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Fulltext Subclinical infection without encephalitis in mice following intranasal exposure to Nipah virus-Malaysia and Nipah virus-Bangladesh

Dups J, Middleton D, Long F, Arkinstall R, Marsh GA, Wang LF

Virol J, 2014;11:102.
PMID: 24890603 DOI: 10.1186/1743-422X-11-102

Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disease recrudescence. In this study we investigated the possibility of developing a similar model of Nipah virus encephalitis.

Matched MeSH terms: Mice, Inbred C57BL
Short term and dosage influences of palm based medium- and long-chain triacylglycerols on body fat and blood parameters in C57BL/6J mice

Lee YY, Tang TK, Ab Karim NA, Alitheen NB, Lai OM

Food Funct, 2014 Jan;5(1):57-64.
PMID: 24247642 DOI: 10.1039/c3fo60358j

Structured lipid medium- and long-chain triacylglycerols (MLCT) are claimed to be able to manage obesity. The present study investigated the body fat influence of enzymatically interesterifed palm-based medium- and long-chain triacylglycerols (P-MLCT) on diet-induced obesity (DIO) C57BL/6J mice compared with commercial MLCT oil (C-MLCT) and a control, which was the non enzymatically modified palm kernel and palm oil blend (PKO-PO blend). It also investigated the low fat and high fat effects of P-MLCT. DIO C57BL/6J mice were fed ad libitum with low fat (7%) and high fat (30%) experimental diets for 8 weeks before being sacrificed to obtain blood serum for analysis. From the results, there is a trend that P-MLCT fed mice were found to have the lowest body weight, body weight gain, total fat pad accumulation (perirenal, retroperitoneal, epididymal and mesenteric), total triglyceride levels and efficiency in controlling blood glucose level, compared with C-MLCT and the PKO-PO blend in both low fat and high fat diets. Nevertheless, the PKO-PO blend and P-MLCT caused significantly (P < 0.05) higher total cholesterol levels compared to C-MLCT. P-MLCT present in low fat and high fat dosage were shown to be able to suppress body fat accumulation. This effect is more prominent with the low fat dosage.

Matched MeSH terms: Mice, Inbred C57BL
Use of prednisolone to aid propagation of Toxoplasma gondii in mice

Puvanesuaran VR, Nowroji K, Sreenivasan S, Noordin R, Balakrishnan V

Eur Rev Med Pharmacol Sci, 2012 Aug;16(8):1028-32.
PMID: 22913152

AIM: To determine the usefulness of prednisolone in increasing the number of Toxoplasma (T.) gondii tachyzoites and bradyzoites in mice.
MATERIALS AND METHODS: The mice were water-fasted prior to being immunosuppressed with oral inoculation of prednisolone. Tachyzoites of 7T gondii RH strain were inoculated into mice and the number of the parasites in the intraperitoneal fluids was then determined at 96 hs post-infection. In addition, tachyzoites of T. gondii ME49 strains were orally introduced into mice and the number of brain cysts formed was observed by microscopic observation at 45 days post-infection.
RESULTS: T. gondii propagation was found to be significantly improved by introduction of the prednisolone (p = 0.0004); and the number of parasite showed positive correlation with the increment in dosage of prednisolone (r = 0.9051).
CONCLUSIONS: The use of prednisolone greatly improved the number of parasite formed in mice: both tachyzoite and cyst forms.

