Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori: A retrospective single center study.

BACKGROUND: Although highly effective as a component of Helicobacter pylori (H. pylori) treatment regimen, tetracycline is associated with a high incidence of medication-related adverse events. Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates. AIM: To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H. pylori infection. METHODS: Consecutive patients (10/2020-12/2021) who received tetracycline and furazolidone quadruple therapy for H. pylori infection at Sir Run Run Shaw Hospital were identified. All patients received tetracycline, furazolidone, proton pump inhibitor, and bismuth for 14 d as primary or rescue therapy. Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily. RESULTS: Three hundred and ninety-four patients [mean age = 46.3 ± 13.9, male = 137 (34.8%), and 309 (78.4%) primary therapy] completed tetracycline and furazolidone quadruple therapy for H. pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118 (750 mg twice daily) and 119 (500 mg three times daily). Eradication rates in the modified tetracycline dose group were 92.40% and in the standard groups, eradication rates were 93.20% for 750 mg twice daily group and 92.43% for 500 mg three times daily group, respectively, without statistical difference (P = 0.959). The incidence of adverse events was lower in the modified tetracycline dose (15.3% vs 32.3% and 29.4%; P = 0.002) compared to the standard dose group. CONCLUSION: In a real-world experience, modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy, comparable to standard tetracycline dose regimens, with a favorable safety profile.

Apostasia Mitochondrial Genome Analysis and Monocot Mitochondria Phylogenomics.

Apostasia shenzhenica belongs to the subfamily Apostasioideae and is a primitive group located at the base of the Orchidaceae phylogenetic tree. However, the A. shenzhenica mitochondrial genome (mitogenome) is still unexplored, and the phylogenetic relationships between monocots mitogenomes remain unexplored. In this study, we discussed the genetic diversity of A. shenzhenica and the phylogenetic relationships within its monocotyledon mitogenome. We sequenced and assembled the complete mitogenome of A. shenzhenica, resulting in a circular mitochondrial draft of 672,872 bp, with an average read coverage of 122× and a GC content of 44.4%. A. shenzhenica mitogenome contained 36 protein-coding genes, 16 tRNAs, two rRNAs, and two copies of nad4L. Repeat sequence analysis revealed a large number of medium and small repeats, accounting for 1.28% of the mitogenome sequence. Selection pressure analysis indicated high mitogenome conservation in related species. RNA editing identified 416 sites in the protein-coding region. Furthermore, we found 44 chloroplast genomic DNA fragments that were transferred from the chloroplast to the mitogenome of A. shenzhenica, with five plastid-derived genes remaining intact in the mitogenome. Finally, the phylogenetic analysis of the mitogenomes from A. shenzhenica and 28 other monocots showed that the evolution and classification of most monocots were well determined. These findings enrich the genetic resources of orchids and provide valuable information on the taxonomic classification and molecular evolution of monocots.

Genome-wide identification of YABBY genes in three Cymbidium species and expression patterns in C. ensifolium (Orchidaceae).

Members of the YABBY gene family play significant roles in lamina development in cotyledons, floral organs, and other lateral organs. The Orchidaceae family is one of the largest angiosperm groups. Some YABBYs have been reported in Orchidaceae. However, the function of YABBY genes in Cymbidium is currently unknown. In this study, 24 YABBY genes were identified in Cymbidium ensifolium, C. goeringii, and C. sinense. We analyzed the conserved domains and motifs, the phylogenetic relationships, chromosome distribution, collinear correlation, and cis-elements of these three species. We also analyzed expression patterns of C. ensifolium and C. goeringii. Phylogenetic relationships analysis indicated that 24 YABBY genes were clustered in four groups, INO, CRC/DL, YAB2, and YAB3/FIL. For most YABBY genes, the zinc finger domain was located near the N-terminus and the helix-loop-helix domain (YABBY domain) near the C-terminus. Chromosomal location analysis results suggested that only C. goeringii YABBY has tandem repeat genes. Almost all the YABBY genes displayed corresponding one-to-one relationships in the syntenic relationships analysis. Cis-elements analysis indicated that most elements were clustered in light-responsive elements, followed by MeJA-responsive elements. Expression patterns showed that YAB2 genes have high expression in floral organs. RT-qPCR analysis showed high expression of CeYAB3 in lip, petal, and in the gynostemium. CeCRC and CeYAB2.2 were highly expressed in gynostemium. These findings provide valuable information of YABBY genes in Cymbidium species and the function in Orchidaceae.

Genome-Wide Identification and Expression Analysis of Terpene Synthase Genes in Cymbidium faberi.

