Different inhaled corticosteroid doses in triple therapy for chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis.

A systematic review and Bayesian network meta-analysis is necessary to evaluate the efficacy and safety of triple therapy with different doses of inhaled corticosteroids (ICS) in stable chronic obstructive pulmonary disease (COPD). We selected 26 parallel randomized controlled trials (41,366 patients) comparing triple therapy with ICS/long-acting beta-agonist (LABA), LABA/long-acting muscarinic antagonist (LAMA), and LAMA in patients with stable COPD for ≥ 12 weeks from PubMed, EMBASE, the Cochrane Library, and clinical trial registries (search from inception to June 30, 2022). Triple therapy with high dose (HD)-ICS exhibited a lower risk of total exacerbation in pre-specified subgroups treated for ≥ 48 weeks than that with low dose (LD)-ICS (odds ratio [OR] = 0.66, 95% credible interval [CrI] = 0.52-0.94, low certainty of evidence) or medium dose (MD)-ICS (OR = 0.66, 95% CrI = 0.51-0.94, low certainty of evidence). Triple therapy with HD-ICS exhibited a lower risk of moderate-to-severe exacerbation in pre-specified subgroups with forced expiratory volume in 1 s < 65% (OR = 0.6, 95% CrI = 0.37-0.98, low certainty of evidence) or previous exacerbation history (OR = 0.6, 95% CrI = 0.36-0.999, very low certainty of evidence) than triple therapy with MD-ICS. Triple therapy with HD-ICS may reduce acute exacerbation in patients with COPD treated with other drug classes including triple therapy with LD- or MD-ICS or dual therapies.

Phycicoccus ochangensis sp. nov., isolated from soil of a potato cultivation field.

Two novel, Gram-positive, motile, coccal bacteria, strains L1b-b9(T) and B5a-b5, were isolated from a potato cultivation field in Ochang, Korea. These isolates grew at 10-45°C, pH 5.0-10.0, and in the presence of 8% (w/v) NaCl. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The major menaquinone was MK-8(H(4)) and the main cellular fatty acids were iso-C(14:0), iso-C(15:0), and anteiso-C(15:0). Polar lipids in strain L1b-b9(T) consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, and an unknown glyco-amino lipid. The G+C content of genomic DNA was 73.6 mol%. A phylogenetic analysis based on 16S rRNA gene sequences showed that strains L1b-b9(T) and B5a-b5 shared 99.36% similarity and formed a robust clade with the type species of the genus Phycicoccus. Strain L1b-b9(T) is related most closely to Phycicoccus cremeus V2M29(T) (97.52% 16S rRNA gene sequence similarity). On the basis of phylogenetic characteristics, the name Phycicoccus ochangensis sp. nov. is proposed for strain LIb-b9(T) (=KCTC 19695(T) [corrected] =JCM 17595(T)).

Paenibacillus pueri sp. nov., isolated from Pu'er tea.

Pu'er tea is a fermented drink made from the leaves of the tea plant, Camellia sinensis. Two novel bacteria, designated strains b09i-3(T) and b13i-1, were isolated during the process of fermentation of this tea. These isolates were Gram-positive, endospore-forming, motile rods that grew at 25-42 degrees C and pH 5.5-10.4. The DNA G+C content was 56.6-58.4 mol%, the predominant isoprenoid quinone was MK-7 and the predominant cellular fatty acid was anteiso-C(15 : 0) (49.0-50 % of the total). Phylogenetic analysis based on 16S rRNA gene sequences showed that strains b09i-3(T) and b13i-1 shared 99.9 % similarity and were affiliated with a cluster within the family Paenibacillaceae. Strains b09i-3(T) and b13i-1 were related most closely to Paenibacillus ginsengihumi DCY16(T) (97 % 16S rRNA gene sequence similarity). Levels of DNA-DNA relatedness between the two novel isolates and P. ginsengihumi DCY16(T) were below 56 %. The phylogenetic and phenotypic characteristics of these novel isolates allowed them to be distinguished clearly from recognized species of the genus Paenibacillus. Based on these data, strains b09i-3(T) and b13i-1 are considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus pueri sp. nov. is proposed. The type species is b09i-3(T) (=KCTC 13223(T)=CECT 7360(T)).

Paenibacillus camelliae sp. nov., isolated from fermented leaves of Camellia sinensis.

A novel bacterium, strain blls-2(T) was isolated from Pu'er tea. The isolate was Gram-positive, endospore-forming motile rod that grew at 15 approximately 42 degrees C and pH 6.0 approximately 10.2. The DNA G+C content was 48.3 mol%, the predominant isoprenoid quinone was MK-7, and the predominant cellular fatty acid was anteiso-C15:0 (54.2%) followed by C16:0 (15.5%) and iso-C16:0 (8.2%). The polar lipid pattern of blls-2(T) was characterized by the presence of diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylglycerol. Phy-logenetic analysis based on 16S rRNA gene sequence showed that the strain was affiliated within the Paenibacillaceae. The strain was most closely related to Paenibacillus granivorans A30(T), with a similarity of 97.1%. Based on the phylogenetic and phenotypic characteristics of strain blls-2(T), the isolate is thought to represent a novel taxon in the genus Paenibacillus. The name Paenibacillus camelliae sp. nov. is proposed for the fermented tea isolate; the type strain is blls-2(T) (= KCTC 13220(T)= CECT 7361(T)).

Genome-wide drug-induced haploinsufficient screening of fission yeast for identification of hydrazinocurcumin targets.

Hydrazinocurcumin (HC), a synthetic derivative of curcumin, has been reported to inhibit angiogenesis via unknown mechanisms. Understanding the molecular mechanisms of the drug's action is important for the development of improved compounds with better pharmacological properties. A genomewide drug-induced haploinsufficiency screening of fission yeast gene deletion mutants has been applied to identify drug targets of HC. As a first step, the 50% inhibition concentration (IC50) of HC was determined to be 2.2 microM. The initial screening of 4,158 mutants in 384-well plates using robotics was performed at concentrations of 2, 3, and 4 microM. A second screening was performed to detect sensitivity to HC on the plates. The first screening revealed 178 candidates, and the second screening resulted in 13 candidates, following the elimination of 165 false positives. Final filtering of the condition-dependent haploinsufficient genes gave eight target genes. Analysis of the specific targets of HC has shown that they are related to septum formation and the general transcription processes, which may be related to histone acetyl transferase. The target mutants showed 65% growth inhibition in response to HC compared with wild-type controls, as shown by liquid culture assay.