Integrated analysis of diverse cancer types reveals a breast cancer-specific serum miRNA biomarker through relative expression orderings analysis.

PURPOSE: Serum microRNA (miRNA) holds great potential as a non-invasive biomarker for diagnosing breast cancer (BrC). However, most diagnostic models rely on the absolute expression levels of miRNAs, which are susceptible to batch effects and challenging for clinical transformation. Furthermore, current studies on liquid biopsy diagnostic biomarkers for BrC mainly focus on distinguishing BrC patients from healthy controls, needing more specificity assessment. METHODS: We collected a large number of miRNA expression data involving 8465 samples from GEO, including 13 different cancer types and non-cancer controls. Based on the relative expression orderings (REOs) of miRNAs within each sample, we applied the greedy, LASSO multiple linear regression, and random forest algorithms to identify a qualitative biomarker specific to BrC by comparing BrC samples to samples of other cancers as controls. RESULTS: We developed a BrC-specific biomarker called 7-miRPairs, consisting of seven miRNA pairs. It demonstrated comparable classification performance in our analyzed machine learning algorithms while requiring fewer miRNA pairs, accurately distinguishing BrC from 12 other cancer types. The diagnostic performance of 7-miRPairs was favorable in the training set (accuracy = 98.47%, specificity = 98.14%, sensitivity = 99.25%), and similar results were obtained in the test set (accuracy = 97.22%, specificity = 96.87%, sensitivity = 98.02%). KEGG pathway enrichment analysis of the 11 miRNAs within the 7-miRPairs revealed significant enrichment of target mRNAs in pathways associated with BrC. CONCLUSION: Our study provides evidence that utilizing serum miRNA pairs can offer significant advantages for BrC-specific diagnosis in clinical practice by directly comparing serum samples with BrC to other cancer types.

Order transfer in a hybrid Raman-laser-optomechanical resonator.

Order is one of the most important concepts to interpret various phenomena such as the emergence of turbulence and the life-evolution process. The generation of laser can also be treated as an ordering process in which the interaction between the laser beam and the gain medium leads to the correlation between photons in the output optical field. Here, we demonstrate experimentally in a hybrid Raman-laser-optomechanical system that an ordered Raman laser can be generated from an entropy-absorption process by a chaotic optomechanical resonator. When the optomechanical resonator is chaotic or disordered enough, the Raman-laser field is in an ordered lasing mode. This can be interpreted by the entropy transfer from the Raman-laser mode to the chaotic motion mediated by optomechanics. Different order parameters, such as the box-counting dimension, the maximal Lyapunov exponent, and the Kolmogorov entropy, are introduced to quantitatively analyze this entropy transfer process, by which we can observe the order transfer between the Raman-laser mode and the optomechanical resonator. Our study presents a new mechanism of laser generation and opens up new dimensions of research such as the modulation of laser by optomechanics.

The SWGEDWGEIW from Soybean Peptides Reduces Insulin Resistance in 3T3-L1 Adipocytes by Activating p-Akt/GLUT4 Signaling Pathway.

Diabetes mellitus, a group of metabolic disorders characterized by persistent hyperglycemia, affects millions of people worldwide and is on the rise. Dietary proteins, from a wide range of food sources, are rich in bioactive peptides with anti-diabetic properties. Notably, the protective mechanism of the single peptide SWGEDWGEIW (TSP) from soybean peptides (SBPs) on insulin resistance of adipocytes in an inflammatory state was investigated by detecting the lipolysis and glucose absorption and utilization of adipocytes. The results showed that different concentrations of TSP (5, 10, 20 µg/mL) intervention can reduce 3T3-L1 adipocytes' insulin resistance induced by inflammatory factors in a dose-dependent manner and increase glucose utilization by 34.2 ± 4.6%, 74.5 ± 5.2%, and 86.7 ± 6.1%, respectively. Thus, TSP can significantly alleviate the lipolysis of adipocytes caused by inflammatory factors. Further mechanism analysis found that inflammatory factors significantly reduced the phosphorylation (p-Akt) of Akt, two critical proteins of glucose metabolism in adipocytes, and the expression of GLUT4 protein downstream, resulting in impaired glucose utilization, while TSP intervention significantly increased the expression of these two proteins. After pretreatment of adipocytes with PI3K inhibitor (LY294002), TSP failed to reduce the inhibition of p-Akt and GLUT4 expression in adipocytes. Meanwhile, the corresponding significant decrease in glucose absorption and the increase in the fat decomposition of adipocytes indicated that TSP reduced 3T3-L1 adipocytes' insulin resistance by specifically activating the p-Akt/GLUT4 signal pathway. Therefore, TSP has the potential to prevent obesity-induced adipose inflammation and insulin resistance.

