MyMedR

Displaying publications 441 - 460 of 2140 in total

Abstract:

Sort:

Fulltext The Acute Effects of Oral Administration of Phytic Acid-Chitosan-Magnetic Iron Oxide Nanoparticles in Mice

Mohd Tamsir N, Mohd Esa N, Shafie NH, Hussein MZ, Hamzah H, Abdullah MA

Int J Mol Sci, 2019 Aug 23;20(17).
PMID: 31450737 DOI: 10.3390/ijms20174114

A nanocomposite, phytic acid-chitosan-magnetic iron oxide nanoparticles (IP6-CS-MNPs) has been used to treat colon cancer in vitro, previously. However, its potential toxicity in vivo has yet to be elucidated. Hence, the present study aimed to evaluate the acute effects of oral administration of IP6-CS-MNPs in mice. In this study, 1000 and 2000 mg/kg body weight (b.w) of IP6-CS-MNPs were orally administered to two different groups of BALB/c mice, once. Additionally, the mice in the control group were given only deionized water. After 14 days of post-IP6-CS-MNPs administration, in a similar way to the untreated mice, the treated mice showed no sign of mortality and abnormalities. However, the serum urea level of mice receiving 2000 mg/kg b.w of IP6-CS-MNPs was significantly higher than the control group (p < 0.05). The mice that received 1000 mg/kg IP6-CS-MNPs showed a significantly higher level of serum alkaline phosphatase (ALP) compared to the control group. However, there were no significant histopathological changes seen in the liver and kidneys of treated mice compared to the untreated group.

Matched MeSH terms: Mice
Lactobacillus fermentum LAB 9-fermented soymilk with enriched isoflavones and antioxidants improved memory in vivo

Mohamad Fakri E, Lim S, Musa N, Hazizul Hasan M, Adam A, Ramasamy K

Sains Malaysiana, 2016;45:1289-1297.

This study examined lactic acid bacteria (LAB)-fermented soymilk for their ability in hydrolyzing glucosides to aglycones
and corresponding antioxidant capacity and memory enhancing effect. Twelve LAB isolated from Malaysian fermented food
and milk products were incubated in commercially available soymilk for 48 h. Generally, soymilk supported LAB growth
and significantly increased (p<0.05) conversion to bioactive aglycone by 2.1-6.5 fold when compared to unfermented
soymilk. Lactobacillus fermentum LAB 9- fermented soymilk, in particular, was presented with increased total phenolic
content (+10%) as opposed to unfermented soymilk. Lactobacilli (LAB 10-12)- and pediococci (LAB 5)-fermented soymilk
elicited maximal DPPH radical-scavenging activity. LAB 1, 7, 8, 9 and 12 exhibited significantly higher (p<0.05) ferrous
ion chelating activity when compared to control. Interestingly, LAB 9 had significantly improved memory deficit (p<0.05)
in LPS-challenged mice. LAB-enriched nutritional value of soymilk could be useful against oxidative stress and memory
deficit.

Matched MeSH terms: Mice
Characterising granuloma regression and liver recovery in a murine model of schistosomiasis japonica

Chuah C, Jones MK, McManus DP, Nawaratna SK, Burke ML, Owen HC, et al.

Int J Parasitol, 2016 Apr;46(4):239-52.
PMID: 26812024 DOI: 10.1016/j.ijpara.2015.12.004

For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced. Inflammatory cell infiltration into the liver was evident, and the numbers of neutrophils, eosinophils and macrophages were significantly decreased. Transcriptomic analysis revealed the up-regulation of fatty acid metabolism genes and the identification of Peroxisome proliferator activated receptor alpha as the upstream regulator of liver recovery. The aryl hydrocarbon receptor signalling pathway which regulates xenobiotic metabolism was also differentially up-regulated. These findings provide a better understanding of the mechanisms associated with the regression of hepatic schistosomiasis.

