Displaying publications 221 - 240 of 831 in total

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  1. Chin KY, Pang KL
    Front Pediatr, 2020;8:563.
    PMID: 33072660 DOI: 10.3389/fped.2020.00563
    Isoflavones are dietary phytoestrogens commonly found in soy-based products. The widespread presence of isoflavones in soy infant formula and breast milk may have long-lasting effects on the development of sex hormone-sensitive organs like the skeleton. Animal early-life programming models are suitable for testing the skeletal effects of pre- and neonatal exposure of soy isoflavones. This review aims to collate the impacts of early-life exposure of soy isoflavones as evidenced in animal models. The isoflavones previously studied include daidzein, genistein, or a combination of both. They were administered to rodent pups during the first few days postnatal, but prolonged exposure had also been studied. The skeletal effects were observed when the animals reached sexual maturity or after castration to induce bone loss. In general, neonatal exposure to soy isoflavones exerted beneficial effects on the skeletal system of female rodents, but the effects on male rodents seem to depend on the time of exposure and require further examinations. It might also protect the animals against bone loss due to ovariectomy at adulthood but not upon orchidectomy. The potential benefits of isoflavones on the skeletal system should be interpreted together with its non-skeletal effects in the assessment of its safety and impacts.
    Matched MeSH terms: Models, Animal
  2. Lum PT, Sekar M, Gan SH, Pandy V, Bonam SR
    Saudi J Biol Sci, 2021 Jan;28(1):917-927.
    PMID: 33424383 DOI: 10.1016/j.sjbs.2020.11.037
    Memory impairment (MI) is one of the predominant criteria generally used to identify schizophrenia, dementia and amnesia that are associated with neurodegenerative disorders by evaluating patient's cognitive symptoms. To date, there is no available treatment that can completely mitigate MI. Currently, there is a trend in recent investigations towards symptomatic therapy approaches using a variety of natural compounds. Mangiferin is one of them that have been investigated extensively. Mangiferin is a naturally occurring potent glucoxilxanthone and is mainly isolated from the Mangifera indica (Mango) plant. This review is aimed at providing a comprehensive overview on the efficacy of mangiferin on MI, based on in-vivo animal studies. After screening through articles identified from Scopus and PubMed based on the inclusion and exclusion criteria, a total of 11 articles between 2009 and 2019 were included. The minimum and maximum dose of mangiferin were 10 and 200 mg/kg respectively and administered over the period of 12-154 days. The results of 11 articles showed that mangiferin effectively improved spatial recognition, episodic aversive events, short- and long-term memories primarily occurring via its antioxidant and anti-inflammatory effects. The outcomes of the review revealed that mangiferin improves memory and cognitive impairment in different animal models, indicating that it has potential preventive and therapeutic roles in MI.
    Matched MeSH terms: Models, Animal
  3. Tan CW, Ng MH, Ohnmar H, Lokanathan Y, Nur-Hidayah H, Roohi SA, et al.
    Indian J Orthop, 2013 Nov;47(6):547-52.
    PMID: 24379458 DOI: 10.4103/0019-5413.121572
    BACKGROUND AND AIM: Synthetic nerve conduits have been sought for repair of nerve defects as the autologous nerve grafts causes donor site morbidity and possess other drawbacks. Many strategies have been investigated to improve nerve regeneration through synthetic nerve guided conduits. Olfactory ensheathing cells (OECs) that share both Schwann cell and astrocytic characteristics have been shown to promote axonal regeneration after transplantation. The present study was driven by the hypothesis that tissue-engineered poly(lactic-co-glycolic acid) (PLGA) seeded with OECs would improve peripheral nerve regeneration in a long sciatic nerve defect.

    MATERIALS AND METHODS: Sciatic nerve gap of 15 mm was created in six adult female Sprague-Dawley rats and implanted with PLGA seeded with OECs. The nerve regeneration was assessed electrophysiologically at 2, 4 and 6 weeks following implantation. Histopathological examination, scanning electron microscopic (SEM) examination and immunohistochemical analysis were performed at the end of the study.

