The mechanism of palmatine-mediated intestinal flora and host metabolism intervention in OA-OP comorbidity rats

BackgroundErXian decoction is a Chinese herbal compound that can prevent and control the course of osteoarthritis (OA) and osteoporosis (OP). OP and OA are two age-related diseases that often coexist in elderly individuals, and both are associated with dysregulation of the gut microbiome. In the initial study, Palmatine (PAL) was obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and network pharmacological screening techniques, followed by 16S rRNA sequencing and serum metabolomics of intestinal contents, to explore the mechanism of PAL in the treatment of OA and OP.MethodsThe rats selected for this study were randomly divided into three groups: a sham group, an OA-OP group and a PAL group. The sham group was intragastrically administered normal saline solution, and the PLA group was treated with PAL for 56 days. Through microcomputed tomography (micro-CT), ELISA, 16S rRNA gene sequencing and non-targeted metabonomics research, we explored the potential mechanism of intestinal microbiota and serum metabolites in PAL treatment of OA-OP rats.ResultsPalmatine significantly repair bone microarchitecture of rat femur in OA-OP rats and improved cartilage damage. The analysis of intestinal microflora showed that PAL could also improve the intestinal microflora disorder of OA-OP rats. For example, the abundance of Firmicutes, Bacteroidota, Actinobacteria, Lactobacillus, unclassified_f_Lachnospiraceae, norank_f_Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Muribaculaceae increased after PAL intervention. In addition, the results of metabolomics data analysis showed that PAL also change the metabolic status of OA-OP rats. After PAL intervention, metabolites such as 5-methoxytryptophol, 2-methoxy acetaminophen sulfate, beta-tyrosine, indole-3-carboxylic acid-O-sulfate and cyclodopa glucoside increased. Association analysis of metabolomics and gut microbiota (GM) showed that the communication of multiple flora and different metabolites played an important role in OP and OA.ConclusionPalmatine can improve cartilage degeneration and bone loss in OA-OP rats. The evidence we provided supports the idea that PAL improves OA-OP by altering GM and serum metabolites. In addition, the application of GM and serum metabolomics correlation analysis provides a new strategy for uncovering the mechanism of herbal treatment for bone diseases

Transcriptome Sequences Resolve Deep Relationships of the Grape Family

Previous phylogenetic studies of the grape family (Vitaceae) yielded poorly resolved deep relationships, thus impeding our understanding of the evolution of the family. Next-generation sequencing now offers access to protein coding sequences very easily, quickly and cost-effectively. To improve upon earlier work, we extracted 417 orthologous single-copy nuclear genes from the transcriptomes of 15 species of the Vitaceae, covering its phylogenetic diversity. The resulting transcriptome phylogeny provides robust support for the deep relationships, showing the phylogenetic utility of transcriptome data for plants over a time scale at least since the mid-Cretaceous. The pros and cons of transcriptome data for phylogenetic inference in plants are also evaluated

Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization

As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded similar to 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of similar to 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs

Genome of the pitcher plant <i>Cephalotus </i>reveals genetic changes associated with carnivory

Carnivorous plants exploit animals as a nutritional source and have inspired long-standing questions about the origin and evolution of carnivory-related traits. To investigate the molecular bases of carnivory, we sequenced the genome of the heterophyllous pitcher plant Cephalotus follicularis, in which we succeeded in regulating the developmental switch between carnivorous and non-carnivorous leaves. Transcriptome comparison of the two leaf types and gene repertoire analysis identified genetic changes associated with prey attraction, capture, digestion and nutrient absorption. Analysis of digestive fluid proteins from C. follicularis and three other carnivorous plants with independent carnivorous origins revealed repeated co-options of stress-responsive protein lineages coupled with convergent amino acid substitutions to acquire digestive physiology. These results imply constraints on the available routes to evolve plant carnivory

Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera

Antibiotic resistance is a severe global threat for public health, causing around 700,000 deaths per year. Horizontal gene transfer (HGT) is one of the most significant pathways to disseminate antibiotic resistance. It is commonly acknowledged that sub-minimum inhibition concentrations of antibiotics are major contributors in promoting antibiotic resistance through HGT. Pharmaceuticals are occurring in our environments at increased levels, yet little is known whether non-antibiotic pharmaceuticals cause or accelerate the dissemination of antibiotic resistance. Here, we report for the first time that the antiepileptic drug, carbamazepine, promotes conjugative transfer of antibiotic resistance genes. It was seen that environmentally relevant concentrations of carbamazepine (e.g., 0.05 mg/L) significantly enhanced the conjugative transfer of multiresistance genes carried by plasmid within and across bacterial genera. The underlying mechanisms of the enhanced HGT were revealed by detecting oxidative stress and cell membrane permeability, in combination with MinION DNA sequencing, genome-wide RNA sequencing, and proteomic analysis. Carbamazepine induced a series of acute responses, including increased levels of reactive oxygen species, the SOS response; increased cell membrane permeability, and pilus generation. Expressional levels of genes related to these processes were significantly upregulated during carbamazepine exposure. Given that HGT occurs widely among different species in various environments, these findings are an early warning for a wide assessment of the roles of non-antibiotic pharmaceuticals in the spread of antibiotic resistance

