Displaying publications 81 - 100 of 831 in total

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  1. Menon RK, Gomez A, Brandt BW, Leung YY, Gopinath D, Watt RM, et al.
    Sci Rep, 2019 12 10;9(1):18761.
    PMID: 31822712 DOI: 10.1038/s41598-019-55056-3
    Routine postoperative antibiotic prophylaxis is not recommended for third molar extractions. However, amoxicillin still continues to be used customarily in several clinical practices worldwide to prevent infections. A prospective cohort study was conducted in cohorts who underwent third molar extractions with (group EA, n = 20) or without (group E, n = 20) amoxicillin (250 mg three times daily for 5 days). Further, a control group without amoxicillin and extractions (group C, n = 17) was included. Salivary samples were collected at baseline, 1-, 2-, 3-, 4-weeks and 3 months to assess the bacterial shift and antibiotic resistance gene changes employing 16S rRNA gene sequencing (Illumina-Miseq) and quantitative polymerase chain reaction. A further 6-month follow-up was performed for groups E and EA. Seven operational taxonomic units reported a significant change from baseline to 3 months for group EA (adjusted p  0.05). In conclusion, the salivary microbiome is resilient to an antibiotic challenge by a low-dose regimen of amoxicillin. Further studies evaluating the effect of routinely used higher dose regimens of amoxicillin on gram-negative bacteria and antibiotic resistance genes are warranted.
    Matched MeSH terms: Dose-Response Relationship, Drug
  2. Abu Bakar K, Mohamad NA, Hodi Z, McCulloch T, Williams A, Christian M, et al.
    Pediatr Nephrol, 2019 12;34(12):2557-2562.
    PMID: 31520127 DOI: 10.1007/s00467-019-04346-z
    BACKGROUND: Late acute cellular rejection (LACR) is associated with poorer graft outcomes and non-adherence. Non-adherence to tacrolimus can be indirectly assessed by the intra-patient variability (IPV) of tacrolimus trough levels. The threshold of IPV associated with rejection is not known.

    METHODS: We conducted a case-control study comparing 25 patients with biopsy-proven LACR against 25 stable controls matched for age group, primary diagnosis and time post-transplant. IPV was calculated using coefficient of variance (CV) and mean absolute deviation (MAD) using tacrolimus levels in the preceding 12 months. We also assessed the percentage time for tacrolimus levels dose (C/D) ratio as a proxy marker of tacrolimus metaboliser status.

    RESULTS: LACR patients had higher CV (median, IQR 44%, 36-61% v. 24%, 19-35%, p 

    Matched MeSH terms: Dose-Response Relationship, Drug
  3. Premakumar CM, Turner MA, Morgan C
    Nutr Rev, 2019 12 01;77(12):878-889.
    PMID: 31504841 DOI: 10.1093/nutrit/nuz049
    CONTEXT: Very preterm neonates (VPNs) are unable to digest breast milk and therefore rely on parenteral nutrition (PN) formulations. This systematic review was prepared following PRISMA-P 2015 guidelines. For the purpose of this review, desirable mean plasma arginine concentration is defined as ≥80 micromoles/L.

    OBJECTIVE: The review was performed to answer the following research question: "In VPNs, are high amounts of arginine in PN, compared with low amounts of arginine, associated with appropriate circulating concentrations of arginine?" Therefore, the aims were to 1) quantify the relationship between parenteral arginine intakes and plasma arginine concentrations in PN-dependent VPNs; 2) identify any features of study design that affect this relationship; and 3) estimate the target parenteral arginine dose to achieve desirable preterm plasma arginine concentrations.

    DATA SOURCES: The PubMed, Scopus, Web of Science, and Cochrane databases were searched regardless of study design; review articles were not included.

    DATA EXTRACTION: Only articles that discussed amino acid (AA) intake and measured plasma AA profile post PN in VPNs were included. Data were obtained using a data extraction checklist that was devised for the purpose of this review.

    DATA ANALYSIS: Twelve articles met the inclusion criteria. The dose-concentration relationship of arginine content (%) and absolute arginine intake (mg/(kg × d)) with plasma arginine concentrations showed a significant positive correlation (P < 0.001).

    CONCLUSION: Future studies using AA solutions with arginine content of 17%-20% and protein intakes of 3.5-4.0 g/kg per day may be needed to achieve higher plasma arginine concentrations.