    RESULTS: Nerve conduction studies revealed a significant improvement of nerve conduction velocities whereby the mean nerve conduction velocity increases from 4.2 ΁ 0.4 m/s at week 2 to 27.3 ΁ 5.7 m/s at week 6 post-implantation (P < 0.0001). Histological analysis revealed presence of spindle-shaped cells. Immunohistochemical analysis further demonstrated the expression of S100 protein in both cell nucleus and the cytoplasm in these cells, hence confirming their Schwann-cell-like property. Under SEM, these cells were found to be actively secreting extracellular matrix.

    CONCLUSION: Tissue-engineered PLGA conduit seeded with OECs provided a permissive environment to facilitate nerve regeneration in a small animal model.

    Matched MeSH terms: Models, Animal
  4. Ahmad Firdaus Khalid, Yoke KY, Jun JT
    Sains Malaysiana, 2018;47:2705-2711.
    The use of honey as a therapeutic agent dates back at 8000 years and has markedly increased interest into its potential
    health benefits. The by-products of the flower nectar have a complex chemical composition which promotes benefits in
    underlying mechanism of human diseases. Malaysian Tualang Honey (MTH) is a multifloral jungle honey produced by
    the rock bee (Apis dorsata). This review consolidates the results of carious studies involving biochemical assays of tissue
    culture and animal trials of anti-cancer properties of MTH. Often studied in the context of breast cancer cell lines, MTH
    has promising data for possible mechanisms in anti-cancer activity. These include apoptosis via depolarization of the
    mitochondrial membrane, caspase-dependent apoptosis, reduction of angiogenesis and the promotion of cell cycle arrest
    without posing cytotoxic effect on normal cell lines. Despite positive outcomes in tissue cultures, the oral administration
    of MTH in breast cancer animal models showed slower tumour progression, reduction in tumour size and better grading
    of histological features. The alleviation of breast carcinogenesis via modulation of hematologic, estrogenic and apoptotic
    activities promotes MTH as a promising anticancer agent. With confidence in a conclusion that MTH is a useful treatment
    for cancer, further experimental and clinical studies should be conducted.
    Matched MeSH terms: Models, Animal
  5. Hor YY, Lew LC, Jaafar MH, Lau AS, Ong JS, Kato T, et al.
    Pharmacol Res, 2019 08;146:104312.
    PMID: 31207344 DOI: 10.1016/j.phrs.2019.104312
    Aging is closely associated with altered gut function and composition, in which elderly were reported with reduced gut microbiota diversity and increased incidence of age-related diseases. Probiotics have been shown to exert beneficial health-promoting effects through modulation of intestinal microflora biodiversity, thus the effects of probiotics administration on D-galactose (D-gal) senescence-induced rat were evaluated based on the changes in gut microbiota and metabolomic profiles. Upon senescence induction, the ratio of Firmicutes/ Bacteroidetes was significantly lowered, while treatment with Lactobacillus helveticus OFS 1515 and L. fermentum DR9 increased the ratio at the phylum level (P 
    Matched MeSH terms: Models, Animal
  6. Hall DA, Plack CJ
    Hear Res, 2019 10;382:107778.
    PMID: 31470340 DOI: 10.1016/j.heares.2019.107778
    Matched MeSH terms: Models, Animal
  7. Teoh JY, Cho CL, Wei Y, Isotani S, Tiong HY, Ong TA, et al.
    World J Urol, 2019 Sep;37(9):1879-1887.
    PMID: 30560297 DOI: 10.1007/s00345-018-2602-2
    PURPOSE: The Asian Urological Surgery Training & Education Group (AUSTEG) has been established to provide training and education to young urologists in Asia. We developed and validated a porcine bladder training model for transurethral resection of bladder tumour (TURBT).

