Displaying publications 541 - 560 of 841 in total

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  1. Zakaria ZA, Roosli RAJ, Marmaya NH, Omar MH, Basir R, Somchit MN
    Biomolecules, 2020 02 12;10(2).
    PMID: 32059475 DOI: 10.3390/biom10020280
    Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant (p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly (p < 0.05) reversed MEDL effect on thermal nociception. Only l-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly (p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.
    Matched MeSH terms: Models, Animal
  2. Karisnan K, Mahzabin T, Bakker AJ, Song Y, Noble PB, Pillow JJ, et al.
    Am J Physiol Regul Integr Comp Physiol, 2018 04 01;314(4):R523-R532.
    PMID: 29212808 DOI: 10.1152/ajpregu.00150.2017
    The preterm diaphragm is functionally immature compared with its term counterpart. In utero inflammation further exacerbates preterm diaphragm dysfunction. We hypothesized that preterm lambs are more vulnerable to in utero inflammation-induced diaphragm dysfunction compared with term lambs. Pregnant ewes received intra-amniotic (IA) injections of saline or 10 mg lipopolysaccharide (LPS) 2 or 7 days before delivery at 121 days (preterm) or ∼145 days (term) of gestation. Diaphragm contractile function was assessed in vitro. Plasma cytokines, diaphragm myosin heavy chain (MHC) isoforms, and oxidative stress were evaluated. Maximum diaphragm force in preterm control lambs was significantly lower (22%) than in term control lambs ( P < 0.001). Despite similar inflammatory cytokine responses to in utero LPS exposure, diaphragm function in preterm and term lambs was affected differentially. In term lambs, maximum force after a 2-day LPS exposure was significantly lower than in controls (by ~20%, P < 0.05). In preterm lambs, maximum forces after 2-day and 7-day LPS exposures were significantly lower than in controls (by ~30%, P < 0.05). Peak twitch force after LPS exposure was significantly lower in preterm than in controls, but not in term lambs. In term lambs, LPS exposure increased the proportion of MHC-I fibers, increased twitch contraction times, and increased fatigue resistance relative to controls. In preterm diaphragm, the cross-sectional area of embryonic MHC fibers was significantly lower after 7-day versus 2-day LPS exposures. We conclude that preterm lambs are more vulnerable to IA LPS-induced diaphragm dysfunction than term lambs. In utero inflammation exacerbates diaphragm dysfunction and may increase susceptibility to postnatal respiratory failure.
    Matched MeSH terms: Disease Models, Animal
  3. Khan AYF, Ahmed QU, Narayanamurthy V, Razali S, Asuhaimi FA, Saleh MSM, et al.
    Biomed Pharmacother, 2019 Jun;114:108841.
    PMID: 30981106 DOI: 10.1016/j.biopha.2019.108841
    Porcupine bezoar (PB) is a calcified undigested material generally found in porcupine's (Hystrix brachyura) gastrointestinal tract. The bezoar is traditionally used in South East Asia and Europe for the treatment of cancer, poisoning, dengue, typhoid, etc. However, limited scientific studies have been performed to verify its anticancer potential to substantiate its traditional claims in the treatment of cancers. Hence, this study was aimed at investigating the in vitro and in vivo anticancer properties of two grassy PB aqueous extract (PB-A and PB-B) using A375 cancer cell line and zebrafish model, respectively. This paper presents the first report on in vitro A375 cell viability assay, apoptosis assay, cell cycle arrest assay, migration assay, invasion assay, qPCR experimental assay and in vivo anti-angiogenesis assay using the grassy PBs. Experimental findings revealed IC50 value are 26.59 ± 1.37 μg/mL and 30.12 ± 3.25 μg/mL for PB-A and PB-B respectively. PBs showed anti-proliferative activity with no significant cytotoxic effect on normal human dermal fibroblast (NHDF). PBs were also found to induce apoptosis via intrinsic pathway and arrest cell cycle at G2/M phase. Additionally, the findings indicated its ability to debilitate migration and invasion of A375 cells. Further evaluation using embryo zebrafish model revealed LC50 = 450.0 ± 2.50 μg/mL and 58.7 ± 5.0 μg/mL for PB-A and PB-B which also exerted anti-angiogenesis effect in zebrafish. Moreover, stearic acid, ursodeoxycholic acid and pregnenolone were identified as possible metabolites that might contribute to the anticancer effect of the both PBs. Overall, this study demonstrated that PB-A and PB-B possess potential in vitro and in vivo anticancer effects which are elicited through selective cytotoxic effect, induction of apoptosis, inhibition of migration and invasion and anti-angiogenesis. This study provides scientific evidence that the porcupine bezoar do possess anti-cancer efficacy and further justifies its traditional utility. However, more experiments with higher vertebrae models are still warranted to validate its traditional claims as an anticancer agent.
    Matched MeSH terms: Disease Models, Animal
  4. Sologashvili T, Saat SA, Tille JC, De Valence S, Mugnai D, Giliberto JP, et al.
    Eur J Pharm Biopharm, 2019 Jun;139:272-278.
    PMID: 31004790 DOI: 10.1016/j.ejpb.2019.04.012
    OBJECTIVE: Vascular prostheses for small caliber bypass grafts in cardiac and vascular diseases or for access surgery are still missing. Poly (Ɛ-caprolactone) (PCL) has been previously investigated by our group and showed good biocompatibility and mechanical properties in vitro and rapid endothelialisation, cellular infiltration and vascularisation in vivo yielding optimal patency in the abdominal aortic position. The aim of the present study is to evaluate our PCL graft in the carotid position and to compare its outcome to the grafts implanted in the abdominal aortic position.