Matched MeSH terms: Mice
Characterization of the depolymerizing activity of commercial lipases and detection of lipase-like activities in animal organ extracts using poly(3-hydroxybutyrate-co-4-hydroxybutyrate) thin film

Mok PS, Ch'ng DH, Ong SP, Numata K, Sudesh K

AMB Express, 2016 Dec;6(1):97.
PMID: 27730572

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is one of the polyhydroxyalkanoate (PHA) copolymers which can be degraded by lipases. In this study, the depolymerizing activity of different known commercial lipases was investigated via microassay using P(3HB-co-92 mol % 4HB) thin film as substrate. Non-enzymatic hydrolysis occurred under conditions in which buffers with pH 12 and 13 were added or temperature of 50 °C and above. Different concentrations of metal ions or detergents alone did not cause the film hydrolysis. The depolymerizing activity of lipases on P(3HB-co-4HB) was optimum in the pH range of 6-8 and at temperatures between 30 and 50 °C. Addition of metal ions and detergents in different concentrations was also shown to cause variable effects on the depolymerizing activity of commercial lipases. Pancreatic extracts from both mouse and chicken showed similar depolymerizing activity as the commercial lipases on the P(3HB-co-4HB) film. The presence of lipolytic enzymes in the organ extracts was confirmed with another lipase activity assay, p-nitrophenyl laurate assay. For the first time this has produced a direct evidence for the involvement of lipase-like enzymes from animal in the degradation of this PHA. Lipase is most likely the enzyme from pancreas that was involved in the degradation.

Matched MeSH terms: Mice
Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells

Omar Zaki SS, Katas H, Hamid ZA

Food Chem Toxicol, 2015 Nov;85:31-44.
PMID: 26051352 DOI: 10.1016/j.fct.2015.05.017

Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1(+)), myeloid-committed progenitors (CD11b(+), Gr-1(+)), and lymphoid-committed progenitors (CD45(+), CD3e(+)). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1(+) cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b(+) and Gr-1(+) cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45(+) and CD3e(+) cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.

Matched MeSH terms: Mice
Fulltext The Molecular Floodgates of Stress-Induced Senescence Reveal Translation, Signalling and Protein Activity Central to the Post-Mortem Proteome

Wasinger VC, Curnoe D, Boel C, Machin N, Goh HM

Int J Mol Sci, 2020 Sep 03;21(17).
PMID: 32899302 DOI: 10.3390/ijms21176422

The transitioning of cells during the systemic demise of an organism is poorly understood. Here, we present evidence that organismal death is accompanied by a common and sequential molecular flood of stress-induced events that propagate the senescence phenotype, and this phenotype is preserved in the proteome after death. We demonstrate activation of "death" pathways involvement in diseases of ageing, with biochemical mechanisms mapping onto neurological damage, embryonic development, the inflammatory response, cardiac disease and ultimately cancer with increased significance. There is sufficient bioavailability of the building blocks required to support the continued translation, energy, and functional catalytic activity of proteins. Significant abundance changes occur in 1258 proteins across 1 to 720 h post-mortem of the 12-week-old mouse mandible. Protein abundance increases concord with enzyme activity, while mitochondrial dysfunction is evident with metabolic reprogramming. This study reveals differences in protein abundances which are akin to states of stress-induced premature senescence (SIPS). The control of these pathways is significant for a large number of biological scenarios. Understanding how these pathways function during the process of cellular death holds promise in generating novel solutions capable of overcoming disease complications, maintaining organ transplant viability and could influence the findings of proteomics through "deep-time" of individuals with no historically recorded cause of death.

