Publications by authors named "Muhammad Amin"

183 Publications

Influence Diagnostic Methods in the Poisson Regression Model with the Liu Estimator.

Comput Intell Neurosci 2021 8;2021:4407328. Epub 2021 Sep 8.

Department of Mathematics, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

There is a long history of interest in modeling Poisson regression in different fields of study. The focus of this work is on handling the issues that occur after modeling the count data. For the prediction and analysis of count data, it is valuable to study the factors that influence the performance of the model and the decision based on the analysis of that model. In regression analysis, multicollinearity and influential observations separately and jointly affect the model estimation and inferences. In this article, we focused on multicollinearity and influential observations simultaneously. To evaluate the reliability and quality of regression estimates and to overcome the problems in model fitting, we proposed new diagnostic methods based on Sherman-Morrison Woodbury (SMW) theorem to detect the influential observations using approximate deletion formulas for the Poisson regression model with the Liu estimator. A Monte Carlo method is done for the assessment of the proposed diagnostic methods. Real data are also considered for the evaluation of the proposed methods. Results show the superiority of the proposed diagnostic methods in detecting unusual observations in the presence of multicollinearity compared to the traditional maximum likelihood estimation method.
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http://dx.doi.org/10.1155/2021/4407328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445724PMC
September 2021

Physiological Predictors of Mental Disorders Among Police Officers in Indonesia.

Asia Pac J Public Health 2021 Sep 6:10105395211027752. Epub 2021 Sep 6.

Universitas Syiah Kuala, Banda Aceh, Indonesia.

Police officers may be at a higher risk of suffering from mental disorders (MDs) compared with other occupations. This study aimed to examine the physiological predictors of MDs among police officers in Indonesia. The mental health status of each participant was examined using a standardized Minnesota Multiphasic Personality Inventory (MMPI) tool and underwent several laboratory examinations including hematology, urine, serology, and electrocardiogram tests. A logistic regression was performed to calculate the odds ratio. Of the 4590 participants, 2.14% were diagnosed with MDs. The study found 19 physiological variables are potential predictors of MDs. In multivariate analysis adjusted for body mass index, sex, and age, the concentration of ketones, protein, and specific gravity in urine and the amount of lymphocyte in the blood are among important predictors of MDs. This suggests that carefully examining the results of urinalysis and hematology tests can help us detect early cases of MDs among police officers.
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http://dx.doi.org/10.1177/10105395211027752DOI Listing
September 2021

Investigation of 9000 hours multi-stress aging effects on High-Temperature Vulcanized Silicone Rubber with silica (nano/micro) filler hybrid composite insulator.

PLoS One 2021 28;16(7):e0253372. Epub 2021 Jul 28.

Manchester Metropolitan University, Manchester, United Kingdom.

Degradation in the polymeric insulators is caused due to the environmental stresses. The main aim of this paper is to explore the improved aging characteristics of hybrid samples by adding nano/micro silica in High Temperature Vulcanized Silicone Rubber (HTV-SiR) under long term accelerated aging conditions for 9000 hours. As HTV-SiR is unable to sustain environmental stresses for a long time, thus a long term accelerated aging behavior is an important phenomenon to be considered for field application. The aging characteristics of nano/micro filled HTV-SiR are analyzed by using techniques such as Scanning Electron Microscopy (SEM), Leakage Current (LC), Fourier Transform Infrared Microscopy (FTIR), Hydrophobicity Classification (HC), and breakdown strength for the aging time of 9000 hours. FTIR and leakage currents are measured after every cycle. All the co-filled samples revealed escalated aging characteristics as compared to the neat sample except the SN8 sample (8% nano-silica+20% micro-silica) after 9000 hours of aging. The highest loading of 6% and 8% nano-silica with 20% micro-silica do not contribute to the improved performance when compared with the neat and hybrid samples. However, from the critical experimental analysis, it is deduced that SN2 sample (2% nano-silica+20% micro-silica) is highly resistant to the long term accelerated aging conditions. SN2 has no cracks, lower loss percentages in the important FTIR absorption peaks, higher breakdown strength and superior HC after aging as compared to the unfilled and hybrid samples.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253372PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318273PMC
July 2021

Simultaneous Left Ventricular Aneurysm and Ventricular Septal Rupture Complicating Delayed STEMI Presentation: A Case-Based Review of Post-MI Mechanical Complications Amid the COVID-19 Pandemic.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211031135

University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

Amid the coronavirus disease 2019 (COVID-19) pandemic, there is an unprecedented increase in public avoidance of hospitals predominantly driven by fear of contracting the virus. Recent publications highlight a re-emergence of rare post-myocardial infarction complications. While mechanical complications are infrequent in the era of primary percutaneous coronary intervention, they are associated with high mortality rates. The concurrent occurrence of mechanical complications such as left ventricular aneurysm and ventricular septal rupture is an extremely rare entity. We hereby delineate a unique case of a 53-year-old Caucasian male who underwent successful concomitant closure of a ventricular septal rupture, left ventricular aneurysmectomy, and 3-vessel coronary artery bypass grafting. Due to a delayed initial presentation owing to the patient's fear of contracting COVID-19, the surgery was carried out 3 months after the myocardial infarction. His postoperative evaluation confirmed normal contractility of the left ventricle and complete closure of the ventricular septal rupture. Six months postoperatively, the patient continues to do well. We also present a literature review of the mechanical complications following delayed presentation of myocardial infarction amid the COVID-19 pandemic. This article illustrates that clinicians should remain cognizant of these extremely rare but potentially lethal collateral effects during the ongoing global public-health challenge. Furthermore, it highlights a significant concern regarding the delay in first medical contact due to the reluctance of patients to visit the hospital during the COVID-19 pandemic.
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http://dx.doi.org/10.1177/23247096211031135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283223PMC
July 2021

Pharmacological evaluation of the gabapentin salicylaldehyde derivative, gabapentsal, against tonic and phasic pain models, inflammation, and pyrexia.

Naunyn Schmiedebergs Arch Pharmacol 2021 Jul 12. Epub 2021 Jul 12.

Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF10 3NB, UK.