Bombilactobacillus apium sp. nov., isolated from the gut of honeybee (Apis cerana).

A novel Gram-reaction positive-, catalase and oxidase negative-, rod-shaped, facultatively anaerobic bacterial strain, DCY120T, was isolated from the gut of honeybee (Apis cerana) in Gyeonggi-do, South Korea. Strain DCY120T belongs to the genus Bombilactobacillus and is moderately related to Bombilactobacillus mellis Hon2T (94.1% similarity), Bombilactobacillus bombi BTLCH M1/2T (93.8%), and Bombilactobacillus mellifer Bin4NT (93.5%) based on 16S rRNA gene sequence analysis. The genome of strain DCY120T was sequenced and the average nucleotide identity (ANI) between strain DCY120T and the related Bombilactobacillus type strains were below the threshold value (95-96%) for species delineation. The major fatty acids were C16:0, C18:1 ω9c, Summed C19:1 ω6c/C19:0 cyclo ω10c/C19:0 ω6 and Summed C18:1 ω7c/C18:1 ω6c. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), one glycolipid (GL), and one unidentified aminophospholipid (APL). The amino acids in peptidoglycan of strain DCY120T were lysine, alanine, glutamic acid, and aspartic acid. In conclusion, the description of phenotypic and genotypic properties support strain DCY120T as a novel species within the genus Bombilactobacillus, for which the name Bombilactobacillus apium sp. nov. is proposed. The type strain is DCY120T (= KCTC 43194T = JCM 34006T).

Paraburkholderia panacisoli sp. nov., a potentially antagonistic bacterium against the root rot fungal pathogen Cylindrocarpon destructans, isolated from ginseng cultivation soil.

A new bacterium, designated DCY113T, was isolated from ginseng cultivation soil in Gochang-gun, South Korea, and its taxonomic position identified by the polyphasic approach. 16S rRNA gene sequence analysis determined that this isolate belongs to the genus Paraburkholderia, and was closest to P. dipogonis DL7T (98.6%), P. phytofirmans PsJNT (98.5%), P. kirstenboschensis Kb15T (98.4%) and P. aromaticivorans BNT (98.1%). Strain DCY113T is Gram-reaction negative, strictly aerobic, rod-shaped, non-motile, and catalase and oxidase positive. The predominant isoprenoid quinone of DCY113T was ubiquinone Q-8. The major cellular fatty acids were C16:0, cyclo-C17:0 and the Summed feature 8 (C18:1ω7c and/or C18:1ω6c). The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and an unknown amino lipid (AL1). The G+C content of the genomic DNA was 62.2 mol%. Average nucleotide identity (ANI) between strain DCY113T and the related Paraburkholderia type strains were below the threshold value for species delineation. This low DNA relatedness in combination with phylogenetic and phenotypic tests indicates that strain DCY113T cannot be assigned to any recognized species. Strain DCY113T was also found to have antifungal activity against the pathogenic fungi Cylindrocarpon destructans. In conclusion, this study found DCY113T to be a novel species within the genus Paraburkholderia, for which the name P. panacisoli is proposed. The type strain is DCY113T (= KCTC 52951T = JCM 32098T).

Comprehensive Genome Analysis on the Novel Species Sphingomonas panacis DCY99T Reveals Insights into Iron Tolerance of Ginseng.

Plant growth-promoting rhizobacteria play vital roles not only in plant growth, but also in reducing biotic/abiotic stress. Sphingomonas panacis DCY99T is isolated from soil and root of Panax ginseng with rusty root disease, characterized by raised reddish-brown root and this is seriously affects ginseng cultivation. To investigate the relationship between 159 sequenced Sphingomonas strains, pan-genome analysis was carried out, which suggested genomic diversity of the Sphingomonas genus. Comparative analysis of S. panacis DCY99T with Sphingomonas sp. LK11 revealed plant growth-promoting potential of S. panacis DCY99T through indole acetic acid production, phosphate solubilizing, and antifungal abilities. Detailed genomic analysis has shown that S. panacis DCY99T contain various heavy metals resistance genes in its genome and the plasmid. Functional analysis with Sphingomonas paucimobilis EPA505 predicted that S. panacis DCY99T possess genes for degradation of polyaromatic hydrocarbon and phenolic compounds in rusty-ginseng root. Interestingly, when primed ginseng with S. panacis DCY99T during high concentration of iron exposure, iron stress of ginseng was suppressed. In order to detect S. panacis DCY99T in soil, biomarker was designed using spt gene. This study brings new insights into the role of S. panacis DCY99T as a microbial inoculant to protect ginseng plants against rusty root disease.