Matched MeSH terms: Mice, Inbred C57BL
Isolation of viable Toxoplasma gondii cysts from brain samples for oral infection

Puvanesuaran VR, Ibrahim N, Noordin R, Balakrishnan V

Eur Rev Med Pharmacol Sci, 2012 Sep;16(9):1179-83.
PMID: 23047500

AIM: A method was developed to separate contaminant-free viable Toxoplasma gondii cysts from brain samples of infected mice for molecular biology studies and reinfection.
MATERIALS AND METHODS: The mice brains were homogenized and washed with phosphate buffered saline (PBS) Tween 80 prior to fractionation using 19-22% dextran solution. Finally, the supernatant was purified by two-step membrane filtration (100-160 microm and < 10 microm) to obtain pure T. gondii cyst. The isolates were analyzed through microscopic observation, qPCR and by reinfection of new batch of mice.
RESULTS: T. gondii cysts were best isolated with 21% dextran solution and two step filtration.
CONCLUSIONS: The method was observed not to disrupt the integrity of the cysts containing bradyzoites. In addition, the isolated cysts in the filtrate were found to be contaminant-free, viable and able to infect healthy mice when introduced orally; which, mimics the natural infectivity pathway.

Matched MeSH terms: Mice, Inbred C57BL
Fulltext Redundant Innate and Adaptive Sources of IL17 Production Drive Colon Tumorigenesis

Housseau F, Wu S, Wick EC, Fan H, Wu X, Llosa NJ, et al.

Cancer Res, 2016 04 15;76(8):2115-24.
PMID: 26880802 DOI: 10.1158/0008-5472.CAN-15-0749

IL17-producing Th17 cells, generated through a STAT3-dependent mechanism, have been shown to promote carcinogenesis in many systems, including microbe-driven colon cancer. Additional sources of IL17, such as γδ T cells, become available under inflammatory conditions, but their contributions to cancer development are unclear. In this study, we modeled Th17-driven colon tumorigenesis by colonizing Min(Ap) (c+/-) mice with the human gut bacterium, enterotoxigenic Bacteroides fragilis (ETBF), to investigate the link between inflammation and colorectal cancer. We found that ablating Th17 cells by knocking out Stat3 in CD4(+) T cells delayed tumorigenesis, but failed to suppress the eventual formation of colonic tumors. However, IL17 blockade significantly attenuated tumor formation, indicating a critical requirement for IL17 in tumorigenesis, but from a source other than Th17 cells. Notably, genetic ablation of γδ T cells in ETBF-colonized Th17-deficient Min mice prevented the late emergence of colonic tumors. Taken together, these findings support a redundant role for adaptive Th17 cell- and innate γδT17 cell-derived IL17 in bacteria-induced colon carcinogenesis, stressing the importance of therapeutically targeting the cytokine itself rather than its cellular sources. Cancer Res; 76(8); 2115-24. ©2016 AACR.

Matched MeSH terms: Mice, Inbred C57BL
Fulltext Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity

Botelho DJ, Leo BF, Massa CB, Sarkar S, Tetley TD, Chung KF, et al.

Nanotoxicology, 2016;10(1):118-27.
PMID: 26152688 DOI: 10.3109/17435390.2015.1038330

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

Matched MeSH terms: Mice, Inbred C57BL
Comparison of three forms of antigens in the demonstration of cell-mediated immune response in murine toxoplasmosis

Rahmah N, Khairul Anuar A

Biochem Biophys Res Commun, 1992 Dec 15;189(2):640-4.
PMID: 1472034

Mice were chronically infected with cysts of ME49 strain of Toxoplasma gondii. At different periods post-infection, their spleens were removed and single cell suspensions were made. Lymphocyte transformation experiments were performed on the lymphocyte suspensions using three different kinds of antigens of ME49 strain of T. gondii, namely soluble, excretory/secretory and cystic forms. The results showed that the pattern of lymphocyte responsiveness was dependent on the kind of antigen employed for induction of the blastogenesis. Using soluble and cystic forms of the antigen, different periods of lymphocyte suppression and lymphocyte proliferation were demonstrated. However, with the use of excretory/secretory antigen, no significant suppression of lymphocyte stimulation was noted throughout the course of infection. Thus excretory/secretory antigen may be the best form of antigen for stimulation of the cell-mediated immune response and hence it appears to be a good candidate for vaccine in toxoplasmosis.

