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Fulltext Unsteady MHD Thin Film Flow of an Oldroyd-B Fluid over an Oscillating Inclined Belt

Gul T, Islam S, Shah RA, Khalid A, Khan I, Shafie S

PLoS One, 2015;10(7):e0126698.
PMID: 26147287 DOI: 10.1371/journal.pone.0126698

This paper studies the unsteady magnetohydrodynamics (MHD) thin film flow of an incompressible Oldroyd-B fluid over an oscillating inclined belt making a certain angle with the horizontal. The problem is modeled in terms of non-linear partial differential equations with some physical initial and boundary conditions. This problem is solved for the exact analytic solutions using two efficient techniques namely the Optimal Homotopy Asymptotic Method (OHAM) and Homotopy Perturbation Method (HPM). Both of these solutions are presented graphically and compared. This comparison is also shown in tabular form. An excellent agreement is observed. The effects of various physical parameters on velocity have also been studied graphically.
Fulltext Endemic goiter in the Lemanak and Ai river villages of Sarawak

Foo LC, Zainab T, Letchuman GR, Nafikudin M, Azriman R, Doraisingam P, et al.

Southeast Asian J. Trop. Med. Public Health, 1994 Sep;25(3):575-8.
PMID: 7777929

In a survey of 974 villagers (408 males, 566 females; ages = 11-82 years) of the Ai (n = 496; 212 males, 284 females) and Lemanak (n = 478; 196 males, 282 females) rivers in the district of Lubuk Antu in Sarawak's Sri Aman Division during July 1993, goiter was found in 31.8% of the subjects. The goiter prevalence was higher in the more interior Ai river area than in the Lemanak river area (36.9% vs 26.5%). In females aged 15 years and above, the goiter prevalence was 75.4% and 49.1%, respectively, in the Ai and Lemanak river areas. The difference in goiter prevalence between the two areas was related to the degree of iodine deficiency in the two areas. The median urinary iodine excretion in the Ai river villagers was 22.1 micrograms/l compared to 72.9 micrograms/l in the Lemanak river villagers (p < 0.0001). Goitrous subjects tended to have lower urinary iodine concentration than non-goitrous subjects. In the males, smoking of tobacco was associated with a two-fold increase in goiter frequency. Despite on-going distribution of iodized salt by the medical and health services in the State, only 23% of the 135 salt samples obtained from the households in the areas contained detectable iodine.
Glutathione S-transferase and gamma-glutamyl transpeptidase activities in cultured rat hepatocytes treated with tocotrienol and tocopherol

Ong FB, Wan Ngah WZ, Shamaan NA, Md Top AG, Marzuki A, Khalid AK

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1993 Sep;106(1):237-40.
PMID: 7903615

1. The effect of tocotrienol and tocopherol on glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (GGT) activities in cultured rat hepatocytes were investigated. 2. Tocotrienol and tocopherol significantly decreased GGT activities at 5 days in culture but tocotrienol also significantly decreased GGT activities at 1-2 days. 3. Tocotrienol and tocopherol treatment significantly decreased GST activities at 3 days compared to the control but tocotrienol also decreased GST activities at 1-3 days. 4. Tocotrienol showed a more pronounced effect at a dosage of greater than 50 microM tocotrienol at 1-3 days in culture compared to the control.
Fulltext Information technology for patient safety

Huckvale C, Car J, Akiyama M, Jaafar S, Khoja T, Bin Khalid A, et al.

Qual Saf Health Care, 2010 Aug;19 Suppl 2:i25-33.
PMID: 20693213 DOI: 10.1136/qshc.2009.038497