Terpene synthases (TPSs) are essential for forming terpenes, which play numerous functional roles in attracting pollinators, defending plants, and moderating the interaction between plants. TPSs have been reported in some orchids, but genome-wide identification of terpenes in Cymbidium faberi is still lacking. In this study, 32 putative TPS genes were classified in C. faberi and divided into three subfamilies (TPS-a, TPS-b, and TPS-e/f). Motif and gene structure analysis revealed that most CfTPS genes had the conserved aspartate-rich DDxxD motif. TPS genes in the TPS-a and TPS-b subfamilies had variations in the RRX8W motif. Most cis-elements of CfTPS genes were found in the phytohormone responsiveness category, and MYC contained most of the numbers associated with MeJA responsiveness. The Ka/Ks ratios of 12/13 CfTPS gene pairs were less than one, indicated that most CfTPS genes have undergone negative selection. The tissue-specific expression patterns showed that 28 genes were expressed in at least one tissue in C. faberi, and TPS genes were most highly expressed in flowers, followed by leaves and pseudobulbs. In addition, four CfTPS genes were selected for the real-time reverse transcription quantitative PCR (RT-qPCR) experiment. The results revealed that CfTPS12, CfTPS18, CfTPS23, and CfTPS28 were mainly expressed in the full flowering stage. CfTPS18 could convert GPP to ß-myrcene, geraniol, and α-pinene in vitro. These findings of CfTPS genes of C. faberi may provide valuable information for further studies on TPSs in orchids.

Genome-Wide Identification of the YABBY Gene Family in Seven Species of Magnoliids and Expression Analysis in Litsea.

The YABBY gene family, specific to seed plants, encodes a class of transcription factors in the lamina maintenance and development of lateral organs. Magnoliids are sisters to the clade-containing eudicots and monocots, which have rapidly diversified among the common ancestors of these three lineages. However, prior to this study, information on the function of the YABBY genes in magnoliids was extremely limited to the third major clades and the early diverging lineage of Mesangiospermae. In this study, the sum of 55 YABBY genes including five genes in INO, six in CRC, eight in YAB2, 22 in YAB5, and 14 in FIL clade were identified from seven magnoliid plants. Sequence analysis showed that all encoded YABBY protein sequences possess the highly conserved YABBY domain and C2C2 zinc-finger domain. Gene and protein structure analysis indicates that a certain number of exons were highly conserved and similar in the same class, and YABBY genes encode proteins of 71-392 amino acids and an open reading frame of 216-1179 bp in magnoliids. Additionally, the predicted molecular weight and isoelectric point of YABBY proteins in three species ranged from 7689.93 to 43578.13 and from 5.33 to 9.87, respectively. Meanwhile, the YABBY gene homolog expression of Litsea was detected at a temporal and spatial level during various developmental stages of leaf and reproductive tissues. This research could provide a brief overview of YABBY gene family evolution and its differential expression in magnoliids. Therefore, this comprehensive diversification analysis would provide a new insight into further understanding of the function of genes in seven magnoliids.

Phosphodiesterase 2 inhibitor Hcyb1 reverses corticosterone-induced neurotoxicity and depression-like behavior.

RATIONALE: Currently available PDE2 inhibitors have poor brain penetration that limits their therapeutic utility in the treatment of depression. Hcyb1 is a novel selective PDE2 inhibitor that was introduced more lipophilic groups with polar functionality to the scaffold pyrazolopyrimidinone to improve the blood-brain barrier (BBB) penetration. Our previous study suggested that Hcyb1 increased the neuronal cell viability and exhibited antidepressant-like effects, which were parallel to the currently available PDE2 inhibitor Bay 60-7550. OBJECTIVES: The present study investigated whether Hcyb1 protected HT-22 cells against corticosterone-induced neurotoxicity and produced antidepressant-like effects in behavioral tests in stressed mice. METHODS: The neuroprotective effects of Hcyb1 against corticosterone-induced cell lesion were examined by cell viability (MTS) assay. The enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis were used to determine the levels of cAMP or cGMP and expression of pCREB or BDNF, respectively, in the corticosterone-treated HT-22 cells. The antidepressant-like effects of Hcyb1 were determined in the tail suspension and novelty suppressed feeding tests in stressed mice. RESULTS: In the cell-based assay, Hcyb1 significantly increased cell viability of HT-22 cells against corticosterone-induced neurotoxicity in a time- and dose-dependent manner. Hcyb1 also rescued corticosterone-induced decreases in both cGMP and cAMP levels, pCREB/CREB and BDNF expression. These protective effects of Hcyb1 were prevented by pretreatment with either the PKA inhibitor H89 or the PKG inhibitor KT5823. Moreover, Hcyb1 reversed acute stress-induced increases in immobility time and the latency to feed in the tail suspension and novelty suppressed feeding tests, respectively, which were prevented by pretreatment with H89 or KT5823. CONCLUSION: These findings provide evidence that the neuroprotective effects of Hcyb1 are mediated by PDE2-dependent cAMP/cGMP signaling.