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Archives of Microbiology Sep 2022A novel marine Gram-stain-negative, aerobic, rod-shaped bacterium, designated as strain PS1, was isolated from the deep-sea sediments of the Mariana Trench and...
A novel marine Gram-stain-negative, aerobic, rod-shaped bacterium, designated as strain PS1, was isolated from the deep-sea sediments of the Mariana Trench and characterized phylogenetically and phenotypically. Bacterial optimal growth occurred at 35 °C (ranging 10-45 °C), pH 6 (ranging pH 5-10) and with 11% (w/v) NaCl (ranging 0-17%). The 16S rRNA gene sequence similarity results revealed that strain PS1 was most closely related to Pseudomonas stutzeri ATCC 17588, Pseudomonas nitrititolerans GL14, Pseudomonas zhaodongensis NEAU-ST5-21, Pseudomonas xanthomarina DSM 18231 and Pseudomonas kunmingensis HL22-2 with 98.3-98.7%. The digital DNA-DNA hybridization values and the average nucleotide identity between strain PS1 and the reference strains were 20.4-40.1% and 78.7-79.4%, respectively. The major respiratory quinone is ubiquinone Q-9. The major polar lipids were phosphatidylethanolamine, diphosphatidyglycerol, phosphatidylglycerol, phosphatidylcholine, aminoglycolipid, two unidentified glycolipids and one unidentified lipid. The predominant cellular fatty acids of strain PS1 were summed feature 8 (Cω7c and/or Cω6c), summed feature 3 (Cω7c and/or Cω6c), C and cyclo-C ω8c. The G + C content of the genomic DNA was 63.0%. The combined genotypic and phenotypic data indicated that strain PS1 represents a novel species of the genus Pseudomonas, for which the name Pseudomonas marianensis sp. nov. is proposed, with the type strain PS1 (= DSM 112238 = MCCC 1K05112).
Topics: Ancitabine; Bacterial Typing Techniques; DNA, Bacterial; Fatty Acids; Glycolipids; Nucleotides; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylglycerols; Phospholipids; Phylogeny; Pseudomonas; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Sodium Chloride; Ubiquinone
PubMed: 36131209
DOI: 10.1007/s00203-022-03250-9 -
PeerJ 2022Cyclocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cyclocytidine on...
BACKGROUND
Cyclocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cyclocytidine on hepatitis B virus (HBV) DNA synthesis, which is reliant on DNA polymerase activity.
MATERIALS AND METHODS
Cyclocytidine HCl was treated to HBV-producing HepAD38 cells or added to an endogenous polymerase reaction, and HBV DNA was detected by Southern blot.
RESULTS
Treatment of 20 µM cyclocytidine HCl significantly decreased the production of relaxed circular (rc) DNA in HepAD38 cells and block rcDNA synthesis in endogenous polymerase reaction (EPR), a cell free assay, possibly by inhibiting the HBV DNA polymerase activity.
CONCLUSION
Cyclocytidine HCl could inhibit the synthesis of HBV rcDNA, the precursor of covalently closed circular DNA, and this result provides a case for the usage of "old" drugs for "new" applications.
Topics: Ancitabine; DNA, Circular; DNA, Viral; DNA-Directed DNA Polymerase; Hepatitis B virus; Virus Replication
PubMed: 35846878
DOI: 10.7717/peerj.13719 -
Journal of Receptor and Signal... Dec 2020Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The...
Virtual screening, ADME/T, and binding free energy analysis of anti-viral, anti-protease, and anti-infectious compounds against NSP10/NSP16 methyltransferase and main protease of SARS CoV-2.
Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The uncontrolled release of cytokines is seen from the primary stages of symptoms to last acute respiratory distress syndrome (ARDS). Thus, it is necessary to find out safe and effective drugs against this deadly coronavirus as soon as possible. Here, we downloaded the three-dimensional model of NSP10/NSP16 methyltransferase (PDB-ID: 6w6l) and main protease (PDB-ID: 6lu7) of COVID-19. Using these molecular models, we performed virtual screening with our anti-viral, inti-infectious, and anti-protease compounds, which are attractive therapeutics to prevent infection of the COVID-19. We found that top screened compound binds with protein molecules with good dock score with the help of hydrophobic interactions and hydrogen bonding. We observed that protease complexed with Cyclocytidine hydrochloride (anti-viral and anti-cancer), Trifluridine (anti-viral), Adonitol, and Meropenem (anti-bacterial), and Penciclovir (anti-viral) bound with a good docking score ranging from -6.8 to -5.1 (Kcal/mol). Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol). In conclusion, the selected compounds may be used as a novel therapeutic agent to combat this deadly pandemic disease, SARS-CoV-2 infection, but needs further experimental research.HighlightsNSP10/NSP16 methyltransferase and main protease complex of SARS CoV-2 bind with selected drugs.NSP10/NSP16 methyltransferase and protease interacted with drugs by hydrophobic interactions.Compounds show good DG binging free energy with protein complexes.Ligands were found to follow the Lipinski rule of five.
