Characterization of Non-Toxigenic Clostridioides difficile Strains Isolated from Preterm Neonates and In Vivo Study of Their Protective Effect

In a previous monocentric study in preterm neonates (PN), we described a high Clostridioides difficile colonization rate (74%) with two uncommon non-toxigenic strains (NTCD) belonging to PCR-ribotype (RT) (CE)847 and (CE)032. To determine the extent of carriage of both NTCD in other spatio-temporal settings, strains isolated in PN stools from two multicenter cohorts were characterized by PCR-ribotyping, MLVA and MLST. We also evaluated the protective role of two NTCD from these RT against C. difficile infection in a hamster caecitis model. Animals were administered either each NTCD alone (n = 7), or followed by a 027 strain (n = 9). A control group received only the 027 strain (n = 8). Clinical activity and colonization by C. difficile in stools were monitored daily until death or sacrifice at D20. We isolated 18 RT(CE)032 (ST-83) strains and 2 RT(CE)847 (ST-26) strains among 247 PN from both cohorts. Within each RT, strains were genetically related. The survival rate was significantly increased when animals received a RT(CE)847 or (CE)032 strain before the 027 strain (4/9 deaths, p = 0.029; 1/9 death, p = 0.0004, respectively). We describe two predominant uncommon NTCD strains, in a PN population from different healthcare facilities. Both NTCD provide a potential protection against C. difficile infection.

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Protective Role of Coenzyme Q10 in Acute Sepsis-Induced Liver Injury in BALB/c Mice

BioMed Research International ◽

10.1155/2020/7598375 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Qian-wei Li ◽

Qin Yang ◽

Hong-Yang Liu ◽

Yu-ling Wu ◽

Yu-Hua Hao ◽

...

Keyword(s):

Liver Injury ◽

Coenzyme Q10 ◽

Cecal Ligation ◽

Protective Role ◽

Hepatic Tissue ◽

Control Group ◽

Cecal Ligation And Puncture ◽

Sequestosome 1

Sepsis increases the risk of the liver injury development. According to the research works, coenzyme Q10 exhibits hepatoprotective properties in vivo as well as in vitro. Current work aimed at investigating the protective impacts of coenzyme Q10 against liver injury in septic BALB/c mice. The male BALB/c mice were randomly segregated into 4 groups: the control group, the coenzyme Q10 treatment group, the puncture and cecal ligation group, and the coenzyme Q10+cecal ligation and puncture group. Cecal ligation and puncture was conducted after gavagaging the mice with coenzyme Q10 during two weeks. Following 48 h postcecal ligation and puncture, we estimated hepatic biochemical parameters and histopathological changes in hepatic tissue. We evaluated the expression of factors associated with autophagy, pyroptosis, and inflammation. Findings indicated that coenzyme Q10 decreased the plasma levels in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in the cecal ligation and puncture group. Coenzyme Q10 significantly inhibited the elevation of sequestosome-1, interleukin-1β, oligomerization domain-like receptor 3 and nucleotide-binding, interleukin-6, and tumor necrosis factor-α expression levels; coenzyme Q10 also increased beclin 1 levels. Coenzyme Q10 might be a significant agent in the treatment of liver injury induced by sepsis.

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THE PROTECTIVE ROLE OF OMEGA-3 AGAINST GENOTOXICITY AND REPRODUCTIVE TOXICITY OF COBALT OXIDE NANOPARTICLES ACUTE TREATMENT IN MALE MICE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i5.25245 ◽

2018 ◽

Vol 11 (5) ◽

pp. 423

Author(s):

Nahed A Hussien ◽

Hanan R. H. Mohamed

Keyword(s):