Matched MeSH terms: Mice
Fulltext Effective composting of empty fruit bunches using potential Trichoderma strains

Siddiquee S, Shafawati SN, Naher L

Biotechnol Rep (Amst), 2017 Mar;13:1-7.
PMID: 28352555 DOI: 10.1016/j.btre.2016.11.001

Oil palm fibres are easy to degrade, eco-friendly in nature and once composted, they can be categorized under nutrient-enriched biocompost. Biocompost is not only a good biofertilizer but also a good biocontrol agent against soil-borne pathogens. In this research, experimental works on the composting of empty fruit bunches (EFB) from the oil palm industry were conducted using two potential Trichoderma strains. Analysis of pH initially found the soils to be slightly acidic. However, after composting, the soils were found to be alkaline. Trichoderma propagules increased by 72% in the soils compared to other fungi. Soil electrical conductivity was found to be 50.40 μS/cm for compost A, 42.10 μS/cm for compost B and 40.11 μS/cm for the control. The highest C:N ratio was obtained for compost A at 3.33, followed by compost B at 2.79, and then the control at 1.55. The highest percentages of nitrogen (N), phosphorus (P), and potassium (K) were found in compost A (0.91:2.13:6.68), which was followed by compost B (0.46:0.83:5.85) and then the control (0.32:0.26:5.76). Thus, the biocomposting of oil palm fibres shows great potential for enhancing soil micronutrient, plant growth performance, and crop yield production.

Matched MeSH terms: Mice
Fulltext Anti-pain and anti-inflammation like effects of Neptune krill oil and fish oil against carrageenan induced inflammation in mice models: Current statues and pilot study

Zadeh-Ardabili PM, Rad SK

Biotechnol Rep (Amst), 2019 Jun;22:e00341.
PMID: 31061816 DOI: 10.1016/j.btre.2019.e00341

Although inflammation is a reactive to injurious stimuli and considered as beneficial process in body, but it causes some discomforts, such as pain. Murine dietary contains appreciable amounts of fatty acids and antioxidants which encourages researchers to focus on their potential therapeutic effects. This study is aimed to examine the analgesic and anti-inflammatory activity of Neptune krill oil (NKO) and fish oil (FO) in rodent model which are two well-known sources of rich content of n-3 polyunsaturated fatty acids (n-3 PUFAs), mostly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). NKO and FO were used at the same dose of 500 mg and also balanced at similar doses of EPA: 12 in NKO vs. 12 in FO wt%, DHA: 7 NKO vs. 8 FO wt%. Application of NKO and FO in acetic acid-induced writhing effect, hot plate, and formalin induced test, indicated the nociceptive activity of the two tested drugs in comparison with normal saline. Also, the anti-inflammatory effect of these supplements was confirmed by carrageenan test. Analysis of cytokines levels in the blood samples of the mice after induction inflammation by carrageenan indicated decreased levels of those proteins compared to that in the normal groups. Both tested drugs, effectively could reduce severe inflammation and pain in rodents in comparison with the references drugs (depends on the tests); however, NKO was found to be more effective.

Matched MeSH terms: Mice
Fulltext Effects of xanthorrhizol on 3T3-L1 adipocyte hyperplasia and hypertrophy [Abstract]

Seok Fang Oon, Meenakshii Nallappan, Mohd Shazrul Fazry Sa’ariwijaya, Nur Kartinee Kassim, Shamarina Shohaimi, Thiam Tsui Tee, et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):41-41.
MyJurnal