    METHODS: Urology residents and specialists were invited to test the training model. They were asked to complete a pre-task questionnaire, to perform piecemeal and en bloc resection of 'bladder tumours' within the training model, and to complete a post-task questionnaire afterwards. Their performances were assessed by faculty members of the AUSTEG. For the face validity, a pre-task questionnaire consisting of six statements on TURBT and the training model were set. For the content validity, a post-task questionnaire consisting of 14 items on the details of the training model were set. For the construct validity, a Global Rating Scale was used to assess the participants' performances. The participants were stratified into two groups (junior surgeons and senior surgeons groups) according to their duration of urology training.

    RESULTS: For the pre-task questionnaire, a mean score of ≥ 4.0 out of 5.0 was achieved in 5 out of 6 statements. For the post-task questionnaire, a mean score of ≥ 4.5 out of 5.0 was achieved in every item. For the Global Rating Scale, the senior surgeons group had higher scores than the junior surgeons group in 8 out of 11 items as well as the total score.

    CONCLUSION: A porcine TURBT training model has been developed, and its face, content and construct validity has been established.

    Matched MeSH terms: Disease Models, Animal
  8. Tan HY, Ng KY, Koh RY, Chye SM
    Cell Mol Neurobiol, 2020 Jan;40(1):25-51.
    PMID: 31435851 DOI: 10.1007/s10571-019-00724-1
    The progressive loss of structure and functions of neurons, including neuronal death, is one of the main factors leading to poor quality of life. Promotion of functional recovery of neuron after injury is a great challenge in neuroregenerative studies. Melatonin, a hormone is secreted by pineal gland and has antioxidative, anti-inflammatory, and anti-apoptotic properties. Besides that, melatonin has high cell permeability and is able to cross the blood-brain barrier. Apart from that, there are no reported side effects associated with long-term usage of melatonin at both physiological and pharmacological doses. Thus, in this review article, we summarize the pharmacological effects of melatonin as neuroprotectant in central nervous system injury, ischemic-reperfusion injury, optic nerve injury, peripheral nerve injury, neurotmesis, axonotmesis, scar formation, cell degeneration, and apoptosis in rodent models.
    Matched MeSH terms: Disease Models, Animal
  9. Abdul Kadir A, Abdul Kadir A, Abd Hamid R, Mat Jais AM, Omar J, Sadagatullah AN, et al.
    Biomed Res Int, 2019;2019:6979585.
    PMID: 31355276 DOI: 10.1155/2019/6979585
    Objectives: The objective of the study is to evaluate the chondroprotective activity of Channa striatus (Channa) and glucosamine sulphate (glucosamine) on histomorphometric examinations, serum biomarker, and inflammatory mediators in experimental osteoarthritis (OA) rabbit model.

    Design: Anterior cruciate ligament transection (ACLT) was performed to induce OA in thirty-three male New Zealand white rabbits and were randomly divided into three groups: Channa, glucosamine, and control group. The control group received drinking water and the Channa and glucosamine groups were orally administered with 51.4 mg/kg of Channa extract and 77.5 mg/kg of glucosamine sulphate in drinking water, respectively, for eight weeks and then sacrificed. The articular cartilage was evaluated macroscopically and histologically using semiquantitative and quantitative methods. Serum cartilage oligomeric matric protein (COMP), cyclooxygenase 2 (COX-2) enzyme, and prostaglandin E2 (PGE2) were also determined.

    Results: Macroscopic analysis revealed that Channa group have a significantly lower severity grade of total macroscopic score compared to the control (p < 0.001) and glucosamine (p < 0.05) groups. Semiquantitative histology scoring showed that both Channa and glucosamine groups had lower severity grading of total histology score compared to the control group (p < 0.001). In comparison with the control, Channa group had lower histopathological changes in three compartments of the joint compared to glucosamine group which had lower histological scoring in two compartments only. The cartilage thickness, area, and roughness of both Channa (p < 0.05) and glucosamine (p < 0.05) groups were superior compared to the control group. However, the Channa group demonstrated significantly less cartilage roughness compared to the glucosamine group (p < 0.05). Serum COMP levels were lower in both Channa (p < 0.05) and glucosamine (p < 0.05) groups compared to the control group.