Matched MeSH terms: Mice, Inbred C57BL
Demonstration of antigenic similarities and variations in excretory/secretory antigens of Toxoplasma gondii

Rahmah N, Anuar AK

Biochem Biophys Res Commun, 1992 Aug 31;187(1):294-8.
PMID: 1520310

C57BL/6 mice were orally infected with different doses of cysts of ME49 strain of Toxoplasma gondii to produce groups of acutely and chronically infected mice. Sera were obtained at different periods post-infection. SDS-PAGE was ran with excretory/secretory antigens of ME49 and RH strains of T. gondii, followed by Western blot analyses using the above sera and anti- IgA, IgM, IgG as conjugates. The SDS-PAGE profiles of the two antigens were similar. However the antigenic bands showed variations in all blots, most evidently in IgA blots of chronic sera. IgG blots showed greatest similarities in reactive bands. In IgM blots, more common bands were shown in chronic sera than in acute sera. Variations and similarities in prominence of some bands and time of their appearance were also noted, especially in IgM and IgG blots of chronic sera. Thus antigenic variations and similarities are present in excretory/secretory products of different strains of T. gondii.

Matched MeSH terms: Mice, Inbred C57BL
Transcriptome composition of the preoptic area in mid-age and escitalopram treatment in male mice

Moriya S, Soga T, Wong DW, Parhar IS

Neurosci Lett, 2016 May 27;622:67-71.
PMID: 27113202 DOI: 10.1016/j.neulet.2016.04.052

The decrease in serotonergic neurotransmission during aging can increase the risk of neuropsychiatric diseases such as depression in elderly population and decline the reproductive system. Therefore, it is important to understand the age-associated molecular mechanisms of brain aging. In this study, the effect of aging and chronic escitalopram (antidepressant) treatment to admit mice was investigated by comparing transcriptomes in the preoptic area (POA) which is a key nucleus for reproduction. In the mid-aged brain, the immune system-related genes were increased and hormone response-related genes were decreased. In the escitalopram treated brains, transcription-, granule cell proliferation- and vasoconstriction-related genes were increased and olfactory receptors were decreased. Since homeostasis and neuroprotection-related genes were altered in both of mid-age and escitalopram treatment, these genes could be important for serotonin related physiologies in the POA.

Matched MeSH terms: Mice, Inbred C57BL
Increased susceptibility of mice obtained from in vitro fertilization to global cerebral ischemia-reperfusion injury: possible role of hydrogen sulphide and its biosynthetic enzymes

Li H, Liu L, Dang M, Zhang W, Liu J

Int J Neurosci, 2020 Jun;130(6):533-540.
PMID: 31516045 DOI: 10.1080/00207454.2019.1667797

Aim of the Study: This study was designed to explore the relative susceptibility of in vitro fertilization (IVF)-conceived mice to global cerebral ischemic injury with the possible role of hydrogen sulphide and enzymes responsible for its production.Materials and Methods: IVF was carried to obtain pups, which were allowed to grow to the age of eight weeks. Thereafter, male mice were subjected to 20 min of global ischemia and 24 h of reperfusion. The mice obtained from other groups including normal mating, superovulation but normal mating and normal mating but embryo implantation were also subjected to global ischemia-reperfusion (I/R) injury.Results: IVF-derived mice exhibited significant more injury in response to I/R injury in comparison to other groups assessed in terms of impairment in locomotor activity, development of motor in coordination, neurological severity score, cerebral infarction and apoptosis markers (caspase-3 activity and Bcl-2 expression). Moreover, there was a relative decrease in the brain levels of hydrogen sulphide (H2S) and its biosynthetic enzymes viz. cystathionine-β-synthase and cystathionine-γ-lyase. Interestingly, the levels of H2S and cystathionine-γ-lyase were significantly low in IVF-derived mice in basal conditions also, i.e. before subjecting to I/R injury and these biochemical alterations were associated with the behavioural deficits in mice, even before subjecting to I/R injury.Conclusion: It is concluded that in vitro fertilization-derived mice are more susceptible to global cerebral I/R injury, which may be possibly due to decreased levels of hydrogen sulphide and its biosynthetic enzymes viz., cystathionine-β-synthase and cystathionine-γ-lyase.