Gabapentinoids are effective drugs in most animal models of pain and inflammation with variable effects in humans. The current study evaluated the pharmacological activity of gabapentin (GBP) and its salicylaldehyde derivative (gabapentsal; [2-(1-(((2-hydroxybenzylidene) amino) methyl) cyclohexyl) acetic acid]; GPS) in well-established mouse models of nociceptive pain, inflammatory edema, and pyrexia at doses of 25-100 mg/kg. GPS allayed tonic visceral pain as reflected by acetic acid-induced nociception and it also diminished thermally induced nociception as a mimic of phasic thermal pain. Antagonism of GPS-induced antinociceptive activities by naloxone (NLX, 1.0 mg/kg, subcutaneously, s.c), beta-funaltrexamine (β-FNT, 5.0 mg/kg, s.c), naltrindole (NT, 1.0 mg/kg, s.c), and nor-binaltorphimine (NOR-BNI, 5.0 mg/kg, s.c), and pentylenetetrazole (PTZ-15 mg/kg, intraperitoneally, i.p) implicated an involvement of both opioidergic and GABAergic mechanisms. Tail immersion test was conducted in order to delineate the mechanistic insights of antinociceptive response. Inflammatory edema induced by carrageenan, histamine, or serotonin was also effectively reversed by GPS in a fashion analogous to aspirin (150 mg/kg, i.p), chlorpheniramine (1.0 mg/kg, i.p), and mianserin (1.0 mg/kg, i.p), respectively. Additionally, yeast-induced pyrexia was decreased by GPS in a comparable manner to acetaminophen (50 mg/kg, i.p). These observations suggest that GPS possesses ameliorative properties in tonic, phasic, and tail immersion tests of nociception via opioidergic and GABAergic mechanisms, curbs inflammatory edema, and is antipyretic in nature.
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http://dx.doi.org/10.1007/s00210-021-02118-xDOI Listing
July 2021

The correlation between self-related adherence, asthma-related quality of life and control of asthma in adult patients.

J Basic Clin Physiol Pharmacol 2021 Jun 25;32(4):453-458. Epub 2021 Jun 25.

Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

Objectives: Medication non-adherence mostly occurs in patients with a wide range of disease severity, including asthma. The aim of the study was to assess the self reported adherence to asthma therapy and investigate the relationship between adherence, asthma control and asthma-related quality of life.

Methods: The study was a cross-sectional study in which participants were recruited from an outpatient department, in one hospital in Surabaya. Patients (aged≥18 years) with asthma who had used any regular asthma medications were included. Standardised questionnaires, including Juniper's Asthma Control Questionnaire (ACQ), Adherence to Refills and Medications Scales (ARMS) and Juniper's Asthma Quality of Life Questionnaire (AQLQ) were used.

Results: A total of 82 adults with asthma were recruited in the study. Male participants' mean age was 49.13 ± 14.10 years (n = 23). Approximately 59 participants (72.0%) were females, 30 participants (36.5%) were using Budesonide inhaler, and 73 participants (89.0%) never smoked. The mean of ACQ, AQLQ, and ARMS scores were 1.62 ± 1.19, 4.96 ± 1.24, and 16.98 ± 4.12, respectively. Of 82 patients studied 53 (64.6 %) had "uncontrolled asthma" and more than 85% participants both showed "non adherence" to asthma therapy and nearly 46% of them indicated that their quality of life was affected by asthma. There was a significant association between ACQ and AQLQ (p<0.05), whereas no statistically significant association was found between ACQ and ARMS.

Conclusions: The majority of patients reported non-adherence to asthma medications. Poor controlled asthma has been associated with lower asthma-related quality of life.
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http://dx.doi.org/10.1515/jbcpp-2020-0434DOI Listing
June 2021

The characteristics of lactic acid bacteria isolated from fermented food as potential probiotics.

J Basic Clin Physiol Pharmacol 2021 Jun 25;32(4):743-749. Epub 2021 Jun 25.

Department of Pulmonology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia.

Objectives: This study aims to determine the characteristics of and from fermented soursop fruit juice and cow's milk, respectively as probiotic candidate based on exposure to pH, bile salts, pathogenic bacteria, and antibiotics.

Methods: studies were conducted to examine the resistance of and in pH 2, 2.5, 3.2, and 7.2, resistance to bile salts, resistance to pathogenic bacteria and antituberculosis antibiotics.

Results: Viability of and isolates remained unchanged (6.3 × 10 CFU/mL and 5.03 × 10 CFU/mL) at various acidic pH, and had a low survival rate in Ox gall 0.3% (bile salts). These isolates also showed antibacterial properties against pathogens in the gastrointestinal tract. Both of these bacteria are quite safe to be used together with ofloxacin, linezolid, moxifloxacin, and levofloxacin, antibiotic for tuberculosis therapy.

Conclusions: The results showed that and from fermented soursop fruit juice and cow's milk respectively fulfilled the characteristics of probiotic and could potentially be used as adjunct therapy in tuberculosis drug-resistance.
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http://dx.doi.org/10.1515/jbcpp-2020-0482DOI Listing
June 2021

Sequential Co-infection of Heligmosomoides polygyrus and Mycobacterium tuberculosis Determine Lung Macrophage Polarization and Histopathological Changes.

Indian J Tuberc 2021 Jul 24;68(3):340-349. Epub 2020 Oct 24.

Department of Tropical Medicine, Jikei University School of Medicine, Tokyo, Japan.

Background: Tuberculosis is a chronic infection caused by Mycobacterium tuberculosis (M.tb), which needs proper macrophage activation for control. It has been debated whether the co-infection with helminth will affect the immune response to mycobacterial infection.

Objective: To determine the effect of sequential co-infection of Heligmosomoides polygyrus (H.pg) nematodes and M.tb on T cell responses, macrophages polarization and lung histopathological changes.

Method: This study used 49 mice divided into 7 treatment groups, with different sequence of infection of M.tb via inhalation and H.pg via oral ingestion for 8 and 16 weeks. T cells response in the lung, intestine, and peripheral blood were determined by flow cytometry. Cytokines (IL-4, IFN-γ, TGB-β1, and IL-10) were measured in peripheral blood using ELISA. Lung macrophage polarization were determined by the expression of iNOS (M1) or Arginase 1 (M2). Mycobacterial count were done in lung tissue. Lung histopathology were measured using Dorman's semiquantitative score assessing peribronchiolitis, perivasculitis, alveolitis, and granuloma formation.

Result: M.tb infection induced Th1 response and M1 macrophage polarization, while H.pg infection induced Th2 and M2 polarization. In sequential co-infection, the final polarization of macrophage was dictated by the sequence of co-infection. However, all groups with M.tb infection showed the same degree of mycobacterial count in lung tissues and lung tissue histopathological changes.

Conclusion: Sequential co-infection of H.pg and M.tb induces different T cell response which leads to different macrophage polarization in lung tissue. Helminth infection induced M2 lung macrophage polarization, but did not cause different mycobacterial count nor lung histopathological changes.
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http://dx.doi.org/10.1016/j.ijtb.2020.10.008DOI Listing
July 2021

An infrared energy harvester based on radar cross-section reduction of chiral metasurfaces through phase cancellation approach.