Diversity of Ginsenoside Profiles Produced by Various Processing Technologies.

Ginseng is a traditional medicinal herb commonly consumed world-wide owing to its unique family of saponins called ginsenosides. The absorption and bioavailability of ginsenosides mainly depend on an individual's gastrointestinal bioconversion abilities. There is a need to improve ginseng processing to predictably increase the pharmacologically active of ginsenosides. Various types of ginseng, such as fresh, white, steamed, acid-processed, and fermented ginsengs, are available. The various ginseng processing methods produce a range ginsenoside compositions with diverse pharmacological properties. This review is intended to summarize the properties of the ginsenosides found in different Panax species as well as the different processing methods. The sugar moiety attached to the C-3, C-6, or C-20 deglycosylated to produce minor ginsenosides, such as Rb1, Rb2, Rc, Rd→Rg3, F2, Rh2; Re, Rf→Rg1, Rg2, F1, Rh1. The malonyl-Rb1, Rb2, Rc, and Rd were demalonylated into ginsenoside Rb1, Rb2, Rc, and Rd by dehydration. Dehydration also produces minor ginsenosides such as Rg3→Rk1, Rg5, Rz1; Rh2→Rk2, Rh3; Rh1→Rh4, Rk3; Rg2→Rg6, F4; Rs3→Rs4, Rs5; Rf→Rg9, Rg10. Acetylation of several ginsenosides may generate acetylated ginsenosides Rg5, Rk1, Rh4, Rk3, Rs4, Rs5, Rs6, and Rs7. Acid processing methods produces Rh1→Rk3, Rh4; Rh2→Rk1, Rg5; Rg3→Rk2, Rh3; Re, Rf, Rg2→F1, Rh1, Rf2, Rf3, Rg6, F4, Rg9. Alkaline produces Rh16, Rh3, Rh1, F4, Rk1, ginsenoslaloside-I, 20(S)-ginsenoside-Rh1-60-acetate, 20(R)-ginsenoside Rh19, zingibroside-R1 through hydrolysis, hydration addition reactions, and dehydration. Moreover, biological processing of ginseng generates the minor ginsenosides of Rg3, F2, Rh2, CK, Rh1, Mc, compound O, compound Y through hydrolysis reactions, and synthetic ginsenosides Rd12 and Ia are produced through glycosylation. This review with respect to the properties of particular ginsenosides could serve to increase the utilization of ginseng in agricultural products, food, dietary supplements, health supplements, and medicines, and may also spur future development of novel highly functional ginseng products through a combination of various processing methods.

Rhizobium panacihumi sp. nov., an isolate from ginseng-cultivated soil, as a potential plant growth promoting bacterium.

A novel bacterial strain designated DCY116T was isolated from ginseng-cultivated soil in Gochang-gun, Republic of Korea. Strain DCY116T, belongs to the genus Rhizobium, and is closely related to Rhizobium yantingense H66T (98.3%), Neorhizobium huautlense S02T (98.2%), Rhizobium soli DS-42T (98.1%), Rhizobium smilacinae PTYR-5T (97.9%), and Neorhizobium alkalisoli CCBAU 01393T (97.9%) based on 16S rRNA gene sequence analysis. Analysis of the housekeeping genes atpD, recA, and glnII showed low levels of sequence similarity (96.8%) between strain DCY116T and other closely related species. Strain DCY116T was Gram-stain negative, motile by peritrichous flagella, rod-shaped, strictly aerobic, catalase- and oxidase-positive. Q-10 was the predominant ubiquinone. The major cellular fatty acids were identified as C16:0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, and an unknown lipid (L1-3). Genomic DNA G + C content of strain DCY116T was determined to be 57.2 mol%. DNA-DNA homology values between strain DCY116T and closely related species of the genus Rhizobium were lower than 40%. Strain DCY116T produced indole-3-acetic acid, siderophores, and was able to solubilize phosphate as a potential plant growth promoting bacterium. In conclusion, the results of this study support strain DCY116T as a novel species of the genus Rhizobium, for which the name Rhizobium panacihumi is proposed. The type strain is DCY116T (= KCTC 62017T = JCM 32251T).