    Matched MeSH terms: Dose-Response Relationship, Drug
  4. Zakaria ZA, Mahmood ND, Omar MH, Taher M, Basir R
    Pharm Biol, 2019 Dec;57(1):335-344.
    PMID: 31068038 DOI: 10.1080/13880209.2019.1606836
    CONTEXT: Muntingia calabura L. (Muntingiaceae) exerts antioxidant and anti-inflammatory activities, thus, it might be a good hepatoprotective agent.

    OBJECTIVE: This study investigates the effect of methanol extract of M. calabura leaves (MMCL) on hepatic antioxidant and anti-inflammatory activities in CCl4-induced hepatotoxic rat.

    MATERIALS AND METHODS: Sprague Dawley rats (n = 6) were treated (p.o.) with 10% DMSO (Groups 1 and 2), 50 mg/kg N-acetylcysteine (Group 3) or, 50, 250, or 500 mg/kg MMCL (Groups 4-6) for 7 consecutive days followed by pretreatment (i.p.) with vehicle (Group 1) or 50% CCl4 in olive oil (v/v) (Groups 2-6) on day 7th. Plasma liver enzymes and hepatic antioxidant enzymes and pro-inflammatory cytokines concentrations were measured while liver histopathology was examined.

    RESULTS: MMCL, at 500 mg/kg, significantly (p 

    Matched MeSH terms: Dose-Response Relationship, Drug
  5. Tatit NS, Kevin P
    Med J Malaysia, 2019 12;74(6):504-508.
    PMID: 31929476
    INTRODUCTION: Choriocarcinoma is malignant cancer originating from placental trophoblast. The incidence of this cancer is estimated at 0.57-1.1 per 1000 births in the United States of America, Australia, Europe, and New Zealand. The rate is much higher in South East Asia and Japan with two occurrences per a thousand births. Telomerase activity is an important part of the apoptotic process. Increased telomerase activity will result in cellular immortality and poor prognosis in cancer. Vitamin A possess an essential role in cell proliferation and differentiation. One of the active metabolites of vitamin A is All-Trans Retinoic Acid (ATRA).

    METHODS: In this study, we examined the role of ATRA against telomerase activity in choriocarcinoma cell. This cell was derived from BeWo cell line (ATCC CCL-98) and were given different doses of ATRA.

    RESULTS: From this study, Choriocarcinoma cell that was given ATRA in dosage of 50μg/ml inhibit telomerase activity by extending the cycle time of 39.51±0.09, compared to the control group with a cycle time of 37.62±0.43. Cycle length change consistently with higher dose of ATRA.

    CONCLUSION: This study has proven that ATRA could inhibit telomerase activity by lengthening the cycle. Changes in the increase of ATRA doses in this experimental test need to be studied further on experimental animals, either administered as a single agent or as an addition to standard treatment of trophoblastic disease.

    Matched MeSH terms: Dose-Response Relationship, Drug
  6. Heng WK, Ng YP, Ooi GS, Habshoh J, Nurazlin J, Nor Azah MN, et al.
    Med J Malaysia, 2019 12;74(6):477-482.
    PMID: 31929472
    BACKGROUND: Simvastatin is usually taken in the evening due to the circadian rhythm of hepatic cholesterol biosynthesis. The degree of reduction of low-density lipoprotein cholesterol (LDL-C) and the level of adherence to different administration time remained unknown in the Malaysian population. This study aims to investigate the effect of simvastatin on the percentage changes of lipid profile and the level of adherence to when simvastatin was instructed to be taken at different timing.

    METHODS: Nine primary care health clinics across Malaysia participated in this study. 147 statin-naive subjects were selected through convenient sampling and randomised into one of the three arms (after breakfast, after dinner or before bedtime). Differences on percentage reduction of LDL-C from baseline and level of adherence among the three groups at week-16 were compared. The main outcomes measured in this study were the percentage change of lipid parameters and the percentage of high-adherence (MMAS=8) at week-16.

    RESULTS: 59.2% of the patients were male. The mean age of the study population was 53.93± 10.85 years. Most of the patients were Malays (69.4%); followed by Indians (22.4%) and Chinese (8.2%). LDL-C decreased from 4.26 (Standard Deviation, SD1.01) to 2.36 (SD0.69)mmol/L at week-16 for patients taking simvastatin before bedtime; an absolute reduction of 44.95%.The differences of LDL-C percentage reduction between three arms were significantly different (p<0.001). The greatest LDL-C reduction was observed when simvastatin was taken before bedtime and revealed 56.2% patients with high-adherence at week-16.

