Publications by authors named "Rizwan Ahmad"

174 Publications

Model of Streptozotocin-Nicotinamide Induced Type 2 Diabetes: A Comparative Review.

Curr Diabetes Rev 2021 Nov 17. Epub 2021 Nov 17.

Maharshi University of Information Technology, Lucknow. India.

The aim of the present study was to review the streptozotocin-nicotinamide (STZ-NA) diabetes model. Type 2 diabetes is more prevalent (90-95%) in adults than type 1. Experimentally-induced diabetes models may be established by chemicals, viral agents, insulin antibodies, surgery, etc. The most advisable and prompt method to induce diabetes is using chemicals, and STZ and alloxan are widely used chemicals. STZ has proven to be a better diabetogenic agent than alloxan because alloxan has many drawbacks, as it induces only type 1 diabetes, has a high mortality rate in rats, and causes ketosis in animals. Moreover, it has lesser selectivity towards β-cells, and the diabetes-induced is reversible. STZ can be used to induce both type 1 and type 2 diabetes. It is noted that the genotoxic behavior of STZ in animals is accomplished through a reduction of nicotinamide adenine dinucleotide (NAD+) in pancreatic β-cells via the GLUT2 (Glucose transporter 2), which can cause cellular damage by DNA (Deoxyribonucleic acid) strand breaks that lead to cell death. NA is a biochemical precursor of NAD+, and it is a poly-ADP-ribose-polymerase-1 (PARP-1) inhibitor. NAD+ is an important redox reaction co-enzyme for the production of adenosine triphosphate (ATP) and many other metabolic pathways. Extreme DNA damage contributes to the over-activation of PARP-1, loss of cellular resources, and necrotic cells death. Some studies have expressed that NA can protect pancreatic β-cells against the severe cytotoxicity of STZ. The review concluded that the STZ-NA model is dependent on the competency of NA to attain partial protection against the β-cytotoxic essence of STZ to induce type-2 diabetes.
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http://dx.doi.org/10.2174/1573399818666211117123358DOI Listing
November 2021

Ensuring respiratory phase consistency to improve cardiac function quantification in real-time CMR.

Magn Reson Med 2021 Oct 31. Epub 2021 Oct 31.

Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA.

Purpose: To develop an automatic method for selecting heartbeats with consistent respiratory phase to improve accuracy of cardiac function quantification in real-time (RT) cardiac MRI.

Methods: The respiratory signal is extracted by a principal component analysis method from RT cine images. Then, a two-step procedure is used to determine the directionality (sign) of the respiratory signal. With the motion in a manually selected region-of-interest as a reference, the quality of the extracted respiratory signal is assessed using multislice RT cine data from 11 volunteers and 10 patients. In addition, the impact of selecting heartbeats with consistent respiratory phase on the cardiac function quantification is evaluated.

Results: The extracted respiratory signal using the proposed method exhibits a high, positive correlation with the reference in all cases and is more robust compared to a recently proposed method. Also, for right ventricular function quantification, selecting heartbeats at expiratory position improves agreement between RT cine and breath-held reference.

Conclusion: The proposed method enables fully automatic extraction and directionality determinations of respiratory signal from RT cardiac cine images, allowing accurate cardiac function quantification.
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http://dx.doi.org/10.1002/mrm.29064DOI Listing
October 2021

Ganoderma lucidum (Reishi) an edible mushroom; a comprehensive and critical review of its nutritional, cosmeceutical, mycochemical, pharmacological, clinical, and toxicological properties.

Phytother Res 2021 Nov 19;35(11):6030-6062. Epub 2021 Aug 19.

Department of Pharmacognosy, Pharmacy College, Umm Al-Qura University, Makkah, Saudi Arabia.

