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BMC Oral Health Jun 2021Pulpal and periodontal healing are two main concerns of delayed replantation of avulsed teeth. The objective of this review was to evaluate the effectiveness of topical...
BACKGROUND
Pulpal and periodontal healing are two main concerns of delayed replantation of avulsed teeth. The objective of this review was to evaluate the effectiveness of topical and systemic application of tetracyclines on pulpal and periodontal healing after tooth replantation.
METHODS
A comprehensive electronic search was conducted in six databases. This systematic review was carried out according to Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS
After exclusion of 246 irrelevant papers, 14 animal studies and one human study were included in this review. The human study showed that avulsed permanent teeth treated with doxycycline did not show a better clinical outcome for pulp and periodontal healing compared with treatment with normal saline. As for animal studies, significant more pulpal healing was observed in immature teeth treated with topical doxycycline in two researches, while another one study showed that there is no difference between teeth treated with normal saline and teeth treated with doxycycline. Systemic doxycycline exerted no significant effect on pulpal revascularization illustrated by one research. Only one out of four articles illustrated the positive effect of systemic tetracyclines on periodontal healing. One paper reported that intracanal application of demeclocycline promoted favorable periodontal healing. Two articles showed topical doxycycline contributed to favorable periodontal healing, while five studies showed no significant effect of topical tetracyclines on periodontal healing.
CONCLUSIONS
As a result of data heterogeneity and limitations of the studies, the effect of topical or systemic application of tetracyclines on pulpal and periodontal healing is inconclusive. More studies are required to get more clinically significant conclusions.
Topics: Animals; Dental Pulp; Humans; Periodontal Ligament; Tetracyclines; Tooth Avulsion; Tooth Replantation; Wound Healing
PubMed: 34090399
DOI: 10.1186/s12903-021-01615-y -
Proceedings of the National Academy of... Mar 2021Previous studies have demonstrated that the synaptic EphB1 receptor tyrosine kinase is a major mediator of neuropathic pain, suggesting that targeting the activity of...
Previous studies have demonstrated that the synaptic EphB1 receptor tyrosine kinase is a major mediator of neuropathic pain, suggesting that targeting the activity of this receptor might be a viable therapeutic option. Therefore, we set out to determine if any FDA-approved drugs can act as inhibitors of the EphB1 intracellular catalytic domain. An in silico screen was first used to identify a number of tetracycline antibiotics which demonstrated potential docking to the ATP-binding catalytic domain of EphB1. Kinase assays showed that demeclocycline, chlortetracycline, and minocycline inhibit EphB1 kinase activity at low micromolar concentrations. In addition, we cocrystallized chlortetracycline and EphB1 receptor, which confirmed its binding to the ATP-binding domain. Finally, in vivo administration of the three-tetracycline combination inhibited the phosphorylation of EphB1 in the brain, spinal cord, and dorsal root ganglion (DRG) and effectively blocked neuropathic pain in mice. These results indicate that demeclocycline, chlortetracycline, and minocycline can be repurposed for treatment of neuropathic pain and potentially for other indications that would benefit from inhibition of EphB1 receptor kinase activity.
Topics: Animals; Central Nervous System; Chlortetracycline; Crystallography, X-Ray; Humans; Male; Mice; Neuralgia; Protein Domains; Protein Kinase Inhibitors; Receptor, EphB1
PubMed: 33627480
DOI: 10.1073/pnas.2016265118 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Dec 2020Streptomyces aureofaciens DM-1 is a high-yielding 6-demethylchlortetracycline producer. The genome sequencing of DM-1 reveals a linear chromosome containing 6 824 334...
Streptomyces aureofaciens DM-1 is a high-yielding 6-demethylchlortetracycline producer. The genome sequencing of DM-1 reveals a linear chromosome containing 6 824 334 bps nucleotides with GC content of 72.6%. In this genome, a total of 6 431 open reading frames were predicted by using glimmer 3.02, Genemark and Z-Curve softwares. Twenty-eight secondary metabolite biosynthetic gene clusters were uncovered by using AntiSMASH gene prediction software, including the complete 6-demethylchlortetracycline biosynthetic gene cluster. A frame-shift mutation in methyltransferase coding region was detected, which may result in the demethylation of chlortetracycline. The complete genome sequence of S. aureofaciens DM-1 provides basic information for functional genomics studies and selection of high-yielding strains for 6-demethylchlortetracycline.
Topics: Base Sequence; Chlortetracycline; Demeclocycline; Multigene Family; Streptomyces aureofaciens
PubMed: 33398964
DOI: 10.13345/j.cjb.200317 -
Frontiers in Microbiology 2020Antibiotic resistance is a growing public health concern, though the constant development of new antibiotics. The combination of high-throughput screening and drug...