BACKGROUND: Research on patient care has identified substantial variations in the quality and safety of healthcare and the considerable risks of iatrogenic harm as significant issues. These failings contribute to the high rates of potentially avoidable morbidity and mortality and to the rising levels of healthcare expenditure seen in many health systems. There have been substantial developments in information technology in recent decades and there is now real potential to apply these technological developments to improve the provision of healthcare universally. Of particular international interest is the use of eHealth applications. There is, however, a large gap between the theoretical and empirically demonstrated benefits of eHealth applications. While these applications typically have the technical capability to help professionals in the delivery of healthcare, inadequate attention to the socio-technical dimensions of their use can result in new avoidable risks to patients.
RESULTS AND DISCUSSION: Given the current lack of evidence on quality and safety improvements and on the cost-benefits associated with the introduction of eHealth applications, there should be a focus on implementing more mature technologies; it is also important that eHealth applications should be evaluated against a comprehensive and rigorous set of measures, ideally at all stages of their application life cycle.
Recent progress on CO-rich syngas production via CO2 gasification of various wastes: A critical review on efficiency, challenges and outlook

Chan YH, Syed Abdul Rahman SNF, Lahuri HM, Khalid A

Environ Pollut, 2021 Mar 01;278:116843.
PMID: 33711630 DOI: 10.1016/j.envpol.2021.116843

Carbon monoxide (CO) is a highly valuable component of syngas which could be used to synthesize various chemicals and fuels. Conventionally, syngas is derived from fossil-based natural gas and coal which are non-renewable. To curb the problem, CO2 gasification offers a win-win solution in which CO2 is converted with wastes to CO, achieving carbon emission mitigation and addressing waste disposal issue simultaneously. In this review, gasification of various wastes by CO2 with particular focus given to generation of CO-rich syngas is presented and critically discussed. This includes the effects of operating parameters (temperature, pressure and physicochemical properties of feedstocks) and advanced CO2 gasification techniques (catalytic CO2 gasification, CO2 co-gasification and microwave-driven CO2 gasification). Furthermore, associated technological challenges are highlighted and way forward in this field are proposed.
In vivo and in vitro effects on cholinesterase of blood of Oreochromis mossambicus by copper

Basirun AA, Ahmad SA, Sabullah MK, Yasid NA, Daud HM, Khalid A, et al.

3 Biotech, 2019 Feb;9(2):64.
PMID: 30729088 DOI: 10.1007/s13205-019-1592-0

The present study is aimed to evaluate the effects of sub-acute toxicity testing of copper sulphate (CuSO4), on behavioural, histological and biochemical changes of the Oreochromis mossambicus (black tilapia) blood tissues. The effects were assessed according to the previous results on sub-acute toxicity test after exposing fish to several concentrations (0.0, 2.5, 5.0, and 10.0 mg/L). The observations of scanning electron microscope, and transmission electron microscope studies revealed severe histopathological changes on the surface and the cellular changes in blood tissues, respectively. The morphological alterations in blood involved irregular structure of red blood cell and blood clot formation. CuSO4 affected the biochemical alteration of the blood cholinesterase also known as serum cholinesterase (ChE). Blood ChE inhibited up to 80% of activity when exposed to 10.0 mg/L CuSO4. The findings from this study can further improve the quality standards of aquaculture industry and the fundamental basis in selecting suitable strains among freshwater fish species to be used as bioindicator.
Pharmacological Effects of Turmeric on Learning, Memory and Expression of Muscarinic Receptor Genes (M1, M3 and M5) in Stress-induced Mouse Model

Khalid A, Shakeel R, Justin S, Iqbal G, Shah SAA, Zahid S, et al.

Curr Drug Targets, 2017;18(13):1545-1557.
PMID: 28302036 DOI: 10.2174/1389450118666170315120627