ABSTRACTS FOR INTERNATIONAL HEALTH AND MEDICAL SCIENCES CONFERENCE 2019 (IHMSC 2019). Accelerating Innovations in Translational and Precision Medicine. Held at Taylor’s University Lakeside Campus, Subang Jaya, Selangor, Malaysia. 8-9th March, 2019
Introduction: According to the National Health and Morbidity Survey (NHMS) 2015, 47.7% of the Malaysian population are either obese or overweight. The increased obesity prevalence has caused major health problems including cardiovascular diseases and diabetes. Although several anti-obesity drugs have been developed, they are limited due to adverse side effects. Previous studies demonstrated that xanthorrhizol (XNT) reduced the levels of serum free fatty acid and triglyceride in vivo, but the detailed anti-obesity activities and its related mechanisms are yet to be reported. Thus, this study aims to evaluate its abilities to inhibit adipocyte hyperplasia and hypertrophy employing 3T3-L1 adipocytes.
Methods: Statistical significance was established by one-way ANOVA, where p < 0.05 was considered statistically significant.
Results: In this study, the IC50 value of XNT (98.3% purity) from Curcuma xanthorrhiza Roxb. in 3T3-L1 adipocytes was 35 ± 0.24 μg/mL. The loss of cell viability was due to 20.01 ± 2.77% of early apoptosis and 24.13 ± 2.03% of late apoptosis. XNT elicited apoptosis via up-regulation of caspase-3 and cleaved PARP-1 protein expression for 4.09-fold and 3.12-fold, respectively. Moreover, XNT decreased adipocyte differentiation for 36.13 ± 3.64% and reduced GPDH activity to 52.26 ± 4.36%. The underlying mechanism was due to impaired expression of PPARγ to 0.36-fold and FAS to 0.38-fold, respectively. On the other hand, XNT increased glycerol release by 45.37 ± 6.08% compared to control. During lipolysis, XNT up-regulated the leptin protein for 2.08-fold but down-regulated the protein level of insulin to 0.36-fold. These results indicated that XNT reduced the volume of adipocytes through modulation of leptin and insulin.
Conclusion: To conclude, XNT exerted its anti-obesity mechanisms by suppression of adipocyte hyperplasia through induction of apoptosis and inhibition of adipogenesis whilst reduction of adipocyte hypertrophy through stimulation of lipolysis. Thus, XNT could be developed as a potential anti-obesity agent in the future.

Matched MeSH terms: Mice
Fulltext Mapping the Age of Laboratory Rabbit Strains to Human

Sengupta P, Dutta S

Int J Prev Med, 2020;11:194.
PMID: 33815718 DOI: 10.4103/ijpvm.IJPVM_530_18

Rabbit strains find immense application in biomedical research with every strain having their discrete advantage in specific research endeavor. Acceptability of rabbit strains as laboratory animals owes to their breeding ease, availability, cost-effectiveness, ethical conveniences, larger size, compared to rats and mice, and responsiveness. With respect to different life phases, the article displays that one human year is equivalent to: (1) in developmental phase, 56.77 days for New Zealand White (NZW) and New Zealand Red (NZR) rabbits, 71.01 days for Dutch belted and Polish rabbits, and 85.28 days for Californian rabbits; (2) in the prepubertal phase, 13.04 days for NZW and Dutch belted, 15.65 days for NZR and Californian, and 10.43 days for Polish rabbits; (3) in the adult phase, 18.25 days for NZW and Californian rabbits, 22.75 days for NZR, and 12 days for Dutch Belted and Polish rabbits; (4) during reproductive senescence, 42.94 days for NZW, NZR and Californian rabbits, 28.62 days for Dutch belted, and 25.05 days for Polish rabbits; (5) in the post-senescence phase, 50.34 days for NZW, 25.17 days for NZR, Dutch Belted and Californian and 31.46 days for Polish rabbits. The laboratory rabbit strains differ in various physiological, developmental and genetic make-ups, which also reflect upon the correlation of their age at different life stages with that of a human. The present article aids selection of laboratory rabbit strain of accurate age as per experimental need, by precisely relating the same with age of human considering different life stages.

Matched MeSH terms: Mice
Stress induces reinstatement of extinguished cocaine conditioned place preference by a sequential signaling via neuropeptide S, orexin, and endocannabinoid

Chou YH, Hor CC, Lee MT, Lee HJ, Guerrini R, Calo G, et al.