Cobalt Oxide ◽

Negative Control Group ◽

Protective Role ◽

Negative Control ◽

Control Group ◽

Omega 3 ◽

Genotoxic Potential ◽

Polychromatic Erythrocytes

Objective: Cobalt nanoparticles (NPs), especially cobalt oxide NPs (Co3O4 NPs) are attracting unique shaped NPs that are used in different biomedical applications and medicine. Different in vitro studies report their toxic and carcinogenic effect but limited in vivo studies were present on its genotoxic potential. The present study was aimed to evaluate the genotoxic potential of Co3O4 NPs on bone marrow cells and sperms and the protective role of omega-3 in male albino mice.Methods: Animals were segregated into four groups that were orally treated for 3 consecutive days, Group 1: Negative control; Group 2: Omega-3 (250 mg/kg); Group 3: Co3O4 NPs (20 mg/kg); and Group 4: Combined group (250 mg/kg Omega-3 and Co3O4 NPs 20 mg/kg).Results: The present results show that Co3O4 NPs administration significantly increased number of micronucleated polychromatic erythrocytes (PCEs)/1000 PCEs, sperm abnormalities, and DNA damage, significantly decreased sperm motility and concentration in comparison to negative control group. However, Omega-3 administration in the combined group modulates the genotoxic potential of Co3O4 NPs in comparison to Co3O4 NPs group.Conclusion: The present study reports the genotoxic potential of Co3O4 NPs in vivo and assesses the protective role of Omega-3 administration due to its antioxidant effect.

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Staphylococcus aureus Infection Induced Oxidative Imbalance in Neutrophils: Possible Protective Role of Nanoconjugated Vancomycin

ISRN Pharmacology ◽

10.5402/2012/435214 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Subhankari Prasad Chakraborty ◽

Panchanan Pramanik ◽

Somenath Roy

Keyword(s):

Oxidative Stress ◽

Staphylococcus Aureus ◽

Cell Damage ◽

Treated Group ◽

Protective Role ◽

Control Group ◽

Similar Dose ◽

Cellular Components

Staphylococcus aureus infection causes oxidative stress in neutrophils. The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was aimed to test the protective role of nanoconjugated vancomycin against vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection induced oxidative stress in neutrophils. VSSA- and VRSA-infection were developed in Swiss mice by intraperitoneal injection of 5×106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was treated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was treated to VSSA and VRSA infected mice at similar dose, respectively, for 10 days. The result reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, and nitrite generation and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group; which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These finding suggests the potential use and beneficial protective role of nanoconjugated vancomycin against VSSA and VRSA infection induced oxidative imbalance in neutrophils.

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2398. Effect of Eosinopenia and Binary Toxin on Clostridioides difficile Infection Clinical Outcomes

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2076 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S828-S828

Author(s):

Travis J Carlson ◽

Bradley T Endres ◽

Julie Le Pham ◽

Anne J Gonzales-Luna ◽

Faris S Alnezary ◽

...

Keyword(s):

Immune Response ◽

Clinical Outcomes ◽

Eosinophil Count ◽

Toxin Production ◽

Albumin Level ◽

Binary Toxin ◽

Inpatient Mortality ◽

Healthcare Facilities ◽

Clostridioides Difficile

Abstract Background The ability of Clostridioides difficile to cause clinical disease in humans is dependent on toxin production. Significantly fewer eosinophils are seen in the peripheral blood of mice infected with a binary toxin positive (CDT+) C. difficile strain. Furthermore, the presence of CDT and eosinopenia have separately been associated with increased mortality in humans with C. difficile infection (CDI). We hypothesized that CDI due to a CDT+ C. difficile strain accompanied by peripheral eosinopenia would be associated with higher odds of inpatient mortality. Methods This multicenter, retrospective cohort study included all patients ≥ 18 years of age with toxigenic CDI in which specimen ribotype data were available as part of our ongoing surveillance study. The cohort was stratified by eosinophil count (0.0 cells/μL vs. > 0.0 cells/μL). The primary outcome was inpatient mortality. A logistic regression model was developed modeling inpatient mortality as a function of the available patient covariates. All P-values were from 2-sided tests, and results were deemed statistically significant at P < 0.05. Results A total of 688 patients from 13 institutions in six cities were included. Of those, 132 had a baseline eosinophil count of 0.0 cells/µL and 556 had a baseline eosinophil count > 0.0 cells/µL. While the odds of inpatient mortality were higher among patients with eosinopenia and those infected with a CDT+ ribotype, the combination of these variables remained an independent predictor of inpatient mortality after adjusting for CCI score, WBC count, and serum albumin level (OR, 7.84; 95% CI, 1.85–33.20; P = 0.005). Conclusion This is the first attempt to study the in vivo relationship between CDT presence, human immune response, and CDI clinical outcome. We identified an association between CDT presence with concomitant eosinopenia and worsened CDI outcomes. Healthcare facilities should consider identifying this important subset of patients at the time of CDI diagnosis. Future CDI drug development might benefit from targeting C. difficile properties that impair host immune response, which may in turn decrease adverse clinical outcomes associated with this disease. Disclosures All authors: No reported disclosures.