    METHODS: PCL grafts (1 mm ID/10 mm long) were implanted into the left common carotid artery in 20 Sprague-Dawley rats and compared to our previously published series of abdominal aortic implants. The animals were followed up to 3, 6, 12 and 24 weeks. At each time point, in vivo compliance, angiography and histological examination with morphology were performed.

    RESULTS: PCL grafts showed good mechanical properties and ease of handling. The average graft compliance was 14.5 ± 1.7%/ mmHg compared to 7.8 ± 0.9% for the abdominal position and 45.1 ± 3.2%/ mmHg for the native carotid artery. The overall patency for the carotid position was 65% as compared to 100% in the abdominal position. Complete endothelialisation was achieved at 3 weeks and cell invasion was more rapid than in the aortic position. In contrast, intimal hyperplasia (IH) and vascular density were less pronounced than in the aortic position.

    CONCLUSION: Our PCL grafts in the carotid position were well endothelialised with early cellular infiltration, higher compliance, lower IH and calcification compared to the similar grafts implanted in the aortic position. However, there was a higher occlusion rate compared to our abdominal aorta series. Anatomical position, compliance mismatch, flow conditions may answer the difference in patency seen.

    Matched MeSH terms: Models, Animal
  5. Azis NA, Agarwal R, Ismail NM, Ismail NH, Kamal MSA, Radjeni Z, et al.
    Mol Biol Rep, 2019 Jun;46(3):2841-2849.
    PMID: 30977084 DOI: 10.1007/s11033-019-04730-w
    This study investigated the effects of a standardised ethanol and water extract of Ficus deltoidea var. Kunstleri (FDK) on blood pressure, renin-angiotensin-aldosterone system (RAAS), endothelial function and antioxidant system in spontaneously hypertensive rats (SHR). Seven groups of male SHR were administered orally in volumes of 0.5 mL of either FDK at doses of 500, 800, 1000 and 1300 mg kg- 1, or captopril at 50 mg kg- 1 or losartan at 10 mg kg- 1 body weight once daily for 4 weeks or 0.5 mL distilled water. Body weight, systolic blood pressures (SBP) and heart rate (HR) were measured every week. 24-hour urine samples were collected at weeks 0 and 4 for electrolyte analysis. At week 4, sera from rats in the control and 1000 mg kg- 1 of FDK treated groups were analyzed for electrolytes and components of RAAS, endothelial function and anti-oxidant capacity. SBP at week 4 was significantly lower in all treatment groups, including captopril and losartan, when compared to that of the controls. Compared to the controls, ACE activity and concentrations of angiotensin I, angiotensin II and aldosterone were lower whereas concentrations of angiotensinogen and angiotensin converting enzyme 2 were higher in FDK treated rats. Concentration of eNOS and total anti-oxidant capacity were higher in FDK treated rats. Urine calcium excretion was higher in FDK treated rats. In conclusion, it appears that ethanol and water extract of FDK decreases blood pressure in SHR, which might involve mechanisms that include RAAS, anti-oxidant and endothelial system.
    Matched MeSH terms: Disease Models, Animal
  6. Najafi R, Hosseini A, Ghaznavi H, Mehrzadi S, Sharifi AM
    Brain Res Bull, 2017 May;131:117-122.
    PMID: 28373151 DOI: 10.1016/j.brainresbull.2017.03.013