Addict Biol, 2020 Oct 19.
PMID: 33078457 DOI: 10.1111/adb.12971

Neurons containing neuropeptide S (NPS) and orexins are activated during stress. Previously, we reported that orexins released during stress, via orexin OX1 receptors (OX1 Rs), contribute to the reinstatement of cocaine seeking through endocannabinoid/CB1 receptor (CB1 R)-mediated dopaminergic disinhibition in the ventral tegmental area (VTA). Here, we further demonstrated that NPS released during stress is an up-stream activator of this orexin-endocannabinoid cascade in the VTA, leading to the reinstatement of cocaine seeking. Mice were trained to acquire cocaine conditioned place preference (CPP) by context-pairing cocaine injections followed by the extinction training with context-pairing saline injections. Interestingly, the extinguished cocaine CPP in mice was significantly reinstated by intracerebroventricular injection (i.c.v.) of NPS (1 nmol) in a manner prevented by intraperitoneal injection (i.p.) of SHA68 (50 mg/kg), an NPS receptor antagonist. This NPS-induced cocaine reinstatement was prevented by either i.p. or intra-VTA microinjection (i.vta.) of SB-334867 (15 mg/kg, i.p. or 15 nmol, i.vta.) and AM 251 (1.1 mg/kg, i.p. or 30 nmol, i.vta.), antagonists of OX1 Rs and CB1 Rs, respectively. Besides, NPS (1 nmol, i.c.v.) increased the number of c-Fos-containing orexin neurons in the lateral hypothalamus (LH) and increased orexin-A level in the VTA. The latter effect was blocked by SHA68. Furthermore, a 30-min restraint stress in mice reinstated extinguished cocaine CPP and was prevented by SHA68. These results suggest that NPS is released upon stress and subsequently activates LH orexin neurons to release orexins in the VTA. The released orexins then reinstate extinguished cocaine CPP via an OX1 R- and endocannabinoid-CB1 R-mediated signaling in the VTA.

Matched MeSH terms: Mice
Fulltext Immunotherapy for head and neck cancer

Sok Ching Cheong

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):5-5.
MyJurnal

Head and neck cancers have been reported to have high immune infiltration scores, and clinical benefits of the anti-PD1 checkpoint inhibitor have been demonstrated in recurrent and metastatic cancers. Recent genetic signa-tures of the immune compartment have provided insights to delineate immune-active and -exhausted subtypes, to understand the immune status of OSCC patients that could further drive the development of novel immunotherapies. Vaccination with tumour-associated antigens is an approach to improve tumour recognition which could result in the eradication of cancer cells. Here, I would describe our efforts in developing antigen-specific vaccines for head and neck cancer. Using the B6.Cg-Tg(HLA-A/H2-D)2Enge/J mice bearing established tumours overexpressing the tumour antigens, we demonstrated that the vaccine delayed tumour growth, and in combination with anti-PD1, completely eliminated the tumour. The vaccine increased the expression of PD1 in T cells, and vaccinated animals showed increased antigen-specific responses by the ELISPOT assay. In summary, our data show that antigen-specific vaccine works synergistically with anti-PD1 and could be a promising therapeutic agent for head and neck cancer.

Matched MeSH terms: Mice
Cytotoxicity and nitric oxide inhibitory activities of Xanthones isolated from Calophyllum hosei Ridl

Daud S, Karunakaran T, Santhanam R, Nagaratnam SR, Jong VYM, Ee GCL

Nat Prod Res, 2020 Sep 09.
PMID: 32901512 DOI: 10.1080/14786419.2020.1819273

Previous studies on Calophyllum species have shown the existence of a wide variety of bioactive xanthones and coumarins. Phytochemical investigations carried out on the plant, Calophyllum hosei led to the isolation of eleven known xanthones, ananixanthone (1), 9-hydroxycalabaxanthone (2), dombakinaxanthone (3), thwaitesixanthone (4), caloxanthone B (5), trapezifolixanthone (6), β-mangostin (7), osajaxanthone (8), caloxanthone A (9), calozeyloxanthone (10) and rubraxanthone (11). The structures of these compounds were identified and elucidated using spectroscopic techniques such as NMR and MS. The cytotoxicity and nitric oxide production inhibitory activities of selected xanthones as well as the extracts were tested against HL-60 cells and RAW 264.7 murine macrophages, respectively. Among all tested compounds, β-mangostin exhibited appreciable cytotoxicity against HL-60 cells with the IC50 value of 7.16 ± 0.70 µg/mL and rubraxanthone exhibited significant nitric oxide inhibitory activity against LPS induced RAW 264.7 murine macrophages with the IC50 value of 6.45 ± 0.15 µg/mL.

