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Structural and rheological changes of texturized mung bean protein induced by feed moisture during extrusion

Hossain Brishti F, Chay SY, Muhammad K, Rashedi Ismail-Fitry M, Zarei M, Karthikeyan S, et al.

Food Chem, 2021 May 15;344:128643.
PMID: 33246681 DOI: 10.1016/j.foodchem.2020.128643

Mung bean protein isolate was texturized at different feed moisture contents (30.0, 49.3, and 60.0%) at a constant temperature (144.57 °C) to evaluate the changes in protein profile, solubility, thermal, structural (at secondary and tertiary levels) and rheological properties. SDS-PAGE, surface hydrophobicity, circular dichroism, FTIR spectroscopy, and fluorescence analyses revealed protein unfolding, aggregation, and structural rearrangement as a function of feed moisture content. Extrusion at 49.3% feed moisture produced texturized mung bean protein (TMBP) with favourable partial denaturation, the formation of small aggregates, improved solubility, and digestibility with strong gel forming behaviour, whereas 30.0 and 60.0% moisture content resulted in complete protein denaturation, the undesirable formation of large aggregates and weak gels. In conclusion, protein denaturation and formation of aggregates can be controlled by manipulating feed moisture content during extrusion, with 49.3% feed moisture prompting favourable partial denaturation to produce TMBP with desirable qualities for use as a vegetarian-based meat extender.
Fulltext Modeling the effect of delay strategy on transmission dynamics of HIV/AIDS disease

Raza A, Ahmadian A, Rafiq M, Salahshour S, Naveed M, Ferrara M, et al.

Adv Differ Equ, 2020;2020(1):663.
PMID: 33250928 DOI: 10.1186/s13662-020-03116-8

In this manuscript, we investigate a nonlinear delayed model to study the dynamics of human-immunodeficiency-virus in the population. For analysis, we find the equilibria of a susceptible-infectious-immune system with a delay term. The well-established tools such as the Routh-Hurwitz criterion, Volterra-Lyapunov function, and Lasalle invariance principle are presented to investigate the stability of the model. The reproduction number and sensitivity of parameters are investigated. If the delay tactics are decreased, then the disease is endemic. On the other hand, if the delay tactics are increased then the disease is controlled in the population. The effect of the delay tactics with subpopulations is investigated. More precisely, all parameters are dependent on delay terms. In the end, to give the strength to a theoretical analysis of the model, a computer simulation is presented.
Fulltext Nationwide Survey of Knowledge and Health Beliefs regarding Human Papillomavirus among HPV-Vaccinated Female Students in Malaysia

Wong LP, Raja Muhammad Yusoff RN, Edib Z, Sam IC, Zimet GD

PLoS One, 2016 09 22;11(9):e0163156.
PMID: 27656876 DOI: 10.1371/journal.pone.0163156

The National HPV Immunization Programme, which offers free human papillomavirus (HPV) vaccines to teenaged female students, was launched in Malaysia in 2010. HPV vaccination paired with adequate knowledge about HPV infection provides the best protection against cervical cancer. To identify the level of knowledge and the health beliefs towards HPV and the HPV vaccine among HPV-vaccinated female students in Malaysia. A nationwide cross-sectional survey among 14 years old female students who had received three doses of the HPV vaccine was conducted in 32 randomly selected schools from 13 states and 3 federal territories in Malaysia between February 2013 and April 2013. Among 2482 respondents, knowledge about HPV infection and the HPV vaccine was extremely poor. The mean total knowledge score was only 3.56 (SD ± 1.76), out of a possible score of 10. The majority of respondents were unaware that vaccinating boys with HPV can help protect girls against HPV infection (91.6%), HPV cannot be cured (81.6%) and that HPV is a sexually transmitted infection (70.3%). Most of the respondents had the misconception that only females get HPV (95.1%), and that the HPV vaccine eliminates the need for Pap smear tests (68.3%). Most respondents (91.6%) believed that they would not get an HPV infection. Almost half of the respondents (42.9%) held the misconception that HPV infection could not lead to serious illness. Findings revealed poor knowledge about both HPV and the HPV vaccine, low perceived susceptibility to HPV infection and misinformation about HPV infection among HPV-vaccinated girls. Therefore, it is essential to increase the knowledge and awareness of health risks regarding HPV infection among teenaged girls who have received the HPV vaccine.
Fulltext Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis

Ab Mutalib NS, Othman SN, Mohamad Yusof A, Abdullah Suhaimi SN, Muhammad R, Jamal R

