays, and RT-PCR were used to evaluate whether brazilin activates FOXO family-dependent autophagy. RESULTS: Brazilin increased autophagic flux in the human osteosarcoma cell line MG-63, as evidenced by the upregulation of LC3-II and the downregulation of P62/SQSTM1. Moreover, the pharmacological or genetic blockade of autophagy decreased brazilin-induced cell death, indicating that brazilin triggered autophagic cell death in MG-63 cells. Specifically, brazilin induced FOXO3A(Ser7) phosphorylation, activated FOXO3A nuclear translocation and increased FOXO3A reporter activity, which contributed to the expression of autophagy-related genes and subsequently initiated autophagic cell death in MG-63 cells. Importantly, the increased expression and nuclear translocation of FOXO3A were tightly related to the disturbance of calcium homeostasis, which could be prevented by chelating intracellular calcium. CONCLUSIONS: Taken together, these data demonstrate that brazilin induces osteosarcoma cell death by inducing excessive autophagy, which is mediated through the Ca2+-FOXO3A pathway. Our study provides a new anti-tumour mechanism for brazilin treatment in osteosarcoma patients.

Ambient PM2.5 and Stroke: Effect Modifiers and Population Attributable Risk in Six Low- and Middle-Income Countries.

BACKGROUND AND PURPOSE: Short-term exposure to ambient fine particulate pollution (PM2.5) has been linked to increased stroke. Few studies, however, have examined the effects of long-term exposure. METHODS: A total of 45 625 participants were interviewed and included in this study, the participants came from the Study on Global Ageing and Adult Health, a prospective cohort in 6 low- and middle-income countries. Ambient PM2.5 levels were estimated for participants' communities using satellite data. A multilevel logistic regression model was used to examine the association between long-term PM2.5 exposure and stroke. Potential effect modification by physical activity and consumption of fruit and vegetables was assessed. RESULTS: The odds of stroke were 1.13 (95% confidence interval, 1.04-1.22) for each 10 µg/m3 increase in PM2.5. This effect remained after adjustment for confounding factors including age, sex, smoking, and indoor air pollution (adjusted odds ratio=1.12; 95% confidence interval, 1.04-1.21). Further stratified analyses suggested that participants with higher levels of physical activity had greater odds of stroke, whereas those with higher consumption of fruit and vegetables had lower odds of stroke. These effects remained robust in sensitivity analyses. We further estimated that 6.55% (95% confidence interval, 1.97%-12.01%) of the stroke cases could be attributable to ambient PM2.5 in the study population. CONCLUSIONS: This study suggests that ambient PM2.5 may increase the risk of stroke and may be responsible for the astounding stroke burden in low- and middle-income countries. In addition, greater physical activity may enhance, whereas greater consumption of fruit and vegetables may mitigate the effect.

Application of the analytic hierarchy approach to the risk assessment of Zika virus disease transmission in Guangdong Province, China.

BACKGROUND: An international spread of Zika virus (ZIKV) infection has attracted global attention in 2015. The infection also affected Guangdong province, which is located in southern China. Multiple factors, including frequent communication with South America and Southeast Asia, suitable climate (sub-tropical) for the habitat of Aedes species, may increase the risk of ZIKV disease transmission in this region. METHODS: An analytic hierarchy process (AHP) method was used to develop a semi-quantitative ZIKV risk assessment model. After selecting indicators, we invited experts in related professions to identify the index weight and based on that a hierarchical structure was generated. Then a series of pairwise comparisons were used to determine the relative importance of the criteria. Finally, the optimal model was established to estimate the spatial and seasonal transmission risk of ZIKV. RESULTS: A total of 15 factors that potentially influenced the risk of ZIKV transmission were identified. The factor that received the largest weight was epidemic of ZIKV in Guangdong province (combined weight [CW] =0.37), followed by the mosquito density (CW = 0.18) and the epidemic of DENV in Guangdong province (CW = 0.14). The distribution of 123 districts/counties' RIs of ZIKV in Guangdong through different seasons were presented, respectively. CONCLUSIONS: Higher risk was observed within Pearl River Delta including Guangzhou, Shenzhen and Jiangmen, and the risk is greater in summer and autumn compared to spring and winter.

Diversity, distribution, and antagonistic activities of rhizobacteria of Panax notoginseng.