Matched MeSH terms: Mice
Fulltext Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors

Sicari D, Centonze FG, Pineau R, Le Reste PJ, Negroni L, Chat S, et al.

EMBO Rep, 2021 May 05;22(5):e51412.
PMID: 33710763 DOI: 10.15252/embr.202051412

In the past decades, many studies reported the presence of endoplasmic reticulum (ER)-resident proteins in the cytosol. However, the mechanisms by which these proteins relocate and whether they exert cytosolic functions remain unknown. We find that a subset of ER luminal proteins accumulates in the cytosol of glioblastoma cells isolated from mouse and human tumors. In cultured cells, ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. Using the ER luminal protein anterior gradient 2 (AGR2) as a proof of concept, we tested whether the refluxed proteins gain new functions in the cytosol. We find that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53. These data suggest that ER reflux constitutes an ER surveillance mechanism to relieve the ER from its contents upon stress, providing a selective advantage to tumor cells through gain-of-cytosolic functions-a phenomenon we name ER to Cytosol Signaling (ERCYS).

Matched MeSH terms: Mice
The Effects of Palm Oil on Plasma and Serum Lipid Parameters: A Systematic Review on Animal Intervention Studies

Syarifah-Noratiqah SB, Fairus S, Zulfarina MS, Nasrullah Z, Qodriyah HMS, Naina-Mohamed I

Front Vet Sci, 2020;7:303.
PMID: 32775343 DOI: 10.3389/fvets.2020.00303

Background: Accumulative evidences on the beneficial effects of palm oil are progressively reported; however, there are still several controversies related to their effects on the risks of cardiovascular disease (CVD). This review explores the effects of palm oil and its liquid fraction namely palm olein, which is commonly used as cooking oil on four lipid parameters; total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), which play an important role as CVD-related biomarkers. A systematic review of the literature was conducted to identify the relevant studies on palm oil and the lipid parameters specifically focusing on the in-vivo animal model. Methods: A comprehensive search was conducted in Medline via EBSCOhost, Medline via OVID and Scopus. Studies were limited to the English language published between the years of 2000 and 2019. The main inclusion criteria were as follows: (1) Study with in-vivo animal experiments [the animal should be limited to mammals] (2) Study should have evaluated the effects of palm oil or palm olein on plasma or serum lipid parameter (3) Study should have used palm oil or palm olein in the form of pure or refined oil (4) The treatment of palm oil or palm olein was assessed using the following outcomes: plasma or serum TC, TG, HDL-C, and LDL-C concentration (5) Study should have control group and (6) studies on specific fatty acid, fraction enriched tocotrienol and tocopherol, crude palm oil, kernel oil, red palm oil, thermally oxidized palm oil, hydrogenated palm oil, and palm oil or palm olein based products namely margarine, palm milk, butter and cream were excluded. The quality and the risk of bias on the selected studies were assessed using the ARRIVE Guideline and SYRCLE's Risk of Bias tools, respectively. Results: The literature search successfully identified 17 potentially relevant articles, whereby nine of them met the inclusion criteria. All research articles included in this review were in vivo studies comprising seven rats, one hamster and one mice model. Conclusion: Significant positive outcomes were observed in several lipid parameters such as TC and LDL-C. The evidence from this review supported that palm oil and palm olein possess high potential as lipid-lowering agents.

Matched MeSH terms: Mice
Fulltext Efficacy of Emu Oil Transfersomes for Local Transdermal Delivery of 4-OH Tamoxifen in the Treatment of Breast Cancer

Sundralingam U, Chakravarthi S, Radhakrishnan AK, Muniyandy S, Palanisamy UD

Pharmaceutics, 2020 Aug 25;12(9).
PMID: 32854385 DOI: 10.3390/pharmaceutics12090807