Reishi owes an exceptional value in nutritional, cosmeceutical, and medical treatments; however, none of the studies has provided its future-driven critical assessment. This study documents an up-to-date review (2015-2020, wherever applicable) and provide valuable insights (preclinical and clinical evidence-based) with comprehensive and critical assessments. Various databases 'Google scholar', 'Web of Science', 'ScienceDirect', 'PubMed', 'Springer Link', books, theses, and library resources were used. The taxonomic chaos of G. lucidum and its related species was discussed in detail with solution-oriented emphasis. Reishi contains polysaccharides (α/β-D-glucans), alkaloids, triterpenoids (ganoderic acids, ganoderenic acids, ganoderol, ganoderiol, lucidenic acids), sterols/ergosterol, proteins (LZ-8, LZ-9), nucleosides (adenosine, inosine, uridine), and nucleotides (guanine, adenine). Some active drugs are explored at an optimum level to make them potential drug candidates. The pharmacological potential was observed in diabetes, inflammation, epilepsy, neurodegeneration, cancer, anxiety, sedation, cardiac diseases, depression, hepatic diseases, and immune disorders; however, most of the studies are preclinical with a number of drawbacks. In particular, quality clinical data are intensely needed to support pharmacological activities for human use. The presence of numerous micro-, macro, and trace elements imparts an essential nutritional and cosmeceutical value to Reishi, and various marketed products are available already, but the clinical studies regarding safety and efficacy, interactions with foods/drinks, chronic use, teratogenicity, mutagenicity, and genotoxicity are missing for Reishi. Reishi possesses many valuable pharmacological activities, and the number of patents and clinical trials is increasing for Reishi. Yet, a gap in research exists for Reishi, which is discussed in detail in the forthcoming sections.
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http://dx.doi.org/10.1002/ptr.7215DOI Listing
November 2021

Colonoscopy-based intramucosal transplantation of cancer cells for mouse modeling of colon cancer and lung metastasis.

Biotechniques 2021 09 16;71(3):456-464. Epub 2021 Aug 16.

Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.

The conventional orthotopic/xenograft models or genetically engineered murine models of colon cancer (CRC) are limited in their scope for a true understanding of tumor growth, progression and eventual metastasis in its natural microenvironment. In the currently used murine models of CRC metastasis, the metastasis occurs primarily in the liver, though lung metastasis accounts for a significant proportion of CRC metastasis. There is an urgent need for a murine model of CRC, which not only allows tumor progression in the colonic mucosa but also metastasis of the lung. The authors describe a minimally invasive murine model of colon cancer progression that may be ideal for a wide range of applications, including evaluating gene function, microenvironment, cancer metastasis and therapeutic translational research.
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http://dx.doi.org/10.2144/btn-2020-0172DOI Listing
September 2021

Green and novel ultrasonic extraction with UHPLC-MSMS analysis of natural sweetener (Glycyrrhizic acid) from Glycyrrhiza glabra; a multifactorial mechanistic evaluation based on statistical analysis.

Ultrason Sonochem 2021 Sep 29;77:105696. Epub 2021 Jul 29.

College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.

A novel, green and eco-friendly, cost-effective, fast, and reliable high energy ultrasonication (US) extraction with UHPLC-MSMS (Ultrahigh performance liquid chromatography with mass spectrometry) quantification of Glycyrrhizic acid (GZA) is reported herein for the first time. The study provides useful insights regarding the effect of US-factors with statistical analysis and mechanisms, involved in GZA-extraction and analysis. An US-extraction method (US-MD) was developed using three levels of US factors: solvents (AC (acetone), EtOH (ethanol), HO (water)), time (1, 2, 3 min), amplitudes (30, 40, 50%), pulse (10/0.5, 20/0.5, 30/0.5 sec), particle sizes (0.5, 1, 1.4 mm), and temperatures (20, 30, 40 °C). The US-MD was further validated with high accuracy 98.96 ± 6.82 and r = 0.995 whereas, an in-house analytical method (UHPLC-MSMS) was developed and validated to quantify the GZAamount. UHPLCMSMS-MD resulted in a retention time of 0.31 min with MSMS (821.400 > 351.200) in a 1 min run time whereas, UHPLCMSMS-MV showed high accuracy and precision with r = 0.998 for GZA. Statistical analysis of K-mean clustering finalized US-set-of-factors showing optimum extract yield (mg/1mg) of 0.48 with sum (2.41 ± 014) and mean (0.27) along with a high GZA-amount (μg/mg) of 8.23 with sum (43.31 ± 2.07) and mean (4.81) for HO in 3 min at 40 °C using particle size (1.4 mm), amplitude (50%), and pulse (30/0.5). Large scale application of US-UHPLCMSMS confirmed the evaluation power of the method showing the order for GZA amount; Egypt > Pakistan > Syria > India > Palestine > America > Georgia > Morocco. A significant effect for US factors Vs extract yield and GZA amount was observed however, solvent*GZA-amount and extract yield*particle size were more significantly correlated compared to time*temperature*amplitude*pulse analyzed via PCA, GLM-UniANOVA, K-mean, and Pearson's correlation (P ≤ 0.05). A combined mechanism of shear stress, macroturbulence due to acoustic cavitation and implosions, sonochemical, and sonocapillary effect were noted for the US technique producing higher extract yield and GZA amount from licorice.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350416PMC
September 2021

MR elastography inversion by compressive recovery.