Topics: Acyclovir; Ancitabine; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Drug Evaluation, Preclinical; Guanine; Humans; Meropenem; Methyltransferases; Models, Molecular; Molecular Docking Simulation; Pandemics; Pneumonia, Viral; Protein Conformation; Ribitol; SARS-CoV-2; Trifluridine; User-Computer Interface; Viral Nonstructural Proteins; Viral Regulatory and Accessory Proteins
PubMed: 32476594
DOI: 10.1080/10799893.2020.1772298 -
Journal of Submicroscopic Cytology and... Jul 2002Rat submandibular glands have been examined electron microscopically at various times after degranulating the granular tubules by injecting cyclocytidine (75 mg/kg...
Rat submandibular glands have been examined electron microscopically at various times after degranulating the granular tubules by injecting cyclocytidine (75 mg/kg i.p.), to study events in the reformation of secretory granules in these cells. The changes were progressive but not synchronous in the cells. The first evidence of recovery was the re-appearance of glycogen particles 6 h after injection. Residual secretory granules were small and located periluminally at that time. More granules were present at 15 h after injection but they were still small and placed periluminally. There was more glycogen in the cells and some was present in aggregates. At 1 day after injection there were more secretory granules and they tended to be larger than previously. The secretory granules increased in size and number progressively thereafter and the cells appeared like normal controls by day 7. During the recovery, fusion profiles were seen between granules from 2 days onwards. Throughout, few Golgi complexes were detected and this may be related with the low glycosylation of the secretory proteins in these cells. The results confirm that the reformation of the secretory granules in granular tubule cells is a slow process that involves fusions of smaller granules.
Topics: Ancitabine; Animals; Antimetabolites, Antineoplastic; Glycogen; Golgi Apparatus; Injections, Intraperitoneal; Male; Microscopy, Electron; Rats; Rats, Wistar; Secretory Vesicles; Submandibular Gland; Time Factors
PubMed: 12408361
DOI: No ID Found -
Clinical Pharmacokinetics 2002Cytarabine (cytosine arabinoside, Ara-C) is an effective chemotherapeutic agent for the treatment of acute myelogenous leukaemia and lymphocytic leukaemias. As... (Review)
Review
Cytarabine (cytosine arabinoside, Ara-C) is an effective chemotherapeutic agent for the treatment of acute myelogenous leukaemia and lymphocytic leukaemias. As cytarabine is an S-phase-specific drug, prolonged exposure of cells to cytotoxic concentrations is critical to achieve maximum cytotoxic activity. However, the activity of cytarabine is decreased by its rapid deamination to the biologically inactive metabolite uracil arabinoside. This rapid deamination is the reason for the ongoing search for effective formulations and derivatives of cytarabine that cannot be deaminated and exhibit better pharmacokinetic parameters. Protection of cytarabine from fast degradation and elimination has been investigated by encapsulating the drug into pharmaceutically acceptable carriers. Cytarabine derivatives have shown promise in vitro and in animal models. For example, ancitabine (cyclocytidine), enocitabine and cytarabine ocfosfate have been used clinically in Japan. Cytarabine encapsulated into multivesicular liposomes has been approved in several countries for the intrathecal treatment of lymphomatous meningitis. Although many compounds have been investigated, few cytarabine derivatives are currently available for clinical use. Further research is needed to improve the efficacy of cytarabine against haematological and solid tumours.
Topics: Animals; Antimetabolites, Antineoplastic; Area Under Curve; Chemistry, Pharmaceutical; Cytarabine; Delayed-Action Preparations; Emulsions; Half-Life; Humans; Liposomes; Metabolic Clearance Rate; Neoplasms
PubMed: 12162758
DOI: 10.2165/00003088-200241100-00002 -
European Journal of Morphology Apr 2000Secretory changes in the cells of granular tubules in rat submandibular glands have been studied sequentially during electrical stimulation of their sympathetic nerves....