Matched MeSH terms: Mice, Inbred C57BL
Generation of induced pluripotent stem cells by a polycistronic lentiviral vector in feeder- and serum- free defined culture

Al Abbar A, Nordin N, Ghazalli N, Abdullah S

Tissue Cell, 2018 Dec;55:13-24.
PMID: 30503056 DOI: 10.1016/j.tice.2018.09.004

Induced pluripotent stem cells (iPSCs) have great potentials for regenerative medicine. However, serious concerns such as the use of the viral-mediated reprogramming strategies and exposure of iPSCs to animal products from feeder cells and serum-containing medium have restricted the application of iPSCs in the clinics. Therefore, the generation of iPSCs with minimal viral integrations and in non-animal sourced and serum-free medium is necessary. In this report, a polycistronic lentiviral vector carrying Yamanaka's factors was used to reprogram mouse fibroblasts into iPSCs in feeder- and xeno-free culture environment. The generated iPSCs exhibited morphology and self-renewal properties of embryonic stem cells (ESCs), expression of specific pluripotent markers, and potentials to differentiate into the three-major distinct specialized germ layers in vitro. The iPSCs were also shown to have the potential to differentiate into neural precursor and neurons in culture, with greater than 95% expression of nestin, Pax6 and βIII-tubulin. This body of work describes an alternative method of generating iPSCs by using polycistronic lentiviral vector that may minimize the risks associated with viral vector-mediated reprogramming and animal derived products in the culture media.

Matched MeSH terms: Mice, Inbred C57BL
Fulltext A High Amylose Wheat Diet Improves Gastrointestinal Health Parameters and Gut Microbiota in Male and Female Mice

Lim SM, Choo JM, Li H, O'Rielly R, Carragher J, Rogers GB, et al.

Foods, 2021 Jan 21;10(2).
PMID: 33494480 DOI: 10.3390/foods10020220

High amylose wheat (HAW) contains more resistant starch than standard amylose wheat (SAW) and may have beneficial effects on gastrointestinal health. However, it is currently unclear whether these effects differ according to the level of HAW included in the diet or between males and females. Male and female C57BL/6 mice (n = 8/group/sex) were fed SAW65 (65% SAW; control), HAW35 (35% HAW), HAW50 (50% HAW) or HAW65 (65% HAW) diet for eight weeks. Female but not male, mice consuming any amount of HAW exhibited accelerated gastric emptying compared to SAW65 group. In both sexes, relative colon weights were higher in the HAW65 group compared to SAW65 group and in females, relative weights of the small intestine and cecum were also higher in the HAW65 group. In females only, colonic expression of Pyy and Ocln mRNAs were higher in the HAW65 group compared to HAW35 and HAW50 groups. In both sexes, mice consuming higher amounts of HAW (HAW50 or HAW65) had increased fecal bacterial load and relative abundance of Bacteroidetes phylum and reduced relative abundance of Firmicutes compared to SAW65 group. These data are consistent with a beneficial impact of HAW on gastrointestinal health and indicate dose-dependent and sex-specific effects of HAW consumption.

Matched MeSH terms: Mice, Inbred C57BL
Fulltext Lung-infiltrating T helper 17 cells as the major source of interleukin-17A production during pulmonary Cryptococcus neoformans infection

Movahed E, Cheok YY, Tan GMY, Lee CYQ, Cheong HC, Velayuthan RD, et al.