Ornithinimicrobium panacihumi sp. nov., Antagonistic Bacteria Against Root Rot Fungal Pathogens, Isolated from Cultivated Ginseng Soil.

A Gram-positive bacterium (DCY118T) was isolated from ginseng-cultivated soil in Gochang-gun, Republic of Korea. This isolate was assigned to the genus Ornithinimicrobium and is closely related to Ornithinimicrobium kibberense K22-20T (98.8%), O. pekingense DSM 21552T (98.5%), O. algicola JC311T (98.2%), and O. humiphilum DSM 12362T (97.9%) based on 16S rRNA gene sequence analysis. However, strain DCY118T showed < 55% DNA-DNA homology with closely related reference strains. Cells were non-motile, non-sporulating, catalase- and oxidase-positive, aerobic, short rods, and cocci, and produced light-yellow, circular, and smooth colonies on TSA medium. MK-8(H4) was the predominant menaquinone. The major cellular fatty acids were iso-C15:0, anteiso-C15:0, and C16:0. The polar lipid profile consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylinositol (PI), an unknown phospholipid (PL1), an unknown amino lipid (AL1), and unidentified polar lipids (L1-5). The genomic DNA G+C content was 71.1 mol%. The peptidoglycan contained L-ornithine as the diagnostic diamino acid. Whole-cell sugars were composed of glucose, arabinose, and xylose. Overall, data collected from phenotypic and genotypic tests during this study indicated that strain DCY118T could not be assigned to a recognized species. Strain DCY118T showed antagonistic activity against the fungal pathogens causing root rot in ginseng, i.e., Fusarium solani (KACC 44891T) and Cylindrocarpon destructans (KACC 44660T). The results from this study confirm the DCY118T strain as a new species within the genus Ornithinimicrobium, for which the name Ornithinimicrobium panacihumi is proposed. The type strain is DCY118T (=KCTC 39962T=JCM 32156T).

Paraburkholderia panacihumi sp. nov., an isolate from ginseng-cultivated soil, is antagonistic against root rot fungal pathogen.

The novel species DCY115T was isolated from ginseng-cultivated soil in Gochang province, Republic of Korea. The isolated strain was assigned to the genus Paraburkholderia due to its 16S rRNA gene sequence proximity to Paraburkholderia xenovorans LB400T (98.8%), Paraburkholderia terricola LMG 20594T (98.4%), Paraburkholderia graminis C4D1MT (98.2%), Paraburkholderia rhynchosiae WSM3937T (98.1%), and Paraburkholderia phytofirmans PsJNT (98.1%). Strain DCY115T is gram-negative, facultative aerobic, rod-shaped, non-motile, non-flagellated, and oxidase and catalase positive. The predominant isoprenoid quinone of DCY115T is ubiquinone Q-8. The major cellular fatty acids are C16:0, cyclo-C17:0, cyclo-C19:0 ω8c, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c) and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The major polar lipids include diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and an unknown amino lipid (AL1). The genomic DNA G + C content is 61.3 mol%. Phenotypic tests and chemotaxonomic analysis place strain DCY115T in the genus Paraburkholderia. DNA-DNA hybridization values between strain DCY115T and closely related reference strains were lower than 51%. The low DNA relatedness data in combination with phylogenetic and biochemical tests showed that strain DCY115T could not be assigned to any recognized species. Finally, strain DCY115T showed antagonistic activity against Fusarium solani (KACC 44891T) and Cylindrocarpon destructans (KACC 44660T), which are two root rot fungal pathogens of ginseng. In conclusion, the results in this study support strain DCY115T as a novel species within the genus Paraburkholderia for which the name Paraburkholderia panacihumi is proposed. The type strain is DCY115T (= KCTC 52952T = JCM 32099T).

Rhodanobacter ginsengiterrae sp. nov., an antagonistic bacterium against root rot fungal pathogen Fusarium solani, isolated from ginseng rhizospheric soil.