Phys Med Biol 2021 Aug 2;66(16). Epub 2021 Aug 2.

Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, United states of America.

Direct inversion (DI) derives tissue shear modulus by inverting the Helmholtz equation. However, conventional DI is sensitive to data quality due to the ill-posed nature of Helmholtz inversion and thus providing reliable stiffness estimation can be challenging. This becomes more problematic in the case of estimating shear stiffness of the lung in which the low tissue density and short T2* result in considerably low signal-to-noise ratio during lung MRE. In the present study, we propose to perform MRE inversion by compressive recovery (MICRo). Such a technique aims to improve the numerical stability and the robustness to data noise of Helmholtz inversion by using prior knowledge on data noise and transform sparsity of the stiffness map. The developed inversion strategy was first validated in simulated phantoms with known stiffness. Next, MICRo was compared to the standard clinical multi-modal DI (MMDI) method forliver MRE in healthy subjects and patients with different stages of liver fibrosis. After establishing the accuracy of MICRo, we demonstrated the robustness of the proposed technique against data noise in lung MRE with healthy subjects. In simulated phantoms with single-directional or multi-directional waves, MICRo outperformed DI with Romano filter or Savitsky and Golay filter, especially when the stiffness and/or noise level was high. In hepatic MRE application, agreement was observed between MICRo and MMDI. Measuringlung stiffness, MICRo demonstrated its advantages over filtered DI by yielding stable stiffness estimation at both residual volume and total lung capacity. These preliminary results demonstrate the potential value of the proposed technique and also warrant further investigation in a larger clinical population.
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http://dx.doi.org/10.1088/1361-6560/ac145aDOI Listing
August 2021

Green Synthesis of Copper Oxide Nanoparticles Using Leaf Extract and Their Characterization and Investigation of Antimicrobial Potential and Cytotoxic Activities.

Evid Based Complement Alternat Med 2021 18;2021:5589703. Epub 2021 Jun 18.

Department of Natural Products and Alternative Medicines, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

The development of green technology is creating great interest for researchers towards low-cost and environmentally friendly methods for the synthesis of nanoparticles. Copper oxide nanoparticles (CuO-NPs) attracted many researchers due to their electric, catalytic, optical, textile, photonic, monofluid, and pharmacological activities that depend on the shape and size of the nanoparticles. This investigation aims copper oxide nanoparticles synthesis using plant leaf extract. Characterization of copper oxide nanoparticles synthesized by green route was performed by three different techniques: X-Ray Diffraction (XRD), Fourier Transform Infrared (FTIR) Spectroscopy, and Scanning Electron Microscopy (SEM). X-ray diffraction (XRD) reveals the crystalline morphology of CuO-NPs and the average crystal size obtained is 15 nm. SEM images showed the spherical nature of the particles and size is lying in the 15-23 nm range. FTIR analysis confirms the functional groups of active components present in the extract which are responsible for reducing and capping agents for the synthesis of CuO-NPs. The synthesized CuO-NPs were studied for their antimicrobial potential against different bacterial as well as fungal pathogens. The results indicated that CuO-NPs show maximum antimicrobial activities against all the selected bacterial and fungal pathogens. Antimicrobial activities of copper oxide nanoparticles were compared with standard drugs Norfloxacin and amphotericin B antibiotics. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of copper oxide nanoparticles were 128 g/mL against all selected bacterial pathogens. MIC of fungus and minimum fungicidal concentration (MFC) of CuO-NPs were 160 g/mL. Thus, CuO-NPs can be utilized as a broad-spectrum antimicrobial agent. The cytotoxic activity of the synthesized CuO-NPs suggested that toxicity was negligible at concentrations below 60 g/mL.
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http://dx.doi.org/10.1155/2021/5589703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235967PMC
June 2021

A Reinforcement Learning Routing Protocol for UAV Aided Public Safety Networks.