BMC Immunol, 2018 Nov 08;19(1):32.
PMID: 30409128 DOI: 10.1186/s12865-018-0269-5

BACKGROUND: IL-17A has emerged as a key player in the pathologies of inflammation, autoimmune disease, and immunity to microbes since its discovery two decades ago. In this study, we aim to elucidate the activity of IL-17A in the protection against Cryptococcus neoformans, an opportunistic fungus that causes fatal meningoencephalitis among AIDS patients. For this purpose, we examined if C. neoformans infection triggers IL-17A secretion in vivo using wildtype C57BL/6 mice. In addition, an enhanced green fluorescence protein (EGFP) reporter and a knockout (KO) mouse models were used to track the source of IL-17A secretion and explore the protective function of IL-17A, respectively.
RESULTS: Our findings showed that in vivo model of C. neoformans infection demonstrated induction of abundant IL-17A secretion. By examining the lung bronchoalveolar lavage fluid (BALF), mediastinal lymph node (mLN) and spleen of the IL-17A-EGFP reporter mice, we showed that intranasal inoculation with C. neoformans promoted leukocytes lung infiltration. A large proportion (~ 50%) of the infiltrated CD4+ helper T cell population secreted EGFP, indicating vigorous TH17 activity in the C. neoformans-infected lung. The infection study in IL-17A-KO mice, on the other hand, revealed that absence of IL-17A marginally boosted fungal burden in the lung and accelerated the mouse death.
CONCLUSION: Therefore, our data suggest that IL-17A is released predominantly from TH17 cells in vivo, which plays a supporting role in the protective immunity against C. neoformans infection.

Matched MeSH terms: Mice, Inbred C57BL
Fulltext Phenotype microarrays reveal metabolic dysregulations of neurospheres derived from embryonic Ts1Cje mouse model of Down syndrome

Seth EA, Lee HC, Yusof HHBM, Nordin N, Cheah YK, Ho ETW, et al.

PLoS One, 2020;15(7):e0236826.
PMID: 32730314 DOI: 10.1371/journal.pone.0236826

Down syndrome (DS), is the most common cause of intellectual disability, and is characterized by defective neurogenesis during perinatal development. To identify metabolic aberrations in early neurogenesis, we profiled neurospheres derived from the embryonic brain of Ts1Cje, a mouse model of Down syndrome. High-throughput phenotypic microarray revealed a significant decrease in utilisation of 17 out of 367 substrates and significantly higher utilisation of 6 substrates in the Ts1Cje neurospheres compared to controls. Specifically, Ts1Cje neurospheres were less efficient in the utilisation of glucose-6-phosphate suggesting a dysregulation in the energy-producing pathway. T Cje neurospheres were significantly smaller in diameter than the controls. Subsequent preliminary study on supplementation with 6-phosphogluconic acid, an intermediate of glucose-6-phosphate metabolism, was able to rescue the Ts1Cje neurosphere size. This study confirmed the perturbed pentose phosphate pathway, contributing to defects observed in Ts1Cje neurospheres. We show for the first time that this comprehensive energetic assay platform facilitates the metabolic characterisation of Ts1Cje cells and confirmed their distinguishable metabolic profiles compared to the controls.

Matched MeSH terms: Mice, Inbred C57BL
Fulltext The Effect of Isoleucine Supplementation on Body Weight Gain and Blood Glucose Response in Lean and Obese Mice

O'Rielly R, Li H, Lim SM, Yazbeck R, Kritas S, Ullrich SS, et al.

Nutrients, 2020 Aug 14;12(8).
PMID: 32823899 DOI: 10.3390/nu12082446

Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces postprandial glucose levels in humans. However, the effect of chronic-isoleucine supplementation on body weight and glucose tolerance in obesity is unknown. This study aimed to investigate the impact of chronic isoleucine on body weight gain and glucose tolerance in lean and high-fat-diet (HFD) induced-obese mice. Male C57BL/6-mice, fed a standard-laboratory-diet (SLD) or HFD for 12 weeks, were randomly allocated to: (1) Control: Drinking water; (2) Acute: Drinking water with a gavage of isoleucine (300 mg/kg) prior to the oral-glucose-tolerance-test (OGTT) or gastric-emptying-breath-test (GEBT); (3) Chronic: Drinking water with 1.5% isoleucine, for a further six weeks. At 16 weeks, an OGTT and GEBT was performed and at 17 weeks metabolic monitoring. In SLD- and HFD-mice, there was no difference in body weight, fat mass, and plasma lipid profiles between isoleucine treatment groups. Acute-isoleucine did not improve glucose tolerance in SLD- or HFD-mice. Chronic-isoleucine impaired glucose tolerance in SLD-mice. There was no difference in gastric emptying between any groups. Chronic-isoleucine did not alter energy intake, energy expenditure, or respiratory quotient in SLD- or HFD-mice. In conclusion, chronic isoleucine supplementation may not be an effective treatment for obesity or glucose intolerance.