    Conclusion: Both oral administration of Channa extract and glucosamine exhibited chondroprotective action on an ACLT OA-induced rabbit model. However, Channa was superior to glucosamine in maintaining the structure of the cartilage.

    Matched MeSH terms: Disease Models, Animal
  10. Mawazi SM, Al-Mahmood SMA, Chatterjee B, Hadi HA, Doolaanea AA
    Pharmaceutics, 2019 Sep 20;11(10).
    PMID: 31547112 DOI: 10.3390/pharmaceutics11100488
    This study aimed to develop a carbamazepine (CBZ) sustained release formulation suitable for pediatric use with a lower risk of precipitation. The CBZ was first prepared as sustained release microparticles, and then the microparticles were embedded in alginate beads, and finally, the beads were suspended in a gel vehicle. The microparticles were prepared by a solvent evaporation method utilizing ethyl cellulose as a sustained release polymer and were evaluated for particle size, encapsulation efficiency, and release profile. The beads were fabricated by the dropwise addition of sodium alginate in calcium chloride solution and characterized for size, shape, and release properties. The gel was prepared using iota carrageenan as the gelling agent and evaluated for appearance, syneresis, drug content uniformity, rheology, release profile, and stability. The microparticles exhibited a particle size of 135.01 ± 0.61 µm with a monodisperse distribution and an encapsulation efficiency of 83.89 ± 3.98%. The beads were monodispersed with an average size of 1.4 ± 0.05 mm and a sphericity factor of less than 0.05. The gel was prepared using a 1:1 ratio (gel vehicle to beads) and exhibited no syneresis, good homogeneity, and good shear-thinning properties. The release profile from the beads and from the gel was not significantly affected, maintaining similarity to the tablet form. The gel properties were maintained for one month real time stability, but the accelerated stability showed reduced viscosity and pH with time. In conclusion, CBZ in a gel sustained release dosage form combines the advantages of the suspension form in terms of dosing flexibility, and the advantages of the tablet form in regards to the sustained release profile. This dosage form should be further investigated in vivo in animal models before being considered in clinical trials.
    Matched MeSH terms: Models, Animal
  11. Samsudin A, Eames I, Brocchini S, Khaw PT
    J Glaucoma, 2016 Jan;25(1):e39-45.
    PMID: 25719236 DOI: 10.1097/IJG.0000000000000243
    PURPOSE: ExPress devices are available as P50 and P200 models, the numbers related to their luminal diameters in μm. We compared their Poiseuille's Law-based theoretical resistance values with experimental values and correlated these with their luminal dimensions derived from electron microscopy.

    METHODS: Scanning electron microscopy was performed on P50 and P200 devices. Bench-top flow studies were performed to find the resistances of the devices. Devices were also incorporated into a perfused, ex vivo porcine sclera model to test and compare their control of pressure, with and without overlying scleral flaps, and with trabeculectomies.

    RESULTS: The luminal dimensions of the P200 device were 206.4±3.3 and 204.5±0.9 μm at the subconjunctival space and anterior chamber ends, respectively. Those of the P50 device were 205.0±5.8 and 206.9±3.7 μm, respectively. There were no significant differences between the P200 and P50 devices (all P>0.05). The resistances of the P200 and P50 devices were 0.010±0.001 and 0.054±0.002 mm Hg/μL/min, respectively (P<0.05). Equilibrium pressures with overlying scleral flaps were 17.81±3.30 mm Hg for the P50, 17.31±4.24 mm Hg for the P200, and 16.28±6.67 mm Hg for trabeculectomies (P=0.850).

    CONCLUSIONS: The luminal diameters of both devices are externally similar. The effective luminal diameter of the P50 is much larger than 50 μm. Both devices have low resistance values, making them unlikely to prevent hypotony on their own. They lead to similar equilibrium pressures as the trabeculectomy procedure when inserted under the scleral flap.