PeerJ, 2016;4:e2119.
PMID: 27350898 DOI: 10.7717/peerj.2119

Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives. We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results. PTC patients with LNM (PTC LNM-P) have a significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found four significant enrichment pathways potentially involved in metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine-cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. Conclusion. We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.
Fabrication of pristine Mn2O3 and Ag-Mn2O3 composite thin films by AACVD for photoelectrochemical water splitting

Naeem R, Ali Ehsan M, Yahya R, Sohail M, Khaledi H, Mazhar M

Dalton Trans, 2016 Oct 14;45(38):14928-39.
PMID: 27549401 DOI: 10.1039/c6dt02656g

Pristine Mn2O3 and Ag-Mn2O3 composite thin films have been developed on fluorine doped tin oxide (FTO) coated glass substrates at 450 °C by aerosol assisted chemical vapor deposition (AACVD) using a methanol solution of a 1 : 2 mixture of acetatoargentate(i), Ag(CH3COO), and a newly synthesized manganese complex, [Mn(dmae)2(TFA)4] (1) (dmae = N,N-dimethylaminoethanolate, TFA = trifluoroacetate). The phase purity and stoichiometric composition of the films were investigated by X-ray diffraction (XRD) and Raman spectroscopy techniques. Energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) analyses revealed a Ag to Mn ratio of 1 : 2 and further confirmed the uniform dispersion of Ag nanoparticles into the Mn2O3 structure. Optical studies showed a direct band gap of 2.0 eV for the pristine Mn2O3 film that was lowered to 1.8 eV for Ag-Mn2O3 due to the plasmonic interaction of Ag with Mn2O3. The Ag-Mn2O3 composite film displayed enhanced photocatalytic activity in photoelectrochemical (PEC) water splitting and yielded a photocurrent of 3 mA cm(-2) at 0.7 V versus Ag/AgCl which was 1.6 times higher than a pristine Mn2O3 film alone, under AM 1.5 G illumination (100 mW cm(-2)). The high PEC efficiency is mainly due to the plasmonic effect of Ag nanoparticles, which enhances the visible light absorption, efficient electron-hole separation and high carrier mobility of the Ag-Mn2O3 photoelectrode. The charge carrier density of Ag-Mn2O3 is two times higher than the pristine Mn2O3 as calculated by the Mott-Schottky plot. Based on the PEC studies a mechanism is proposed to elucidate the high activity of Ag-Mn2O3 in PEC water splitting.
Fulltext Antimicrobial Susceptibility of Klebsiella pneumoniae and Escherichia coli with Extended-Spectrum β-lactamase associated Genes in Hospital Tengku Ampuan Afzan, Kuantan, Pahang

Mahdi Yahya Mohsen S, Hamzah HA, Muhammad Imad Al-Deen M, Baharudin R

Malays J Med Sci, 2016 Mar;23(2):14-20.
PMID: 27547110 MyJurnal

To assess antimicrobial susceptibility of extended-spectrum β-lactamase- (ESBL-) producing Klebsiella pneumoniae and Escherichia coli isolates from Hospital Tengku Ampuan Afzan (HTAA), as well as to identify ESBL genes.
Optoelectronic properties of naphtho[2, 1-b:6, 5-b']difuran derivatives for photovoltaic application: a computational study

Chaudhry AR, Ahmed R, Irfan A, Mohamad M, Muhammad S, Ul Haq B, et al.

J Mol Model, 2016 Oct;22(10):248.
PMID: 27683259

Some important optoelectronic properties of naphtho[2,1-b:6,5-b']difuran (DPNDF) and its two derivatives have been limelighted by applying the density functional theory (DFT). Due to their low cost, high stability and earth abundance, the DPNDF and its derivatives are considered as potential organic semiconductor materials for their optoelectronics applications. Highly proficient derivatives are obtained systematically by attaching -CN (cyanide) to DPNDF at various sites. Our calculations indicate that DPNDF has a wide and direct band gap with an energy gap of 3.157 eV. Whereas the band gaps of its derivatives are found to be decreased by 88 meV for derivative "a" and 300 meV for derivative "b" as a consequence of p orbitals present in C and N atoms in derivative structures. The narrowing of the energy gap and density of states for the derivatives of DPNDF in the present investigation suggest that energy gap can be engineered for desirable optoelectronic applications via derivatives designing. Furthermore, their obtained results for optical parameters such as the dielectric and conductivity functions, reflectivity, refractive index, and the extinction coefficients endorses their aptness for optoelectronic applications. Graphical Abstract Real part of dielectric function for derivative "b".
Molecular hybridization conceded exceptionally potent quinolinyl-oxadiazole hybrids through phenyl linked thiosemicarbazide antileishmanial scaffolds: In silico validation and SAR studies

Taha M, Ismail NH, Ali M, Rashid U, Imran S, Uddin N, et al.