    OBJECTIVE: Neuropathies are a nerve disorders that caused by diabetes. Neuropathy affects over 50% of diabetic patients. High blood glucose and their toxic byproducts are the main causes for nerve dysfunction. In the present study, we examined the neroprotective effects of cerium oxide (CeO2) nanoparticles in diabetic rats.

    METHOD: Rats divided into four groups: control group, diabetic group, the diabetic group treated with CeO2nanoparticle at a dose of 65mg/kg and diabetic group received CeO2nanoparticle at a dose of 85mg/kg. Diabetes was induced by single intraperitoneal injection of 65mg/kg streptozotocin (STZ). 8 weeks after the induction of diabetes, body weight and pain sensitivity in all groups were measured. The blood sample was collected for biochemical analysis. The dorsal root ganglion (DRG) neurons were isolated for histopathological stain and morphometric parameters studies.

    RESULTS: Reduction of body weight, total thiol molecules (TTM), total antioxidant power (TAP) and ADP/ATP ratio in diabetic rat was reversed by CeO2nanoparticles administration. We showed that lipid peroxidation (LPO) and nociception latency were significantly increased in STZ-treated rats and decreased after CeO2nanoparticles administration. DRG neurons showed obvious vacuole and various changes in diameter, area and the count of A and B cells in STZ-diabetic rat. CeO2nanoparticles improved the histopathology and morphological abnormalities of DRG neurons.

    CONCLUSION: Our study concluded the CeO2nanoparticles have a protective effect against the development of DN.

    Matched MeSH terms: Disease Models, Animal
  7. Mihardja M, Roy J, Wong KY, Aquili L, Heng BC, Chan YS, et al.
    Ann N Y Acad Sci, 2020 10;1478(1):43-62.
    PMID: 32700392 DOI: 10.1111/nyas.14436
    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the hallmark pathologies of amyloid-beta plaques and neurofibrillary tangles. Symptoms of this devastating disease include behavioral changes and deterioration of higher cognitive functions. Impairment of neurogenesis has also been shown to occur in AD, which adversely impacts new neuronal cell growth, differentiation, and survival. This impairment possibly results from the cumulative effects of the various pathologies of AD. Preclinical studies have suggested that the administration of melatonin-the pineal hormone primarily responsible for the regulation of the circadian rhythm-targets the effects of AD pathologies and improves cognitive impairment. It is postulated that by mitigating the effect of these pathologies, melatonin can also rescue neurogenesis impairment. This review aims to explore the effect of AD pathologies on neurogenesis, as well as the mechanisms by which melatonin is able to ameliorate AD pathologies to potentially promote neurogenesis.
    Matched MeSH terms: Disease Models, Animal
  8. Newton AMJ, Lakshmanan P
    PMID: 30657050 DOI: 10.2174/1871523018666190118112230
    OBJECTIVE: A number of natural polymer-based drug delivery systems targeting the colon are reported for different applications. Most of the research is based on the class of natural polymers such as polysaccharides. This study compares the anti-inflammatory effect of different polysaccharide based tablets on IBD when a drug carrier is targeted to the colon as matrix and coated systems.