Sci Rep 2021 Jun 1;11(1):11492. Epub 2021 Jun 1.

Electrical Engineering Department, College of Engineering, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia.

Conventional metasurface absorbers rely on high dissipation losses by incorporating lossy materials. In this paper, we propose a novel mechanism of absorption based on phase cancellation of polarization states of scattered fields emerging from adjacent L-shaped chiral meta-atoms (unit cells). A linearly polarized wave forms helicoidal currents in each meta-atom leading to diagonally polarized radiated waves. When phase cancellation is employed by reorienting four such meta-atoms in a supercell configuration, contra-directed chiral currents flow in adjacent cells to cancel all the radiated fields in far-field region leading to a minimal broadside radar cross-section. From the reciprocity, the currents that are induced in the meta-atoms produce a null towards the incident direction which can be utilized for infrared energy harvesting. Full wave electromagnetic simulation indicates near perfect resonant absorption around 52.2 THz frequency. Enhanced bandwidth is shown by adding smaller resonators inside the supercell in nested form leading to dual band absorption at 45.2 THz and 53.15 THz.
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http://dx.doi.org/10.1038/s41598-021-90886-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169907PMC
June 2021

Switchable Binding Energy of Ionic Compounds and Application in Customizable Ligand Exchange for Colloid Nanocrystals.

J Phys Chem Lett 2021 Jun 1;12(22):5271-5278. Epub 2021 Jun 1.

Key Laboratory for Physical Electronics and Devices of the Ministry of Education, School of Electronic Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shannxi 710049, P. R. China.

The ability to engineer the surface ligands or adsorbed molecules on colloid nanocrystals (NCs) is important for various applications, as the physical and chemical properties are strongly affected by the surface chemistry. Here, we develop a facile and generalized ionic compound-mediated ligand-exchange strategy based on density functional theory calculations, in which the ionic compounds possess switchable bonding energy when they transfer between the ionized state and the non-ionized state, hence catalyzing the ligand-exchange process. By using an organic acid as the intermediate ligand, ligands such as oleylamine, butylamine, polyvinylpyrrolidone, and poly(vinyl alcohol) can be freely exchanged on the surface of Au NCs. Benefiting from this unique ligand-exchange strategy, the ligands with strong bonding energy can be replaced by weak ones, which is hard to realize in traditional ligand-exchange processes. The ionic compound-mediated ligand exchange is further utilized to improve the catalytic properties of Au NCs, facilitate the loading of nanoparticles on substrates, and tailor the growth of colloid NCs. These results indicate that the mechanism of switchable bonding energy can be significantly expanded to manipulate the surface property and functionalization of NCs that have applications in a wide range of chemical and biomedical fields.
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http://dx.doi.org/10.1021/acs.jpclett.1c00669DOI Listing
June 2021

Solution-Based SERS Detection of Weak Surficial Affinity Molecules Using Cysteamine-Modified Au Bipyramids.

Anal Chem 2021 06 20;93(21):7657-7664. Epub 2021 May 20.

School of Electronics and Information Engineering, Xi'an Jiaotong University, Xi'an, Shannxi 710049, China.

To achieve ultrasensitive detection of trace targets through solution-based surface-enhanced Raman spectroscopy (SERS), direct adsorption of the target molecules on a SERS-active surface is vital. In this work, cetyltrimethylammonium bromide (CTAB)-capped gold nano-bipyramids (Au BPs) with different aspect ratios (ARs) are prepared and the surface is successfully modified by a simple ligand exchange method. Cysteamine-capped gold nano-bipyramids (cyst-Au BPs) are obtained by means of replacement of CTAB by cysteamine using Au-S covalent bonding and applied in the solution-based SERS detection of different pigment molecules, which always have weak affinity to the gold surface. The hydrogen bonding between the pigment molecule and cysteamine causes the aggregation of Au BPs to generate local electromagnetic field enhancement. The influence of the AR and concentration of Au BPs on SERS properties is investigated. The SERS detection of weak-affinity molecules to an extremely low limit shows that the cyst-Au BPs are highly sensitive compared to CTAB-capped Au BPs. The limit of detection (LOD) of allura red as low as 0.1 ppb and that of sunset yellow as low as 1 ppb show that the proposed strategy has many advantages due to its simplicity and fast and rapid detection for the sensitivity analysis of weak-affinity molecules.
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http://dx.doi.org/10.1021/acs.analchem.1c00439DOI Listing
June 2021

Enhanced efficacy and drug delivery with lipid coated mesoporous silica nanoparticles in cancer therapy.

Eur J Pharm Biopharm 2021 Aug 4;165:31-40. Epub 2021 May 4.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany. Electronic address:

The exposure of cancer cells to subtherapeutic drug concentrations results in multidrug resistance (MDR). The uniqueness of mesoporous silica nanoparticles (MSNPs) with larger surface area for higher drug loading can solve the issue by delivering higher amounts of chemotherapeutics to the cancer cells. However, premature drug release and lower biocompatibility remain challenging. Lipid coating of MSNPs at the same time, can enhance the stability and biocompatibility of nanocarriers. Furthermore, the lipid coating can reduce the systemic drug release and deliver higher amounts to the tumor site. Herein, lipid coated MSNPs were prepared by utilizing cationic liposomes and further investigations were made. Our studies have shown the higher entrapment of doxorubicin (Dox) to MSNPs due to availability of porous structure. Lipid coating could provide a barrier to sustain the release of drug along with reduced premature leakage. In addition, the biocompatibility and enhanced interaction of cationic liposomes to cell membranes resulted in better cellular uptake. Lipid coated silica nanoparticles have shown higher cellular toxicity as compared to non-lipid coated particles. The increase in cytotoxicity with time supports the hypothesis of sustained release of drug from lipid coated MSNPs. We propose the Lip-Dox-MSNPs as an effective approach to treat cancer by delivering and maintaining effective concentration of drugs to the tumor site without systemic side effects.
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http://dx.doi.org/10.1016/j.ejpb.2021.04.020DOI Listing
August 2021

Potential application of Allium Cepa seeds as a novel biosorbent for efficient biosorption of heavy metals ions from aqueous solution.

Chemosphere 2021 Sep 12;279:130545. Epub 2021 Apr 12.