Antidepressant fluoxetine induces multiple antibiotics resistance in Escherichia coli via ROS-mediated mutagenesis

Antibiotic resistance poses a great threat to global public health. Overuse of antibiotics is generally considered as the major factor contributing to it. However, little is known about whether non-antibiotic drugs could play potential roles in the emergence of antibiotic resistance.We aimed to investigate whether antidepressant fluoxetine induces multiple antibiotic resistances and reveal underlying mechanisms.Escherichia coli K12 was exposed to different concentrations of fluoxetine (0, 0.5, 5, 50 and 100 mg/L) and the resistant strains were isolated by plating on antibiotic containing plates. Resistant strains were randomly selected to determine the increase of minimum inhibition concentration (MIC) of multiple antibiotics. Genome-wide DNA sequencing was performed on cells cultured in lysogeny broth (LB) without any fluoxetine or antibiotics exposure. RNA sequencing and proteomic profiling of isolated mutants grown in LB with 100 mg/L fluoxetine were analyzed to reveal the underlying mechanisms.Exposure of Escherichia coli to fluoxetine at 5-100 mg/L after repeated subculture in LB for 30 days promoted its mutation frequency resulting in increased resistance against the antibiotics chloramphenicol, amoxicillin and tetracycline. This increase was up to 5.0 × 10 fold in a dose-time pattern. Isolated mutants with resistance to one of these antibiotics also exhibited multiple resistances against fluoroquinolone, aminoglycoside, β-lactams, tetracycline and chloramphenicol. According to global transcriptional and proteomic analyses, the AcrAB-TolC pump together with the YadG/YadH transporter, a Tsx channel and the MdtEF-TolC pump have been triggered to export the antibiotics to the exterior of the cell. Whole-genome DNA analysis of the mutants further revealed that ROS-mediated mutagenesis (e.g., deletion, insertion, and substitution) of DNA-binding transcriptional regulators (e.g., marR, rob, sdiA, cytR and crp) to up-regulate the expression of efflux pumps, may further enhance the antibiotic efflux.Our findings for the first time demonstrated that the exposure to antidepressant fluoxetine induces multiple antibiotic resistance in E. coli via the ROS-mediated mutagenesis

miR-103a-3p Suppresses Cell Proliferation and Invasion by Targeting Tumor Protein D52 in Prostate Cancer

Growing evidence points at an association between microRNAs and tumor development. Although dysregulation of microRNA-103a-3p (miR-103a-3p) in multiple human cancers has been reported, its expression in prostate cancer (PCa) remains unknown and there is currently no research on the relationship between miR-103a-3p and tumor protein D52 (TPD52) in PCa. Our aim in this study was to explore the effect and potential mechanism of miR-103a-3p in PCa. qRT-PCR was performed to detected the level of miR-103a-3p in PCa tissues and cells, and in normal tissues. Colony, wound-healing, invasion, proliferation, and apoptosis assays were performed in search miR-103a-3p effect in PCa. TargetScan was used to predict potential targets of miR-103a-3p. Additionally, dual-luciferase reporter, western blot, and immunofluorescence assays were performed to detected the target gene of miR-103a-3p. Finally, we explore the differences in tumor xenograft experiments between nude mice injected with stably miR-103a-3p expressing cells and those expressing a miR-negative control. Low level of miR-103a-3p was detected in PCa tissues and cells, when compared with normal tissues. Enhancement of miR-103a-3p significantly inhibited migration and invasion of PCa cells, and negatively regulated expression of the oncogenic tumor protein D52 (TPD52) through direct binding to its 3’-UTR. Interestingly, overexpression of TPD52 significantly attenuated the effect of mir-103a-3p on PCa. Our study provides the first evidence that miR-103a-3p directly targets TPD52 and inhibits the proliferation and invasion of PCa. This finding helps clarify the role of mir-103a-3p-TPD52 axis in PCa and may provide new therapeutic targets for the disease