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  1. Stem cells as a potential therapy in managing various disorders of metabolic syndrome: a systematic review
    Shamsuddin SA, Chan AML, Ng MH, Yazid MD, Law JX, Hj Idrus RB, et al.
    Am J Transl Res, 2021;13(11):12217-12227.
    PMID: 34956448
    Recent explorations on mesenchymal stem/stromal cells (MSC) have reported a promising future for cell-based therapies. MSCs are widely sourced from various tissues and express unique properties of regenerative potential and immunomodulation. Currently, there is a growing interest in utilizing MSC for treatment of chronic diseases to overcome the drawbacks of chemical drugs. Metabolic Syndrome (MetS) is described as a cluster of metabolic abnormalities categorized as abdominal obesity, dyslipidaemia, hypertension, hypertriglyceridemia, and hyperglycaemia. Patients diagnosed with MetS have a high predisposition for developing cardiovascular complications, diabetes, non-alcoholic fatty liver diseases, bone loss, cancer, and mortality. Hence, research on MSC as therapy for MetS and related diseases, is greatly valued and are advantaged by the low immunogenicity with high regenerative capacity. However, there are many obstacles to be addressed such as the safety, efficacy, and consistency of different MSC sources. Additionally, factors such as effective dose level and delivery method are equally important to achieve uniform therapeutic outcomes. This systematic review discusses the potential roles of MSC in managing the multiple clusters of MetS. Research articles during the past 20 years were systematically searched and filtered to update the progress in the field of MSC therapy in managing various components of MetS. The different sources of MSC, dosage, method of delivery and outcome measures for the stem cell therapies were compiled from the systematically selected research articles. It can be concluded from the review of the selected articles that MSCs can improve the various disorders of MetS such as abdominal obesity, hyperglycaemia, hypertriglyceridemia and hypertension, and represent a promising alternative to conventional therapy of the MetS cluster.
  2. Fulltext Macroalgae in biomonitoring of metal pollution in the Bay of Bengal coastal waters of Cox's Bazar and surrounding areas
    Rakib MRJ, Jolly YN, Dioses-Salinas DC, Pizarro-Ortega CI, De-la-Torre GE, Khandaker MU, et al.
    Sci Rep, 2021 10 25;11(1):20999.
    PMID: 34697391 DOI: 10.1038/s41598-021-99750-7
    Although coastal water marine algae have been popularly used by others as indicators of heavy metal pollution, data within the Bay of Bengal for the estuarine Cox's Bazar region and Saint Martin's Island has remained scarce. Using marine algae, the study herein forms an effort in biomonitoring of metal contamination in the aforementioned Bangladesh areas. A total of 10 seaweed species were collected, including edible varieties, analyzed for metal levels through the use of the technique of EDXRF. From greatest to least, measured mean metal concentrations in descending order have been found to be K > Fe > Zr > Br > Sr > Zn > Mn > Rb > Cu > As > Pb > Cr > Co. Potential toxic heavy metals such as Pb, As, and Cr appear at lower concentration values compared to that found for essential mineral elements. However, the presence of Pb in Sargassum oligocystum species has been observed to exceed the maximum international guidance level. Given that some of the algae species are cultivated for human consumption, the non-carcinogenic and carcinogenic indices were calculated, shown to be slightly lower than the maxima recommended by the international organizations. Overall, the present results are consistent with literature data suggesting that heavy metal macroalgae biomonitoring may be species-specific. To the best of our knowledge, this study represents the first comprehensive macroalgae biomonitoring study of metal contamination from the coastal waters of Cox's Bazar and beyond.
  3. Fulltext Prevalence of nocturia among community-dwelling adults: a population-based study in Malaysia
    Yow HY, Tiong JJL, Mai CW, van der Werf E, Zainuddin ZM, Toh CC, et al.
    BMC Urol, 2021 Jun 29;21(1):95.