    METHODS: The TNBS induced IBD Wistar rats were used as a model for the study. The microscopic and macroscopic parameters were studied in detail. Almost all the important IBD parameters were reported in this work.

    RESULTS: The results demonstrated that the polysaccharides are efficient in carrying the drugs to the colon. Reduction in the level of ulcer index (UI), Myeloperoxidase (MPO), and Malondialdehyde MDA, confirmed the inhibitory activity on the development of Reactive oxygen species (ROS). The increased level of Tumor necrosis factor (TNFα) an expression of colonic inducible nitric oxide synthase (iNOS) was lowered in treatments as compared to TNBS control.

    CONCLUSION: The different polymer-based mesalamine (DPBM) confirmed the efficient anti- inflammatory activity on IBD induced rats. The increased level of glutathione (GSH), and superoxide dismutase (SOD) also confirmed the effective anti-inflammatory effect. A significant decrease in the ulcer score and ulcer area was reported. The investigation revealed that chitosan is superior to pectin in IBD treatment likewise polysaccharide-based matrix systems are superior to the coated system.

    Matched MeSH terms: Disease Models, Animal
  9. Wong CY, Cheong SK, Mok PL, Leong CF
    Pathology, 2008 Jan;40(1):52-7.
    PMID: 18038316
    AIMS: Adult human bone marrow contains a population of mesenchymal stem cells (MSC) that contributes to the regeneration of tissues such as bone, cartilage, muscle, tendon, and fat. In recent years, it has been shown that functional stem cells exist in the adult bone marrow, and they can contribute to renal remodelling or reconstitution of injured renal glomeruli, especially mesangial cells. The purpose of this study is to examine the ability of MSC isolated from human bone marrow to differentiate into mesangial cells in glomerular injured athymic mice.

    METHODS: MSC were isolated from human bone marrow mononuclear cells based on plastic adherent properties and expanded in vitro in the culture medium. Human mesenchymal stem cells (hMSC) were characterised using microscopy, immunophenotyping, and their ability to differentiate into adipocytes, chondrocytes, and osteocytes. hMSC were then injected into athymic mice, which had induced glomerulonephropathy (GN).

    RESULTS: Test mice (induced GN and infused hMSC) were shown to have anti-human CD105(+) cells present in the kidneys and were also positive to anti-human desmin, a marker for mesangial cells. Furthermore, immunofluorescence assays also demonstrated that anti-human desmin(+) cells in the glomeruli of these test mice were in the proliferation stage, being positive to anti-human Ki-67.

    CONCLUSIONS: These findings indicate that hMSC found in renal glomeruli differentiated into mesangial cells in vivo after glomerular injury occurred.