Bioorg Chem, 2017 04;71:192-200.
PMID: 28228228 DOI: 10.1016/j.bioorg.2017.02.005

The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC50=0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis. In silico analysis were also performed to probe the mode of action while all the compounds structure were established by NMR and Mass spectral analysis.
Carbohydrazones as new class of carbonic anhydrase inhibitors: Synthesis, kinetics, and ligand docking studies

Iqbal S, Saleem M, Azim MK, Taha M, Salar U, Khan KM, et al.

Bioorg Chem, 2017 06;72:89-101.
PMID: 28390994 DOI: 10.1016/j.bioorg.2017.03.014

Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.
Fulltext Physical and psychosocial impacts of pregnancy on adolescents and their coping strategies: a descriptive study in Kuala Lumpur, Malaysia

Su XV, Muhammad NA, Tan PS, Tan KTM, Tohid H, Omar K

Malaysian Journal of Public Health Medicine, 2014;14(3):0-0.
MyJurnal

Teenage pregnancy carries serious impacts on adolescent health. This study aimed to examine the effects of pregnancy on adolescents and to explore how they cope with the problems they faced during the pregnancy. It involved 26 adolescents residing in a government shelter home in Kuala Lumpur. A self-administered questionnaire containing a mixture of open- and closed-ended questions was used. Among physical (sleeping problem and self-care problem), psychological (emotional difficulties and low self-efficacy) and social (stigma and discrimination, financial difficulty, friendship problem and school dropout) problems, emotional difficulties were the most common problems, whereas stigma and discrimination was the least common. Young adolescents aged less than 16 years old were significantly associated with poor self-care (p=0.01). To cope with their problems, the adolescents generally used avoidance, withdrawal, and social support, particularly from parents and peers. Doctors were the least popular among all. In conclusion, holistic and individualised care is needed. Strategies to reduce emotional problem experienced by pregnant adolescents should be implemented. The available healthcare services for teenage pregnancy should also be promoted.
Intra- and Inter-database Study for Arabic, English, and German Databases: Do Conventional Speech Features Detect Voice Pathology?

Ali Z, Alsulaiman M, Muhammad G, Elamvazuthi I, Al-Nasheri A, Mesallam TA, et al.

J Voice, 2017 May;31(3):386.e1-386.e8.
PMID: 27745756 DOI: 10.1016/j.jvoice.2016.09.009

A large population around the world has voice complications. Various approaches for subjective and objective evaluations have been suggested in the literature. The subjective approach strongly depends on the experience and area of expertise of a clinician, and human error cannot be neglected. On the other hand, the objective or automatic approach is noninvasive. Automatic developed systems can provide complementary information that may be helpful for a clinician in the early screening of a voice disorder. At the same time, automatic systems can be deployed in remote areas where a general practitioner can use them and may refer the patient to a specialist to avoid complications that may be life threatening. Many automatic systems for disorder detection have been developed by applying different types of conventional speech features such as the linear prediction coefficients, linear prediction cepstral coefficients, and Mel-frequency cepstral coefficients (MFCCs). This study aims to ascertain whether conventional speech features detect voice pathology reliably, and whether they can be correlated with voice quality. To investigate this, an automatic detection system based on MFCC was developed, and three different voice disorder databases were used in this study. The experimental results suggest that the accuracy of the MFCC-based system varies from database to database. The detection rate for the intra-database ranges from 72% to 95%, and that for the inter-database is from 47% to 82%. The results conclude that conventional speech features are not correlated with voice, and hence are not reliable in pathology detection.
Passive bioremediation technology incorporating lignocellulosic spent mushroom compost and limestone for metal- and sulfate-rich acid mine drainage

Muhammad SN, Kusin FM, Md Zahar MS, Mohamat Yusuff F, Halimoon N

Environ Technol, 2017 Aug;38(16):2003-2012.
PMID: 27745113 DOI: 10.1080/09593330.2016.1244568