    PMID: 34187440 DOI: 10.1186/s12894-021-00860-1
    BACKGROUND: Nocturia is widely prevalent condition with detrimental effects on quality of life and general health. In Malaysia, there is a lack of up-to-date prevalence study on nocturia. This study aimed to investigate the prevalence of nocturia and awareness pertaining to nocturia among Malaysian adults.

    METHODS: A cross-sectional population-based study was conducted among Malaysian adults aged ≥ 18 years old. The data was collected by mixed mode self-administered questionnaire from May 2019 to September 2019. Nocturia was defined as one or more voids at night.

    RESULTS: There were a total of 4616 respondents with 74.5% of response rate. The overall prevalence of nocturia among Malaysian adults was found to be 57.3%. In multivariate analysis, respondents aged 31-40 (1.91 [1.52-2.40]) or > 60 years old (2.03 [1.48-2.71]), and those who presented with hypertension (2.84 [2.28-3.53]), diabetes mellitus (1.78 [1.42-2.25]), renal disease (3.58 [1.93-6.63]) or overactive bladder (1.61 [1.10-2.35]) were associated with higher prevalence of nocturia. A significantly lower disease prevalence (p 

  4. Fulltext Optimized Rivastigmine Nanoparticles Coated with Eudragit for Intranasal Application to Brain Delivery: Evaluation and Nasal Ciliotoxicity Studies
    Bhanderi M, Shah J, Gorain B, Nair AB, Jacob S, Asdaq SMB, et al.
    Materials (Basel), 2021 Oct 22;14(21).
    PMID: 34771817 DOI: 10.3390/ma14216291
    Rivastigmine, a reversible cholinesterase inhibitor, is frequently indicated in the management of demented conditions associated with Alzheimer disease. The major hurdle of delivering this drug through the oral route is its poor bioavailability, which prompted the development of novel delivery approaches for improved efficacy. Due to numerous beneficial properties associated with nanocarriers in the drug delivery system, rivastigmine nanoparticles were fabricated to be administer through the intranasal route. During the development of the nanoparticles, preliminary optimization of processing and formulation parameters was done by the design of an experimental approach. The drug-polymer ratio, stirrer speed, and crosslinking time were fixed as independent variables, to analyze the effect on the entrapment efficiency (% EE) and in vitro drug release of the drug. The formulation (D8) obtained from 23 full factorial designs was further coated using Eudragit EPO to extend the release pattern of the entrapped drug. Furthermore, the 1:1 ratio of core to polymer depicted spherical particle size of ~175 nm, % EE of 64.83%, 97.59% cumulative drug release, and higher flux (40.39 ± 3.52 µg.h/cm2). Finally, the intranasal ciliotoxicity study on sheep nasal mucosa revealed that the exposure of developed nanoparticles was similar to the negative control group, while destruction of normal architecture was noticed in the positive control test group. Overall, from the in vitro results it could be summarized that the optimization of nanoparticles' formulation of rivastigmine for intranasal application would be retained at the application site for a prolonged duration to release the entrapped drug without producing any local toxicity at the mucosal region.
  5. Fulltext Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging
    Mittal P, Condina MR, Klingler-Hoffmann M, Kaur G, Oehler MK, Sieber OM, et al.
    Cancers (Basel), 2021 Oct 27;13(21).
    PMID: 34771551 DOI: 10.3390/cancers13215388
    Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.2% sensitivity and 98.6% specificity). Moreover, our machine learning approach predicted the presence of lymph node metastasis (LNM) for primary tumours of EC with an accuracy of 80% (90% sensitivity and 69% specificity). Our results demonstrate the capability of MALDI MSI for complementing classic histopathological examination for cancer diagnostic applications.
  6. Fulltext Blood Transfusion Knowledge among Nurses in Malaysia: A University Hospital Experience
    Mohd Noor NH, Saad NH, Khan M, Hassan MN, Ramli M, Bahar R, et al.