Department of Chemical Engineering, College of Engineering, Khalifa University, P.O Box 127788, Abu Dhabi, United Arab Emirates; Center for Catalysis and Separation (CeCaS), Khalifa University, P.O Box 127788, Abu Dhabi, United Arab Emirates. Electronic address:

Abatement of pollutants i.e. heavy metals by using green biomaterials is an emerging area of interest due to its cost-effective and renewability. In the present study, the potential of Alium Cepa seed biomass (ACSB) as a novel biosorbent for the adsorption of Cr(VI), Cd(II), Zn(II), Cu(II) and Pb(II) was investigated. The FTIR spectrum of ACSB confirmed a presence of surface OH bond, an essential functional group for metal uptake. Biosorption factors such as pH (2-10), time (15-190 min), dosage (1-5 g/L) and initial metal concentration (50-200 mg/L) were optimized at the ambient conditions. The equilibrium adsorption time was obtained at 90 min for Cd(II), Cu(II) and Pb(II), as well as 120 min for Cr(VI) and Zn(II), respectively, for the mentioned metal ions removal. The maximum removal efficiency was obtained at 4 g/L of ASCB for 50 mg/L adsorbate and a neutral pH. Under this condition, the maximum uptake was 0.67, 1.50, 1.68, 1.03 and 1.75 mg/L for Cr(VI), Cd(II), Zn(II), Cu(II) and Pb(II), respectively. Monolayer biosorption was determined for the studied heavy metals. The removal of the metal ions by ACSB followed a pseudo 2nd order sorption kinetics. The results suggested that ACSB is more suitable to remove (99%) Pb(II), Cu(II), Cd(II) as compared to Zn(II) and Cr(VI).
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http://dx.doi.org/10.1016/j.chemosphere.2021.130545DOI Listing
September 2021

A novel gabapentin analogue assuages neuropathic pain response in chronic sciatic nerve constriction model in rats.

Behav Brain Res 2021 05 16;405:113190. Epub 2021 Feb 16.

Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF103NB, UK. Electronic address:

Gabapentin (GBP) is an established drug that has been used in the management of symptoms of neuropathy but it is associated with unwanted side effects such as sedation and motor incoordination. The goal of the study was to find out a drug with greater efficacy and safety for the treatment of neuropathic pain. Our previously synthesized GABA analogue (Gabapentsal, GPS) was tested (25-100 mg/kg, i.p) in chronic constriction injury (CCI) induced nociceptive model of static allodynia, dynamic allodynia, thermal hyperalgesia, mechanical hyperalgesia and cold allodynia in rats (Sprague Dawley). Open field and rotarod tests were performed to assess the impact of GPS on the motor performance of the animals. GBP (100 mg/kg, i.p) was used as a standard for comparison. GPS dose dependently reduced static (P <0.001) and dynamic allodynia (P <0.001), thermal hyperalgesia (P <0.001), mechanical hyperalgesia (P < 0.001) and cold allodynia (P < 0.001). In comparison to GBP, GPS failed to alter any significantly the motor performance of rats in both the open field and rotarod assays. These results suggest that GPS is effective in alleviating nociception in CCI neuropathic pain model but free from the side effect of motor discoordination seen in the treatment with GBP. In conclusion, GPS may prove to be a prospectively more effective and safer option in the management of neuropathic syndromes.
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http://dx.doi.org/10.1016/j.bbr.2021.113190DOI Listing
May 2021

Lipoparticles for Synergistic Chemo-Photodynamic Therapy to Ovarian Carcinoma Cells: In vitro and in vivo Assessments.

Int J Nanomedicine 2021 11;16:951-976. Epub 2021 Feb 11.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany.

Purpose: Lipoparticles are the core-shell type lipid-polymer hybrid systems comprising polymeric nanoparticle core enveloped by single or multiple pegylated lipid layers (shell), thereby melding the biomimetic properties of long-circulating vesicles as well as the mechanical advantages of the nanoparticles. The present study was aimed at the development of such an integrated system, combining the photodynamic and chemotherapeutic approaches for the treatment of multidrug-resistant cancers.

Methods: For this rationale, two different sized Pirarubicin (THP) loaded poly lactic-co-glycolic acid (PLGA) nanoparticles were prepared by emulsion solvent evaporation technique, whereas liposomes containing Temoporfin (mTHPC) were prepared by lipid film hydration method. Physicochemical and morphological characterizations were done using dynamic light scattering, laser doppler anemometry, atomic force microscopy, and transmission electron microscopy. The quantitative assessment of cell damage was determined using MTT and reactive oxygen species (ROS) assay. The biocompatibility of the nanoformulations was evaluated with serum stability testing, haemocompatibility as well as acute in vivo toxicity using female albino (BALB/c) mice.

Results And Conclusion: The mean hydrodynamic diameter of the formulations was found between 108.80 ± 2.10 to 405.70 ± 10.00 nm with the zeta (ζ) potential ranging from -12.70 ± 1.20 to 5.90 ± 1.10 mV. Based on the physicochemical evaluations, the selected THP nanoparticles were coated with mTHPC liposomes to produce lipid-coated nanoparticles (LCNPs). A significant (p< 0.001) cytotoxicity synergism was evident in LCNPs when irradiated at 652 nm, using an LED device. No incidence of genotoxicity was observed as seen with the comet assay. The LCNPs decreased the generalized in vivo toxicity as compared to the free drugs and was evident from the serum biochemical profile, visceral body index, liver function tests as well as renal function tests. The histopathological examinations of the vital organs revealed no significant evidence of toxicity suggesting the safety and efficacy of our lipid-polymer hybrid system.
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http://dx.doi.org/10.2147/IJN.S285950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884954PMC
March 2021

Influence of Lime and Volcanic Ash on the Properties of Dune Sand as Sustainable Construction Materials.

Materials (Basel) 2021 Jan 30;14(3). Epub 2021 Jan 30.

Department of Civil and Environmental Engineering, College of Engineering, King Faisal University (KFU), Al-Ahsa 31982, Saudi Arabia.

This study focused on evaluating dune sand stabilized with lime and volcanic ash as base course materials in engineering construction. Dune sands are found in Saudi Arabia in huge quantities. Due to the high demand for construction materials, this makes them highly suitable for construction. A testing program was designed to investigate the effect of adding different percentages by weight of lime (L: 0, 2, 4, and 6%) and volcanic ash (VA: 0, 1, 3, and 5%) on the engineering properties of the stabilized mixture. Unconfined compressive strength (UCS) and California bearing ratio (CBR) tests were conducted. In addition, Raman spectroscopy and laser-scanning microscopy (LSM) tests were performed to explore the chemical characteristic, packing, and structure of the mixture. The results showed that the UCS, CBR, and the Young's modulus (E) of the treated dune sand increased with the increase in percentage of both stabilizers. Furthermore, LSM images of mortar blended with intermediate L-to-VA blend ratio ≈0.55 (L: 6% and VA: 5%) exhibit compact packing of sand grains, indicating strong adhesion and higher cementing value. The results of the study are promising and encourage using the treated dune sand in engineering construction even with a low percentage use of lime (2%) and volcanic ash (1-3%) as stabilizers.
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http://dx.doi.org/10.3390/ma14030645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866797PMC
January 2021

Age, neutrophil lymphocyte ratio, and radiographic assessment of the quantity of lung edema (RALE) score to predict in-hospital mortality in COVID-19 patients: a retrospective study.

