Abstract
Transcriptional regulation enables cells to respond to environmental changes. Of the estimated 304 candidate transcription factors (TFs) in Escherichia coli K-12 MG1655, 185 have been ...experimentally identified, but ChIP methods have been used to fully characterize only a few dozen. Identifying these remaining TFs is key to improving our knowledge of the E. coli transcriptional regulatory network (TRN). Here, we developed an integrated workflow for the computational prediction and comprehensive experimental validation of TFs using a suite of genome-wide experiments. We applied this workflow to (i) identify 16 candidate TFs from over a hundred uncharacterized genes; (ii) capture a total of 255 DNA binding peaks for ten candidate TFs resulting in six high-confidence binding motifs; (iii) reconstruct the regulons of these ten TFs by determining gene expression changes upon deletion of each TF and (iv) identify the regulatory roles of three TFs (YiaJ, YdcI, and YeiE) as regulators of l-ascorbate utilization, proton transfer and acetate metabolism, and iron homeostasis under iron-limited conditions, respectively. Together, these results demonstrate how this workflow can be used to discover, characterize, and elucidate regulatory functions of uncharacterized TFs in parallel.
Enhanced recovery after surgery programs are widely known as a far-reaching approach to help patients with surgeries recover rapidly by giving optimized care. However, especially in the spine ...medicinal domain, relevant studies are scarce. In order to manage proper recovery after surgery, practitioners need to take a comprehensive look at the suppression of pain, strategies for improving the results of surgery, improving the quality of life, and mental support of patients. To this end, a recovery-enhancing program through integrated medical technology which covers both conventional and Korean medicine is highly required. We want to develop an integrated medical program that covers a wide range of medicinal domains for the early recovery of patients after spinal surgery. The aim of the present study is to check out which thermal stimulation with meridian points are more effective than others to enhance recovery after spinal surgery.
The following online databases will be retrieved in the present study: PubMed; Scopus; the Cochrane Central Register of Controlled Trials; Ovid MEDLINE; Ovid EMBASE; Chinese Biomedical Literature Database; China National Knowledge Infrastructure; and Chinese Scientific Journal Database (VIP database). We will independently classify articles and will encapsulate characteristics of the study components. Primary outcomes will be categorized into visual analog scale, Tolerance to liquid and solid diet, postoperative hospitalization period, and quality of life. Secondary outcomes will be analyzed based on the study findings.
The results of this study will be submitted to a peer-reviewed journal for publication. Furthermore, the outcomes of this study would afford the documentation of whether thermal stimulation on meridian points can be effective for enhanced recovery after spine surgery.
Inflammatory bowel disease (IBD) manifests as intestinal barrier destruction, mucosal immunity dysregulation, and disrupted gut microbiome homeostasis. Conventional anti-inflammatory medications for ...IBD therapy partially alleviate symptoms but are unable to restore normal barrier and immune function. Here, we report a nanomedicine comprising bilirubin (BR)-attached low-molecular-weight, water-soluble chitosan nanoparticles (LMWC-BRNPs), that promotes restoration of the intestinal barrier, mucosal immunity, and the gut microbiome, thereby exerting robust therapeutic efficacy. In a mouse model of dextran sulfate sodium salt (DSS)-induced colitis, orally administered LMWC-BRNPs were retained in the GI tract much longer than other nonmucoadhesive BRNPs owing to the mucoadhesiveness of LMWC via electrostatic interaction. Treatment with LMWC-BRNPs led to considerable recovery of the damaged intestinal barrier compared with the current IBD medication, 5-aminosalicylic acid (5-ASA). Orally administered LMWC-BRNPs were taken up by pro-inflammatory macrophages and inhibited their activity. They also concurrently increased the population of regulatory T cells, thereby leading to the recovery of dysregulated mucosal immunity. An analysis of the gut microbiome revealed that LMWC-BRNPs treatment significantly attenuated the increase Turicibacter, an inflammation-related microorganism, resulting in protection of gut microbiome homeostasis. Taken together, our findings indicate that LMWC-BRNPs restored normal functions of the intestine and have high potential for use as a nanomedicine for IBD therapy.
Abstract
Two major transcriptional regulators of carbon metabolism in bacteria are Cra and CRP. CRP is considered to be the main mediator of catabolite repression. Unlike for CRP, in vivo DNA binding ...information of Cra is scarce. Here we generate and integrate ChIP-exo and RNA-seq data to identify 39 binding sites for Cra and 97 regulon genes that are regulated by Cra in Escherichia coli. An integrated metabolic-regulatory network was formed by including experimentally-derived regulatory information and a genome-scale metabolic network reconstruction. Applying analysis methods of systems biology to this integrated network showed that Cra enables optimal bacterial growth on poor carbon sources by redirecting and repressing glycolysis flux, by activating the glyoxylate shunt pathway, and by activating the respiratory pathway. In these regulatory mechanisms, the overriding regulatory activity of Cra over CRP is fundamental. Thus, elucidation of interacting transcriptional regulation of core carbon metabolism in bacteria by two key transcription factors was possible by combining genome-wide experimental measurement and simulation with a genome-scale metabolic model.