BACKGROUND: Stress is involved in memory impairment through multiple mechanisms, including activation of hypothalamic-pituitary axis, which in turn activates release of corticosterone in blood. Cholinergic system blockade by the muscarinic antagonist, scopolamine, also impairs memory.
OBJECTIVE: This study aimed to investigate the effect of turmeric (20mg/kg) on learning and memory and cholinergic system in a mouse model of stress along with cholinergic blockade.
METHODS: Restrained stress was induced and cholinergic receptors were blocked using scopolamine in mice. Animals were treated with turmeric (turmeric rhizome powder which was also subjected to NMR analyses) and learning and social behavior was examined. Effect of turmeric on cholinergic muscarinic receptors (mAChR; M1, M3 and M5) gene expression was assessed by RT-PCR in both pre-frontal cortex and hippocampus.
RESULTS: Ar-turmerone, curcuminoids and α-linolenic acid were the lead compounds present in turmeric extract. Increased serum corticosterone levels were observed in stressed mice when compared to the control group, while turmeric treatment significantly reduced serum corticosterone level. Turmeric treatment caused an improved learning and memory in Morris water maze test in stressed animals. Social novelty preference was also restored in turmeric treated animals. Following turmeric treatment, M5 expression was improved in the cortex and M3 expression was improved in the hippocampus of stress + scopolamine + turmeric treated group.
CONCLUSIONS: These findings highlight the therapeutic role of turmeric by increasing the expression of M3, M5 and improving learning and memory. Turmeric can be an effective candidate for the treatment of amnesia caused by the stress.
Fulltext A qualitative study exploring perceptions and attitudes of community pharmacists about extended pharmacy services in Lahore, Pakistan

Hashmi FK, Hassali MA, Khalid A, Saleem F, Aljadhey H, Babar ZUD, et al.

BMC Health Serv Res, 2017 07 19;17(1):500.
PMID: 28724411 DOI: 10.1186/s12913-017-2442-6

BACKGROUND: In recent decades, community pharmacies reported a change of business model, whereby a shift from traditional services to the provision of extended roles was observed. However, such delivery of extended pharmacy services (EPS) is reported from the developed world, and there is scarcity of information from the developing nations. Within this context, the present study was aimed to explore knowledge, perception and attitude of community pharmacists (CPs) about EPS and their readiness and acceptance for practice change in the city of Lahore, Pakistan.
METHODS: A qualitative approach was used to gain an in-depth knowledge of the issues. By using a semi-structured interview guide, 12 CPs practicing in the city of Lahore, Pakistan were conveniently selected. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework.
RESULTS: Thematic content analysis yielded five major themes. (1) Familiarity with EPS, (2) current practice of EPS, (3) training needed to provide EPS, (4) acceptance of EPS and (5) barriers toward EPS. Majority of the CPs were unaware of EPS and only a handful had the concept of extended services. Although majority of our study respondents were unaware of pharmaceutical care, they were ready to accept practice change if provided with the required skills and training. Lack of personal knowledge, poor public awareness, inadequate physician-pharmacist collaboration and deprived salary structures were reported as barriers towards the provision of EPS at the practice settings.
CONCLUSION: Although the study reported poor awareness towards EPS, the findings indicated a number of key themes that can be used in establishing the concept of EPS in Pakistan. Over all, CPs reported a positive attitude toward practice change provided to the support and facilitation of health and community based agencies in Pakistan.
Assessing regional left ventricular thickening dysfunction and dyssynchrony via personalized modeling and 3D wall thickness measurements for acute myocardial infarction

Khalid A, Lim E, Chan BT, Abdul Aziz YF, Chee KH, Yap HJ, et al.

J Magn Reson Imaging, 2019 04;49(4):1006-1019.
PMID: 30211445 DOI: 10.1002/jmri.26302

BACKGROUND: Existing clinical diagnostic and assessment methods could be improved to facilitate early detection and treatment of cardiac dysfunction associated with acute myocardial infarction (AMI) to reduce morbidity and mortality.
PURPOSE: To develop 3D personalized left ventricular (LV) models and thickening assessment framework for assessing regional wall thickening dysfunction and dyssynchrony in AMI patients.
STUDY TYPE: Retrospective study, diagnostic accuracy.
SUBJECTS: Forty-four subjects consisting of 15 healthy subjects and 29 AMI patients.
FIELD STRENGTH/SEQUENCE: 1.5T/steady-state free precession cine MRI scans; LGE MRI scans.
ASSESSMENT: Quantitative thickening measurements across all cardiac phases were correlated and validated against clinical evaluation of infarct transmurality by an experienced cardiac radiologist based on the American Heart Association (AHA) 17-segment model.
STATISTICAL TEST: Nonparametric 2-k related sample-based Kruskal-Wallis test; Mann-Whitney U-test; Pearson's correlation coefficient.
RESULTS: Healthy LV wall segments undergo significant wall thickening (P 50% transmurality) underwent remarkable wall thinning during contraction (thickening index [TI] = 1.46 ± 0.26 mm) as opposed to healthy myocardium (TI = 4.01 ± 1.04 mm). For AMI patients, LV that showed signs of thinning were found to be associated with a significantly higher percentage of dyssynchrony as compared with healthy subjects (dyssynchrony index [DI] = 15.0 ± 5.0% vs. 7.5 ± 2.0%, P
Fulltext Insulin-like growth factor-I and fast growth-hormone levels in mild and moderately malnourished children