F1000Res 2020 30;9:1286. Epub 2020 Oct 30.

Department of Radiology, Universitas Airlangga Hospital, Surabaya, East Java, 60115, Indonesia.

Available data suggest that case fatality rate of COVID-19 patients in Surabaya is higher than global cases. Thus, it is important to identify risk factors to prevent the mortality. This study aimed to assess the factors associated with hospital mortality of COVID-19 patients, and develop a prediction score based on these findings. We analyzed 111 patients, who were diagnosed with COVID-19 based on reverse-transcriptase polymerase chain reaction. The following patient characteristics were obtained from records: age, gender, type of symptoms, onset of symptoms, neutrophil lymphocyte ratio (NLR), absolute lymphocyte count, chest x-ray abnormalities, lung involvement, type of lesion, radiographic assessment of the quantity of lung edema (RALE) score, and mortality. Data were analyzed using SPSS 25.0. Multivariate analysis showed that age >50 years ( =0.043), NLR score >5.8 ( =0.016) and RALE score >2 ( =0.002) can predict the mortality of COVID-19 patients in the hospital. ROC curve analysis of the score ability to predict mortality showed an area under the curve of 0.794. The cut-off point is 4.5, with a sensitivity of 96.7% and specificity of 49.4% to predict the mortality of COVID-19 patient in the hospital. Age, NLR score and RALE score were associated with mortality of COVID-19 patients in the hospital and might be used as a predictor for mortality of COVID-19 patients in health care centre where radiologists are available. The prediction score may be useful for frontline physicians to effectively manage patients with a higher score to prevent mortality.
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http://dx.doi.org/10.12688/f1000research.26723.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836085PMC
February 2021

Wave discrimination at C-band frequencies in microstrip structures inspired by electromagnetically induced transparency.

Sci Rep 2021 Feb 3;11(1):2983. Epub 2021 Feb 3.

Research Institute for Microwave and Millimeter-Wave Studies, National University of Sciences and Technology, Islamabad, Pakistan.

We present the design and practical implementation of a microstrip diplexer based on the wave discrimination property associated with the electromagnetically induced transparency (EIT)-like effect. The EIT is a quantum interference phenomenon which happens between two atomic transition pathways and allows wave propagation within a medium's absorption spectrum. Here, we exploit an analogous interference mechanism in a three-port microstrip structure to demonstrate a diplexer based on the EIT-like effect in the microwave regime. Since the transparency is accompanied by a high transmission and strong dispersion characteristics, compact frequency discriminating structures that can resolve nearby frequencies with high isolation can be devised. Our proposed C-band diplexer consists of pairs of unequal open-circuit stubs, which resonate at detuned frequencies and interfere to form the EIT-like passbands for diplexer action. The design is highly compact and scalable in frequency for both PCB and on-chip applications. A prototype of diplexer is fabricated for the center frequencies of lower and upper passbands at 4.6 GHz and 5.5 GHz respectively. The transmission zeros are designed at the complementary channels so that the two passbands are highly isolated presenting the isolation of about 40 dB. The measured insertion loss of lower and upper passband is 0.59 dB and 0.61 dB respectively. Measured input return loss is better than - 15 dB, while the output return losses are well below - 12 dB. Moreover, a decent value of about 200 is achieved for the group refractive index around the EIT-like passbands, which reveals the slow wave characteristics of the proposed EIT-based diplexer.
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http://dx.doi.org/10.1038/s41598-021-82618-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859401PMC
February 2021

A decrease in PPD specific CD4 T cell CD38 and HLA-DR expression in pulmonary tuberculosis patients after 8 weeks of therapy correlates with successful anti-tuberculosis treatment.

J Clin Tuberc Other Mycobact Dis 2021 Feb 7;22:100214. Epub 2021 Jan 7.

Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

Tuberculosis (TB) is a major health problem in Indonesia with a million new cases each year. The CD4 T cell adaptive immune response against (MTB) is central to the control of this disease. We investigated whether standard therapy of TB causes changes to these cells in the early stages of treatment. To do this we took blood samples from 2 groups of TB patients in Banda Aceh, Indonesia; one from a group of patients before treatment, and the other from a group who become smear negative after 8 weeks treatment. MTB specific CD4 T cells were identified by stimulation with PPD and flow cytometric measurement of intracellular cytokines and surface markers. We found no difference in total PPD specific CD4 T cells between the groups, but that the proportion of these cells CD38 + HLA-DR+ was significantly lower in the treatment group. This decrease was not specific to Interferon gamma (IFNg), Interleukin-2 (IL-2) or Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) producing cells. Our findings show that anti-MTB treatment affects the adaptive immune response, and that measuring the decrease of the PPD specific CD4 T cell CD38+HLA-DR+ phenotype could be a useful parameter for determination of treatment success.
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http://dx.doi.org/10.1016/j.jctube.2021.100214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808949PMC
February 2021

Viral arthralgia a new manifestation of COVID-19 infection? A cohort study of COVID-19-associated musculoskeletal symptoms.

Int J Infect Dis 2021 Mar 18;104:363-369. Epub 2021 Jan 18.

Department of Medicine, Woodlands Health Campus, Singapore.

Objectives: Musculoskeletal symptoms are often unrecognised as a prominent feature of COVID-19 infection. This study hypothesised that viral arthralgia is an uncommon but distinct manifestation of COVID-19 infection. In addition, it aimed to characterise the other musculoskeletal presentations of COVID-19 infection and study their prognostic implications.

Methods: Patients hospitalised with COVID-19 infection were divided into two groups: those with and without musculoskeletal symptoms. Those with musculoskeletal symptoms were subdivided according to four patterns of musculoskeletal involvement: myalgia, arthralgia, backache and generalised body ache. Using binary regression logistic analysis, the risk of developing a viral pneumonia in patients with and without musculoskeletal complaints was compared.

Results: Of 294 hospitalised patients with COVID-19, 88 (30%) reported musculoskeletal complaints. Among these 88 patients, 37.5% had myalgia, 5.7% arthralgia, 6.8% new-onset backache and 50% generalised body ache. The presence of musculoskeletal complaints was not associated with the risk of developing viral pneumonia (6.8% vs. 9.7%, OR 0.68, 95% CI 0.26-1.76, p = 0.426). COVID-19 arthralgia was often more severe and had variable onset, while generalised body ache and myalgia were milder and coincided with the occurrence of fever or respiratory symptoms.