Sensors (Basel) 2021 Jun 15;21(12). Epub 2021 Jun 15.

Department of Electrical Engineering, Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad 45650, Pakistan.

In Public Safety Networks (PSNs), the conservation of on-scene device energy is critical to ensure long term connectivity to first responders. Due to the limited transmit power, this connectivity can be ensured by enabling continuous cooperation among on-scene devices through multipath routing. In this paper, we present a Reinforcement Learning (RL) and Unmanned Aerial Vehicle- (UAV) aided multipath routing scheme for PSNs. The aim is to increase network lifetime by improving the Energy Efficiency (EE) of the PSN. First, network configurations are generated by using different clustering schemes. The RL is then applied to configure the routing topology that considers both the immediate energy cost and the total distance cost of the transmission path. The performance of these schemes are analyzed in terms of throughput, energy consumption, number of dead nodes, delay, packet delivery ratio, number of cluster head changes, number of control packets, and EE. The results showed an improvement of approximately 42% in EE of the clustering scheme when compared with non-clustering schemes. Furthermore, the impact of UAV trajectory and the number of UAVs are jointly analyzed by considering various trajectory scenarios around the disaster area. The EE can be further improved by 27% using Two UAVs on Opposite Axis of the building and moving in the Opposite directions (TUOAO) when compared to a single UAV scheme. The result showed that although the number of control packets in both the single and two UAV scenarios are comparable, the total number of CH changes are significantly different.
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http://dx.doi.org/10.3390/s21124121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232606PMC
June 2021

PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells.

Cancers (Basel) 2021 Apr 30;13(9). Epub 2021 Apr 30.

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-6125, USA.

Despite recent advances in therapies, resistance to chemotherapy remains a critical problem in the clinical management of colorectal cancer (CRC). Cancer stem cells (CSCs) play a central role in therapy resistance. Thus, elimination of CSCs is crucial for effective CRC therapy; however, such strategies are limited. Autophagy promotes resistance to cancer therapy; however, whether autophagy protects CSCs to promote resistance to CRC-therapy is not well understood. Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful. Colon cancer cells and tumoroids were used. Fluorescent reporter-based analysis of autophagy flux, spheroid and side population (SP) culture, and qPCR were done. We synthesized 36-077, a potent inhibitor of PIK3C3/VPS34 kinase, to inhibit autophagy. Combination treatments were done using 5-fluorouracil (5-FU) and 36-077. The 5-FU treatment induced autophagy only in a subset of the treated colon cancer. These autophagy-enriched cells also showed increased expression of CSC markers. Co-treatment with 36-077 significantly improved efficacy of the 5-FU treatment. Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.
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http://dx.doi.org/10.3390/cancers13092168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124755PMC
April 2021

Evaluation of clinical trials for natural products used in diabetes: An evidence-based systemic literature review.

Medicine (Baltimore) 2021 Apr;100(16):e25641

First Health Cluster in Eastern Province, Dammam Medical Complex, Dammam, Saudi Arabia.

Background Relevance: A plethora of literature is available regarding the clinical trials for natural products however; no information is available for critical assessments of the quality of these clinical trials.

Aim Of Study: This is a first time report to critically evaluate the efficacy, safety and large scale applications of up-to-date clinical trials for diabetes, based on the three scales of Jadad, Delphi, and Cochrane.

Methodology: An in-depth and extensive literature review was performed using various databases, journals, and books. The keywords searched included, "clinical trials," "clinical trial in diabetes," "diabetes," "natural products in diabetes," "ethnopharmacological relevance of natural products in diabetes," etc.

Results: Based on eligibility criteria, 16 plants with 74 clinical trials were found and evaluated. Major drawbacks observed were; "non-randomization and blindness of the studies," "non-blindness of patients/healthcare/outcome assessors," "lack of patient compliance and co-intervention reports," "missing information regarding drop-out/withdrawal procedures," and "inappropriate baseline characteristics." Principal component analysis and Pearson correlation revealed four components with %variability; PC1: 23.12, PC2: 15.83, PC3: 13.11, and PC4: 11.38 (P ≤ .000). According to descriptive statistics, "non-blinding of outcome assessors" was the major drawback (82%) whereas, "not mentioning the timing of outcome assessment" was observed lowest (6.8%). An in-house quality grading (scale 0-24) classified these clinical trials as; poor (67.6%), acceptable (19.9%), and good quality trials (13.5%).