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The Effects of Rosmarinic Acid on Expression of Akt Genes in the Hippocampus of Diabetic Rats and DNA Glycation Inhibition.

10.21203/rs.3.rs-701800/v1 ◽

2021 ◽

Author(s):

Ameer Alrubaye ◽

Majid Motovali-Bashi ◽

Mehran Miroliaei

Keyword(s):

Rosmarinic Acid ◽

Hippocampal Neurons ◽

Protective Role ◽

Diabetic Rats ◽

In Vivo Studies ◽

Control Group ◽

Pathogenic Factors ◽

Genes Expression

Abstract Non-enzymatic glycation of DNA and the associated effects are among pathogenic factors in diabetes mellitus. Natural polyphenols have anti-diabetic activity. Herein, the protective role of one of the phytochemicals, rosmarinic acid (RA), was evaluated in glycation (with fructose) of human DNA and expression of Akt genes in the hippocampus of diabetic rats. In-vitro studies using fluorescence, agarose gel electrophoresis, fluorescence microscopy, and thermal denaturation analyses revealed that glycation causes DNA damage and that RA inhibits it. In-vivo studies were performed by induction of diabetes in rats using streptozotocin. The diabetic rats were given RA daily through gavage feeding. The expression of Akt genes (inhibitors of apoptosis) in the hippocampus was evaluated using RT-qPCR. In diabetic rats, Akt1 and Akt3 were significantly down-regulated compared to the control group. Treating the diabetic rats with RA returned the expression of Akt1 and Akt3 relatively to the normal condition. Past studies have shown that diabetes induces apoptosis in the hippocampal neurons. Given that glycation changes the genes expression and causes cell death, apoptosis of the hippocampal neurons can be due to the glycation of DNA. The results also suggest that RA has reliable potency against the gross modification of DNA under hyperglycemic conditions.

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Role of Quercetin in chemoprevention against wide range of carcinogens and mutagens

International Journal of Drug Delivery ◽

10.5138/09750215.2040 ◽

2017 ◽

Vol 9 (1) ◽

pp. 09

Author(s):

Savithiri Shivakumar ◽

Yasodha Lakshmi Tadakaluru ◽

Raja Ratna Reddy Yakkanti ◽

Sannidhi Ranga Suresh ◽

Pasula Chandra Sekhar

Keyword(s):

Alkylating Agents ◽

Antioxidant Properties ◽

Metabolic Activation ◽

Protective Role ◽

Clinical Activity ◽

Wide Range ◽

Cyp1a Activity

Quercetin is a ubiquitous plant flavoniod with significant pharmacological and clinical activity. In this study we determined to demonstrate the protective role of quercetin against range of mutagens and carcinogens in a combination of in vitro and in vivo studies via different mechanisms. Quercetin demonstrated significant protective role against sodium azide, benzo(a)pyrene, cyclophosphamide monohydrate, methyl methane sulphonate and etoposide compared to other mutagens. Quercetin is effective in both in vitro and in vivo test conditions and also in the presence as well as in the absence of metabolic activation system (Rat liver S9). Auto oxidation, antioxidant properties, inhibition of pro-mutagens metabolism by CYP1A activity and multiple antimutagenic and adaptive response, mechanisms of quercetin may account for its protective role in cancer prevention. In conclusion, the results clearly indicate that quercetin plays a significant role against mutagens that act by direct DNA binding (form DNA adducts), pro-mutagens and alkylating agents with free radical generation; which could be the rationale for its potent anticancer activity against particular cancer types.