    Matched MeSH terms: Disease Models, Animal
  12. Moorthy M, Sundralingam U, Palanisamy UD
    Foods, 2021 Feb 02;10(2).
    PMID: 33540692 DOI: 10.3390/foods10020299
    Obesity is a disease growing at an alarming rate and numerous preclinical studies have proven the role of polyphenols in managing this disease. This systematic review explores the prebiotic effect of polyphenols in the management of obesity among animals fed on a high-fat diet. A literature search was carried out in PubMed, Scopus, CINAHL, Web of Science, and Embase databases following the PRISMA guidelines. Forty-four studies reported a significant reduction in obesity-related parameters. Most notably, 83% of the studies showed a decrease in either body weight/visceral adiposity/plasma triacylglyceride. Furthermore, 42 studies reported a significant improvement in gut microbiota (GM), significantly affecting the genera Akkermansia, Bacteroides, Blautia, Roseburia, Bifidobacteria, Lactobacillus, Alistipes, and Desulfovibrio. Polyphenols' anti-obesity, anti-hyperglycaemic, and anti-inflammatory properties were associated with their ability to modulate GM. This review supports the notion of polyphenols as effective prebiotics in ameliorating HFD-induced metabolic derangements in animal models.
    Matched MeSH terms: Models, Animal
  13. Gopalsamy B, Chia JSM, Farouk AAO, Sulaiman MR, Perimal EK
    Molecules, 2020 Aug 26;25(17).
    PMID: 32858809 DOI: 10.3390/molecules25173880
    Zerumbone, a monocyclic sesquiterpene from the wild ginger plant Zingiber zerumbet (L.) Smith, attenuates allodynia and hyperalgesia. Currently, its mechanisms of action in neuropathic pain conditions remain unclear. This study examines the involvement of potassium channels and opioid receptors in zerumbone-induced analgesia in a chronic constriction injury (CCI) neuropathic pain mice model. Male Institute of Cancer Research (ICR) mice were subjected to CCI and behavioral responses were tested on day 14. Responses toward mechanical allodynia and thermal hyperalgesia were tested with von Frey's filament and Hargreaves' tests, respectively. Symptoms of neuropathic pain were significantly alleviated following treatment with zerumbone (10 mg/kg; intraperitoneal, i.p.). However, when the voltage-dependent K+ channel blocker tetraethylammonium (TEA, 4 mg/kg; i.p.), ATP-sensitive K+ channel blocker, glibenclamide (GLIB, 10 mg/kg; i.p.); small-conductance Ca2+-activated K+ channel inhibitor apamin (APA, 0.04 mg/kg; i.p.), or large-conductance Ca2+-activated K+ channel inhibitor charybdotoxin (CHAR, 0.02 mg/kg; i.p.) was administered prior to zerumbone (10 mg/kg; i.p.), the antiallodynic and antihyperalgesic effects of zerumbone were significantly reversed. Additionally, non-specific opioid receptors antagonist, naloxone (NAL, 10 mg/kg; i.p.), selective µ-, δ- and κ-opioid receptor antagonists; β-funaltrexamine (β-FN, 40 mg/kg; i.p.), naltrindole (20 mg/kg; s.c.), nor-binaltorphamine (10 mg/kg; s.c.) respectively attenuated the antiallodynic and antihyperalgesic effects of zerumbone. This outcome clearly demonstrates the participation of potassium channels and opioid receptors in the antineuropathic properties of zerumbone. As various clinically used neuropathic pain drugs also share this similar mechanism, this compound is, therefore, a highly potential substitute to these therapeutic options.
    Matched MeSH terms: Disease Models, Animal
  14. Byrne L, Obonyo NG, Diab SD, Dunster KR, Passmore MR, Boon AC, et al.
    Am J Respir Crit Care Med, 2018 10 15;198(8):1043-1054.
    PMID: 29882682 DOI: 10.1164/rccm.201801-0064OC
    RATIONALE: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question.