Matched MeSH terms: Mice, Inbred C57BL
Caffeic acid phenethyl ester (CAPE) reverses fibrosis caused by chronic colon inflammation in murine model of colitis

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: Mice, Inbred C57BL
Isolation and characterization of primary microglia from post-natal murine brain tissues: a comparison of two methods

Jose S, Tan SW, Tong CK, Vidyadaran S

Cell Biol Int, 2015 Dec;39(12):1355-63.
PMID: 26194799 DOI: 10.1002/cbin.10516

Microglia are resident macrophages of the central nervous system (CNS). Apart from playing vital roles as sentinel cells, they are crucial in physiological processes such as synaptic pruning during brain development. CNS disorders require an understanding of the contribution of each cellular compartment to the pathogenesis. Elucidating the role of microglia in disease development and progression in the intricate CNS environment is technically challenging and requires the establishment of reliable, reproducible techniques to isolate and culture microglia. A number of different protocols have been developed for isolation of neonatal microglia and here we compare two widely used methods, namely, mild trypsinization and EasySep® magnetic separation. EasySep® magnetic separation provided higher microglia yield, and flow cytometric evaluation of CD11b and F4/80 markers revealed that EasySep® separation method also produced significantly higher purity compared to mild trypsinization. Microglia isolated using EasySep® separation method were functional, as demonstrated by the generation of nitric oxide, IL-6, TNF-α, and MCP-1 in response to lipopolysaccharide stimulation. In summary, this study has revealed that magnetic separation is superior to mild trypsinization in terms of yield and purity of microglia.

Matched MeSH terms: Mice, Inbred C57BL
Fulltext Glutathione (GSH) improves sperm quality and testicular morphology in streptozotocin-induced diabetic mice

Abdullah F, Khan Nor-Ashikin MN, Agarwal R, Kamsani YS, Abd Malek M, Bakar NS, et al.

Asian J Androl, 2021 1 22;23(3):281-287.
PMID: 33473013 DOI: 10.4103/aja.aja_81_20

Diabetes mellitus (DM) is known to cause reproductive impairment. In men, it has been linked to altered sperm quality and testicular damage. Oxidative stress (OS) plays a pivotal role in the development of DM complications. Glutathione (GSH) is a part of a nonenzymatic antioxidant defense system that protects lipid, protein, and nucleic acids from oxidative damage. However, the protective effects of exogenous GSH on the male reproductive system have not been comprehensively examined. This study determined the impact of GSH supplementation in ameliorating the adverse effect of type 1 DM on sperm quality and the seminiferous tubules of diabetic C57BL/6NTac mice. GSH at the doses of 15 mg kg-1 and 30 mg kg-1 was given intraperitoneally to mice weekly for 6 consecutive weeks. The mice were then weighed, euthanized, and had their reproductive organs excised. The diabetic (D Group) showed significant impairment of sperm quality and testicular histology compared with the nondiabetic (ND Group). Diameters of the seminiferous lumen in diabetic mice treated with 15 mg kg-1 GSH (DGSH15) were decreased compared with the D Group. Sperm motility was also significantly increased in the DGSH15 Group. Improvement in testicular morphology might be an early indication of the protective roles played by the exogenous GSH in protecting sperm quality from effects of untreated type 1 DM or diabetic complications. Further investigation using different doses and different routes of GSH is necessary to confirm this suggestion.