Passive bioremediation of metal- and sulfate-containing acid mine drainage (AMD) has been investigated in a batch study. Multiple substrates were used in the AMD remediation using spent mushroom compost (SMC), limestone, activated sludge (AS), and woodchips (WC) under anoxic conditions suitable for bacterial sulfate reduction (BSR). Limestones used were of crushed limestone (CLS) and uncrushed limestone, provided at two different ratios in mixed substrates treatment and varied by the proportion of SMC and limestone. The SMC greatly assisted the removals of sulfate and metals and also acted as an essential carbon source for BSR. The mixed substrate composed of 40% CLS, 30% SMC, 20% AS, and 10% WC was found to be effective for metal removal. Mn, Cu, Pb, and Zn were greatly removed (89-100%) in the mixed substrates treatment, while Fe was only removed at 65%. Mn was found to be removed at a greatly higher rate than Fe, suggesting important Mn adsorption onto organic materials, that is, greater sorption affinity to the SMC. Complementary with multiple treatment media was the main mechanism assisting the AMD treatment through microbial metal reduction reactions.
Fulltext Evaluation of the antioxidant activity of Betula pendula leaves extract and its effects on model foods

Azman NA, Skowyra M, Muhammad K, Gallego MG, Almajano MP

Pharm Biol, 2017 Dec;55(1):912-919.
PMID: 28152668 DOI: 10.1080/13880209.2017.1282528

CONTEXT: Betula pendula Roth (Betulaceae) exhibits many pharmacological activities in humans including anticancer, antibacterial, and antiviral effects. However, the antioxidant activity of BP towards lipid degradation has not been fully determined.
OBJECTIVE: The BP ethanol and methanol extracts were evaluated to determine antioxidant activity by an in vitro method and lyophilized extract of BP was added to beef patties to study oxidative stability.
MATERIALS AND METHODS: Antioxidant activities of extracts of BP were determined by measuring scavenging radical activity against methoxy radical generated by Fenton reaction 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (TEAC) radical cation, the oxygen radical absorbance capacity (ORAC) and the ferric reducing antioxidant power (FRAP) assays. The lipid deterioration in beef patties containing 0.1% and 0.3% (w/w) of lyophilized extract of BP stored in 80:20 (v/v) O2:CO2 modified atmosphere (MAP) at 4 °C for 10 days was determined using thiobarbituric acid reacting substances (TBARS), % metmyoglobin and colour value.
RESULTS: The BP methanol extract revealed the presence of catechin, myricetin, quercetin, naringenin, and p-coumaric acid. The BP ethanol (50% w/w) extract showed scavenging activity in TEAC, ORAC and FRAP assays with values of 1.45, 2.81, 1.52 mmol Trolox equivalents (TE)/g DW, respectively. Reductions in lipid oxidation were found in samples treated with lyophilized BP extract (0.1% and 0.3% w/w) as manifested by the changes of colour and metmyoglobin concentration. A preliminary study film with BP showed retard degradation of lipid in muscle food.
CONCLUSION: The present results indicated that the BP extracts can be used as natural food antioxidants.
Fulltext Fermented Brown Rice Flour as Functional Food Ingredient

Ilowefah M, Chinma C, Bakar J, Ghazali HM, Muhammad K, Makeri M

Foods, 2014 Feb 12;3(1):149-159.
PMID: 28234309 DOI: 10.3390/foods3010149

As fermentation could reduce the negative effects of bran on final cereal products, the utilization of whole-cereal flour is recommended, such as brown rice flour as a functional food ingredient. Therefore, this study aimed to investigate the effect of fermented brown rice flour on white rice flour, white rice batter and its steamed bread qualities. Brown rice batter was fermented using commercial baker's yeast (Eagle brand) according to the optimum conditions for moderate acidity (pH 5.5) to obtain fermented brown rice flour (FBRF). The FBRF was added to white rice flour at 0%, 10%, 20%, 30%, 40% and 50% levels to prepare steamed rice bread. Based on the sensory evaluation test, steamed rice bread containing 40% FBRF had the highest overall acceptability score. Thus, pasting properties of the composite rice flour, rheological properties of its batter, volume and texture properties of its steamed bread were determined. The results showed that peak viscosity of the rice flour containing 40% FBRF was significantly increased, whereas its breakdown, final viscosity and setback significantly decreased. Viscous, elastic and complex moduli of the batter having 40% FBRF were also significantly reduced. However, volume, specific volume, chewiness, resilience and cohesiveness of its steamed bread were significantly increased, while hardness and springiness significantly reduced in comparison to the control. These results established the effectiveness of yeast fermentation in reducing the detrimental effects of bran on the sensory properties of steamed white rice bread and encourage the usage of brown rice flour to enhance the quality of rice products.
Fulltext Treating an infected transcatheter pacemaker system via percutaneous extraction