    Matched MeSH terms: Disease Models, Animal
  10. Lau YS, Ling WC, Murugan D, Mustafa MR
    J Cardiovasc Pharmacol, 2015 Jun;65(6):522-31.
    PMID: 25469805 DOI: 10.1097/FJC.0000000000000185
    Epidemiological and clinical studies have demonstrated that a growing list of natural products, as components of the daily diet or phytomedical preparations, are a rich source of antioxidants. Boldine [(S)-2,9-dihydroxy-1,10-dimethoxy-aporphine], an aporphine alkaloid, is a potent antioxidant found in the leaves and bark of the Chilean boldo tree. Boldine has been extensively reported as a potent "natural" antioxidant and possesses several health-promoting properties like anti-inflammatory, antitumor promoting, antidiabetic, and cytoprotective. Boldine exhibited significant endothelial protective effect in animal models of hypertension and diabetes mellitus. In isolated thoracic aorta of spontaneously hypertensive rats, streptozotocin-induced diabetic rats, and db/db mice, repeated treatment of boldine significantly improved the attenuated acetylcholine-induced endothelium-dependent relaxations. The endothelial protective role of boldine correlated with increased nitric oxide levels and reduction of vascular reactive oxygen species via inhibition of the nicotinamide adenine dinucleotide phosphate oxidase subunits, p47 and nicotinamide adenine dinucleotide phosphate oxidase 2, and angiotensin II-induced bone morphogenetic protein-4 oxidative stress cascade with downregulation of angiotensin II type 1 receptor and bone morphogenetic protein-4 expression. Taken together, it seems that boldine may exert protective effects on the endothelium via several mechanisms, including protecting nitric oxide from degradation by reactive oxygen species as in oxidative stress-related diseases. The present review supports a complimentary therapeutic role of the phytochemical, boldine, against endothelial dysfunctions associated with hypertension and diabetes mellitus by interfering with the oxidative stress-mediated signaling pathway.
    Matched MeSH terms: Disease Models, Animal
  11. Islam MT, Rahman MA, Saeed M, Ul-Haq Z, Alam MJ, Mondal M, et al.
    Cell Mol Biol (Noisy-le-grand), 2020 Jun 25;66(4):243-249.
    PMID: 32583783
    Phytol (PHY), a chlorophyll-derived diterpenoid, exhibits numerous pharmacological properties, including antioxidant, antimicrobial, and anticancer activities. This study evaluates the anti-diarrheal effect of phytol (PHY) along with its possible mechanism of action through in-vivo and in-silico models. The effect of PHY was investigated on castor oil-induced diarrhea in Swiss mice by using prazosin, propranolol, loperamide, and nifedipine as standards with or without PHY. PHY at 50 mg/kg (p.o.) and all other standards exhibit significant (p < 0.05) anti-diarrheal effect in mice. The effect was prominent in the loperamide and propranolol groups. PHY co-treated with prazosin and propranolol was found to increase in latent periods along with a significant reduction in diarrheal section during the observation period than other individual or combined groups. Furthermore, molecular docking studies also suggested that PHY showed better interactions with the α- and β-adrenergic receptors, especially with α-ADR1a and β-ADR1. In the former case, PHY showed interaction with hydroxyl group of Ser192 at a distance of 2.91Å, while in the latter it showed hydrogen bond interactions with Thr170 and Lys297 with a distance of 2.65 and 2.72Å, respectively. PHY exerted significant anti-diarrheal effect in Swiss mice, possibly through blocking α- and β-adrenergic receptors.
    Matched MeSH terms: Disease Models, Animal
  12. Hu T, Zheng Y, Zhang Y, Li G, Qiu W, Yu J, et al.
    BMC Microbiol, 2012;12:305.
    PMID: 23268691 DOI: 10.1186/1471-2180-12-305
    The identification of new virus strains is important for the study of infectious disease, but current (or existing) molecular biology methods are limited since the target sequence must be known to design genome-specific PCR primers. Thus, we developed a new method for the discovery of unknown viruses based on the cDNA--random amplified polymorphic DNA (cDNA-RAPD) technique. Getah virus, belonging to the family Togaviridae in the genus Alphavirus, is a mosquito-borne enveloped RNA virus that was identified using the Virus-Discovery-cDNA RAPD (VIDISCR) method.