Oral tamoxifen used in the prevention and treatment of ductal carcinoma in situ (DCIS) (estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of tamoxifen is related to its major metabolite, 4-hydroxytamoxifen. Local transdermal therapy of 4-hydroxytamoxifen to the breast might avert the toxicity of oral tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without emu oil, using a syngeneic mouse model of breast cancer. We also quantified tamoxifen/4-hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure emu oil and transfersome formulations with or without the emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC-MS/MS method for the quantification of tamoxifen and 4-hydroxytamoxifen was developed and validated. Studies on tumor volume and necrosis (histopathology) using the breast cancer mouse model showed that the 4-OHT transfersomal formulations, with and without emu oil, showed comparable efficacy with that of orally administered tamoxifen. However, the transfersomal formulations, with and without emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of 4-hydroxytamoxifen, compared to the oral tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of emu oil in a local transdermal formulation for the treatment of breast cancer and its reduced adverse effects.

Matched MeSH terms: Mice
Fulltext Malacca leaf ethanolic extract (Phyllanthus emblica) as a hepatoprotector of the liver of mice (Mus musculus) infected with Plasmodium berghei

Asmilia N, Aliza D, Fahrimal Y, Abrar M, Ashary S

Vet World, 2020 Jul;13(7):1457-1461.
PMID: 32848324 DOI: 10.14202/vetworld.2020.1457-1461

Background and Aim: Although existing research confirms the antiparasitic effect of the Malacca plant against Plasmodium, its effect on the liver, one of the target organs of Plasmodium has not been investigated. Therefore, this study was conducted to explore the potential of the ethanolic extract of Malacca (Phyllanthus emblica) leaves in preventing liver damage in mice (Mus musculus) caused by Plasmodium berghei infection.
Materials and Methods: This study was conducted using the livers of 18 mice fixed in 10% neutral-buffered formalin. A completely randomized design with a unidirectional pattern comprising six treatments was used in this study, with each treatment consisting of three replications. Treatment 0 was the negative control group infected with P. berghei, treatment 1 was the positive control group infected with P. berghei followed by chloroquine administration at a dose of 5 mg/kg BW, and treatments 2, 3, 4, and 5 were groups infected with P. berghei and administered Malacca leaf ethanolic extracts at doses of 100, 300, 600, and 1200 mg/kg BW, respectively. The extracts were administered orally using a gastric tube for 4 consecutive days. Mice were sacrificed on the 7th day and livers were collected for histopathological examination.
Results: Histopathological examination of the livers of mice infected with P. berghei demonstrated the presence of hemosiderin, hydropic degeneration, fat degeneration, necrosis, and megalocytosis. However, all these histopathological changes were reduced in the livers of P. berghei-infected mice treated with various doses of Malacca leaf ethanolic extract. The differences between the treatments were found be statistically significant (p<0.05).
Conclusion: Ethanolic extract of Malacca leaves has the potential to protect against liver damage in mice infected with P. berghei. The dose of 600 mg/kg BW was found to be the most effective compared with the doses of 100, 300, and 1200 mg/kg BW.

Matched MeSH terms: Mice
Fulltext Computational approaches: discovery of GTPase HRas as prospective drug target for 1,3-diazine scaffolds

Kumar S, Sharma D, Narasimhan B, Ramasamy K, Shah SAA, Lim SM, et al.

BMC Chem, 2019 Dec;13(1):96.
PMID: 31355369 DOI: 10.1186/s13065-019-0613-8

Heterocyclic 1,3-diazine nucleus is a valuable pharmacophore in the field of medicinal chemistry and exhibit a wide spectrum of biological activities. PharmMapper, a robust online tool used for establishing the target proteins based on reverse pharmacophore mapping. PharmMapper study is carried out to explore the pharmacological activity of 1,3-diazine derivatives using reverse docking program. PharmMapper, an open web server was used to recognize for all the feasible target proteins for the developed compounds through reverse pharmacophore mapping. The results were analyzed via molecular docking with maestro v11.5 (Schrodinger 2018-1) using GTPase HRas as possible target. The molecular docking studies displayed the binding behavior of 1,3-diazine within GTP binding pocket. From the docking study compounds s3 and s14 showed better docked score with anticancer potency against cancer cell line (HCT116). Hence, the GTPase HRas may be the possible target of 1,3-diazine derivatives for their anticancer activity where the retrieved information may be quite useful for developing rational drug designing. Furthermore the selected 1,3-diazine compounds were evaluated for their in vitro anticancer activity against murine macrophages cell line. 1,3-Diazine compounds exhibited good selectivity of the compounds towards the human colorectal carcinoma cell line instead of the murine macrophages. The toxicity study of the most active compounds was also performed on non cancerous HEK-293 cell line.