Conclusion: Viral arthralgia is a novel clinical manifestation of COVID-19, and untypical of a viral prodrome or a reactive arthropathy. While musculoskeletal symptoms were not associated with developing a pneumonia, to avoid missing a diagnosis of COVID-19, clinicians should be aware of its variable onset, particularly when respiratory symptoms are absent at the time of presentation.
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http://dx.doi.org/10.1016/j.ijid.2021.01.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813485PMC
March 2021

Imaging trend and disease course in admitted COVID-19 patients.

Saudi Med J 2021 Jan;42(1):30-37

Radiology Department, Military Medical Complex, Dhahran, Kingdom of Saudi Arabia. E-mail.

Objectives: To describe radiographic imaging findings and disease course in admitted Coronavirus disease 2019 (COVID-19) patients.

Methods: This retrospective study was carried in the Radiology Department, King Fahad Military Medical Complex, Dhahran between March to August 2020 (6 months). All laboratory confirmed COVID-19 admitted cases were evaluated for their symptoms, duration of hospital stays (in a ward or intensive care unit [ICU]), and imaging findings (ground-glass opacity [GGO], air-space shadowing/consolidation, and others such as atelectasis, reticulation, peribronchovascular thickening, lymphadenopathy and pleural effusion) on chest radiograph (CXR) and computed tomography (CT) studies. Cavitation, nodularity, bronchiectasis, and embolism detected on CT scans were considered as complications. Disease course in terms of recovery (radiographic regression or resolution of findings), worsening (shifting from ward to ICU), and unfavorable outcome (persistent ICU stay or death) were recorded. Imaging findings were interpreted by 2 experienced radiologists and consensus reporting was made. Chi-square test was used to determine association. Results: Out of 106 patients, majority were males (n=82, 77.4%). Forty-six patients (43.3%) had abnormal imaging with mostly peripheral GGO (56.5%), followed by consolidations (34.7%), and others (26%). Complications were detected in 6 ICU patients. All patients with unfavorable outcomes were above 60 years having comorbidities or complications (p less than 0.0005). Fatality rate was calculated as 2.8. Conclusion: Coronavirus disease 2019 is seen mostly affecting males, with peripheral opacities as common imaging findings. Elderly patients with co-morbidities may show unfavorable outcomes.
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http://dx.doi.org/10.15537/smj.2021.1.25642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989308PMC
January 2021

Comparative Removal of Lead and Nickel Ions onto Nanofibrous Sheet of Activated Polyacrylonitrile in Batch Adsorption and Application of Conventional Kinetic and Isotherm Models.

Membranes (Basel) 2020 Dec 23;11(1). Epub 2020 Dec 23.

Alamoudi Water Research Chair, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia.

We investigated the adsorption of lead (Pb) and nickel (Ni) ions by electrospun membranes of polyacrylonitrile (PAN) nanofiber activated with NaHCO (PANmod). Analysis by Fourier-transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), and energy dispersive X-ray spectroscopy (EDX) validated the functionalization of PAN nanofibers with NaHCO, and the successful agglomeration of Pb and Ni onto PANmod. After a rapid uptake of the heavy metal ions (15 min), the equilibrium contact time was attained (60 min) following a linear increase of both adsorption capacity and removal efficiency. PANmod showed a better affinity for Ni than Pb. The adsorption on PANmod was best described by the pseudo-second-order kinetic model for both studied models, supporting chemisorption. By varying the solution pH from 2.0 to 9.0, we found that the adsorption capacity followed an increasing trend, reaching a maximum at the pH of 7.0. Despite increasing adsorption capacities, the removal efficiency of both heavy metal ions exhibited a decreasing trend with increase in initial concentrations. The amount of PANmod directly affects the removal efficiency, with 0.7 and 0.2 g being the optimum dose for maximum uptake of Pb and Ni, respectively. The Langmuir model fitted well the Pb adsorption data suggesting monolayer adsorption, and the Freundlich model perfectly fitted the Ni adsorption data, indicating heterogeneous adsorption. The estimated values of the mean free energy of adsorption in the D-R isotherm indicated a physical adsorption of both heavy metal ions into the surface of the PANmod.
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http://dx.doi.org/10.3390/membranes11010010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823771PMC
December 2020

Mechanical Performance of High-Strength Sustainable Concrete under Fire Incorporating Locally Available Volcanic Ash in Central Harrat Rahat, Saudi Arabia.

Materials (Basel) 2020 Dec 23;14(1). Epub 2020 Dec 23.

Department of Civil and Environmental Engineering, College of Engineering, King Faisal University (KFU), Al-Ahsa 31982, Saudi Arabia.

This study investigated the effect of elevated temperatures on the mechanical properties of high-strength sustainable concrete incorporating volcanic ash (VA). For comparison, control and reference concrete specimens with fly ash (FA) were also cast along with additional specimens of VA and FA containing electric arc furnace slag (EAFS). Before thermal exposure, initial tests were performed to evaluate the mechanical properties (compressive strength, tensile strength, and elastic modulus) of cylindrical concrete specimens with aging. Additionally, 91 day moist-cured concrete specimens, after measuring their initial weight and ultrasonic pulse velocity (UPV), were exposed up to 800 °C and cooled to air temperature. Subsequently, the weight loss, residual UPV, and mechanical properties of concrete were measured with respect to exposure temperature. For all concrete specimens, test results demonstrated a higher loss of weight, UPV, and other mechanical properties under exposure to higher elevated temperature. Moreover, all the results of concrete specimens incorporating VA were observed before and after exposure to elevated temperature as either comparable to or slightly better than those of control and reference concrete with FA. According to the experimental results, a correlation was developed between residual UPV and residual compressive strength (RCS), which can be used to assess the RCS of fire-damaged concrete (up to 800 °C) incorporating VA and EAFS.
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http://dx.doi.org/10.3390/ma14010021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793147PMC
December 2020

Association of disease severity with toll-like receptor polymorphisms in multidrug-resistant tuberculosis patients.

Int J Mycobacteriol 2020 Oct-Dec;9(4):380-390

Department of Clinical Microbiology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia.

Background: The disease severity in pulmonary Multidrug-resistant tuberculosis (MDR-TB) varies from mild to severe, which is determined by host and pathogen virulence factors. The difference of symptoms felt by TB patients were interesting to investigate in discovering whether its the human immune response or bacteria's virulence gene that plays the role. The aim of this research was to analyze association between disease severity degree of pulmonary MDR-TB patients with Single nucleotide polymorphisms (SNPs) found in toll-like receptors (TLRs) gene.