Antibiotic resistance is a growing public health concern, though the constant development of new antibiotics. The combination of high-throughput screening and drug repurposing is an effective way to develop new therapeutic uses of drugs. In this study, we screened a drug library consisting of 1,573 drugs already approved by the Food and Drug Administration and 903 drugs from the natural product library, to identify antimicrobials against . A high-throughput screening assay based on microtiter plate was used to screen 39 drugs that inhibit the planktonic or biofilm formation of while most of them are antibiotics. The antimicrobial activities of these drugs were evaluated by phenotypic analysis. Further studies showed the combined therapy of tetracycline antibiotics demeclocycline hydrochloride (DMCT) and the novel antimicrobial peptide SAAP-148 has an effective synergistic antibacterial effect on PAO1 and ATCC27853. Moreover, the time-kill curve assay and murine model of cutaneous abscesses further confirmed the synergistic effect. In addition, the combination of DMCT and SAAP-148 has the potential to combat clinically isolated multidrug-resistant (MDR) strains. Our results clearly indicate that DMCT and SAAP-148 combined therapy could be an effective method to combat MDR -related infections.
PubMed: 33362739
DOI: 10.3389/fmicb.2020.591426 -
Cartilage Dec 2021The temporomandibular joint (TMJ) is a unique fibrocartilaginous joint that adapts to mechanical loading through cell signaling pathways such as the Wnt pathway....
OBJECTIVE
The temporomandibular joint (TMJ) is a unique fibrocartilaginous joint that adapts to mechanical loading through cell signaling pathways such as the Wnt pathway. Increased expression of low-density lipoprotein receptor-related protein 5 (Lrp5), a co-receptor of the Wnt pathway, is associated with a high bone mass (HBM) phenotype. The objective of this study was to analyze the effect of overexpression of Lrp5 on the subchondral bone and cartilage of the TMJ in mice exhibiting the HBM phenotype.
DESIGN
Sixteen-week-old Lrp5 knock-in transgenic mice carrying either the A214V (EXP-A) or G171V (EXP-G) missense mutations, and wildtype controls (CTRL) were included in this study. Fluorescent bone labels, calcein, alizarin complexone, and demeclocycline were injected at 3.5, 7.5, and 11.5 weeks of age, respectively. The left mandibular condyle was used to compare the subchondral bone micro-computed tomography parameters and the right TMJ was used for histological analyses. Cartilage thickness, matrix proteoglycan accumulation, and immunohistochemical localization of Lrp5 and sclerostin were compared between the groups.
RESULTS
Subchondral bone volume (BV) and percent bone volume (BV/TV) were significantly increased in both EXP-A and EXP-G compared with CTRL ( < 0.05) whereas trabecular spacing (Tb.Sp) was decreased. Cartilage thickness, extracellular matrix production, and expression of Lrp5 and Sost were all increased in the experimental groups. The separation between the fluorescent bone labels indicated increased endochondral maturation between 3.5 and 7.5 weeks.
CONCLUSIONS
These data demonstrate that Lrp5 overexpression leads to adaptation changes in the mandibular condylar cartilage of the TMJ to prevent cartilage degradation.
Topics: Animals; Bone and Bones; Cartilage; Low Density Lipoprotein Receptor-Related Protein-5; Mice; Temporomandibular Joint; X-Ray Microtomography
PubMed: 33124433
DOI: 10.1177/1947603520968875 -
Food Frontiers Jun 2020Angiotensin converting enzyme 2 (ACE2) and main protease (M) are significant target proteins, mainly involved in the attachment of viral genome to host cells and aid in...
Angiotensin converting enzyme 2 (ACE2) and main protease (M) are significant target proteins, mainly involved in the attachment of viral genome to host cells and aid in replication of severe acute respiratory syndrome-coronaviruses or SARS-CoV genome. In the present study, we identified 11 potent bioactive compounds from ethanolic leaf extract of (L.) by using GC-MS analysis. These potential bioactive compounds were considered for molecular docking studies against ACE2 and M target proteins to determine the antiviral effects against SARS-COV. Results exhibits that among 11 compounds from (L.), urso-deoxycholic acid, demeclocycline, tetracycline, chlorotetracycline, and ethyl iso-allocholate had potential viral inhibitory activity. Hence, the present findings suggested that chemical constitution present in (L.) will address inhibition of corona viral replication in host cells.