    Int J Environ Res Public Health, 2021 10 25;18(21).
    PMID: 34769712 DOI: 10.3390/ijerph182111194
    Blood transfusion is a fundamental and life-saving procedure where the consequence of errors can be fatal. Nurses' knowledge plays an essential role in ensuring quality and safety in blood transfusion. The objective of this study was to assess blood transfusion-associated knowledge of tertiary hospital nurses on the east coast of Malaysia. This was a cross-sectional study with 200 registered nurses involved in blood transfusion procedures at Hospital Universiti Sains Malaysia. The knowledge of the nurses was evaluated by using the routine blood transfusion knowledge questionnaire based on five parts, and <50%, 50-74%, or ≥75% of the knowledge was considered as poor, moderate, or high, respectively. Based on the scoring system, the overall knowledge of blood transfusion among Malaysian nurses (33.2 ± 8.4 years) was estimated to be 54.9 ± 7.6%. In individual items, the scoring was 81.0%, 45.4%, 49.2%, 63.0%, and 90.0% in knowledge prior to blood transfusion, on pre-transfusion, on post-transfusion, on complications, and on transfusion policy, respectively. The findings of this study indicated that most of the nurses' overall knowledge of blood transfusion was at a moderate level; therefore, training courses and continuous medical education are warranted to improve knowledge and skills of the nurses to ensure good practices of blood transfusion.
  7. Fulltext Trifolium pratense ethanolic extract alters the gut microbiota composition and regulates serum lipid profile in the ovariectomized rats
    Quah Y, Park NH, Lee EB, Lee KJ, Yi-Le JC, Ali MS, et al.
    BMC Complement Med Ther, 2022 Jan 04;22(1):5.
    PMID: 34983484 DOI: 10.1186/s12906-021-03486-w
    BACKGROUND: Trifolium pratense (red clover) ethanolic extract (TPEE) has been used as a popular over-the-counter remedy for the management of menopausal symptoms. Prolonged consumption of herbal extract has been shown to regulate the composition of gut microbiota. This study was designed to elucidate the influence of TPEE on the gut microbiota composition in the ovariectomized (OVX) rats.

    METHODS: OVX rats were treated with TPEE at 125, 250, 500 mg/kg/day, or controls (pomegranate extract, 500 mg/kg/day; estradiol, 25 μg/kg/day) for 12 weeks. Gut microbiota analysis was conducted by extracting the microbial DNA from fecal samples and microbiome taxonomic profiling was carried out by using next-generation sequencing. The levels of serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA) kit. The prediction of functional biomarker of microbiota was performed using PICRUSt to investigate the potential pathways associated with gut health and serum lipid profile regulation. To study the correlation between gut microbiota composition and serum lipid levels, Spearman's correlation coefficients were defined and analyzed. Additionally, gas chromatography-mass spectrometry analysis was conducted to uncover additional physiologically active ingredients.

    RESULTS: TPEE-treated OVX rats showed significant reduction in serum triglycerides (TG), total cholesterols (TCHOL), and LDL/VLDL levels but increase in HDL level. The alteration in the pathways involve in metabolism was the most common among the other KEGG categories. Particularly, TPEE also significantly reduced the relative abundance of sequences read associated with inflammatory bowel disease (IBD) and the peroxisome proliferator-activated receptor (PPAR) signalling pathway. TPEE intervention was seen to reduce the Firmicutes to Bacteroidetes (F/B) ratio in the OVX rats, denoting a reduction in microbial dysbiosis in the OVX rats. Correlation analysis at the phylum level revealed that Bacteriodetes and Proteobacteria were strongly correlated with serum TG, TCHOL and HDL levels. At the species level, Bifidobacterium pseudolongum group was seen to positively correlate with serum HDL level and negatively correlated with serum AST, ALT, LDL/VLDL, TCHOL, and TG levels.