Method: Blood samples were obtained from pulmonary MDR-TB patients in Dr. Soetomo Hospital, Surabaya, Indonesia. Polymerase chain reaction (PCR) multiplex and target SNPs were analyze using DigiTag2 assay. The variant of esxA gene was determined using PCR and sequencing. Severity degree was determined by chest X-ray, the lesions were scored according to their severity, score of =2.5 ranking as mild, 2.5-6 as moderate and =6 as severe. Association level between SNP in TLRs gene degree of pulmonary MDR-TB was analyzed using Chi-square test. Bonferroni correction for multiple comparison was used to anticipate genotyping error.

Results: A total of 22 MDR-TB patients were classified into severe degree group, while 16 patients were moderate/mild degree. SNPs in encoding gene of TLRs were mostly found in intron, specifically in TLR-1, TLR-2, and TLR-6. HWE P value in rs5743572 was 0.841; in rs3804100 was 0.0176; and in rs5743808 was 0.562. Association analysis between SNP in TLRs genes and degree of disease revealed significant association in rs5743572, SNP of TLR-1, with P < 0.05; odds ratio [OR] = 11.67 (95% confidence interval [CI]: 3.94-34.52); rs3804100, SNP of TLR-2 had P < 0.05; OR = 37.59 (95% CI: 9.30-151.88); and rs5743808, the SNP of TLR-6 had P < 0.05; OR = 31.5 (95% CI: 8.60-115.34).

Conclusions: We concluded that SNPs in TLR-1, TLR-2, and TLR-6 of pulmonary MDR-TB patients was found to have an association with disease severity. TLRs polymorphism had significant association was present in TLR-1 rs5743572 in intron, TLR-2 rs3804100 in exon, and TLR-6 rs5743808 in exon and among MDR-TB isolates from patients with pulmonary MDR-TB of severe and moderate/mild degree.
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http://dx.doi.org/10.4103/ijmy.ijmy_175_20DOI Listing
September 2021

Lipodendriplexes mediated enhanced gene delivery: a cellular to pre-clinical investigation.

Sci Rep 2020 12 8;10(1):21446. Epub 2020 Dec 8.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037, Marburg, Germany.

Clinical success of effective gene therapy is mainly hampered by the insufficiency of safe and efficient internalization of a transgene to the targeted cellular site. Therefore, the development of a safe and efficient nanocarrier system is one of the fundamental challenges to transfer the therapeutic genes to the diseased cells. Polyamidoamine (PAMAM) dendrimer has been used as an efficient non-viral gene vector (dendriplexes) but the toxicity and unusual biodistribution induced by the terminal amino groups (-NH) limit its in vivo applications. Hence, a state of the art lipid modification with PAMAM based gene carrier (lipodendriplexes) was planned to investigate theirs in vitro (2D and 3D cell culture) and in vivo behaviour. In vitro pDNA transfection, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, cellular protein contents, live/dead staining and apoptosis were studied in 2D cell culture of HEK-293 cells while GFP transfection, 3D cell viability and live/dead staining of spheroids were performed in its 3D cell culture. Acute toxicity studies including organ to body index ratio, hematological parameters, serum biochemistry, histopathological profiles and in vivo transgene expression were assessed in female BALB/c mice. The results suggested that, in comparison to dendriplexes the lipodendriplexes exhibited significant improvement of pDNA transfection (p < 0.001) with lower LDH release (p < 0.01) and ROS generation (p < 0.05). A substantially higher cellular protein content (p < 0.01) and cell viability were also observed in 2D culture. A strong GFP expression with an improved cell viability profile (p < 0.05) was indicated in lipodendriplexes treated 3D spheroids. In vivo archives showed the superiority of lipid-modified nanocarrier system, depicted a significant increase in green fluorescent protein (GFP) expression in the lungs (p < 0.01), heart (p < 0.001), liver (p < 0.001) and kidneys (p < 0.001) with improved serum biochemistry and hematological profile as compared to unmodified dendriplexes. No tissue necrosis was evident in the animal groups treated with lipid-shielded molecules. Therefore, a non-covalent conjugation of lipids with PAMAM based carrier system could be considered as a promising approach for an efficient and biocompatible gene delivery system.
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http://dx.doi.org/10.1038/s41598-020-78123-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723038PMC
December 2020

Physicochemical characteristics and permeation of loratadine solid lipid nanoparticles for transdermal delivery.

Ther Deliv 2020 11 23;11(11):685-700. Epub 2020 Nov 23.

Bavarian Polymer Institute, KeyLab 'Electron & Optical Microscopy', University of Bayreuth, Bayreuth, Germany.

To prepare loratadine-loaded solid lipid nanoparticles (SLNs) using a modified two-step ultrasound-assisted phase inversion temperature (PIT) process. Loratadine was dissolved in beeswax and Tween 80 was dissolved in water. The two phases were mixed together to prepare a water-in-oil emulsion preconcentrate (w/o) at a PIT of 85°C, followed by gradual water addition at 25°C to trigger nanoparticles formation (o/w). Kinetic stability was investigated. No change in the size was observed within 6 months. Fourier-transform infrared spectroscopy demonstrated stability of the emulsions via molecular structure of water at the interface of the o/w nanoemulsions. SLNs enhanced the skin permeation of loratadine. Stable SLNs were successfully prepared by ultrasound-assisted PIT.
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http://dx.doi.org/10.4155/tde-2020-0075DOI Listing
November 2020

Bone marrow-derived mesenchymal stem cells attenuate pulmonary inflammation and lung damage caused by highly pathogenic avian influenza A/H5N1 virus in BALB/c mice.

BMC Infect Dis 2020 Nov 11;20(1):823. Epub 2020 Nov 11.

Indonesia-Japan Collaborative Research Center for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Airlangga University, Surabaya, Indonesia.

Background: The highly pathogenic avian influenza A/H5N1 virus is one of the causative agents of acute lung injury (ALI) with high mortality rate. Studies on therapeutic administration of bone marrow-derived mesenchymal stem cells (MSCs) in ALI caused by the viral infection have been limited in number and have shown conflicting results. The aim of the present investigation is to evaluate the therapeutic potential of MSC administration in A/H5N1-caused ALI, using a mouse model.

Methods: MSCs were prepared from the bone marrow of 9 to 12 week-old BALB/c mice. An H5N1 virus of A/turkey/East Java/Av154/2013 was intranasally inoculated into BALB/c mice. On days 2, 4, and 6 after virus inoculation, MSCs were intravenously administered into the mice. To evaluate effects of the treatment, we examined for lung alveolar protein as an indicator for lung injury, PaO/FiO ratio for lung functioning, and lung histopathology. Expressions of NF-κB, RAGE (transmembrane receptor for damage associated molecular patterns), TNFα, IL-1β, Sftpc (alveolar cell type II marker), and Aqp5+ (alveolar cell type I marker) were examined by immunohistochemistry. In addition, body weight, virus growth in lung and brain, and duration of survival were measured.