Secretory changes in the cells of granular tubules in rat submandibular glands have been studied sequentially during electrical stimulation of their sympathetic nerves. Results were assessed in a series of biopsied lobes from the same gland, taken at different times during the sympathetic stimulation. Changes were not synchronous between adjacent cells and it appeared that the time for the onset of secretory events differed between cells but, once set in action, a chain of similar events occurred. Nevertheless, some cells appeared to remain refractory throughout. Initially, some alignment of granules to the adjacent plasma membrane occurred and occasional evidence for classical exocytosis was seen. However, from early on microvesicles appeared in more luminally located granule membranes and were associated with granule fusions, that became common and led to the formation of large irregular aggregates. Most of the secretion of granule contents appeared to be through openings of aggregates into lumina. With granule fusions the intra-membrane microvesicles became internalised and tended to increase in size with time; they were commonly expelled with the contents of the aggregates. Fragments of cytoplasm also became incorporated in aggregate formation. Cytoplasm, often containing glycogen, also formed luminal blebs over some granular tubule cells and appeared to pass into the secretion by an apocrine process. At the end of stimulation multivesicular bodies were seen in association with redundant aggregates.
Topics: Ancitabine; Animals; Biopsy; Cytoplasm; Cytoplasmic Granules; Electric Stimulation; Exocytosis; Male; Membrane Fusion; Microscopy, Electron; Rats; Rats, Wistar; Submandibular Gland; Sympathetic Nervous System
PubMed: 10694903
DOI: 10.1076/0924-3860(200004)38:2;1-f;ft069 -
International Journal of Radiation... Jan 1998Irradiation [IR]-induced damage to major salivary glands is an entity first described at the beginning of our century, yet its underlying mechanism is still enigmatic....
PURPOSE
Irradiation [IR]-induced damage to major salivary glands is an entity first described at the beginning of our century, yet its underlying mechanism is still enigmatic. Exposure of the salivary glands to IR is often inevitable when delivering radiotherapy for malignancies of the head and neck region. Frequently, this results in rapidly developing, life-long severe xerostomia for which no adequate prevention or treatment is available. The purpose of this study was to examine the role of secretion granules in serous cells of the parotid (P) and submandibular (SM) glands as mediators in the IR-induced salivary damage. Functional parameters (flow rate and gland weight), and total body weight were examined at both early term (4 days) and extended term (2 months) post-IR in male Wistar rats exposed to 15 Gy of head and neck irradiation following stimulation for granule secretion (degranulation).
METHODS AND MATERIALS
At 4 days, it was demonstrated that IR reduced P flow rate, P gland weight, total body weight, and submandibular/sublingual gland weight by 89, 33, 30, and 32% (p < 0.01), respectively, while SM flow rate was not altered significantly. At 2 months, these parameters were reduced by 59, 37, 31, and 37%, respectively, and the SM flow rate was reduced by 39% (p < 0.01).
RESULTS
Pilocarpine, a muscarinsic agonist which, albeit its efficacy as a salivary watery secretion stimulator, causes only limited degranulation, did not protect significantly any of the reduced parameters at either term. In contrast, cyclocytidine, an adrenergic agonist that is a very potent salivary degranulating agent, protected the P against the weight loss at 4 days and 2 months, and against the flow rate reduction at 2 months. The P weight and flow rate were protected to the extent that their values were not significantly different than those of the nonirradiated controls. Cyclocytidine also partially protected against the body weight reduction at 2 months. Our results emphasize the importance of secretion granules as mediatory agents in IR-induced P damage, and more so at the extended term. The demonstrated protective role of adrenergic agonists against IR damage to the P may be of importance in the clinical setting.
Topics: Adrenergic Agonists; Ancitabine; Animals; Cell Degranulation; Cytoplasmic Granules; Male; Parotid Gland; Pilocarpine; Radiation Injuries, Experimental; Radiation Protection; Rats; Rats, Wistar; Submandibular Gland
PubMed: 9457838
DOI: 10.1016/s0360-3016(97)00574-9 -
Archives of Otolaryngology--head & Neck... Sep 1997The healing-promotion property of saliva has been observed in the past, but its underlying mechanism has never been elucidated. We hypothesized a mechanism based on... (Comparative Study)
Comparative Study
BACKGROUND
The healing-promotion property of saliva has been observed in the past, but its underlying mechanism has never been elucidated. We hypothesized a mechanism based on salivary proteins binding to redox active metal ions, rendering them nonactive in their capacity for free radical production.