    CONCLUSION: Simvastatin showed superior LDL-reduction and higher level of adherence when being instructed to be taken before bedtime.

    Matched MeSH terms: Dose-Response Relationship, Drug
  7. El-Sayed NNE, Almaneai NM, Ben Bacha A, Al-Obeed O, Ahmad R, Abdulla M, et al.
    J Enzyme Inhib Med Chem, 2019 Dec;34(1):672-683.
    PMID: 30821525 DOI: 10.1080/14756366.2019.1574780
    Some new 3H-quinazolin-4-one derivatives were synthesised and screened for anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities. Compound 15d was more potent in reducing the cell viabilities of HT-29 and SW620 cells lines to 38%, 36.7%, compared to 5-FU which demonstrated cell viabilities of 65.9 and 42.7% respectively. The IC50 values of 15d were ∼20 µg/ml. Assessment of apoptotic activity revealed that 15d decreased the cell viability by down regulating Bcl2 and BclxL. Moreover, compounds, 8j, 8d/15a/15e, 5b, and 8f displayed lowered IC50 values than oleanolic acid against proinflammatory isoforms of hGV, hG-X, NmPLA2, and AmPLA2. In addition, 8d, 8h, 8j, 15a, 15b, 15e, and 15f showed better anti-α-amylase than quercetin, whereas 8g, 8h, and 8i showed higher anti-α-glucosidase activity than allopurinol. Thus, these compounds can be considered as potential antidiabetic agents. Finally, none of the compounds showed higher antiproteases or xanthine oxidase activities than the used reference drugs.
    Matched MeSH terms: Dose-Response Relationship, Drug
  8. Zhang X, Tan Z, Jia K, Zhang W, Dang M
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):2171-2178.
    PMID: 31159596 DOI: 10.1080/21691401.2019.1620249
    Nanomedicine is a rapidly emerging field and is reported to be a promising tool for treating various diseases. Green synthesized nanoparticles are documented to possess a potent anticancer effect. Rabdosia rubescens is a Chinese plant which is also one of the components of PC-SPES and used to treat prostate cancer. In the present study, we synthesized the gold nanoparticles from R. rubescens (RR-AuNP) and analyzed its anticancer activity against the lung carcinoma A549 cell lines. Since lung cancer is reported to be with increased morbidity and decreased survival rate. The biosynthesized RR-AuNP were confirmed using UV-Visible spectrophotometer, size and shape of RR-AuNP were assessed by DLS, TEM and EDX. The biomolecules present in RR-AuNP and its topographical structure were detected using FTIR, SAED and AFM analysis. MTT assay was performed to detect the IC50 dose of RR-AuNP and its apoptotic effect was assessed by detecting the caspases activation, ROS generation. The anticancer effect of RR-AuNP was confirmed by DAPI staining, TUNEL assay and its molecular mechanism were confirmed by assessing the apoptotic signalling molecules protein expression. Our results illustrate that RR-AuNP showed a strong absorption peak at 550 nm and the RRAuNP were polydispersed nanospheres with size of 130 nm. RR-AuNP IC50 dose against A549 lung carcinoma cell line was detected to be at 25 µg/ml. The results of DAPI staining, TUNEL and immunoblotting analysis confirms both the 25 µg/ml and 50 µg/ml of RR-AuNP possess potent anticancer and apoptotic effect, suggesting that RR-AuNP that it may be a persuasive molecule to treat lung cancer.
    Matched MeSH terms: Dose-Response Relationship, Drug
  9. Anwar A, Shahbaz MS, Saad SM, Kanwal, Khan KM, Siddiqui R, et al.
    Eur J Med Chem, 2019 Nov 15;182:111575.
    PMID: 31415900 DOI: 10.1016/j.ejmech.2019.111575