PubMed: 32838301
DOI: 10.1002/fft2.29 -
Journal of Bone and Joint Infection 2020is gaining recognition as a leading pathogen after orthopaedic shoulder procedures. Photodynamic therapy, a combination of light and a photosensitizer, has...
is gaining recognition as a leading pathogen after orthopaedic shoulder procedures. Photodynamic therapy, a combination of light and a photosensitizer, has demonstrated antimicrobial activity against in the treatment of acne vulgaris. We sought to evaluate the effect of photodynamic therapy using blue light and photosensitizers on isolates from shoulder prosthetic joint infections. strains isolated from 19 patients with shoulder PJI were exposed to blue light alone (415 nm) or in combination with photosensitizers (fluorescein, riboflavin and demeclocycline). strains were divided into 4 categories: , to blue light. 13 of 19 strains (68% were or to blue light alone. Of these 19 strains tested, 11 were tested with blue light and fluorescein or blue light plus riboflavin. Fluorescein (1 µg/mL) enhanced the effect of blue light in 6 of 11 strains (55%). Blue light plus riboflavin (10 µg/mL) resulted enhanced killing in 3 of 11 strains (27%), but produced a paradoxical photoprotective effect in 4 of 11 strains (36%), resulting in a net decrease compared to blue light alone. Demeclocycline, however, enhanced the effect of blue light in 16 of 17 strains (94 %). Blue light with the addition of photosensitizers killed from periprosthetic shoulder infections , with demeclocycline having the most pronounced effect.
PubMed: 32670773
DOI: 10.7150/jbji.46199 -
Life Sciences Sep 2020The COVID-19 pandemic raised by SARS-CoV-2 is a public health emergency. However, lack of antiviral drugs and vaccine against human coronaviruses demands a concerted...
The COVID-19 pandemic raised by SARS-CoV-2 is a public health emergency. However, lack of antiviral drugs and vaccine against human coronaviruses demands a concerted approach to challenge the SARS-CoV-2 infection. Under limited resource and urgency, combinatorial computational approaches to identify the potential inhibitor from known drugs could be applied against risen COVID-19 pandemic. Thereof, this study attempted to purpose the potent inhibitors from the approved drug pool against SARS-CoV-2 main protease (M). To circumvent the issue of lead compound from available drugs as antivirals, antibiotics with broad spectrum of viral activity, i.e. doxycycline, tetracycline, demeclocycline, and minocycline were chosen for molecular simulation analysis against native ligand N3 inhibitor in SARS-CoV-2 M crystal structure. Molecular docking simulation predicted the docking score >-7 kcal/mol with significant intermolecular interaction at the catalytic dyad (His41 and Cys145) and other essential substrate binding residues of SARS-CoV-2 M. The best ligand conformations were further studied for complex stability and intermolecular interaction profiling with respect to time under 100 ns classical molecular dynamics simulation, established the significant stability and interactions of selected antibiotics by comparison to N3 inhibitor. Based on combinatorial molecular simulation analysis, doxycycline and minocycline were selected as potent inhibitor against SARS-CoV-2 M which can used in combinational therapy against SARS-CoV-2 infection.
Topics: Anti-Bacterial Agents; Antiviral Agents; Betacoronavirus; Binding Sites; COVID-19; Computational Biology; Coronavirus Infections; Databases, Genetic; Humans; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; Pandemics; Peptide Hydrolases; Pneumonia, Viral; Protease Inhibitors; Protein Binding; SARS-CoV-2; Tetracyclines; Viral Nonstructural Proteins
PubMed: 32653520
DOI: 10.1016/j.lfs.2020.118080 -
Synthetic and Systems Biotechnology Sep 2020Demecycline (DMTC) and demeclocycline (DMCTC) are C6-demethylated derivatives of tetracycline (TC) and chlortetracycline (CTC), respectively. They are precursors of...
Demecycline (DMTC) and demeclocycline (DMCTC) are C6-demethylated derivatives of tetracycline (TC) and chlortetracycline (CTC), respectively. They are precursors of minocycline and tigecycline, which showed remarkable bioactivity against TC-resistant bacteria and have been used clinically for decades. In order to biosynthesize drug precursors DMTC and DMCTC, the function of a possible C-methyltransferase encoding gene was studied systematically in the CTC high-yielding industrial strain F3. The mutant accumulated two new products, which were turned out to be DMTC and DMCTC. Meanwhile, time-course analysis of the fermentation products detected the epimers of DMTC and DMCTC transformed spontaneously. Finally, an engineering strain with higher productivity of DMCTC was constructed by deleting and overexpressing of three extra copies simultaneously. Construction of these two engineering strains not only served as a successful example of synthesizing required products through metabolic engineering, but also provided original strains for following elaborate engineering to synthesize more effective tetracycline derivatives.
PubMed: 32637665
DOI: 10.1016/j.synbio.2020.06.001