A modified Delphi method was used to establish a consensus. Stakeholders and experts were invited to participate in the expert panel. Best practice statements and decision-making questionnaires were ...distributed to the panel. Panel members were asked to mark "Strongly disagree" to "Strongly agree" after a series of statements over several rounds until either a consensus was reached or the decision-making method was deemed unsuitable for reaching a consensus.The most common cause of lumbar pain is intervertebral degeneration, which leads to degenerative disc disease and lumbar disc herniation. There is a lack of unanimity regarding appropriate patient protocols and rehabilitation expectations for Korean medical care. The long-term viability of Korean medical treatment, further adoption in the institutional setting, and specific patient outcomes are contingent on the existence of appropriate Korean medical programs.A Korean medical expert panel of 17 practitioners employed a modified Delphi method to achieve consensus on Korean medical care for lumbar disc herniation. The panel first reviewed the literature and guidelines relevant to Korean medical treatment for lumbar disc herniation. The panel members considered questionnaires intended to determine "standardized" Korean medical care recommendations for patients with a wide range of symptoms of lumbar disc herniation. Each panel member participated in a round of voting, which was followed by an opinion-collecting session online. Consensus was defined as a ≥75% agreement among the respondents.In the first round, 144 questionnaires across 5 domains were administered to the expert panels. After reviewing the responses and open-ended comments collected in the first round, the authors modified the questionnaires to 53 items and proceeded. In round 2, consensus was achieved in all 53 survey questions. The final treatment pathway comprised a standardized and comprehensive care approach for lumbar disc herniations in 4 types of medical institutions.This study identified a core set of evidence- and consensus-based principles that are essential to a comprehensive model of care, incorporating identification, referral, and management of patients with lumbar disc herniation.
A transcription factor (TF), OmpR, plays a critical role in transcriptional regulation of the osmotic stress response in bacteria. Here, we reveal a genome-scale OmpR regulon in Escherichia coli K-12 ...MG1655. Integrative data analysis reveals that a total of 37 genes in 24 transcription units (TUs) belong to OmpR regulon. Among them, 26 genes show more than two-fold changes in expression level in an OmpR knock-out strain. Specifically, we find that: 1) OmpR regulates mostly membrane-located gene products involved in diverse fundamental biological processes, such as narU (encoding nitrate/nitrite transporter), ompX (encoding outer membrane protein X), and nuoN (encoding NADH:ubiquinone oxidoreductase); 2) by investigating co-regulation of entire sets of genes regulated by other stress-response TFs, stresses are surprisingly independently regulated among each other; and, 3) a detailed investigation of the physiological roles of the newly discovered OmpR regulon genes reveals that activation of narU represents a novel strategy to significantly improve osmotic stress tolerance of E. coli. Thus, the genome-scale approach to elucidating regulons comprehensively identifies regulated genes and leads to fundamental discoveries related to stress responses.
This study, utilizing the claims data from the Health Insurance Review and Assessment Service of Korea, aimed to examine the 10-year (2010-2019) trends in various types of lumbar spine surgeries ...performed on patients diagnosed with lumbar herniated intervertebral disc (HIVD), and the current status of opioid prescriptions, as well as the duration of postoperative hospital stays based on the type of surgery performed.
This retrospective cross-sectional study examined patients with one or more national health insurance claims carrying a primary or secondary diagnosis of HIVD (ICD-10 codes: M511, M518, M519) over a 10-year period (2010-2019). From the patients undergoing lumbar spine surgery, we selected those who did not require reoperation within 30 days following the initial lumbar surgery. Our final study sample comprised patients who underwent only one type of surgery.
Among the patients diagnosed with HIVD and subsequently undergoing lumbar surgery between 2010 and 2019, a slight downward trend was observed in those undergoing open discectomy (OD); however, OD persistently accounted for the highest proportion over the 10 years. Percutaneous endoscopic lumbar discectomy (PELD) demonstrated a consistent upward trend from 2016 to 2018. When inspecting trends, we noted a consistent escalation over the decade in the postoperative opioid prescription rates of strong opioids (50.7% in 2010 to 77.8% in 2019) and tramadol (50.9% in 2010 to 76.8% in 2019). Analyzing these trends by surgery type, spinal fusion exhibited a slightly higher rate of opioid prescriptions than other lumbar surgeries. Regarding the length of postoperative hospital stays, patients undergoing PELD recorded the shortest stay (7.04 ± 6.78 days), while spinal fusion necessitated the longest (20.14 ± 12.18 days).