    CONCLUSIONS: TPEE treatment showed therapeutic benefits by improving the intestinal microbiota composition which strongly correlated with the serum lipid and cholesterol levels in the OVX rats.

  8. Fulltext Localized Surface Plasmon Resonance Decorated with Carbon Quantum Dots and Triangular Ag Nanoparticles for Chlorophyll Detection
    Nazri NAA, Azeman NH, Bakar MHA, Mobarak NN, Luo Y, Arsad N, et al.
    Nanomaterials (Basel), 2021 Dec 23;12(1).
    PMID: 35009983 DOI: 10.3390/nano12010035
    This paper demonstrates carbon quantum dots (CQDs) with triangular silver nanoparticles (AgNPs) as the sensing materials of localized surface plasmon resonance (LSPR) sensors for chlorophyll detection. The CQDs and AgNPs were prepared by a one-step hydrothermal process and a direct chemical reduction process, respectively. FTIR analysis shows that a CQD consists of NH2, OH, and COOH functional groups. The appearance of C=O and NH2 at 399.5 eV and 529.6 eV in XPS analysis indicates that functional groups are available for adsorption sites for chlorophyll interaction. A AgNP-CQD composite was coated on the glass slide surface using (3-aminopropyl) triethoxysilane (APTES) as a coupling agent and acted as the active sensing layer for chlorophyll detection. In LSPR sensing, the linear response detection for AgNP-CQD demonstrates R2 = 0.9581 and a sensitivity of 0.80 nm ppm-1, with a detection limit of 4.71 ppm ranging from 0.2 to 10.0 ppm. Meanwhile, a AgNP shows a linear response of R2 = 0.1541 and a sensitivity of 0.25 nm ppm-1, with the detection limit of 52.76 ppm upon exposure to chlorophyll. Based on these results, the AgNP-CQD composite shows a better linearity response and a higher sensitivity than bare AgNPs when exposed to chlorophyll, highlighting the potential of AgNP-CQD as a sensing material in this study.
  9. A lignan with glucose uptake activity in 3T3-L1 adipocytes from the stem bark of Knema patentinervia
    Taher M, Amiroudine MZAM, Jaffri JM, Amri MS, Susanti D, Abd Hamid S, et al.
    Pak J Pharm Sci, 2017 Jul;30(4):1335-1339.
    PMID: 29039334
    A new naturally occurring dibenzylbutyrolactone lignan named isocubebinic ether has been isolated from Knema patentinervia. The structure was established by spectroscopic methods, which include Ultraviolet, Infrared, Nuclear Magnetic Resonance and Mass Spectrometry. The compound showed activity in the stimulation of glucose uptake by 3T3-L1 adipocytes.
  10. Fulltext Genome-Wide Discovery of Genes Required for Capsule Production by Uropathogenic Escherichia coli
    Goh KGK, Phan MD, Forde BM, Chong TM, Yin WF, Chan KG, et al.
    mBio, 2017 10 24;8(5).