    Matched MeSH terms: Disease Models, Animal
  13. Sundaram A, Siew Keah L, Sirajudeen KN, Singh HJ
    Hypertens Res, 2013 Mar;36(3):213-8.
    PMID: 23096233 DOI: 10.1038/hr.2012.163
    Although oxidative stress has been implicated in the pathogenesis of hypertension in spontaneously hypertensive rats (SHRs), there is little information on the levels of primary antioxidant enzymes status (AOEs) in pre-hypertensive SHR. This study therefore determined the activities of primary AOEs and their mRNA levels, levels of hydrogen peroxide (H2O2), malondialdehyde (MDA) and total antioxidant status (TAS) in whole kidneys of SHR and age-matched Wistar-Kyoto (WKY) rats aged between 2 and 16 weeks. Compared with age-matched WKY rats, catalase (CAT) activity was significantly higher from the age of 2 weeks (P<0.001) and glutathione peroxide (GPx) activity was lower from the age of 3 weeks (P<0.001) in SHR. CAT mRNA levels were significantly higher in SHR aged 2, 4, 6 and 12 weeks. GPx mRNA levels were significantly lower in SHR at 8 and 12 weeks. Superoxide dismutase activity or its mRNA levels were not different between the two strains. H2O2 levels were significantly lower in SHR from the age of 8 weeks (P<0.01). TAS was significantly higher in SHR from the age of 3 weeks (P<0.05). MDA levels were only significantly higher at 16 weeks of age in the SHR (P<0.05). The data suggest that altered renal CAT and GPx mRNA expression and activity precede the development of hypertension in SHR. The raised CAT activity perhaps contributes to the higher TAS and lower H2O2 levels in SHR. In view of these findings, the precise role of oxidative stress in the pathogenesis of hypertension in SHR needs to be investigated further.
    Matched MeSH terms: Disease Models, Animal
  14. Narasingam M, Pandy V, Mohamed Z
    Exp Anim, 2016 May 20;65(2):157-64.
    PMID: 26744024 DOI: 10.1538/expanim.15-0088
    The present study was designed to investigate the effect of a methanolic extract of Morinda citrifolia Linn. fruit (MMC) on the rewarding effect of heroin in the rat conditioned place preference (CPP) paradigm and naloxone-precipitated withdrawal in mice. In the first experiment, following a baseline preference test (preconditioning score), the rats were subjected to conditioning trials with five counterbalanced escalating doses of heroin versus saline followed by a preference test conducted under drug-free conditions (post-conditioning score) using the CPP test. Meanwhile, in the second experiment, withdrawal jumping was precipitated by naloxone administration after heroin dependence was induced by escalating doses for 6 days (3×/ day). The CPP test results revealed that acute administration of MMC (1, 3, and 5 g/kg body weight (bw), p.o.), 1 h prior to the CPP test on the 12th day significantly reversed the heroin-seeking behavior in a dose-dependent manner, which was similar to the results observed with a reference drug, methadone (3 mg/kg bw, p.o.). On the other hand, MMC (0.5, 1, and 3 g/kg bw, p.o.) did not attenuate the heroin withdrawal jumps precipitated by naloxone. These findings suggest that the mechanism by which MMC inhibits the rewarding effect of heroin is distinct from naloxone-precipitated heroin withdrawal.
    Matched MeSH terms: Models, Animal
  15. Zain MA, Rouhollahi E, Pandy V, Mani V, Majeed ABA, Wong WF, et al.
    Exp Anim, 2018 Nov 01;67(4):421-429.
    PMID: 29731492 DOI: 10.1538/expanim.18-0006
    Phencyclidine (PCP) has been used to model cognitive deficits related to schizophrenia in rats and mice. However, the model in mice is not consistent in terms of the PCP effective dose reported. Furthermore, most of the previous studies in mice excluded the presence of drug washout period in the regime. Thus, we aimed to optimize the dose of PCP in producing robust cognitive deficits by implementing it in a PCP regime which incorporates a drug washout period. The regimen used was 7 days' daily injection of PCP or saline for treatment and vehicle groups, respectively; followed by 24 h drug washout period. After the washout period, the test mice