Conclusion: Proper measures in terms of more strict regulations with pharmacovigilance of plants are utmost needed in order to achieve quality compliance of clinical trials.
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http://dx.doi.org/10.1097/MD.0000000000025641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078398PMC
April 2021

High-dimensional fast convolutional framework (HICU) for calibrationless MRI.

Magn Reson Med 2021 09 4;86(3):1212-1225. Epub 2021 Apr 4.

Electrical and Computer Engineering, The Ohio State University, Columbus, OH, USA.

Purpose: To present a computational procedure for accelerated, calibrationless magnetic resonance image (Cl-MRI) reconstruction that is fast, memory efficient, and scales to high-dimensional imaging.

Theory And Methods: Cl-MRI methods can enable high acceleration rates and flexible sampling patterns, but their clinical application is limited by computational complexity and large memory footprint. The proposed computational procedure, HIgh-dimensional fast convolutional framework (HICU), provides fast, memory-efficient recovery of unsampled k-space points. For demonstration, HICU is applied to 6 2D T2-weighted brain, 7 2D cardiac cine, 5 3D knee, and 1 multi-shot diffusion weighted imaging (MSDWI) datasets.

Results: The 2D imaging results show that HICU can offer 1-2 orders of magnitude computation speedup compared to other Cl-MRI methods without sacrificing imaging quality. The 2D cine and 3D imaging results show that the computational acceleration techniques included in HICU yield computing time on par with SENSE-based compressed sensing methods with up to 3 dB improvement in signal-to-error ratio and better perceptual quality. The MSDWI results demonstrate the feasibility of HICU for a challenging multi-shot echo-planar imaging application.

Conclusions: The presented method, HICU, offers efficient computation and scalability as well as extendibility to a wide variety of MRI applications.
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http://dx.doi.org/10.1002/mrm.28721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184615PMC
September 2021

Amyloid Precursor-like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer.

Cancers (Basel) 2021 Mar 26;13(7). Epub 2021 Mar 26.

Eppley Institute for Research in Cancer & Allied Diseases and the Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.

In the United States, pancreatic cancer is a major cause of cancer-related deaths. Although substantial efforts have been made to understand pancreatic cancer biology and improve therapeutic efficacy, patients still face a bleak chance of survival. A greater understanding of pancreatic cancer development and the identification of novel treatment targets are desperately needed. Our analysis of gene expression data from patient samples showed an increase in amyloid precursor-like protein 2 (APLP2) expression within primary tumor epithelium relative to pancreatic intraepithelial neoplasia (PanIN) epithelial cells. Augmented expression of APLP2 in primary tumors compared to adjacent stroma was also observed. Genetically engineered mouse models of spontaneous pancreatic ductal adenocarcinoma were used to investigate APLP2's role in cancer development. We found that APLP2 expression intensifies significantly during pancreatic cancer initiation and progression in the ; ; (KPC) mouse model, as shown by immunohistochemistry analysis. In studies utilizing pancreas-specific heterozygous and homozygous knockout of APLP2 in the KPC mouse model background, we observed significantly prolonged survival and reduced metastatic progression of pancreatic cancer. These results demonstrate the importance of APLP2 in pancreatic cancer initiation and metastasis and indicate that APLP2 should be considered a potential therapeutic target for this disease.
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http://dx.doi.org/10.3390/cancers13071535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036577PMC
March 2021

Simultaneous Quantitation of Lipid Biomarkers for Inflammatory Bowel Disease Using LC-MS/MS.

Metabolites 2021 Feb 12;11(2). Epub 2021 Feb 12.

Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Eicosanoids are key mediators and regulators of inflammation and oxidative stress that are often used as biomarkers for severity and therapeutic responses in various diseases. We here report a highly sensitive LC-MS/MS method for the simultaneous quantification of at least 66 key eicosanoids in a widely used murine model of colitis. Chromatographic separation was achieved with Shim-Pack XR-ODSIII, 150 × 2.00 mm, 2.2 µm. The mobile phase was operated in gradient conditions and consisted of acetonitrile and 0.1% acetic acid in water with a total flow of 0.37 mL/min. This method is sensitive, with a limit of quantification ranging from 0.01 to 1 ng/mL for the various analytes, has a large dynamic range (200 ng/mL), and a total run time of 25 min. The inter- and intraday accuracy (85-115%), precision (≥85%), and recovery (40-90%) met the acceptance criteria per the US Food and Drug Administration guidelines. This method was successfully applied to evaluate eicosanoid metabolites in mice subjected to colitis versus untreated, healthy control mice. In summary, we developed a highly sensitive and fast LC-MS/MS method that can be used to identify biomarkers for inflammation and potentially help in prognosis of the disease in inflammatory bowel disease (IBD) patients, including the response to therapy.
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http://dx.doi.org/10.3390/metabo11020106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918109PMC
February 2021

Claudin-2 inhibits renal clear cell carcinoma progression by inhibiting YAP-activation.

J Exp Clin Cancer Res 2021 Feb 23;40(1):77. Epub 2021 Feb 23.

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198-5870, USA.

Background: Claudin-2 expression is upregulated in multiple cancers and promotes cancer malignancy. Remarkably, the regulation of claudin-2 expression in kidney cell lines contrasts its reported regulation in other organs. However, claudin-2 role in renal clear cell carcinoma (RCC) remains unknown despite its predominant expression in the proximal tubular epithelium (PTE), the site of RCC origin.

Methods: Publicly available and independent patient databases were examined for claudin-2 association with RCC. The novel protein function was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by Mass spectroscopy, immunoprecipitation and mutational studies, and functional evaluations.

Results: We show that the significant decrease in claudin-2 expression characterized PTE cells and Ex-vivo cultured mouse kidney subjected to dedifferentiation. Inhibition of claudin-2 was enough to induce mesenchymal plasticity and invasive mobility in these models. Further, a progressive loss of claudin-2 expression associated with the RCC progression and poor patient survival. Overexpression of claudin-2 in RCC-derived cancer cells inhibited tumorigenic abilities and xenograft tumor growth. These data supported a novel tumor-suppressive role of claudin-2 in RCC. Mechanistic insights further revealed that claudin-2 associates with YAP-protein and modulates its phosphorylation (S127) and nuclear expression. The tumor suppressive effects of claudin-2 expression were lost upon deletion of its PDZ-binding motif emphasizing the critical role of the PDZ-domain in claudin-2 interaction with YAP in regulating RCC malignancy.

Conclusions: Our results demonstrate a novel kidney specific tumor suppressive role for claudin-2 protein and further demonstrate that claudin-2 co-operates with the YAP signaling in regulating the RCC malignancy.
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http://dx.doi.org/10.1186/s13046-021-01870-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901196PMC
February 2021

Next-generation sequencing technology in the diagnosis of mitochondrial disorders.

Int J Health Sci (Qassim) 2021 Jan-Feb;15(1):1-2

Department of Biomedical Sciences, School of Biomedical Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786442PMC
January 2021

Gut Microbiota and Metabolic Specificity in Ulcerative Colitis and Crohn's Disease.

Front Med (Lausanne) 2020 27;7:606298. Epub 2020 Nov 27.

Department of Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, United States.

Inflammatory bowel disease (IBD) represents multifactorial chronic inflammatory conditions in the gastrointestinal tract and includes Crohn's disease (CD) and ulcerative colitis (UC). Despite similarities in pathobiology and disease symptoms, UC and CD represent distinct diseases and exhibit diverse therapeutic responses. While studies have now confirmed that IBD is associated with dramatic changes in the gut microbiota, specific changes in the gut microbiome and associated metabolic effects on the host due to CD and UC are less well-understood. To address this knowledge gap, we performed an extensive unbiased meta-analysis of the gut microbiome data from five different IBD patient cohorts from five different countries using QIIME2, DIAMOND, and STAMP bioinformatics platforms. profiling of the metabolic pathways and community metabolic modeling were carried out to identify disease-specific association of the metabolic fluxes and signaling pathways. Our results demonstrated a highly conserved gut microbiota community between healthy individuals and IBD patients at higher phylogenetic levels. However, at or below the order level in the taxonomic rank, we found significant disease-specific alterations. Similarly, we identified differential enrichment of the metabolic pathways in CD and UC, which included enriched pathways related to amino acid and glycan biosynthesis and metabolism, in addition to other metabolic pathways. In conclusion, this study highlights the prospects of harnessing the gut microbiota to improve understanding of the etiology of CD and UC and to develop novel prognostic, and therapeutic approaches.
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http://dx.doi.org/10.3389/fmed.2020.606298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729129PMC
November 2020

Compact electron spin resonance skin oximeter: Properties and initial clinical results.