    PMID: 29066548 DOI: 10.1128/mBio.01558-17
    Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract and bloodstream infections and possesses an array of virulence factors for colonization, survival, and persistence. One such factor is the polysaccharide K capsule. Among the different K capsule types, the K1 serotype is strongly associated with UPEC infection. In this study, we completely sequenced the K1 UPEC urosepsis strain PA45B and employed a novel combination of a lytic K1 capsule-specific phage, saturated Tn5 transposon mutagenesis, and high-throughput transposon-directed insertion site sequencing (TraDIS) to identify the complement of genes required for capsule production. Our analysis identified known genes involved in capsule biosynthesis, as well as two additional regulatory genes (mprA and lrhA) that we characterized at the molecular level. Mutation of mprA resulted in protection against K1 phage-mediated killing, a phenotype restored by complementation. We also identified a significantly increased unidirectional Tn5 insertion frequency upstream of the lrhA gene and showed that strong expression of LrhA induced by a constitutive Pcl promoter led to loss of capsule production. Further analysis revealed loss of MprA or overexpression of LrhA affected the transcription of capsule biosynthesis genes in PA45B and increased sensitivity to killing in whole blood. Similar phenotypes were also observed in UPEC strains UTI89 (K1) and CFT073 (K2), demonstrating that the effects were neither strain nor capsule type specific. Overall, this study defined the genome of a UPEC urosepsis isolate and identified and characterized two new regulatory factors that affect UPEC capsule production.IMPORTANCE Urinary tract infections (UTIs) are among the most common bacterial infections in humans and are primarily caused by uropathogenic Escherichia coli (UPEC). Many UPEC strains express a polysaccharide K capsule that provides protection against host innate immune factors and contributes to survival and persistence during infection. The K1 serotype is one example of a polysaccharide capsule type and is strongly associated with UPEC strains that cause UTIs, bloodstream infections, and meningitis. The number of UTIs caused by antibiotic-resistant UPEC is steadily increasing, highlighting the need to better understand factors (e.g., the capsule) that contribute to UPEC pathogenesis. This study describes the original and novel application of lytic capsule-specific phage killing, saturated Tn5 transposon mutagenesis, and high-throughput transposon-directed insertion site sequencing to define the entire complement of genes required for capsule production in UPEC. Our comprehensive approach uncovered new genes involved in the regulation of this key virulence determinant.
  11. Fulltext Survival predictors in paraquat intoxification and role of immunosuppression
    Koh KH, Tan CH, Hii LW, Lee J, Ngu LL, Chai AJ, et al.
    Toxicol Rep, 2014;1:490-495.
    PMID: 28962262 DOI: 10.1016/j.toxrep.2014.06.010
    Paraquat poisoning resulted in multiorgan failure and is associated with high mortality. We audited 83 historical cases of paraquat poisoning in past 2 years treated with conventional decontamination and supportive treatment, followed by enrolling 85 patients over a 2 year period into additional immunosuppression with intravenous (i.v.) methylprednisolone and i.v. cyclophosphamide. Our results showed that age, poor renal function and leucocytosis are the main predictors of fatal outcome. Immunosuppression regime rendered higher survival (6 out of 17 patients (35.3%)) versus historical control (1 out of 18 patients (5.6%)) (p = 0.041) in the cohort with admission eGFR < 50 ml/min/1.73 m(2) and WBC count > 11,000/μL. In contrast, there was no difference in survival with immunosuppression regime (38 out of 64 patients (59.4%)) compared to historical control (30 out of 52 patients (57.7%)) (p = 0.885) in those with eGFR > 50 ml/min/1.73 m(2) or WBC < 11,000/μL at presentation. Multivariable logistic regression showed survival probability = exp(logit)/(1 + exp(logit)), in which logit = 13.962 - (0.233 × ln(age (year))) - (1.344 × ln(creatinine (μmol/L))) - (1.602 × ln(rise in creatinine (μmol/day))) - (0.614 × ln(WBC (,000/μL))) + (2.021 × immunosuppression) and immunosuppression = 1 if given and 0 if not. Immunosuppression therapy yielded odds ratio of 0.132 (95% confidential interval: 0.029-0.603, p = 0.009). In conclusion, immunosuppression therapy with intravenous methylprednisolone and cyclophosphamide may counteract immune mediated inflammation after paraquat poisoning and improve survival of patients with admission eGFR < 50 ml/min/1.73 m(2) and WBC count > 11,000/μL.
  12. Fulltext Association of copy number variations in complement factor H-Related genes among age-related macular degenerative subjects
    Bakri NM, Ramachandran V, Kee HF, Subrayan V, Isa H, Ngah NF, et al.
    Kaohsiung J. Med. Sci., 2017 Dec;33(12):602-608.