    We report one-pot synthesis of a series of new 3-aryl-8-methylquinazolin-4(3H)-ones (QNZ) and their antimicrobial activity against Acanthamoeba castellanii belonging to T4 genotype. A library of fifteen synthetic derivatives of QNZs was synthesized, and their structural elucidation was performed by using nuclear magnetic resonance (NMR) spectroscopy and electron impact mass spectrometry (EI-MS). Elemental analyses and high-resolution mass spectrometry data of all derivatives were found to be in agreeable range. Amoebicidal assays performed at concentrations ranging from 50 to 100 μg/mL revealed that all derivatives of QNZ significantly decreased the viability of A. castellanii and QNZ 2, 5, 8, and 13 were found to have efficient antiamoebic effects. Field emission scanning electron microscopy (FESEM) imaging of amoeba treated with compounds 5 and 15 showed that these compounds cause structural alterations on the walls of A. castellanii. Furthermore, several QNZs inhibited the encystation and excystationas as well as abolished A. castellanii-mediated host cells cytopathogenicity in human cells. Whereas, these QNZs showed negligible cytotoxicity when tested against human cells in vitro. Hence, this study identified potential lead molecules having promising properties for drug development against A. castellanii. A brief structure-activity relationship is also developed to optimize the hit of most potent compounds from the library. To the best of our knowledge, it is first of its kind medicinal chemistry approach on a single class of compounds i.e., quinazolinone against keratitis and brain infection causing free-living amoeba, A. castellanii.
    Matched MeSH terms: Dose-Response Relationship, Drug
  10. Abdelgawad MA, Bakr RB, Ahmad W, Al-Sanea MM, Elshemy HAH
    Bioorg Chem, 2019 11;92:103218.
    PMID: 31536956 DOI: 10.1016/j.bioorg.2019.103218
    To enhance the cytotoxicity of benzimidazole and/or benzoxazole core, the benzimidazole/benzoxazole azo-pyrimidine were synthesized through diazo-coupling of 3-aminophenybenzimidazole (6a) or 3-aminophenylbenzoxazole (6b) with diethyl malonate. The new azo-molanates 6a&b mixed with urea in sodium ethoxide to afford the benzimidazolo/benzoxazolopyrimidine 7a&b. The structure elucidation of new synthesized targets was proved using spectroscopic techniques NMR, IR and elemental analysis. The cytoxicity screening had been carried out against five cancer cell lines: prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), pancreas cancer (PaCa-2) and colon cancer (HT-29). Furthermore, the antioxidant activity, phospholipase A2-V and cyclooxygenases inhibitory activities of the target compounds 7a&b were evaluated and the new compounds showed potent activity (cytotoxicity IC50 range from 4.3 to 9.2 µm, antioxidant activity from 40% to 80%, COXs or LOX inhibitory activity from 1.92 µM to 8.21 µM). The docking of 7a&b was made to confirm the mechanism of action.
    Matched MeSH terms: Dose-Response Relationship, Drug
  11. Shehzad MT, Hameed A, Al-Rashida M, Imran A, Uroos M, Asari A, et al.
    Bioorg Chem, 2019 11;92:103244.
    PMID: 31541804 DOI: 10.1016/j.bioorg.2019.103244