A novel bacterium, designated DCY112T, was isolated from the rhizospheric soil of a ginseng-cultivated field in Gochang-gun, Republic of Korea. Based on 16S rRNA gene sequence analysis, this isolate was assigned to the genus Rhodanobacter and is closely related to Rhodanobacter soli DCY45T (98.0%) and R. umsongensis GR24-2T (98.0%). Strain DCY112T is Gram-negative, catalase- and oxidase-positive, aerobic, non-motile, rod-shaped, and produces yellow-pigmented colonies on R2A medium. Q-8 was the predominant respiratory quinone. The major cellular fatty acids were iso-C15:0, iso-C17:0, and summed feature 9 (iso-C17:1 ω9c and/or 10-methyl-C16:0). The major polar lipids were phosphatidylglycerol (PG), phosphatidylethanolamine (PE), an unknown amino lipid (AL1), and an unidentified polar lipid (L3). The genomic DNA G + C content was 65.2 mol%. DNA-DNA homology values between strain DCY112T and related strains were lower than 55%. The low DNA relatedness data in combination with phenotypic and genotypic tests indicated that strain DCY112T could not be assigned to a recognized species. Strain DCY112T showed antagonistic activity against the fungal pathogen Fusarium solani (KACC 44891T), which causes ginseng root rot. The results of this study support that strain DCY112T is a novel species belonging to the genus Rhodanobacter, for which the name Rhodanobacter ginsengiterrae is proposed. The type strain is DCY112T (= KCTC 62018T = JCM 32167T).

Paenibacillus panacihumi sp. nov., a potential plant growth-promoting bacterium isolated from ginseng-cultivated soil.

A novel bacterium, designated DCY114T, was isolated from ginseng-cultivated soil in Gochang-gun, Republic of Korea. This isolate was assigned to the genus Paenibacillus and is closely related to Paenibacillus amylolyticus NRRL NRS-290T (98.3%), P. dongdonensis KUDC0114T (98.0%), P. tylopili MK2T (97.9%), P. tundrae A10bT (97.8%), and P. xylanexedens B22aT (97.5%) based on 16S rRNA gene sequence analysis. Strain DCY114T is a Gram-reaction positive, catalase and oxidase positive, facultatively aerobic rod that is motile by peritrichous flagella. Strain DCY114T produces siderophores and indole-3-acetic acid (IAA) and is able to solubilize phosphate as a plant growth-promoting bacterium. MK-7 was the diagnostic menaquinone. The major cellular fatty acids were anteiso-C15:0, C16:0, and C18:0, and the major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), and an unknown amino lipid (AL1,2). The genomic DNA G + C content was 46.0 mol%. Phenotypic and chemotaxonomic results also placed strain DCY114T within the genus Paenibacillus. DNA-DNA homology values between strain DCY114T and closely related reference strains were lower than 43%. The low DNA relatedness data in combination with phylogenetic and biochemical tests indicated that strain DCY114T could not be assigned to a recognized species. The results of this study support that the DCY114T strain is a novel species belonging to the genus Paenibacillus, for which the name Paenibacillus panacihumi is proposed. The type strain is DCY114T (= KCTC 33915T = JCM 32073T).

Effects of ischemic postconditioning on expressions of pentraxin-related protein 3 and neutrophil CD11b in the plasma of patients with acute myocardial infarction after percutaneous coronary intervention.

OBJECTIVE: To evaluate the effects of ischemic postconditioning on expressions of pentraxin-related protein 3 (PTX3) and neutrophil CD11b in the plasma of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). METHODS: Fifty-six patients who had AMI with ST-segment elevation were randomly divided into a control group and an ischemic postconditioning group (n=28). Both groups received emergency PCI. After recanalization of infarct-related arteries, the control group did not receive intervention within three minutes, while the ischemic postconditioning group was treated by low-pressure filling and emptying of balloon within one minute. The plasma expressions of PTX3 before and 24 hour after PCI were detected by ELISA, and those of neutrophil CD11b were detected by flow cytometry. RESULTS: PTX3 and neutrophil CD11b expressions of the two groups were similar before PCI, but those of the ischemic postconditioning group significantly decreased 24 hour after PCI (P<0.05). CONCLUSION: Ischemic postconditioning lowered the expressions of PTX3 and neutrophil CD11b in AMI patients after PCI, inhibited inflammatory response, reduced the adhesion between leukocytes and endothelial cells, and protected the ischemic-reperfused myocardium.

Optimization of Ti-PA efficiently catalytic the alcoholysis of waste PET using response surface methodology.