This study analyzed the trends in types of lumbar spine surgeries, opioid analgesic prescriptions, and length of hospital stays over 10 years (2010-2019) among patients with HIVD in Korea. Our data and findings provide valuable evidence that may prove beneficial for clinicians and researchers involved in HIVD-related practices.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genome-wide transcription start site (TSS) profiles of the enterobacteria Escherichia coli and Klebsiella pneumoniae were experimentally determined through modified 5' RACE followed by deep ...sequencing of intact primary mRNA. This identified 3,746 and 3,143 TSSs for E. coli and K. pneumoniae, respectively. Experimentally determined TSSs were then used to define promoter regions and 5' UTRs upstream of coding genes. Comparative analysis of these regulatory elements revealed the use of multiple TSSs, identical sequence motifs of promoter and Shine-Dalgarno sequence, reflecting conserved gene expression apparatuses between the two species. In both species, over 70% of primary transcripts were expressed from operons having orthologous genes during exponential growth. However, expressed orthologous genes in E. coli and K. pneumoniae showed a strikingly different organization of upstream regulatory regions with only 20% identical promoters with TSSs in both species. Over 40% of promoters had TSSs identified in only one species, despite conserved promoter sequences existing in the other species. 662 conserved promoters having TSSs in both species resulted in the same number of comparable 5' UTR pairs, and that regulatory element was found to be the most variant region in sequence among promoter, 5' UTR, and ORF. In K. pneumoniae, 48 sRNAs were predicted and 36 of them were expressed during exponential growth. Among them, 34 orthologous sRNAs between two species were analyzed in depth, and the analysis showed that many sRNAs of K. pneumoniae, including pleiotropic sRNAs such as rprA, arcZ, and sgrS, may work in the same way as in E. coli. These results reveal a new dimension of comparative genomics such that a comparison of two genomes needs to be comprehensive over all levels of genome organization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Numerous studies have reported the variable quality of clinical practice guidelines (CPGs) across various domains. The aim of this study was to systematically assess the quality, methodology, and ...consistency of recently developed traditional and conventional medicine CPGs that focus on the management of osteoporosis and provide helpful recommendations for patients with osteoporosis.From June 2020 to July 2020, CPGs with osteoporosis targeting any age were systematically retrieved. All CPGs of traditional and conventional medicine related to the assessment and diagnosis, management, and clinical therapeutic and pharmacological recommendations with osteoporosis were eligible for inclusion in this study. The excluded documents included guidelines without recommendations, secondary publications derived from CPGs, consensus statements, or consensus conferences based on the opinion of panelists, systematic reviews, editorials, clinical trials, and single-author documents. The quality of CPGs was independently examined by three assessors using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. AGREE II consists of 6 domains; scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. Consequently, selected CPGs were graded as recommended (A), recommended with modifications (B), or not recommended (C), and the specific treatments and preventive recommendations in the CPGs were summarized.The quality of the 15 CPGs assessed varied across the AGREE II domains. The overall quality ranged from 3.0 to 6.0 out of 7. The domain that had the highest scores were "clarity of presentation," with a mean value of 69.0% (range 46%-83%); "editorial independence" had the lowest score of 30.2% (range 0%-75%). The conventional CPGs focused on pharmacological treatments, calcium and vitamin D intake, and prevention, while the traditional CPGs consistently emphasized on herbal medicine and non-pharmaceutical treatment and management.Further development of CPGs will require improvement in domains where low item scores have been obtained in the quality assessment in this present study. Further research is needed on alternative modalities for osteoporosis, especially complementary approaches, and higher quality CPGs are needed to facilitate evidence-based clinical practice.
Bee venom acupuncture (BVA) is an effective treatment for chronic low back pain (CLBP) through the pharmacological effects of bee venom and the simultaneous stimulation of acupoints. However, ...evidence of its efficacy and safety in humans remains unclear. Using a double-blind, randomized study, 54 patients with non-specific CLBP were assigned to the BVA and sham groups. All participants underwent six sessions of real or sham BVA for 3 weeks, in addition to administration of 180 mg of loxonin per day. The primary outcome, that is, "bothersomeness" derived from back pain, was assessed using the visual analog scale. Secondary outcomes included pain intensity, dysfunction related to back pain (Oswestry Disability Index), quality of life (EuroQol 5-Dimension), and depressive mood (Beck's depression inventory). Outcomes were evaluated every week during the treatment period and followed up at weeks 4, 8, and 12. After 3 weeks of the treatment, significant improvements were observed in the bothersomeness, pain intensity, and functional status in the BVA group compared with the sham group. Although minimal adverse events were observed in both groups, subsequent recovery was achieved without treatment. Consequently, our results suggest that it can be used along with conventional pharmacological therapies for the treatment of CLBP.
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