    The role of aldose reductase (ALR2) in diabetes mellitus is well-established. Our interest in finding ALR2 inhibitors led us to explore the inhibitory potential of new thiosemicarbazones. In this study, we have synthesized adamantyl-thiosemicarbazones and screened them as aldehyde reductase (ALR1) and aldose reductase (ALR2) inhibitors. The compounds bearing phenyl 3a, 2-methylphenyl 3g and 2,6-dimethylphenyl 3m have been identified as most potent ALR2 inhibitors with IC50 values of 3.99 ± 0.38, 3.55 ± 0.26 and 1.37 ± 0.92 µM, respectively, compared with sorbinil (IC50 = 3.14 ± 0.02 μM). The compounds 3a, 3g, and 3m also inhibit ALR1 with IC50 value of 7.75 ± 0.28, 7.26 ± 0.39 and 7.04 ± 2.23 µM, respectively. Molecular docking was also performed for putative binding of potent inhibitors with target enzyme ALR2. The most potent 2,6-dimethylphenyl bearing thiosemicarbazone 3m (IC50 = 1.37 ± 0.92 µM for ALR2) and other two compound 3a and 3g could potentially lead for the development of new therapeutic agents.
    Matched MeSH terms: Dose-Response Relationship, Drug
  12. Rahim F, Tariq S, Taha M, Ullah H, Zaman K, Uddin I, et al.
    Bioorg Chem, 2019 11;92:103284.
    PMID: 31546207 DOI: 10.1016/j.bioorg.2019.103284
    New triazinoindole bearing thiazole/oxazole analogues (1-21) were synthesized and characterized through spectroscopic techniques such as HREI-MS, 1H and 13C NMR. The configuration of compound 2i and 2k was confirmed through NOESY. All analogues were evaluated against α-amylase inhibitory potential. Among the synthesized analogues, compound 1h, 1i, 1j, 2a and 2f having IC50 values 1.80 ± 0.20, 1.90 ± 0.30, 1.2 ± 0.30, 1.2 ± 0.01 and 1.30 ± 0.20 μM respectively, showed excellent α-amylase inhibitory potential when compared with acarbose as standard (IC50 = 0.91 ± 0.20 µM). All other analogues showed good to moderate inhibitory potential. Structural activity relationship (SAR) has been established and binding interactions were confirmed through docking studies.
    Matched MeSH terms: Dose-Response Relationship, Drug
  13. Butt MA, Bhatti JA, Khalique A, Shahid MQ
    Trop Anim Health Prod, 2019 Nov;51(8):2595-2601.
    PMID: 31230253 DOI: 10.1007/s11250-019-01976-1
    The objective of current study was to determine the effect of fat supplement on physiological and reproductive performance of Holstein Friesian bulls during subtropical summer in Pakistan. Eighteen bulls were randomly divided into 3 treatment groups: (1) CTL, basal diet without fat supplementation; (2) FS100, basal diet with 100 g fat supplementation (Energizer-RP-10®, IFFCO, Johor, Malaysia); (3) FS200, basal diet with 200 g fat supplementation. Basal diet consisted of 50% green fodder (corn silage), 25% wheat straw, and 25% concentrate on dry matter basis. Diets were offered for 14 weeks from May to August 2016. The average daily temperature-humidity index ranged from 85 to 88 for the experimental period. The results indicated that there was no difference in dry matter intake, water intake, rectal temperature, pulse rate, and respiration rate among the treatment groups. Fat supplementation did not influence semen traits including sperm motility, progressive motility, amplitude of lateral head displacement, live-to-dead ratio, normal acrosomal ridge, plasma membrane integrity, and DNA integrity. The interaction of season with fat revealed that FA200 significantly increased post thaw semen motility and progressive motility during hot humid summer (P 
    Matched MeSH terms: Dose-Response Relationship, Drug
  14. Chiavaroli V, Derraik JGB, Jalaludin MY, Albert BB, Ramkumar S, Cutfield WS, et al.
    Pediatr Diabetes, 2019 11;20(7):892-900.
    PMID: 31237756 DOI: 10.1111/pedi.12881
    BACKGROUND: Partial remission (PREM) by the insulin dose-adjusted HbA1c (IDAA1c) method has not been evaluated for the combined associations of ethnicity and socioeconomic status in children and adolescents with type 1 diabetes (T1D).