A new type of titanium phthalate (Ti-PA) catalyst was prepared by exchange method of phthalic acid and isopropyl titanate, which is never been reported before. The Ti-PA catalyst was characterized by FT-IR, TG, Uv-vis, BET, SEM, and EDS. The Ti-PA catalyst shows good catalytic activity in the alcoholysis reaction of polyethylene terephthalate (PET) and optimal experimental conditions for the alcoholysis process were optimized by response surface methodology; the Ti-PA catalyst provided a BHET yield of 81.98% for reaction lasting 3.98 h at 191 °C of 0.86% catalyst and 13.7 ml ethylene glycol; the model has good reliability. The kinetics and reaction mechanism of the process were explored and apparent activation energy is 75.52 kJ/mol. Finally, the good catalytic activity of Ti-PA was illustrated by comparing it with currently reported catalysts.

REDH: A database of RNA editome in hematopoietic differentiation and malignancy.

BACKGROUND: The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking. METHODS: We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases. RESULTS: We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control. CONCLUSIONS: REDH is accessible at http://www.redhdatabase.com/ . This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

Efficacy and Safety of Risankizumab in Patients with Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. METHODS: We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. RESULTS: Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24 weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR 1.760, 95% CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR 1.827, 95% CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95% CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95% CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95% CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95% CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR 0.76, 95% CI 0.45-1.28, P = 0.31; RR 0.99, 95% CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR 1.10, 95% CI 0.63-1.94, P = 0.73). CONCLUSION: Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. TRIAL REGISTRATION: Retrospectively registered (CRD42023451894, 16 August 2023).

Efficacy and safety of bimekizumab in the treatment of psoriatic arthritis: a systematic review and meta-analysis.

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

Genetically determined type 1 diabetes mellitus and risk of osteoporosis.

BACKGROUND: Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. METHODS: T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8,143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. RESULTS: Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012-1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005-1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975-1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985-1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. CONCLUSIONS: This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.

Ischemic postconditioning may increase serum fetuin-A level in patients with acute ST-segment elevation myocardial infarction undergoing percutaneous intervention.

BACKGROUND: Fetuin-A inhibits inflammation and has a protective effect against myocardial ischemia. We investigated the influence of ischemic postconditioning on serum fetuin-A levels and high-sensitive C-reactive protein (hs-CRP) in patients with acute ST-segment elevation myocardial infarction undergoing percutaneous intervention. METHODS: Forty-five patients undergoing percutaneous coronary intervention (PCI) were randomly assigned to a control (n = 21) or postconditioning (PC, n = 24) group within 90 minutes after admission. After predilatation, in the control group, no intervention was applied in the first 3 minutes of reperfusion, while in the postconditioning group, three cycles of 30-second angioplasty balloon deflation and 30-second inflation were repetitively applied. Blood samples were obtained and assayed for creatine kinase MB (CK-MB), fetuin-A and hs-CRP. RESULTS: The control group presented with higher peak CK-MB as compared with the PC group (123.67 +/- 44.19 vs. 93.08 +/- 35.29 U/L, p < 0.05). After PCI, PC was associated with a lower level of hs-CRP in comparison with the control group (6.07 +/- 1.35 vs. 7.03 +/- 1.27 mg/L, p < 0.05). Serum fetuin-A levels in the PC group was higher than in the control (161.06 +/- 23.98 mg/L vs. 144.59 +/- 22.76 mg/L, p < 0.05). CONCLUSIONS: Postconditioning may increase serum fetuin-A levels and decrease high-sensitive C-reactive protein in myocardial infarction patients.

Optimization of Ti-BA efficiently for the catalytic alcoholysis of waste PET using response surface methodology.

A titanium benzoate (Ti-BA) catalyst was prepared by hydrothermal method, which has an ordered eight-face structure, and was used for polyethylene terephthalate (PET) depolymerization. With bis(2-hydroxyethyl)terephthalate (BHET) as the target molecule and ethylene glycol (EG) as the solvent, the best reaction conditions for catalytic alcoholysis via a PET alcoholic solution were investigated via response surface experiments and found to be a EG/PET mass ratio of 3.59, temperature of 217 °C and reaction time of 3.3 h. Under these conditions, the amount of the catalyst required was only 2% of the mass of the PET, and the yield of BHET reached 90.01% and under the same conditions, the yield of BHET could still reach 80.1%. Based on the experimental results, the mechanism of alcoholysis, Ti-BA catalyst activated ethylene glycol deprotonation to achieve the progressive degradation of polymers. This experiment provides a reference for the degradation of polymer waste and other transesterification reactions.