    OBJECTIVES: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia.

    METHODS: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.9% saline or commenced hemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney, and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, atrial natriuretic peptide, brain natriuretic peptide, and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation.

    MEASUREMENTS AND MAIN RESULTS: After resuscitation, animals that received fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 hours (68.9 mg vs. 39.6 mg; P = 0.04). Serum cytokines were similar between groups. Atrial natriuretic peptide increased significantly after fluid resuscitation compared with that observed in animals managed without fluid resuscitation (335 ng/ml [256-382] vs. 233 ng/ml [144-292]; P = 0.04). Cross-sectional time-series analysis showed that the rate of increase of the glycocalyx glycosaminoglycan hyaluronan was greater in the fluid-resuscitated group over the course of the study (P = 0.02).

    CONCLUSIONS: Fluid resuscitation resulted in a paradoxical increase in vasopressor requirement. Additionally, it did not result in improvements in any of the measured microcirculatory- or organ-specific markers measured. The increase in vasopressor requirement may have been due to endothelial/glycocalyx damage secondary to atrial natriuretic peptide-mediated glycocalyx shedding.

    Matched MeSH terms: Disease Models, Animal
  15. Qi Y, Montague P, Loney C, Campbell C, Shafie INF, Anderson TJ, et al.
    Eur J Neurosci, 2019 12;50(12):3896-3905.
    PMID: 31336405 DOI: 10.1111/ejn.14526
    Canine degenerative myelopathy (DM) is a progressive neurological disorder that may be considered to be a large animal model for specific forms of the fatal human disease, familial amyotrophic lateral sclerosis (fALS). DM is associated with a c118G>A mutation of the superoxide dismutase 1 (Sod1) gene, and a significant proportion of cases are inherited in an autosomal recessive manner in contrast to the largely, but not exclusively, dominant mode of inheritance in fALS. The consensus view is that these Sod1/SOD1 mutations result in a toxic gain of function but the mechanisms remain unclear. Here we used an in vitro neuroblastoma cell line transfection system to monitor wild-type and mutant forms of SOD1 fusion proteins containing either a Cherry or an enhanced green fluorescent protein (EGFP) tag. These fusion proteins retained SOD1 enzymatic activity on a native gel assay system. We demonstrate that SOD1 aggregate density is significantly higher in DM transfectants compared to wild-type. In addition, we show by co-immunoprecipitation and confocal microscopy, evidence for a potential interaction between wild-type and mutant forms of SOD1 in co-transfected cells. While in vitro studies have shown SOD1 heterodimer formation in fALS models, this is the first report for DM SOD1. Therefore, despite for the majority of cases there is a difference in the mode of inheritance between fALS and DM, a similar interaction between wild-type and mutant SOD1 forms can occur. Clarifying the role of SOD1 in DM may also be of benefit to understanding the role of SOD1 in fALS.
    Matched MeSH terms: Disease Models, Animal
  16. Chia WK, Cheah FC, Abdul Aziz NH, Kampan NC, Shuib S, Khong TY, et al.
    Front Pediatr, 2021;9:615508.
    PMID: 33791258 DOI: 10.3389/fped.2021.615508
    Bronchopulmonary dysplasia (BPD) is a devastating lung disorder of preterm infants as a result of an aberrant reparative response following exposures to various antenatal and postnatal insults. Despite sophisticated medical treatment in this modern era, the incidence of BPD remains unabated. The current strategies to prevent and treat BPD have met with limited success. The emergence of stem cell therapy may be a potential breakthrough in mitigating this complex chronic lung disorder. Over the last two decades, the human placenta and umbilical cord have gained increasing attention as a highly potential source of stem cells. Placenta-derived stem cells (PDSCs) and umbilical cord-derived stem cells (UCDSCs) display several advantages such as immune tolerance and are generally devoid of ethical