BACKGROUND: Rhizobacteria play an important role in plant defense and could be promising sources of biocontrol agents. This study aimed to screen antagonistic bacteria and develop a biocontrol system for root rot complex of Panax notoginseng. METHODS: Pure-culture methods were used to isolate bacteria from the rhizosphere soil of notoginseng plants. The identification of isolates was based on the analysis of 16S ribosomal RNA (rRNA) sequences. RESULTS: A total of 279 bacteria were obtained from rhizosphere soils of healthy and root-rot notoginseng plants, and uncultivated soil. Among all the isolates, 88 showed antagonistic activity to at least one of three phytopathogenic fungi, Fusarium oxysporum, Fusarium solani, and Phoma herbarum mainly causing root rot disease of P. notoginseng. Based on the 16S rRNA sequencing, the antagonistic bacteria were characterized into four clusters, Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetesi. The genus Bacillus was the most frequently isolated, and Bacillus siamensis (Hs02), Bacillus atrophaeus (Hs09) showed strong antagonistic activity to the three pathogens. The distribution pattern differed in soil types, genera Achromobacter, Acidovorax, Brevibacterium, Brevundimonas, Flavimonas, and Streptomyces were only found in rhizosphere of healthy plants, while Delftia, Leclercia, Brevibacillus, Microbacterium, Pantoea, Rhizobium, and Stenotrophomonas only exist in soil of diseased plant, and Acinetobacter only exist in uncultivated soil. CONCLUSION: The results suggest that diverse bacteria exist in the P. notoginseng rhizosphere soil, with differences in community in the same field, and antagonistic isolates may be good potential biological control agent for the notoginseng root-rot diseases caused by F. oxysporum, Fusarium solani, and Panax herbarum.

Increased hemagglutinin content in a reassortant 2009 pandemic H1N1 influenza virus with chimeric neuraminidase containing donor A/Puerto Rico/8/34 virus transmembrane and stalk domains.

The glycoproteins, heamagglutinin (HA) and neuraminidase (NA) of influenza virus confer host protective immune responses during vaccination, which is the most effective approach for preventing influenza-associated morbidity and mortality. Since the functional balance between the HA and NA proteins may affect viral receptor binding and replication, a pandemic influenza A virus (H1N1 pdm09), strain A/Texas/05/2009, was optimized to elevate its HA antigen content by modifying the NA gene. In this study, we have constructed two 2:6 reassortant viruses between pdmH1N1 (A/Texas/05/2009) and A/Puerto Rico/8/34 (PR8), in which the NA gene of A/Texas/05/2009 was modified to contain part of the NA gene from PR8. One chimeric NA virus has the PR8 transmembrane (TM) region (HNtm 2:6) and the other contains both the PR8 NA TM and stem regions (HNst 2:6). Using quantitative reverse phase-HPLC (RP-HPLC) analysis, we observed that the HNst2:6 virus contains a higher HA1 content than HN2:6 wild type. In addition, this mutant virus displays a higher HA1 to nucleoprotein (NP) ratio, based on gel electrophoresis densitometry analysis. Furthermore, the neuraminidase activity of purified HNst 2:6 virus is approximately 30% lower than that of HN2:6 virus, which is suggestive of a lower incorporation of NA into the viral envelope. Therefore, we propose that the reduction of NA packaging in the virion may lead to a compensatory increase of HA. Such an improvement in HA yield is possibly beneficial to H1N1 pdm09 vaccine production.

Two new C(13) nor-isoprenoids from the leaves of Casearia sylvestris.

Two new C(13) nor-isoprene glycosides, (6S,9S)-6,9-dihydroxymegastiman-4-en-9-O-beta-D-glucopyranoside (1) and (6S,9S)-6,9-dihydroxymegastiman-4-en-9-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (2) were isolated from the leaves of Casearia sylvestris, along with icariside B(5) (3), byzantionoside B (4), blumenol B (5), blumenol C (6) and loliolide (7). The structures of these compounds were determined on the basis of 1D and 2D NMR, MS and circular dichroism (CD) spectroscopic analyses, chemical methods and comparison with the literature data.

Sorocenols G and H, anti-MRSA oxygen heterocyclic Diels-Alder-type adducts from Sorocea muriculata roots.

Bioassay-guided fractionation of a root extract of Sorocea muriculata led to the isolation and identification of two new oxygen heterocyclic Diels-Alder-type adducts, sorocenols G (1) and H (2), along with lupeol-3-(3' R-hydroxytetradecanoate) and oxyresveratrol. The structures of 1 and 2 were elucidated using 1D and 2D NMR spectroscopic and HRMS data and by comparison with reported values. The absolute configurations of 1 and 2 were established by analysis of their experimental and theoretically calculated CD spectra. Compounds 1 and 2 showed significant and selective activity against methicillin-resistant Staphylococcus aureus with IC50 values of 1.5 and 0.5 microM, respectively. Compound 2 also displayed antifungal activity against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, with IC 50 values of 5.4, 5.4, and 10.0 microM, respectively.

Capisterones A and B, which enhance fluconazole activity in Saccharomyces cerevisiae, from the marine green alga Penicillus capitatus.

A whole-cell-based assay using Saccharomyces cerevisiae strains that overexpress Candida albicans CDR1 and MDR1 efflux pumps has been employed to screen natural product extracts for reversal of fluconazole resistance. The tropical green alga Penicillus capitatus was selected for bioassay-guided isolation, leading to the identification of capisterones A and B (1 and 2), which were recently isolated from this alga and shown to possess antifungal activity against the marine pathogen Lindra thallasiae. Current work has assigned their absolute configurations using electronic circular dichroism and determined their preferred conformations in solution based on detailed NOE analysis. Compounds 1 and 2 significantly enhanced fluconazole activity in S. cerevisiae, but did not show inherent antifungal activity when tested against several opportunistic pathogens or cytotoxicity to several human cancer and noncancerous cell lines (up to 35 microM). These compounds may have a potential for combination therapy of fungal infections caused by clinically relevant azole-resistant strains.