Matched MeSH terms: Mice
Immunosuppressive and hepatoprotective potential of Sarcococca saligna and its biomarker components

Ali H, Musharraf SG, Iqbal N, Adhikari A, Abdalla OM, Ahmed Mesaik M, et al.

Int Immunopharmacol, 2015 Sep;28(1):235-43.
PMID: 26093268 DOI: 10.1016/j.intimp.2015.06.009

Sarcococca saligna methanolic extract, fractions and isolated pure compounds saracocine (1), saracodine (2), pachyximine-A (3) and terminaline (4) were found to possess potent immunosuppressive activities. The fractions and compounds were tested in-vitro for their effects on human T-cell proliferation, and cytokine (IL-2) production. All the fractions, sub-fractions and purified compounds showed significant suppressive effect on IL-2 production in a dose-dependent manner. They also exhibited a suppressive effect on the phytohemagglutinin-stimulated T-cell proliferation. None of the extracts and purified compounds showed any cytotoxicity effects on the 3T3 mice fibroblast cell line. The crude extract, DCM fraction (pH9), DCM fractions (pH7) and one of the steroidal alkaloids (terminaline) were checked in-vivo for their hepato-protective potential against CCl4-induced liver injury. In in-vivo experiments, the basic and neutral DCM fractions and terminaline (4) significantly reduced inflammation in the liver. DCM fraction (pH9), DCM fractions (pH7) and compound 4 reduced the serum enzyme levels (ALT, AST, and ALP) down to control levels despite CCl4 treatment. They also reduced the CCl4-induced damaged area to almost zero as assessed by histopathology. The pale necrotic areas and mixed inflammatory infiltrate which are seen after CCl4 treatment were absent in the cases of basic, neutral fractions and terminaline treatment. These hepato-protective effects were better than the positive control silymarin. Our results suggest the therapeutic effect of S. saligna extract, fractions and bioactive steroidal alkaloids against CCl4-induced liver injury in vivo and their immunosuppressive function in vitro.

Matched MeSH terms: Mice
A novel sponge-derived protein thrombocorticin is a new agonist for thrombopoietin receptor

Watari H, Nakajima H, Atsuumi W, Nakamura T, Nanya T, Ise Y, et al.

Comp Biochem Physiol C Toxicol Pharmacol, 2019 Jul;221:82-88.
PMID: 30978513 DOI: 10.1016/j.cbpc.2019.04.003

We screened 868 marine extracts in search of hematopoietic molecules resulted in findings of several extracts that proliferated Ba/F3-HuMpl cells but not the cells expressed with other hematopoietic cytokine receptors, EPO and G-CSF. Separation of the most potent extract of a Micronesian sponge Corticium sp., guided by the cell proliferation assay using Ba/F3-HuMpl cells resulted in an isolation of thrombocorticin (ThC), a novel 14 kDa protein as an active principal. ThC displayed concentration-dependent proliferation of Ba/F3-HuMpl cells, and had a stronger activity than that of eltrombopag, a small molecule drug used to treat thrombocytopenia. ThC induced phosphorylation of STAT5, suggesting that it activates Jak/STAT pathway as in the case of TPO. These results together indicated that ThC is a specific agonist for c-Mpl, although the size and shape differs largely from TPO. Here we present isolation, characterization and biological activity of ThC.

Matched MeSH terms: Mice

Filters

Please provide feedback to Administrator ([email protected])

External Links