Matched MeSH terms: Mice, Inbred C57BL
Fulltext Liposomes derived from Mycobacterium smegmatis promote immune activation of mice bone marrow-derived dendritic cells

Mat Luwi NE, Kadir R, Mohamud R, A Garcia-Santana ML, Acevedo R, Sarmiento ME, et al.

Int J Mycobacteriol, 2020 8 31;9(3):261-267.
PMID: 32862158 DOI: 10.4103/ijmy.ijmy_82_20

Background: Tuberculosis (TB) is the leading cause of mortality due to infectious diseases. The development of new generation vaccines against TB is of paramount importance for the control of the disease. In previous studies, liposomes obtained from lipids of Mycobacterium smegmatis (LMs) demonstrated their immunogenicity and protective capacity against Mycobacterium tuberculosis in mice. To characterize the immunomodulatory capacity of this experimental vaccine candidate, in the current study, the stimulatory capacity of LMs was determined on bone marrow-derived dendritic cells (BMDCs) from mice.
Methods: LMs were obtained and incubated with mature BMDCs. The internalization of LMs by BMDCs was studied by confocal microscopy, and the LMs immune-stimulatory capacity was determined by the expression of surface molecules (CD86 and MHCII) and the cytokine production (interleukin [IL]-12, interferon-Υ, tumor necrosis factor-α, and IL-10) 24 h after exposure to LMs.
Results: The interaction of LMs with BMDCs and its internalization was demonstrated as well as the immune activation of BMDCs, characterized by the increased expression of CD86 and the production of IL-12. The LMs internalization and immune activation of BMDCs were blocked in the presence of cytochalasin, filipin III and chlorpromazine, which demonstrated that internalization of LMs by BMDCs is a key process for the LMs induced immune activation of BMDCs.
Conclusions: The results obtained support the further evaluation of LMs as a mycobacterial vaccine, adjuvant, and in immunotherapy.

Matched MeSH terms: Mice, Inbred C57BL
Insights into immunopathology and triggering of apoptosis in chronic cerebral toxoplasmosis using murine models

El Saftawy EA, Shash RY, Aboulhoda BE, Arsanyos SF, Albadawi EA, Abou-Fandoud SM, et al.

Trop Biomed, 2021 Jun 01;38(2):53-62.
PMID: 33973573 DOI: 10.47665/tb.38.2.037

BACKGROUND: toxoplasmosis is a cosmopolitan protozoan disease with a wide range of neuropathology. Recent studies identified its potential association with several mental disorders e.g. schizophrenia dependable on apoptosis in their pathogenesis. We investigated value of toxoplasmosis to induce apoptosis of the neuronal cells.
METHODS: per-orally infected C57BL/6 mice with 15-20 cysts of the avirulent T. gondii Beverly strain at 9-11 weeks of age were examined 12 weeks later during parasite establishment. Distributions of the parasite's cysts and the histopathological lesions in the brains were analyzed using Image J software. Relative expression of TNF-α and iNOS of cell-mediated immunity (CMI), Bax (pro-apoptosis) and Bcl-2 (anti-apoptosis) were all assessed using immunohistochemistry.
RESULTS: higher parasite burden was seen in the forebrain with p value <= 0.05. Dramatically increased TNF-α, iNOS, and Bax expressions with Bax/Bcl-2 ratio 2.42:0.52 were reported (p value <= 0.05). The significant correlation between Bax data and different CMI biomarkers including TNF-α and i-NOS was evaluated. Interestingly, no significant correlation was seen between TNF-α, iNOS, Bax and Bcl-2 expressions and location of the parasite. However, Bax/Bcl-2 ratio was statistically correlated with CMI biomarkers and whole sample mean parasite burden, p value <= 0.05.
CONCLUSION: Chronic toxoplasmosis exhibits an immense pro-apoptotic signal on the cerebral tissues of experimental mice.

Matched MeSH terms: Mice, Inbred C57BL

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