Phenolic glycosides from Potalia amara.

Investigation of the stem bark of the unique Amazonian herbal plant Potalia amara yielded two new phenolic glycosides, potalioside A (1) and B (2), along with di-O-methylcrenatin (3), 2,6-dimethoxy-4-hydroxyphenol 1-glucoside and sweroside. The structures of potalioside A and B were established by interpretation of spectral data as 4-hydroxymethyl-2,6-dimethoxyphenyl 1-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside and 4-hydroxymethyl-2,6-dimethoxyphenyl 1-O-beta- D-xylopyranosyl(1-->6)- beta-D-glucopyranoside, respectively.

Naturally occurring proteasome inhibitors from mate tea (Ilex paraguayensis) serve as models for topical proteasome inhibitors.

Proteasome inhibitors have emerged as a clinically important therapy for neoplastic disease, with velcade, an organoboron compound used extensively in multiple myeloma. Recently, (-)-epigallocatechin gallate has been found to be a potent inhibitor of the proteasomal chymotrypsin-like activity. Other compounds that inhibit angiogenesis and are active as chemopreventive agents, such as curcumin, also inhibit proteasome activity. We have screened natural product extracts using ras-transformed endothelial cells (SVR cells) as a bioassay, and found that extracts of mate tea (Ilex paraguayensis) inhibit the growth of these endothelial cells. The extract was fractionated and found to have novel cinnamate esters that inhibit proteasome activity. Based upon the structures of the compounds isolated from mate tea, we examined synthetic analogs of these compounds for proteasome activity. Cinnamic acid amides had no inhibitory activity against proteasomes, whereas cinnamate esters displayed the activity. Based upon these findings, preclinical and clinical trials of topical cinnamate esters as proteasome inhibitors are warranted for psoriasis and other inflammatory disorders.

Acetylenic acids inhibiting azole-resistant Candida albicans from Pentagonia gigantifolia.

Antifungal bioassay-guided isolation of the ethanol extract of the roots of Pentagonia gigantifolia yielded 6-octadecynoic acid (1) and the new 6-nonadecynoic acid (2). Compounds 1 and 2 inhibited the growth of fluconazole-susceptible and -resistant Candida albicans strains. Their antifungal potencies were comparable to those of amphotericin B and fluconazole. Of particular significance is the low cytotoxicity and specific activity of 1 and 2 against C. albicans.

Antimicrobial and antiparasitic (+)-trans-hexahydrodibenzopyrans and analogues from Machaerium multiflorum.

Machaerium multiflorum yielded two additional new (+)-trans-hexahydrodibenzopyrans (HHDBP's), machaeriol C (1) and machaeriol D (2), and three new 5,6-seco-HHDBP's, machaeridiol A (3), machaeridiol B (4), and machaeridiol C (5). Their structures and stereochemistries were determined by 1D and 2D NMR data, including HMBC, NOESY, and circular dichroism experiments. Machaeriol C (1) demonstrated in vitro antibacterial activity against Staphylococcus aureus (IC(50) 0.65 microg/mL) and methicillin-resistant S. aureus (MRSA) (IC(50) 0.70 microg/mL), while its corresponding 5,6-seco-analogues machaeridiol A (3) and machaeridiol B (4) showed antibacterial activity against S. aureus and MRSA (IC(50) 1.0-2.6 microg/mL) and antifungal activity against Candida albicans (IC(50), 2.0-3.5 microg/mL). In addition, machaeridiol B (4) demonstrated antiparasitic activities against Plasmodium falciparum D6 and W2 clones and Leishmania donavani with IC(50) values of 0.64, 0.22, and 0.9 microg/mL, respectively.

Flavanone glycosides from Miconia trailii.

Assay-guided fractionation of the ethanol extract of the twigs and leaves of Miconia trailii yielded two new flavanone glycosides, matteucinol 7-O-alpha-l-arabinopyranosyl(1-->6)-beta-d-glucopyranoside (miconioside A, 1) and farrerol 7-O-beta-d-apiofuranosyl(1-->6)-beta-d-glucopyranoside (miconioside B, 2), along with the known compounds matteucinol 7-O-beta-d-apiofuranosyl(1-->6)-beta-d-glucopyranoside (3), matteucinol (4), 2alpha,3beta,19alpha-trihydroxyolean-12-ene-24,28-dioic acid (bartogenic acid, 5), 2alpha,3beta,23-trihydroxyolean-12-ene-28-oic acid (arjunolic acid, 6), 2alpha,3alpha,19alpha, 23-tetrahydroxyurs-12-ene-28-oic acid (myrianthic acid, 7), and stigmast-4-ene-3,6-dione (8). The structures of 1-8 were elucidated by spectroscopic methods, including 2D NMR.