Wan Nazaimoona WM, Osman A, Ng ML, Tan TT, Wu LL, Sakinah O, et al.

Asia Pac J Clin Nutr, 1992 Dec;1(4):207-10.
PMID: 24323236

Insulin-like growth factor-I (IGF-I)and fasting growth hormone levels were measured in a group of 255 children (163 males and 92 females. age ranged 6-17 years) of varying pubertal development and body mass index (BMI); well-nourished (BMI> 18). mildly-malnourished (BMI = 15-18) and moderately-malnourished (BMI<15). In well-nourished children IGF-I levels increased significantly (P = 0.02) with pubertal development. where girls at Tanner 5 had significantly higher (p = 0.03) IGF-I levels than the boys. Whilst there was no change in fasting GH levels with nutritional status, IGF-I levels of prepubertal boys and girls decreased significantly with BMI (P<0.001 and P = 0.01 respectively). Hence. measurement of IGF-I levels is a sensitive biochemical index in the assessment of mild and moderate form of malnutrition in prepubertal children.
Toxic effects of copper on liver and cholinesterase of Clarias gariepinus

Padrilah SN, Ahmad SA, Yasid NA, Sabullah MK, Daud HM, Khalid A, et al.

Environ Sci Pollut Res Int, 2017 Oct;24(28):22510-22523.
PMID: 28804856 DOI: 10.1007/s11356-017-9923-3

The release of pollutants, especially heavy metals, into the aquatic environment is known to have detrimental effects on such an environment and on living organisms including humans when those pollutants are allowed to enter the food chain. The aim of this study is to analyse the damage to Clarias gariepinus' liver caused by exposure to different concentrations of copper. In the present study, samples of C. gariepinus were exposed to sub-lethal copper sulphate (CuSO4) concentrations (from 0.2 to 20.0 mg/L) for 96 h. Physiological and behavioural alterations were observed with respect to their swimming pattern, mucus secretion and skin colour. Mortality was also observed at high concentrations of copper. Histopathological alterations of the liver were analysed under light, transmission and scanning electron microscopies. The liver of the untreated group showed normal tissue structures, while histopathological abnormalities were observed in the treated fish under light and electron microscopes with increased copper concentrations. Histopathological abnormalities include necrosis, melanomacrophage, hepatic fibrosis and congested blood vessels. In addition, the enzyme activity of liver cholinesterase (ChE) was also found to be affected by copper sulphate, as 100% of cholinesterase activity was inhibited at 20.0 mg/L. Thus, liver enzyme activity and histopathological changes are proven to be alternative sources for biomarkers of metal toxicity.
Protective and stochastic correlation between infectious diseases and autoimmune disorders

Aboulaghras S, Bouyahya A, El Kadri K, Khalid A, Abdalla AN, Hassani R, et al.