    PMID: 29132549 DOI: 10.1016/j.kjms.2017.08.003
    Age-related macular degeneration (AMD) is the most widely recognised cause of irreversible vision loss and previous studies have suggested that the advancement of wet AMD is influenced by both modifiable and non-modifiable elements. Single nucleotide polymorphism (SNPs) and copy number of variations (CNVs) have been associated with AMD in various populations, however the results are conflicting. Our aim is to determine the CNVs of Complement Factor H-Related genes among Malaysian subjects with wet AMD. 130 patients with wet AMD and 120 healthy controls were included in this research. DNA was extracted from all subjects and CNVs of CFH, CFHR1 and CFHR3 genes; determined using quantitative real-time PCR and were compared between the two groups. A consistent association was observed between CFH gene and wet AMD susceptibility (P 
  13. Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway
    Break MKB, Hossan MS, Khoo Y, Qazzaz ME, Al-Hayali MZK, Chow SC, et al.
    Fitoterapia, 2018 Mar;125:161-173.
    PMID: 29355749 DOI: 10.1016/j.fitote.2018.01.006
    Cardamonin is a natural chalcone that has been shown to exhibit high anticancer activity. In an attempt to discover analogues of cardamonin with enhanced anticancer activity, 19 analogues were synthesized and tested against A549 and HK1 cell lines. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin's phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19). Compound 19 was the most active analogue possessing IC50 values of 13.2μM and 0.7μM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. It was also able to significantly inhibit the migration of A549 and HK1 cells. Further mode of action studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell- cycle arrest in both cell lines. These events further led to the induction of apoptosis by the compound via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Moreover, 19 inhibited the expression levels of p-mTOR and p-4EBP1, which indicated that it exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway.
  14. α-glucosidase inhibitors isolated from Mimosa pudica L
    Tasnuva ST, Qamar UA, Ghafoor K, Sahena F, Jahurul MHA, Rukshana AH, et al.
    Nat Prod Res, 2019 May;33(10):1495-1499.
    PMID: 29281898 DOI: 10.1080/14786419.2017.1419224
    The aim of the study was to isolate digestive enzymes inhibitors from Mimosa pudica through a bioassay-guided fractionation approach. Repeated silica gel and sephadex LH 20 column chromatographies of bioactive fractions afforded stigmasterol, quercetin and avicularin as digestive enzymes inhibitors whose IC50 values as compared to acarbose (351.02 ± 1.46 μg mL-1) were found to be as 91.08 ± 1.54, 75.16 ± 0.92 and 481.7 ± 0.703 μg mL-1, respectively. In conclusion, M. pudica could be a good and safe source of digestive enzymes inhibitors for the management of diabetes in future.
  15. Occurrence of Blastocystis sp. in water catchments at Malay villages and Aboriginal settlement during wet and dry seasons in Peninsular Malaysia
    Noradilah SA, Lee IL, Anuar TS, Salleh FM, Abdul Manap SN, Mohd Mohtar NS, et al.
    PeerJ, 2016;4:e2541.
    PMID: 27761331
    In the tropics, there are too few studies on isolation of Blastocystis sp. subtypes from water sources; in addition, there is also an absence of reported studies on the occurrence of Blastocystis sp. subtypes in water during different seasons. Therefore, this study was aimed to determine the occurrence of Blastocystis sp. subtypes in river water and other water sources that drained aboriginal vicinity of highly endemic intestinal parasitic infections during wet and dry seasons. Water samples were collected from six sampling points of Sungai Krau (K1-K6) and a point at Sungai Lompat (K7) and other water sources around the aboriginal villages. The water samples were collected during both seasons, wet and dry seasons. Filtration of the water samples were carried out using a flatbed membrane filtration system. The extracted DNA from concentrated water sediment was subjected to single round polymerase chain reaction and positive PCR products were subjected to sequencing. All samples were also subjected to filtration and cultured on membrane lactose glucuronide agar for the detection of faecal coliforms. During wet season, Blastocystis sp. ST1, ST2 and ST3 were detected in river water samples. Blastocystis sp. ST3 occurrence was sustained in the river water samples during dry season. However Blastocystis sp. ST1 and ST2 were absent during dry season. Water samples collected from various water sources showed contaminations of Blastocystis sp. ST1, ST2, ST3 and ST4, during wet season and Blastocystis sp. ST1, ST3, ST8 and ST10 during dry season. Water collected from all river sampling points during both seasons showed growth of Escherichia coli and Enterobacter aerogenes, indicating faecal contamination. In this study, Blastocystis sp. ST3 is suggested as the most robust and resistant subtype able to survive in any adverse environmental condition. Restriction and control of human and animal faecal contaminations to the river and other water sources shall prevent the transmission of Blastocystis sp. to humans and animals in this aboriginal community.