constraints, in addition to their stemness qualities. They possess the characteristics of both embryonic and mesenchymal stromal/stem cells. Recently, there are many preclinical studies investigating the use of these cells as therapeutic agents in neonatal disease models for clinical applications. In this review, we describe the preclinical and clinical studies using PDSCs and UCDSCs as treatment in animal models of BPD. The source of these stem cells, routes of administration, and effects on immunomodulation, inflammation and regeneration in the injured lung are also discussed. Lastly, a brief description summarized the completed and ongoing clinical trials using PDSCs and UCDSCs as therapeutic agents in preventing or treating BPD. Due to the complexity of BPD, the development of a safe and efficient therapeutic agent remains a major challenge to both clinicians and researchers.
    Matched MeSH terms: Models, Animal
  17. Loke YL, Chew MT, Ngeow YF, Lim WWD, Peh SC
    PMID: 33364203 DOI: 10.3389/fcimb.2020.603086
    Colorectal cancer (CRC) incidence increases yearly, and is three to four times higher in developed countries compared to developing countries. The well-known risk factors have been attributed to low physical activity, overweight, obesity, dietary consumption including excessive consumption of red processed meats, alcohol, and low dietary fiber content. There is growing evidence of the interplay between diet and gut microbiota in CRC carcinogenesis. Although there appears to be a direct causal role for gut microbes in the development of CRC in some animal models, the link between diet, gut microbes, and colonic carcinogenesis has been established largely as an association rather than as a cause-and-effect relationship. This is especially true for human studies. As essential dietary factors influence CRC risk, the role of proteins, carbohydrates, fat, and their end products are considered as part of the interplay between diet and gut microbiota. The underlying molecular mechanisms of colon carcinogenesis mediated by gut microbiota are also discussed. Human biological responses such as inflammation, oxidative stress, deoxyribonucleic acid (DNA) damage can all influence dysbiosis and consequently CRC carcinogenesis. Dysbiosis could add to CRC risk by shifting the effect of dietary components toward promoting a colonic neoplasm together with interacting with gut microbiota. It follows that dietary intervention and gut microbiota modulation may play a vital role in reducing CRC risk.
    Matched MeSH terms: Models, Animal
  18. Hooi YT, Ong KC, Tan SH, Perera D, Wong KT
    J Comp Pathol, 2020 Apr;176:19-32.
    PMID: 32359633 DOI: 10.1016/j.jcpa.2020.02.001
    Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are the major causes of hand, foot and mouth disease in young children. Although less so with CV-A16, both viruses are associated with serious neurological syndromes, but the differences between their central nervous system infections remain unclear. We conducted a comparative infection study using clinically-isolated CV-A16 and EV-A71 strains in a 1-day-old mouse model to better understand the neuropathology and neurovirulence of the viruses. New serotype-specific probes for in situ hybridization were developed and validated to detect CV-A16 and EV-A71 RNA in infected tissues. Demonstration of CV-A16 virus antigens/RNA, mainly in the brainstem and spinal cord neurons, confirmed neurovirulence, but showed lower densities than in EV-A71 infected animals. A higher lethal dose50 for CV-A16 suggested that CV-A16 is less neurovirulent. Focal virus antigens/RNA in the anterior horn white matter and adjacent efferent motor nerves suggested that neuroinvasion is possibly via retrograde axonal transport in peripheral motor nerves.
    Matched MeSH terms: Disease Models, Animal
  19. Cheah FC, Lai CH, Tan GC, Swaminathan A, Wong KK, Wong YP, et al.
    Front Pediatr, 2020;8:593802.
    PMID: 33553066 DOI: 10.3389/fped.2020.593802