METHODS
Examination of this mechanism was conducted by comparing the redox activity of protein-rich saliva with protein-poor saliva. We also examined the redox activity mediated by these 2 kinds of saliva following the in vitro addition of iron, copper, and manganese. Saliva samples were analyzed for their redox activity by measuring the ascorbate-driven and saliva (diluted 1:2)-mediated conversion of salicylate to its 2,3- and 2.5-dihydroxybenzoates and catechol metabolites.
RESULTS
The concentrations of salicylate metabolites formed by protein-rich saliva were significantly lower by 45% (P < .05), 66% (P < .01), and 54% (P < .05), respectively, when compared with those formed by protein-poor saliva. The capacity of saliva in suppressing redox activity was found to be inversely related to the concentrations of iron and copper added (but not manganese), but correlated well with the protein content. When the highest concentrations of iron (15 mumol/L) and copper (10 mumol/L) were added to protein-rich saliva, the concentrations of salicylate metabolites produced were only 0.3% to 1% of those of non-saliva-containing controls (P < .01). However, when these concentrations of iron and copper were added to protein-poor saliva, significantly higher values of redox activity were detected, and the concentrations of the salicylate derivatives produced were 2.1% to 8.1% of those of non-saliva-containing controls (P < .01). In contrast, when the lowest concentrations of iron (2 mumol/L) and copper (0.1 mumol/L) were added, 2.8 to 4 times lower concentrations of salicylate derivatives were produced (P < .01).
CONCLUSION
These results substantiate our hypothesis that saliva has a profound capacity for reducing redox activity rendered by transition metal ions, correlating well with its protein content.
Topics: Ancitabine; Animals; Antimetabolites, Antineoplastic; Antioxidants; Ascorbic Acid; Catechols; Copper; Free Radicals; Gentisates; Hydroxybenzoates; Iron; Iron Chelating Agents; Male; Manganese; Metals; Oxidation-Reduction; Parasympathomimetics; Parotid Gland; Pilocarpine; Protein Binding; Rats; Rats, Wistar; Salicylates; Saliva; Salivary Proteins and Peptides; Wound Healing
PubMed: 9305252
DOI: 10.1001/archotol.1997.01900090105016 -
Radiation Research Apr 1997The mechanism of irradiation-induced hypofunction of the salivary glands is a process that is not fully understood. Here we examine the hypothesis that intracellular and...
The mechanism of irradiation-induced hypofunction of the salivary glands is a process that is not fully understood. Here we examine the hypothesis that intracellular and redox-active ions of iron and copper, which are associated with the secretion granules, play a catalytic role in the irradiation-induced damage. Rats were subjected to head and neck irradiation (15 Gy X rays) and allowed to recover for 2 months. The function of the parotid and submandibular glands was then determined by pilocarpine-stimulated salivary secretion. A 45% decrease in the function of both glands was obtained when compared to nonirradiated controls. Treatment prior to irradiation (90 min) with cyclocytidine (200 mg/kg) led to a massive degranulation of the parotid gland and yielded nearly complete protection from radiation-induced damage. In contrast, pilocarpine stimulation prior to irradiation led to a marginal degranulation of the parotid gland and yielded only 13% protection. Neither agent caused degranulation of the submandibular gland mucous cells or yielded functional protection of this gland. Treatment with both agents yielded a marked increase in iron, copper and manganese levels in the parotid gland saliva. An analogous marked increase in the redox activity of iron and copper ions was recorded for the parotid saliva stimulated by pilocarpine and cyclocytidine. Pilocarpine-stimulated submandibular gland saliva contained metal levels similar to those of the parotid gland saliva. However, no redox activity and no increase in metal mobilization could be demonstrated in the submandibular gland saliva stimulated by both agents. The correlation between the patterns of gland degranulation, mobilization of redoxactive metals and the protection of gland function, for both parotid and submandibular glands, focuses attention on the catalytic roles played by transition metal ions in promoting free radical reactions, which likely participate in the process of injury to the tissue.
Topics: Ancitabine; Animals; Copper; Cytoplasmic Granules; Iron; Male; Oxidation-Reduction; Parotid Gland; Pilocarpine; Radiation Protection; Rats; Rats, Wistar; Saliva; Submandibular Gland; X-Rays
PubMed: 9092927
DOI: No ID Found -
Biochemical Society Transactions Feb 1997
Topics: Ancitabine; Animals; Benzaldehydes; Cats; Coloring Agents; Cytoplasmic Granules; Dogs; Ferrets; Histocytochemistry; Kallikreins; Mice; Salivary Ducts; Sodium Nitrite; Submandibular Gland
PubMed: 9056926
DOI: 10.1042/bst025028s