Microb Pathog, 2024 Sep 06;196:106919.
PMID: 39245422 DOI: 10.1016/j.micpath.2024.106919

A priori, early exposure to a wide range of bacteria, viruses, and parasites appears to fortify and regulate the immune system, potentially reducing the risk of autoimmune diseases. However, improving hygiene conditions in numerous societies has led to a reduction in these microbial exposures, which, according to certain theories, could contribute to an increase in autoimmune diseases. Indeed, molecular mimicry is a key factor triggering immune system reactions; while it seeks pathogens, it can bind to self-molecules, leading to autoimmune diseases associated with microbial infections. On the other hand, a hygiene-based approach aimed at reducing the load of infectious agents through better personal hygiene can be beneficial for such pathologies. This review sheds light on how the evolution of the innate immune system, following the evolution of molecular patterns associated with microbes, contributes to our protection but may also trigger autoimmune diseases linked to microbes. Furthermore, it addresses how hygiene conditions shield us against autoimmune diseases related to microbes but may lead to autoimmune pathologies not associated with microbes.
Contamination and ecological risk assessment of Cr, As, Cd and Pb in water and sediment of the southeastern Bay of Bengal coast in a developing country

Islam MS, Islam MT, Antu UB, Saikat MSM, Ismail Z, Shahid S, et al.

Mar Pollut Bull, 2023 Dec;197:115720.
PMID: 37939519 DOI: 10.1016/j.marpolbul.2023.115720

Safe levels of heavy metals in the surface water and sediment of the eastern Bay of Bengal coast have not been universally established. Current study characterized heavy metals such as arsenic (As), chromium (Cr), cadmium (Cd) and lead (Pb) in surface water and sediments of the most important fishing resource at the eastern Bay of Bengal coast, Bangladesh. Both water and sediment samples were analyzed using inductively coupled plasma mass spectrometer. Considering both of the seasons, the mean concentrations of Cr, As, Cd, and Pb in water samples were 33.25, 8.14, 0.48, and 21.14 μg/L, respectively and in sediment were 30.47, 4.48, 0.20, and 19.98 mg/kg, respectively. Heavy metals concentration in water samples surpassed the acceptable limits of usable water quality, indicating that water from this water resource is not safe for drinking, cooking, bathing, and any other uses. Enrichment factors also directed minor enrichment of heavy metals in sediment of the coast. Other indexes for ecological risk assessment such as pollution load index (PLI), contamination factor (CF), geoaccumulation index (Igeo), modified contamination degree (mCd), and potential ecological risk index (PERI) also indicated that sediment of the coastal watershed was low contamination. In-depth inventorying of heavy metals in both water and sediment of the study area are required to determine ecosystem health for holistic risk assessment and management.
WITHDRAWN: Trace metals translocation from soil to plants: Health risk assessment via consumption of vegetables in the urban sprawl of a developing country

Haque KS, Islam MS, Ahmed S, Rahman MZ, Hemy DH, Islam MT, et al.

Food Chem Toxicol, 2024 Mar 11.
PMID: 38467293 DOI: 10.1016/j.fct.2024.114580

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.
Fulltext First observation of haemoglobin Malay alpha 2B2 26 (B1) Asn----Ser--a case report

George E, Huisman TH, Yang KG, Kutlari F, Wilson JB, Kutlar A, et al.

Med J Malaysia, 1989 Sep;44(3):259-62.
PMID: 2626142

A new haemoglobin, Haemoglobin Malay is described in a 22 year old Malay. Structural analysis showed a AAC----AGC mutation in codon 17, with the production of an abnormal beta chain (beta Malay) that has an Asn----Ser substitution at position beta 19. This haemoglobin variant could not be detected by conventional procedures.
Fulltext Frequency and predictors of anxiety and depression among pregnant women attending tertiary healthcare institutes of Quetta City, Pakistan

Ghaffar R, Iqbal Q, Khalid A, Saleem F, Hassali MA, Baloch NS, et al.

BMC Womens Health, 2017 Jul 25;17(1):51.
PMID: 28743261 DOI: 10.1186/s12905-017-0411-1

BACKGROUND: Anxiety and depression (A&D) are commonly reported among pregnant women from all over the world; however, there is a paucity of workable data from the developing countries including Pakistan. The current study, therefore, aims to find out the frequency and predictors of A&D among pregnant women attending a tertiary healthcare institutes in the city of Quetta, in the Balochistan province, Pakistan.
METHODS: A questionnaire based, cross-sectional survey was conducted. The pre-validated Hospital Anxiety and Depression Scale (HADS) were used to assess the frequency of A&D among study respondents. Anxiety and depression scores were calculated via standard scoring procedures while logistic regression was used to identify the predictors of A&D. SPSS v. 20 was used for data analysis and p
Fulltext Knowledge and practice of adolescent females about menstruation and menstruation hygiene visiting a public healthcare institute of Quetta, Pakistan

Michael J, Iqbal Q, Haider S, Khalid A, Haque N, Ishaq R, et al.