were tested in water maze (5 days of acquisition + 1 day of probe trial) for assessment of spatial learning and memory. Initially, we investigated the effect of PCP at 2mg/kg, however, no apparent impairment in spatial learning and memory was observed. Subsequently, we examined the effect of higher doses of PCP at 5, 10 and 20 mg/kg. We found that the PCP at 10 mg/kg produced a significant increase in "latency to reach the platform" during the acquisition days and a significant increase in "latency of first entry to previous platform" during the probe day. There was no significant change observed in "swim speed" during the test days. Thus, we concluded that PCP at 10 mg/kg produced robust deficits in spatial learning and memory without being confounded by motor disturbances.
    Matched MeSH terms: Disease Models, Animal
  16. Beatson SA, Ben Zakour NL, Totsika M, Forde BM, Watts RE, Mabbett AN, et al.
    Infect Immun, 2015 May;83(5):1749-64.
    PMID: 25667270 DOI: 10.1128/IAI.02810-14
    Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.
    Matched MeSH terms: Models, Animal
  17. Azad AK, Doolaanea AA, Al-Mahmood SMA, Kennedy JF, Chatterjee B, Bera H
    Int J Biol Macromol, 2021 Aug 31;185:861-875.
    PMID: 34237363 DOI: 10.1016/j.ijbiomac.2021.07.019
    Peppermint oil (PO) is the most prominent oil using in pharmaceutical formulations with its significant therapeutic value. In this sense, this oil is attracting considerable attention from the scientific community due to its traditional therapeutic claim, biological and pharmacological potential in recent research. An organic solvent-free and environment-friendly electrohydrodynamic assisted (EHDA) technique was employed to prepared PO-loaded alginate microbeads. The current study deals with the development, optimization, in vitro characterization, in vivo gastrointestinal tract drug distribution and ex-vivo mucoadhesive properties, antioxidant, and anti-inflammatory effects of PO-loaded alginate microbeads. The optimization results indicated the voltage and flow rate have a significant influence on microbeads size and sphericity factor and encapsulation efficiency. All these optimized microbeads showed a better drug release profile in simulated intestinal fluid (pH 6.8) at 2 h. However, a minor release was found in acidic media (pH 1.2) at 2 h. The optimized formulation showed excellent mucoadhesive properties in ex-vivo and good swelling characterization in intestine media. The microbeads were found to be well distributed in various parts of the intestine in in vivo study. PO-loaded alginate microbeads similarly showed potential antioxidant effects with drug release. The formulation exhibited possible improvement of irritable bowel syndrome (IBS) in MO-induced rats. It significantly suppressed proinflammatory cytokines, i.e., interleukin- IL-1β, and upregulated anti-inflammatory cytokine expression, i.e., IL-10. It would be a promising approach for targeted drug release after oral administration and could be considered an anti-inflammatory therapeutic strategy for treating IBS.
    Matched MeSH terms: Disease Models, Animal
  18. Shah SA, Sohail M, Minhas MU, Khan S, Hussain Z, Mahmood A, et al.
    Int J Biol Macromol, 2021 Aug 31;185:350-368.
    PMID: 34171251 DOI: 10.1016/j.ijbiomac.2021.06.119
    Injectable hydrogel with multifunctional tunable properties comprising biocompatibility, anti-oxidative, anti-bacterial, and/or anti-infection are highly preferred to efficiently promote diabetic wound repair and its development remains a challenge. In this study, we report hyaluronic acid and Pullulan-based injectable hydrogel loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade compared to other treatment groups. The physical interaction and self-assembly of hyaluronic acid-Pullulan-grafted-pluronic F127 injectable hydrogel were confirmed using nuclear magnetic resonance (1H NMR) and Fourier transformed infrared spectroscopy (FT-IR), and cytocompatibility was confirmed by fibroblast viability assay. The CUR-laden hyaluronic acid-Pullulan-g-F127 injectable hydrogel promptly undergoes a sol-gel transition and has proved to potentiate wound healing in a streptozotocin-induced diabetic rat model by promoting 