Results: The administration of MSCs lowered the level of lung damage in the virus-infected mice, as shown by measuring lung alveolar protein, PaO/FiO ratio, and histopathological score. In the MSC-treated group, the expressions of NF-κB, RAGE, TNFα, and IL-1β were significantly suppressed in comparison with a mock-treated group, while those of Sftpc and Aqp5+ were enhanced. Body weight, virus growth, and survival period were not significantly different between the groups.

Conclusion: The administration of MSCs prevented further lung injury and inflammation, and enhanced alveolar cell type II and I regeneration, while it did not significantly affect viral proliferation and mouse morbidity and mortality. The results suggested that MSC administration was a promissing strategy for treatment of acute lung injuries caused by the highly pathogenic avian influenza A/H5N1 virus, although further optimization and combination use of anti-viral drugs will be obviously required to achieve the goal of reducing mortality.
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http://dx.doi.org/10.1186/s12879-020-05525-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656227PMC
November 2020

Attenuation of Spatial Memory in 5xFAD Mice by Halting Cholinesterases, Oxidative Stress and Neuroinflammation Using a Cyclopentanone Derivative.

Pharmaceuticals (Basel) 2020 Oct 19;13(10). Epub 2020 Oct 19.

Department of Chemistry, University of Malakand, Chakdara 18000, Dir (L), KPK, Pakistan.

Alzheimer's disease (AD) is an irreversible and chronic neurological disorder that gradually destroys memory and thinking skills. The research study was designed to investigate the underlying molecular signaling involved in the neuroprotective effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) as a therapeutic agent for AD. In this study, In vivo studies were carried out on a well-known 5xFAD mice model using different behavioural test models such as open field, rotarod, Morris water maze (MWM), and Y-maze tests. Furthermore, in vitro cholinesterase inhibition activity assays were carried out. The frontal cortex (FC) and hippocampus (HC) homogenates were tested for the levels/activities of cholinesterases, glutathione (GSH), glutathione S-transferase (GST), and catalase. Furthermore, the hippocampal expression of inflammatory cytokines was observed via RT-PCR and western blot. The results of in vivo studies show an enhancement in the learning behavior. The 3NCP treatment reduced latency time in MWM and Y-maze tests, also increase spontaneous alternation indicate significant effect of 3NCP on memory. Furthermore, open field and rotarod studies revealed that 3NCP does not cause motor coordination deficit. The results of the in vitro studies revealed that the IC values of the 3NCP against acetylcholinesterase () and butyrylcholinesterase () were 16.17 and 20.51 µg/mL, respectively. This decline in and was further supported by ex vivo studies. Further, the 3NCP mitigates the GSH level, GST, and catalase activities in HC and FC. The mRNA and protein expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) markedly declined in RT-PCR and western blotting. The results of the current study conclusively demonstrate that 3NCP reduces oxidative stress and mitigates neuroinflammation in 5xFAD mice, implying that 3NCP may be a potential therapeutic candidate for AD treatment in the future.
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http://dx.doi.org/10.3390/ph13100318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603158PMC
October 2020

Downregulation of MDR 1 gene contributes to tyrosine kinase inhibitor induce apoptosis and reduction in tumor metastasis: A gravity to space investigation.

Int J Pharm 2020 Dec 18;591:119993. Epub 2020 Oct 18.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany. Electronic address:

P-glycoprotein (P-gp) associated multidrug resistance (MDR) represents a major failure in cancer treatment. The overexpression of P-gp is responsible for ATP-dependent efflux of drugs that decrease their intracellular accumulation. An effective downregulation of MDR1 gene using small interfering RNA (siRNA) is one of the safe and effective tools to overcome the P-gp triggered MDR. Therefore, the development of an efficient and non-toxic carrier system for siRNA delivery is a fundamental challenge for effective cancer treatment. Polyamidoamine (PAMAM) dendrimer has been used for efficient delivery of siRNA (dendriplexes) to the tumor cells but the associated toxicity problems render its use in biological applications. A non-covalent lipid modification (lipodendriplexes) is supposed to offer a promising strategy to overcome the demerits linked to the naked dendriplexes system. In the current study, we deliver siRNA, designed against MDR1 gene (si-MDR1), in colorectal carcinoma cells (Caco-2), having overexpression of P-gp, to check the role of MDR1 gene in tumor progression and multidrug resistance using two dimensional (2D) and three dimensional (3D) environment. Imatinib mesylate (IM), a P-gp substrate, was used as model drug. Our results revealed that the effective knockdown by lipodendriplexes system can significantly reduce the tumor cell migration in 2D (p < 0.001) and 3D (p < 0.001) cell cultures as compared to unmodified dendriplexes and si-Control groups. It was also observed that lipodendriplexes aided downregulation of MDR1 gene effectively, re-sensitized the Caco-2 cells for IM uptake and showed a significantly (p < 0.001) higher apoptosis. Our findings imply that our lipodendriplexes system has a great potential for siRNA delivery, however, further in vivo application using a suitable targeted system can play a major role for better cancer therapeutics.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119993DOI Listing
December 2020

Recognition of Pashto Handwritten Characters Based on Deep Learning.

Sensors (Basel) 2020 Oct 17;20(20). Epub 2020 Oct 17.

Department of Robot System Engineering, Tongmyong University, Busan 48520, Korea.

Handwritten character recognition is increasingly important in a variety of automation fields, for example, authentication of bank signatures, identification of ZIP codes on letter addresses, and forensic evidence. Despite improved object recognition technologies, Pashto's hand-written character recognition (PHCR) remains largely unsolved due to the presence of many enigmatic hand-written characters, enormously cursive Pashto characters, and lack of research attention. We propose a convolutional neural network (CNN) model for recognition of Pashto hand-written characters for the first time in an unrestricted environment. Firstly, a novel Pashto handwritten character data set, "Poha", for 44 characters is constructed. For preprocessing, deep fusion image processing techniques and noise reduction for text optimization are applied. A CNN model optimized in the number of convolutional layers and their parameters outperformed common deep models in terms of accuracy. Moreover, a set of benchmark popular CNN models applied to Poha is evaluated and compared with the proposed model. The obtained experimental results show that the proposed model is superior to other models with test accuracy of 99.64 percent for PHCR. The results indicate that our model may be a strong candidate for handwritten character recognition and automated PHCR applications.
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http://dx.doi.org/10.3390/s20205884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590197PMC
October 2020
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