BMC Womens Health, 2020 01 06;20(1):4.
PMID: 31906921 DOI: 10.1186/s12905-019-0874-3

BACKGROUND: The current study is aimed to assess menstruation-related knowledge and practices of adolescent females visiting a public health care institute of Quetta city, Pakistan.
METHODS: A questionnaire-based cross-sectional survey was conducted. Nine hundred and twenty three female adolescents attending general out-patient departments of Mohtarma Shaheed Benazir Bhutto Hospital Quetta, Balochistan, was approached for data collection. Based on the objectives of the study, descriptive analysis was conducted and SPSS v. 21.0 was used for the data analysis.
RESULTS: Demographic characteristics revealed that the mean age of the respondents was 15 years. Mothers' (67%) were the main source of menstruation-related information. Majority (77.7%) of our respondents never had a class or session regarding menstruation-related education in their schools. About (44%) knew that menstruation is a physiological phenomenon while 60.2% knew that menstrual blood comes from the vagina. Nearly 40% of our study respondents missed their schools because of menarche. The use of absorbent material was frequent (90%) among the adolescent females and (68.7%) used commercially available sanitary napkins/pads. Although majority of the respondents (58.2%) were not taking baths during menstruation, 80.5% do cleaned their genitalia with water during menstruation.
CONCLUSION: Female adolescents of our study had certain misconception regarding menstruation because of poor access to health-related education. Education can be provided at healthcare facilities, residential area as well as religious centers. Adolescent reproductive health should be included in the school curriculum; this will influence general reproductive health of females.
Fulltext How Are We Educating Future Physicians and Pharmacists in Pakistan? A Survey of the Medical and Pharmacy Student's Perception on Learning and Preparedness to Assume Future Roles in Antibiotic Use and Resistance

Mubarak N, Arif S, Irshad M, Aqeel RM, Khalid A, Ijaz UEB, et al.

Antibiotics (Basel), 2021 Oct 03;10(10).
PMID: 34680785 DOI: 10.3390/antibiotics10101204

BACKGROUND: Medical and pharmacy students are future healthcare professionals who will be on the forefront in dealing with antibiotics in hospitals or community settings. Whether the current medical and pharmacy education in Pakistan prepares students to take future roles in antibiotic use remains an under-researched area.
AIM: This study aims to compare medical and pharmacy students' perceived preparedness, learning practices and usefulness of the education and training on antibiotic use and resistance imparted during undergraduate studies in Pakistan.
DESIGN AND SETTING: It was amulti-centre cross-sectional survey of medical and pharmacy colleges in Punjab, Pakistan.
METHOD: A self-administered questionnaire was used to collect data from final year medical and pharmacy students. Descriptive statistics were used for categorical variables while independent t-test and One-way ANOVA computed group differences.
RESULT: Nine hundred forty-eight respondents (526 medical and 422 pharmacy students) completed the survey from 26 medical and 19 pharmacy colleges. Majority (76.1%) of the pharmacy students had not completed a clinical rotation in infectious diseases. The top three most often used sources of learning antibiotic use and resistance were the same among the medical and the pharmacy students; included textbooks, Wikipedia, and smart phone apps. Overall self-perceived preparedness scores showed no significant difference between pharmacy and medical students. The least prepared areas by medical and pharmacy students included transition from intravenous to oral antibiotics and interpretation of antibiograms. Both medical and pharmacy students found problem solving sessions attended by a small group of students to be the most useful (very useful) teaching methodology to learn antibiotic use and resistance.
CONCLUSIONS: Differences exist between medical and pharmacy students in educational resources used, topics covered during undergraduate degree. To curb the growing antibiotic misuse and resistance, the concerned authorities should undertake targeted educational reforms to ensure that future physicians and pharmacists can play a pivotal role in rationalizing the use of antibiotics.
Fulltext Synergistic effects of Cu-doped ZnO nanoantibiotic against Gram-positive bacterial strains

Khalid A, Ahmad P, Alharthi AI, Muhammad S, Khandaker MU, Faruque MRI, et al.