Koay A, Khelae S, Wei KK, Muhammad Z, Mohd Ali R, Omar R

HeartRhythm Case Rep, 2016 Jul;2(4):360-362.
PMID: 28491710 DOI: 10.1016/j.hrcr.2016.04.006
Gene Expression Profiling associated with Hepatoxicity in Pregnant Rats treated with Ubi Gadong (Dioscorea hispida) Extract

Faradianna Lokman E, Muhammad H, Awang N, Hasyima Omar M, Mansor F, Saparuddin F

Int J Biomed Sci, 2017 Mar;13(1):26-34.
PMID: 28533734

Dioscorea hispida (D.hispida) is the most well-known starchy tuber in Malaysia and called 'ubi gadong'. Despite concerns over toxicity effects, the tuber is known to possess therapeutic values due to the presence of bioactive compounds such as saponins. This study was performed to identify the changes in gene expression profiles associated with hepatoxicity in pregnant rat treated with D.hispida using RT² Profiler PCR Array. The identification of steroidal saponins from D.hispida was carried out by UHPLC/MS method. Treatment of D.hispida caused mortality when dosage above 2000 mg/kg b.w. was given to pregnant rats. The PCR array showed that several genes were significantly up and down-regulated upon treatment with D.hispida. Treatment of D.hispida at 2000 mg/kg b.w leads to significant upregulation of several genes such as Btg2, Gsr, L2hgdn, S100a8, Slc17a3, Bhmt, Cd68, Cyp1a2 whereas several genes were downregulated such as Abcb1a, Aldoa, Cdc14b, Icam1, Krt18, Hpn and Maob. The consumption of D.hispida extract when taken at lower dosage of 2000 mg/kg may not be harmful to rats. D.hispida extract given at the highest dosage to pregnant rats caused alterations of several genes categorized in different hepatotoxic group functions such as necrosis, cholestasis and phospholipodisis.
Swelling mechanism of urea cross-linked starch-lignin films in water

Sarwono A, Man Z, Bustam MA, Subbarao D, Idris A, Muhammad N, et al.

Environ Technol, 2018 Jun;39(12):1522-1532.
PMID: 28524800 DOI: 10.1080/09593330.2017.1332108

Coating fertilizer particles with thin films is a possibility to control fertilizer release rates. It is observed that novel urea cross-linked starch-lignin composite thin films, prepared by solution casting, swell on coming into contact with water due to the increase in volume by water uptake by diffusion. The effect of lignin content, varied from 0% to 20% in steps of 5% at three different temperatures (25°C, 35°C and 45°C), on swelling of the film was investigated. By gravimetric analysis, the equilibrium water uptake and diffusion coefficient decrease with lignin content, indicating that the addition of lignin increases the hydrophobicity of the films. When temperature increases, the diffusion coefficient and the amount of water absorbed tend to increase. Assuming that swelling of the thin film is by water uptake by diffusion, the diffusion coefficient is estimated. The estimated diffusion coefficient decreases from 4.3 to 2.1 × 10-7 cm2/s at 25°C, from 5.3 to 2.9 × 10-7 cm2/s at 35°C and from 6.2 to 3.8 × 10-7 cm2/s at 45°C depending on the lignin content. Activation energy for the increase in diffusion coefficient with temperature is observed to be 16.55 kJ/mol. An empirical model of water uptake as a function of percentage of lignin and temperature was also developed based on Fick's law.
Fulltext Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies

Ashraf Z, Rafiq M, Nadeem H, Hassan M, Afzal S, Waseem M, et al.