  16. Fulltext Semipurified Ethyl Acetate Partition of Methanolic Extract of Melastoma malabathricum Leaves Exerts Gastroprotective Activity Partly via Its Antioxidant-Antisecretory-Anti-Inflammatory Action and Synergistic Action of Several Flavonoid-Based Compounds
    Ismail Suhaimy NW, Noor Azmi AK, Mohtarrudin N, Omar MH, Tohid SF, Cheema MS, et al.
    Oxid Med Cell Longev, 2017;2017:6542631.
    PMID: 28168011 DOI: 10.1155/2017/6542631
    Recent study has demonstrated the gastroprotective activity of crude methanolic extract of M. malabathricum leaves. The present study evaluated the gastroprotective potential of semipurified extracts (partitions): petroleum ether, ethyl acetate (EAMM), and aqueous obtained from the methanolic extract followed by the elucidation of the gastroprotective mechanisms of the most effective partition. Using the ethanol-induced gastric ulcer assay, all partitions exerted significant gastroprotection, with EAMM being the most effective partition. EAMM significantly (i) reduced the volume and acidity (free and total) while increasing the pH of gastric juice and enhanced the gastric wall mucus secretion when assessed using the pylorus ligation assay, (ii) increased the enzymatic and nonenzymatic antioxidant activity of the stomach tissue, (iii) lost its gastroprotective activity following pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME; NO blocker) or carbenoxolone (CBXN; NP-SH blocker), (iv) exerted antioxidant activity against various in vitro oxidation assays, and (v) showed moderate in vitro anti-inflammatory activity via the LOX-modulated pathway. In conclusion, EAMM exerts a remarkable NO/NP-SH-dependent gastroprotective effect that is attributed to its antisecretory and antioxidant activities, ability to stimulate the gastric mucus production and endogenous antioxidant system, and synergistic action of several gastroprotective-induced flavonoids.
  17. Prediction of Anti-Alzheimer's Activity of Flavonoids Targeting Acetylcholinesterase in silico
    Das S, Laskar MA, Sarker SD, Choudhury MD, Choudhury PR, Mitra A, et al.
    Phytochem Anal, 2017 Jul;28(4):324-331.
    PMID: 28168765 DOI: 10.1002/pca.2679
    INTRODUCTION: Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AChE) inhibitory, anti-cholinergic, anti-inflammatory, anti-microbial, anti-oxidant, anti-proliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer's disease.

    OBJECTIVE: The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease.

    METHODOLOGY: Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method.

    RESULTS: In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC50 was predicted as 6.025 nM.

    CONCLUSION: Results indicated that flavonoids could be efficient inhibitors of AChE and thus, could be useful in the management of Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Fulltext Palm Raceme as a Promising Biomass Precursor for Activated Carbon to Promote Lipase Activity with the Aid of Eutectic Solvents
    Abed KM, Hayyan A, Elgharbawy AAM, Hizaddin HF, Hashim MA, Hasan HA, et al.
    Molecules, 2022 Dec 09;27(24).