    OBJECTIVE: To investigate prevalence and predictors of PREM defined by IDAA1c.

    METHODS: Six hundred fourteen of 678 children (aged <15 years) with new-onset T1D (2000-2013) from a regional pediatric diabetes service (Auckland, New Zealand).

    RESULTS: Overall rate of PREM at 3 months was 42.4%, and lower in Māori/Pacific children (28.6%; P = .006) and those of other ethnicities (28.8%; P = .030) compared with New Zealand Europeans (50.4%). Comparing the most and least deprived socioeconomic quintiles, the odds of PREM were lower among the most deprived (adjusted odds ratio [aOR] 0.44; P = .019). Lower rates of PREM were seen in children aged 0 to 4.9 years (23.8%) and 10 to 14 years (40.9%) than in children aged 5 to 9.9 years (57.4%; P

    Matched MeSH terms: Dose-Response Relationship, Drug
  15. Rosini M, Simoni E, Caporaso R, Basagni F, Catanzaro M, Abu IF, et al.
    Eur J Med Chem, 2019 Oct 15;180:111-120.
    PMID: 31301562 DOI: 10.1016/j.ejmech.2019.07.011
    N-methyl-d-aspartate receptors (NMDAR) are critically involved in the pathogenesis of Alzheimer's disease (AD). Acting as an open-channel blocker, the anti-AD drug memantine preferentially targets NMDAR overactivation, which has been proposed to trigger neurotoxic events mediated by amyloid β peptide (Aβ) and oxidative stress. In this study, we applied a multifunctional approach by conjugating memantine to ferulic acid, which is known to protect the brain from Aβ neurotoxicity and neuronal death caused by ROS. The most interesting compound (7) behaved, like memantine, as a voltage-dependent antagonist of NMDAR (IC50 = 6.9 μM). In addition, at 10 μM concentration, 7 exerted antioxidant properties both directly and indirectly through the activation of the Nrf-2 pathway in SH-SY5Y cells. At the same concentration, differently from the parent compounds memantine and ferulic acid alone, it was able to modulate Aβ production, as revealed by the observed increase of the non-amyloidogenic sAPPα in H4-SW cells. These findings suggest that compound 7 may represent a promising tool for investigating NMDAR-mediated neurotoxic events involving Aβ burden and oxidative damage.
    Matched MeSH terms: Dose-Response Relationship, Drug
  16. Mohd A, Zainal N, Tan KK, AbuBakar S
    Sci Rep, 2019 10 04;9(1):14336.
    PMID: 31586088 DOI: 10.1038/s41598-019-50674-3
    Zika virus (ZIKV) infection is a serious public health concern. ZIKV infection has been associated with increased occurrences of microcephaly among newborns and incidences of Guillain-Barré syndrome among adults. No specific therapeutics or vaccines are currently available to treat and protect against ZIKV infection. Here, a plant-secreted phytoalexin, resveratrol (RES), was investigated for its ability to inhibit ZIKV replication in vitro. Several RES treatment regimens were used. The ZIKV titers of mock- and RES-treated infected cell cultures were determined using the focus-forming assay and the Zika mRNA copy number as determined using qRT-PCR. Our results suggested that RES treatment reduced ZIKV titers in a dose-dependent manner. A reduction of >90% of virus titer and ZIKV mRNA copy number was achieved when infected cells were treated with 80 µM of RES post-infection. Pre-incubation of the virus with 80 µM RES showed >30% reduction in ZIKV titers and ZIKV mRNA copy number, implying potential direct virucidal effects of RES against the virus. The RES treatment reduced >70% virus titer in the anti-adsorption assay, suggesting the possibility that RES also interferes with ZIKV binding. However, there was no significant decrease in ZIKV titer when a short-period of RES treatment was applied to cells before ZIKV infection (pre-infection) and after the virus bound to the cells (virus internalization inhibition), implying that RES acts through its continuous presence in the cell cultures after virus infection. Overall, our results suggested that RES exhibited direct virucidal activity against ZIKV and possessed anti-ZIKV replication properties, highlighting the need for further exploration of RES as a potential antiviral molecule against ZIKV infection.
    Matched MeSH terms: Dose-Response Relationship, Drug
  17. Ngaha Njila MI, Massoma Lembè D, Koloko BL, Yong Meng G, Ebrahimi M, Awad EA, et al.
    Andrologia, 2019 Oct;51(9):e13359.
    PMID: 31353623 DOI: 10.1111/and.13359
    The effect of the methanolic extract of Alchornea cordifolia leaves on the fertility of senescent male rats was assessed in this study. 40 rats received daily distilled water, testosterone, 200 and 400 mg/kg of extract of Alchornea cordifolia. The reproductive organs weight, the gonadotropins, testosterone and cholesterol level, the sperm parameters, histology of the testes and epididymis were assessed. The weight of testes and prostate (400 mg/kg) significantly increased (p dose of 400 mg/kg, respectively, while the cholesterol decreased at a dose of 200 mg/kg (p dose of 400 mg/kg. The sperm count and morphology significantly increased at both doses of 200 mg/kg (p dose of 200 mg/kg and decreased at a dose of 400 mg/ kg. The overall results provide the strong evidence of the fertility potential of the methanolic extract of Alchornea cordifolia leaves in senescent male rats.