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Rosmarinic acid inhibits DNA glycation and modulates the expression of Akt1 and Akt3 partially in the hippocampus of diabetic rats

Scientific Reports ◽

10.1038/s41598-021-99286-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ameer Alrubaye ◽

Majid Motovali-Bashi ◽

Mehran Miroliaei

Keyword(s):

Rosmarinic Acid ◽

Hippocampal Neurons ◽

Protective Role ◽

Diabetic Rats ◽

In Vivo Studies ◽

Control Group ◽

Pathogenic Factors ◽

Genes Expression

AbstractNon-enzymatic glycation of DNA and the associated effects are among pathogenic factors in diabetes mellitus. Natural polyphenols have anti-diabetic activity. Herein, the protective role of one of the phytochemicals, rosmarinic acid (RA), was evaluated in glycation (with fructose) of human DNA and expression of Akt genes in the hippocampus of diabetic rats. In-vitro studies using fluorescence, agarose gel electrophoresis, fluorescence microscopy, and thermal denaturation analyses revealed that glycation causes DNA damage and that RA inhibits it. In-vivo studies were performed by induction of diabetes in rats using streptozotocin. The diabetic rats were given RA daily through gavage feeding. The expression of Akt genes (inhibitors of apoptosis) in the hippocampus was evaluated using RT-qPCR. In diabetic rats, Akt1 and Akt3 were significantly down-regulated compared to the control group. Treating the diabetic rats with RA returned the expression of Akt1 and Akt3 relatively to the normal condition. Past studies have shown that diabetes induces apoptosis in the hippocampal neurons. Given that glycation changes the genes expression and causes cell death, apoptosis of the hippocampal neurons can be due to the glycation of DNA. The results also suggest that RA has reliable potency against the gross modification of DNA under hyperglycemic conditions.

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Nitric oxide inhibits superoxide production by inflammatory polymorphonuclear leukocytes

AJP Cell Physiology ◽

10.1152/ajpcell.1998.274.3.c827 ◽

1998 ◽

Vol 274 (3) ◽

pp. C827-C830 ◽

Cited By ~ 65

Author(s):

Jesús Ródenas ◽

M. Teresa Mitjavila ◽

Teresa Carbonell

Keyword(s):

Nitric Oxide ◽

Superoxide Anion ◽

Polymorphonuclear Leukocytes ◽

Protective Role ◽

Saline Control ◽

Control Group ◽

Text Production ◽

Phosphate Buffered Saline

Nitric oxide (NO ⋅) has a complex role in the inflammatory response. In this study, we modified the levels of endogenous NO ⋅ in vivo in an acute model of inflammation and evaluated the interactions between NO ⋅ and superoxide anion ([Formula: see text]) produced by polymorphonuclear leukocytes (PMNs) accumulated in the inflamed area. We injected phosphate-buffered saline (control group), 6 μmol ofl- N 5-(1-iminoethyl)ornithine (l-NIO group), or 6 μmol ofl-arginine (l-arginine group) into the granuloma pouch induced by carrageenan in rats.[Formula: see text] plus[Formula: see text] (indicative of NO ⋅ generation) was 188 nmol in the exudate of the control group, but it decreased in the l-NIO group ( P < 0.05) and increased in thel-arginine group ( P < 0.05). When PMNs from treated rats were incubated in vitro, the production of superoxide anion ([Formula: see text]) decreased by ∼46% in thel-arginine group. Furthermore,[Formula: see text] was inhibited in PMNs whenl-arginine was added to the incubation medium before phorbol 12-myristate 13-acetate stimulation but not when added simultaneously. Our results suggest a protective role for NO ⋅ in inflammation, through the inactivation of NADPH oxidase and the consequent impairment of[Formula: see text] production for cell-mediated injury.

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Facilitated migration of cells from a transected peripheral nerve over collagen fibers: in vivo observations

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100156420 ◽

1989 ◽

Vol 47 ◽

pp. 888-889

Author(s):

Arthur J. Wasserman ◽

Azam Rizvi ◽

George Zazanis ◽

Frederick H. Silver

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Collagen Gel ◽

Collagen Fibers ◽

Control Group ◽

Guide Tube ◽

Sprague Dawley ◽

Silicone Tube ◽

Thin Sections

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.

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