PLoS One, 2017;12(5):e0178069.
PMID: 28542395 DOI: 10.1371/journal.pone.0178069

The present work describesthe development of highly potent mushroom tyrosinase inhibitor better than the standard kojic acid. Carvacrol derivatives 4a-f and 6a-d having substituted benzoic acid and cinnamic acidresidues were synthesized with the aim to possess potent tyrosinase inhibitory activity.The structures of the synthesized compounds were ascertained by their spectroscopic data (FTIR, 1HNMR, 13CNMR and Mass Spectroscopy).Mushroom tyrosinase inhibitory activity of synthesized compounds was determined and it was found that one of the derivative 6c possess higher activity (IC50 0.0167μM) than standard kojic acid (IC50 16.69μM). The derivatives 4c and 6b also showed good tyrosinase inhibitory activity with (IC50 16.69μM) and (IC50 16.69μM) respectively.Lineweaver-Burk and Dixon plots were used for the determination of kinetic mechanism of the compounds 4c and 6b and 6c. The kinetic analysis revealed that compounds 4c and 6b showed mixed-type inhibition while 6c is a non-competitive inhibitor having Ki values19 μM, 10 μM, and 0.05 μMrespectively. The enzyme inhibitory kinetics further showed thatcompounds 6b and 6c formed irreversible enzyme inhibitor complex while 4c bind reversibly with mushroom tyrosinase.The docking studies showed that compound 6c have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-7.90 kcal/mol) as compared to others.The 2-hydroxy group in compound 6c interacts with amino acid HIS85 which is present in active binding site. The wet lab results are in good agreement with the dry lab findings.Based upon our investigation we may propose that the compound 6c is promising candidate for the development of safe cosmetic agent.
Fulltext Phytochemical and In Vitro Genotoxicity Studies of Standardized Ficus deltoidea var. kunstleri Aqueous Extract

Muhammad H, Omar MH, Rasid ENI, Suhaimi SN, Mohkiar FH, Siu LM, et al.

Plants (Basel), 2021 Feb 11;10(2).
PMID: 33670296 DOI: 10.3390/plants10020343

The present study was carried out to assess the genotoxicity potential of Ficus deltoidea var. kunstleri aqueous extract (FDAE) using standard in vitro assays. The DNA damage of V79B cells was measured using the alkaline comet assay treated at 0.1 mg/mL (IC10) and 0.3 mg/mL (IC25) of FDAE together with positive and negative controls. For in vitro micronucleus assay, the V79B cells were treated with FDAE at five different concentrations (5, 2.5, 1.25, 0.625, and 0.3125 mg/mL) with and without S9 mixture. The bacteria reverse mutation assay of FDAE was performed on Salmonella typhimurium strains TA98, 100, 1535, 1537, and Escherichia coli strain WP2uvrA using pre-incubation method in the presence or in the absence of an extrinsic metabolic system (S9 mixture). FDAE at 0.1 and 0.3 mg/mL significantly increased DNA damage in both comet tail and tail moment (p < 0.05). No significant changes were detected in the number of micronucleated cell when compared to control. Tested at the doses up to 5000 µg/plate, the FDAE did not increase the number of revertant colonies for all strains. In conclusion, further investigation needs to be conducted in animal model to confirm the non-genotoxicity activities of FDAE.
Depression and Severity of Glaucoma Among Older Adults in Urban and Suburban Areas

Tharmathurai S, Muhammad-Ikmal MK, Razak AA, Che-Hamzah J, Azhany Y, Fazilawati Q, et al.

J Glaucoma, 2021 May 01;30(5):e205-e212.
PMID: 33710066 DOI: 10.1097/IJG.0000000000001830

PRCIS: Depression increases with severity of visual field defect in older adults with primary open-angle glaucoma (POAG).
PURPOSE: This study aimed to determine the prevalence of depression among patients with POAG and examine the relationship between depression and the severity of POAG in older adults.
MATERIALS AND METHODS: Three hundred and sixty patients with POAG aged 60 years or above were recruited from 2 tertiary centers located in an urban and suburban area. The participants were stratified according to the severity of their glaucoma based on the scores from the modified Advanced Glaucoma Intervention Study (AGIS) to mild, moderate, severe, and end stage. Face-to-face interviews were performed using the Malay Version Geriatric Depression Scale 14 (mGDS-14) questionnaire. Depression is diagnosed when the score is ≥8. One-way analysis of variance was used to compare the subscores between the groups. Multifactorial analysis of variance was also applied with relevant confounding factors.
RESULTS: Depression was detected in 16% of older adults with POAG; a higher percentage of depression was seen in those with end stage disease. There was a significant increase in the mean score of mGDS-14 according to the severity of POAG. There was evidence of an association between depression and severity of visual field defect (P<0.001). There was a significant difference in mGDS-14 score between the pairing of severity of POAG [mild-severe (P=0.003), mild-end stage (P<0.001), moderate-severe (P<0.001), and moderate-end stage (P<0.001)] after adjustment to living conditions, systemic disease, and visual acuity.
CONCLUSION: Ophthalmologists should be aware that older adults with advanced visual field defects in POAG may have depression. The detection of depression is important to ensure adherence and persistence to the treatment of glaucoma.

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