    Matched MeSH terms: Dose-Response Relationship, Drug
  18. Rahim F, Taha M, Ullah H, Wadood A, Selvaraj M, Rab A, et al.
    Bioorg Chem, 2019 10;91:103112.
    PMID: 31349115 DOI: 10.1016/j.bioorg.2019.103112
    Alpha-amylase and urease enzyme over expression endorses various complications like rheumatoid arthritis, urinary tract infection, colon cancer, metabolic disorder, cardiovascular risk, and chronic kidney disease. To overcome these complications, we have synthesized new arylhydrazide bearing Schiff bases/thiazolidinone analogues as α-amylase and urease inhibitors. The analogues 1a-r were evaluated for α-amylase inhibitory potential. All analogues were found active and show IC50 value ranging between 0.8 ± 0.05 and 12.50 ± 0.5 μM as compare to standard acarbose (IC50 = 1.70 ± 0.10 μM). Among the synthesized analogs, compound 1j, 1r, 1k, 1e, 1b and 1f having IC50 values 0.8 ± 0.05, 0.9 ± 0.05, 1.00 ± 0.05, 1.10 ± 0.10, 1.20 ± 0.10 and 1.30 ± 0.10 μM respectively showed an excellent inhibitory potential. Analogs 2a-o were evaluated against urease activity. All analogues were found active and show IC50 value ranging between 4.10 ± 0.02 and 38.20 ± 1.10 μM as compare to standard thiourea (IC50 = 21.40 ± 0.21 μM). Among the synthesized analogs, compound 2k, 2a, 2h, 2j, 2f, 2e, 2g, 2b and 2l having IC50 values 4.10 ± 0.02, 4.60 ± 0.02, 4.70 ± 0.03, 5.40 ± 0.02, 6.70 ± 0.05, 8.30 ± 0.3, 11.20 ± 0.04, 16.90 ± 0.8 and 19.80 ± 0.60 μM respectively showed an excellent inhibitory potential. All compounds were characterized through 1H, 13C NMR and HR-EIMS analysis. Structure activity relationship of the synthesized analogs were recognized and confirmed through molecular docking studies.
    Matched MeSH terms: Dose-Response Relationship, Drug
  19. Chen HJ, Dai FJ, Chang CR, Lau YQ, Chew BS, Chau CF
    J Food Drug Anal, 2019 10;27(4):869-875.
    PMID: 31590758 DOI: 10.1016/j.jfda.2019.06.005
    In the present study, the influences of diets (i.e. chow and AIN-93 diets) on the interpretation of various fecal parameters including viable microbiota, moisture, weight, and short-chain fatty acids in rats fed different amounts of inulin (0.5-2 g/kg). Eight groups of rats (n = 8/group) were fed, for 4 weeks, chow or AIN-93 diets with or without inulin supplementation. Fecal samples were analyzed for different fecal parameters. After a 2-week adaptation, apparent differences in some fecal parameters were observed between the chow and AIN-93 diet groups. Throughout the 4-week intervention period, significantly (p dose (0.5 g/kg) of inulin in chow diet groups, while most of these changes could merely be seen at medium-dose (1 g/kg) in AIN-93 diet groups. These results demonstrated that the choice of experimental diets would affect the comparison of fecal parameters as well as the interpretation of effective dosage of prebiotic in intestinal health assessments.
    Matched MeSH terms: Dose-Response Relationship, Drug
  20. Narayani SS, Saravanan S, Ravindran J, Ramasamy MS, Chitra J
    Int J Biol Macromol, 2019 Oct 01;138:618-628.
    PMID: 31344415 DOI: 10.1016/j.ijbiomac.2019.07.127
    Fucoidan is a marine sulfated polysaccharide, which is extracted from brown seaweed that has a wide range of bioactivities including anti-cancer properties. However, the underlying mechanism of fucoidan on its anti-cancer and apoptotic activity against colon cancer cell line Caco-2 remains to be elucidated. Hence, the present study evaluated the cytotoxicity, apoptotic and anti-cancer activity of fucoidan extracted from brown seaweed Sargassum cinereum against Caco-2 cell line. Cytotoxicity, morphological examination of nuclei, mitochondrial membrane potential, flow cytometry, reactive oxygen species (ROS) formation and detection of apoptotic efficacy of fucoidan were assessed by different assay protocols. Fucoidan inhibited growth of Caco-2 cells in a dose-dependent manner. IC50 concentration of fucoidan was found to be 250 μg/ml. AO/EB, Hoechst and Annexin V/PI staining confirmed the apoptosis induced by fucoidan in Caco-2 cells. Fucoidan was also found to increase ROS production and augment mitochondrial membrane permeability. The findings of the study suggest that fucoidan exerts potent anti-cancer and apoptotic effect on Caco-2 cells by enhancing ROS production. Thus, fucoidan may be used as a promising therapeutic regimen against various cancer cell types.
    Matched MeSH terms: Dose-Response Relationship, Drug
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