93% of wound closure compared to other groups having 35%, 38%, and 62%. The comparative in vivo study and histological examination was conducted which demonstrated an expeditious recovery rate by significantly reducing the wound healing days i.e. 35 days in a control group, 33 days in the CUR suspension group, 21 days in unloaded injectable, and 13 days was observed in CUR loaded hydrogel group. Furthermore, we suggest that the injectable hydrogel laden with CUR showed a prompt wound healing potential by increasing the cell proliferation and serves as a drug delivery platform for sustained and targeted delivery of hydrophobic moieties.
    Matched MeSH terms: Disease Models, Animal
  19. Ortiz RH, Leon DA, Estevez HO, Martin A, Herrera JL, Romo LF, et al.
    Clin Exp Immunol, 2009 Aug;157(2):271-81.
    PMID: 19604267 DOI: 10.1111/j.1365-2249.2009.03941.x
    Buruli ulcer (BU) is the third most common mycobacterial disease in immunocompetent hosts. BU is caused by Mycobacterium ulcerans, which produces skin ulcers and necrosis at the site of infection. The principal virulence factor of M. ulcerans is a polyketide-derived macrolide named mycolactone, which has cytotoxic and immunosuppressive activities. We determined the severity of inflammation, histopathology and bacillary loads in the subcutaneous footpad tissue of BALB/c mice infected with 11 different M. ulcerans isolates from diverse geographical areas. Strains from Africa (Benin, Ghana, Ivory Coast) induced the highest inflammation, necrosis and bacillary loads, whereas the strains collected from Australia, Asia (Japan, Malaysia, New Guinea), Europe (France) and America (Mexico) induced mild inflammation. Subsequently, animals were infected with the strain that exhibited the highest (Benin) or lowest (Mexico) level of virulence in order to analyse the local immune response generated. The Mexican strain, which does not produce mycolactone, induced a predominantly T helper type 1 (Th1) cytokine profile with constant high expression of the anti-microbial peptides beta defensins 3 and 4, in co-existence with low expression of the anti-inflammatory cytokines interleukin (IL)-10, IL-4 and transforming growth factor (TGF)-beta. The highly virulent strain from Benin which produces mycolactone A/B induced the opposite pattern. Thus, different local immune responses were found depending on the infecting M. ulcerans strain.
    Matched MeSH terms: Models, Animal
  20. Guo W, Wu X, Li Y, Gao J, Wang F, Jin Y, et al.
    J Drug Target, 2020 01;28(1):41-45.
    PMID: 30943812 DOI: 10.1080/1061186X.2019.1601199
    Purpose: The present study evaluated biochemical as well as biophysical mechanisms behind the synergistic effects of curcumin and resveratrol during prostate carcinogenesis.Methods: The rats were segregated into five groups that included normal control, 3,2'-dimethyl-4-aminobiphenyl (DMAB)treated, DMAB + curcumin treated, DMAB + resveratrol-treated and DMAB + curcumin + resveratrol-treated.Results: The DMAB treatment resulted in a significant increase in the levels of lipid peroxidation (LPO) in DMAB treated rats. Also, significant changes were recorded in the enzyme activities of both drug metabolising enzyme and antioxidant enzymes after DMAB treatment. Further, radiorespirometric studies showed a significant increase in the 14C-glucose turnover as well as 14C-glucose uptake in the prostate slices of DMAB treated rats. Moreover, a significant rise in cell proliferation was confirmed indirectly by enhanced uptake of 3H-thymidine in the prostate slices of DMAB treated rats. Interestingly, combined treatment of curcumin and resveratrol to DMAB treated animals resulted in a significant decrease in lipid peroxidation, 14C glucose uptakes/turnover and 3H-thymidine uptake in the DMAB treated rats. Besides this, curcumin and resveratrol in combination significantly modulated biochemical indices including drug-metabolising enzymes; antioxidant enzymes in DMBA treated rats.Conclusion: The study, therefore, concludes that the combination of curcumin and resveratrol holds strong modulatory potential against prostate carcinogenesis.
    Matched MeSH terms: Disease Models, Animal
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