PLoS One, 2021;16(5):e0251082.
PMID: 33989295 DOI: 10.1371/journal.pone.0251082

A viable hydrothermal technique has been explored for the synthesis of copper doped Zinc oxide nanoparticles (Cu-doped ZnO-NPs) based on the precursor's mixture of Copper-II chloride dihydrate (CuCl2.2H2O), Zinc chloride (ZnCl2), and potassium hydroxide (KOH). X-ray diffraction (XRD) reported the hexagonal wurtzite structure of the synthesized Cu-doped ZnO-NPs. The surface morphology is checked via field emission scanning electron microscopy (FE-SEM), whereas, the elemental compositions of the samples were confirmed by Raman, and X-ray photoelectron spectroscopy (XPS), respectively. The as-obtained ZnO-NPs and Cu-doped ZnO-NPs were then tested for their antibacterial activity against clinical isolates of Gram-positive (Staphylococcus aureus, Streptococcus pyogenes) and Gram-negative (Escherichia coli, Klebsiella pneumonia) bacteria via agar well diffusion method. The zone of inhibition (ZOI) for Cu-doped ZnO-NPs was found to be 24 and 19 mm against S. Aureus and S. pyogenes, and 18 and 11 mm against E. coli and K. pneumoniae, respectively. The synthesized Cu-doped ZnO-NPs can thus be found as a potential nano antibiotic against Gram-positive multi-drug resistant bacterial strains.
Fulltext Molecular mechanisms underlying the clinical efficacy of panobinostat involve Stochasticity of epigenetic signaling, sensitization to anticancer drugs, and induction of cellular cell death related to cellular stresses

El Omari N, Bakrim S, Khalid A, Abdalla AN, Almalki WH, Lee LH, et al.

Biomed Pharmacother, 2023 Aug;164:114886.
PMID: 37224752 DOI: 10.1016/j.biopha.2023.114886

Panobinostat, also known as Farydak®, LBH589, PNB, or panobinostat lactate, is a hydroxamic acid that has been approved by the Food and Drug Administration (FDA) for its anti-cancer properties. This orally bioavailable drug is classified as a non-selective histone deacetylase inhibitor (pan-HDACi) that inhibits class I, II, and IV HDACs at nanomolar levels due to its significant histone modifications and epigenetic mechanisms. A mismatch between histone acetyltransferases (HATs) and HDACs can negatively affect the regulation of the genes concerned, which in turn can contribute to tumorigenesis. Indeed, panobinostat inhibits HDACs, potentially leading to acetylated histone accumulation, re-establishing normal gene expression in cancer cells, and helping to drive multiple signaling pathways. These pathways include induction of histone acetylation and cytotoxicity for the majority of tested cancer cell lines, increased levels of p21 cell cycle proteins, enhanced amounts of pro-apoptotic factors (such as caspase-3/7 activity and cleaved poly (ADP-ribose) polymerase (PARP)) associated with decreased levels of anti-apoptotic factors [B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra-large (Bcl-XL)], as well as regulation of immune response [upregulated programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression] and other events. The therapeutic outcome of panobinostat is therefore mediated by sub-pathways involving proteasome and/or aggresome degradation, endoplasmic reticulum, cell cycle arrest, promotion of extrinsic and intrinsic processes of apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this investigation, we aimed to pinpoint the precise molecular mechanism underlying panobinostat's HDAC inhibitory effect. A more thorough understanding of these mechanisms will greatly advance our knowledge of cancer cell aberrations and, as a result, provide an opportunity for the discovery of significant new therapeutic perspectives through cancer therapeutics.

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