    PMID: 36557866 DOI: 10.3390/molecules27248734
    This study concerns the role of activated carbon (AC) from palm raceme as a support material for the enhancement of lipase-catalyzed reactions in an aqueous solution, with deep eutectic solvent (DES) as a co-solvent. The effects of carbonization temperature, impregnation ratio, and carbonization time on lipase activity were studied. The activities of Amano lipase from Burkholderia cepacia (AML) and lipase from the porcine pancreas (PPL) were used to investigate the optimum conditions for AC preparation. The results showed that AC has more interaction with PPL and effectively provides greater enzymatic activity compared with AML. The optimum treatment conditions of AC samples that yield the highest enzymatic activity were 0.5 (NaOH (g)/palm raceme (g)), 150 min, and a carbonization temperature of 400 °C. DES was prepared from alanine/sodium hydroxide and used with AC for the further enhancement of enzymatic activity. Kinetic studies demonstrated that the activity of PPL was enhanced with the immobilization of AC in a DES medium.
  19. Fulltext Virtual Screening, Synthesis, and Biological Evaluation of Some Carbohydrazide Derivatives as Potential DPP-IV Inhibitors
    Jadhav PB, Jadhav SB, Zehravi M, Mubarak MS, Islam F, Jeandet P, et al.
    Molecules, 2022 Dec 24;28(1).
    PMID: 36615348 DOI: 10.3390/molecules28010149
    Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a-5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber's guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents.
  20. Fulltext An Automatic Premature Ventricular Contraction Recognition System Based on Imbalanced Dataset and Pre-Trained Residual Network Using Transfer Learning on ECG Signal
    Ullah H, Heyat MBB, Akhtar F, Muaad AY, Ukwuoma CC, Bilal M, et al.
    Diagnostics (Basel), 2022 Dec 28;13(1).
    PMID: 36611379 DOI: 10.3390/diagnostics13010087
    The development of automatic monitoring and diagnosis systems for cardiac patients over the internet has been facilitated by recent advancements in wearable sensor devices from electrocardiographs (ECGs), which need the use of patient-specific approaches. Premature ventricular contraction (PVC) is a common chronic cardiovascular disease that can cause conditions that are potentially fatal. Therefore, for the diagnosis of likely heart failure, precise PVC detection from ECGs is crucial. In the clinical settings, cardiologists typically employ long-term ECGs as a tool to identify PVCs, where a cardiologist must put in a lot of time and effort to appropriately assess the long-term ECGs which is time consuming and cumbersome. By addressing these issues, we have investigated a deep learning method with a pre-trained deep residual network, ResNet-18, to identify PVCs automatically using transfer learning mechanism. Herein, features are extracted by the inner layers of the network automatically compared to hand-crafted feature extraction methods. Transfer learning mechanism handles the difficulties of required large volume of training data for a deep model. The pre-trained model is evaluated on the Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) Arrhythmia and Institute of Cardiological Technics (INCART) datasets. First, we used the Pan-Tompkins algorithm to segment 44,103 normal and 6423 PVC beats, as well as 106,239 normal and 9987 PVC beats from the MIT-BIH Arrhythmia and IN-CART datasets, respectively. The pre-trained model employed the segmented beats as input after being converted into 2D (two-dimensional) images. The method is optimized with the using of weighted random samples, on-the-fly augmentation, Adam optimizer, and call back feature. The results from the proposed method demonstrate the satisfactory findings without the using of any complex pre-processing and feature extraction technique as well as design complexity of model. Using LOSOCV (leave one subject out cross-validation), the received accuracies on MIT-BIH and INCART are 99.93% and 99.77%, respectively, suppressing the state-of-the-art methods for PVC recognition on unseen data. This demonstrates the efficacy and generalizability of the proposed method on the imbalanced datasets. Due to the absence of device-specific (patient-specific) information at the evaluating stage on the target datasets in this study, the method might be used as a general approach to handle the situations in which ECG signals are obtained from different patients utilizing a variety of smart sensor devices.
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