    Background:Gardnerella vaginalis (GV) is most frequently associated with bacterial vaginosis and is the second most common etiology causing intrauterine infection after Ureaplasma urealyticum. Intrauterine GV infection adversely affects pregnancy outcomes, resulting in preterm birth, fetal growth restriction, and neonatal pneumonia. The knowledge of how GV exerts its effects is limited. We developed an in vivo animal model to study its effects on fetal development. Materials and Methods: A survival mini-laparotomy was conducted on New Zealand rabbits on gestational day 21 (28 weeks of human pregnancy). In each dam, fetuses in the right uterine horn received intra-amniotic 0.5 × 102 colony-forming units of GV injections each, while their littermate controls in the left horn received sterile saline injections. A second laparotomy was performed seven days later. Assessment of the fetal pups, histopathology of the placenta and histomorphometric examination of the fetal lung tissues was done. Results: Three dams with a combined total of 12 fetuses were exposed to intra-amniotic GV, and 9 fetuses were unexposed. The weights of fetuses, placenta, and fetal lung were significantly lower in the GV group than the saline-inoculated control group [mean gross weight, GV (19.8 ± 3.8 g) vs. control (27.9 ± 1.7 g), p < 0.001; mean placenta weight, GV (5.5 ± 1.0 g) vs. control (6.5 ± 0.7 g), p = 0.027; mean fetal lung weight, GV (0.59 ± 0.11 g) vs. control (0.91 ± 0.08 g), p = 0.002. There was a two-fold increase in the multinucleated syncytiotrophoblasts in the placenta of the GV group than their littermate controls (82.9 ± 14.9 vs. 41.6 ± 13.4, p < 0.001). The mean alveolar septae of GV fetuses was significantly thicker than the control (14.8 ± 2.8 μm vs. 12.4 ± 3.8 μm, p = 0.007). Correspondingly, the proliferative index in the interalveolar septum was 1.8-fold higher in the GV group than controls (24.9 ± 6.6% vs. 14.2 ± 2.9%, p = 0.011). The number of alveoli and alveolar surface area did not vary between groups. Discussion: Low-dose intra-amniotic GV injection induces fetal growth restriction, increased placental multinucleated syncytiotrophoblasts and fetal lung re-modeling characterized by alveolar septal hypertrophy with cellular proliferative changes. Conclusion: This intra-amniotic model could be utilized in future studies to elucidate the acute and chronic effects of GV intrauterine infections.
    Matched MeSH terms: Models, Animal
  20. Tambuwala MM, Kesharwani P, Shukla R, Thompson PD, McCarron PA
    Pathol Res Pract, 2018 Nov;214(11):1909-1911.
    PMID: 30170869 DOI: 10.1016/j.prp.2018.08.020
    Fibrosis is known to be the hallmarks of chronic inflammation of the bowel. Epithelial damage due to inflammation compromises the barrier function of the gastrointestinal tract. This barrier dysfunction leads to further spread of inflammation resulting in a chronic state of inflammation. This chronic inflammation leads to development of fibrosis, which has very limited therapeutic options and usually requires surgical removal of the affected tissue. Our previous work has shown that Caffeic acid phenethyl ester (CAPE) is a naturally occurring anti-inflammatory agent, found in propolis, has been found to be protective in experimental colitis via enhancement of epithelial barrier function. However, the impact of CAPE on resolution of fibrosis in the long-term is unknown. The aim of this follow up study was to investigate the effect of CAPE on colon fibrosis in a chronic model of Dextran sulphate sodium induced colitis in mice. Dextran sulphate sodium (DSS) 2.5% w/v was administered in drinking water to induce colitis in C57/BL6 mice for 5 days on the 6th day DSS was stopped and test group mice were treated with intraperitoneal administration of CAPE (30 mg kg-1 day-1) for a further 7 days. Disease activity index (DAI) score, colon length and tissue histology and level of tissue fibrosis was observed. CAPE-treated mice had significantly lower levels of DAI, tissue inflammation scores and fibrosis as compared with control group. Our results show that CAPE is effective in resolving colon fibrosis in chronic inflammation. Thus, we can conclude CAPE could be a potential therapeutic agent for further clinical investigations for treatment of fibrosis in inflammatory bowel diseases in humans.
    Matched MeSH terms: Disease Models, Animal
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