Magn Reson Med 2021 05 18;85(5):2915-2925. Epub 2020 Nov 18.

Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, Israel.

Purpose: Skin oxygen level is of significance for the diagnosis and treatment of many clinical problems, such as chronic wounds and diabetic foot ulcers. Furthermore, skin oxygen levels can be correlated to arterial oxygen partial pressure, thereby revealing potentially dangerous conditions such as hyperoxia (too much oxygen), which may occur in ventilated neonates. Traditionally, skin oxygen levels are measured using electrochemical methods and, more recently, also by fluorescence lifetime techniques. These approaches suffer from several drawbacks, rendering them suboptimal. The purpose of this work is to develop an electron spin resonance (ESR) -based method for monitoring oxygen partial pressure (pO ) in skin tissue.

Methods: A compact sensor for pulsed ESR is designed and constructed. Our ESR-based method makes use of a unique exogenous paramagnetic spin probe that is placed on the skin in a special partially sealed sticker, and subsequently measuring its signal with the compact pulsed ESR sensor that includes a miniature magnet and a small S-band (~2.3 GHz) microwave resonator. The inverse of the spin-spin relaxation time (1/T ) measured by ESR is shown to be linearly correlated with pO levels.

Results: The sensor and its matching sticker were tested both in vitro and in vivo (with human subjects). Measured skin pO levels reached equilibrium after ~2-3 h and were found to be comparable to those measured by continuous-wave (CW) ESR using a large electromagnet.

Conclusions: A compact pulsed ESR sensor with a matching paramagnetic sticker can be used for pO monitoring of the skin tissue, similar to large bulky CW ESR systems.
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http://dx.doi.org/10.1002/mrm.28595DOI Listing
May 2021

Evaluation of solvent and temperature effect on green accelerated solvent extraction (ASE) and UHPLC quantification of phenolics in fresh olive fruit (Olea europaea).

Food Chem 2021 Apr 5;342:128248. Epub 2020 Oct 5.

College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O Box # 1982, Dammam 31441, Saudi Arabia.

A green ASE (accelerated solvent extraction) with a shorter UHPLC (ultra-high performance liquid chromatography) method was developed for simultaneous determination of phenolics. High extract yield (130 mg/g) was observed for water at 100 °C in a short time of 19.5 min using 33.5 mL solvent whereas, UHPLC showed more phenolics of GA (gallic acid), QT (quercetin), LT (luteolin) in ACE (acetone) and RT (rutin) in EtOH (ethanol) solvent at 60 °C. The binary solvent system of ACE: EtOH (1:1) at 60 °C was optimized as extraction set. UHPLC runtime was 3 min with retention times of (min); 0.63 (GA), 0.97 (RT), 2.00 (QT) and 2.41 (LT). Average for phenolics (ppm) was, QT (10.91) > GA (7.33) > LT (4.10) > RT (3.90) whereas, Spanish whole green olive (SP2) showed more phenolics (20.72). Individual phenolic was, GA (47.06) > RT (26.21) > QT (19.34) > LT (6.18). Multivariate, K-mean and PCA (principal component analysis) for solvent*extract yield showed significant correlation and temperature showed no significant correlation for phenolics.
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http://dx.doi.org/10.1016/j.foodchem.2020.128248DOI Listing
April 2021

Fully self-gated whole-heart 4D flow imaging from a 5-minute scan.

Magn Reson Med 2021 03 30;85(3):1222-1236. Epub 2020 Sep 30.

Biomedical Engineering, The Ohio State University, Columbus, OH, USA.

Purpose: To develop and validate an acquisition and processing technique that enables fully self-gated 4D flow imaging with whole-heart coverage in a fixed 5-minute scan.

Theory And Methods: The data are acquired continuously using Cartesian sampling and sorted into respiratory and cardiac bins using the self-gating signal. The reconstruction is performed using a recently proposed Bayesian method called ReVEAL4D. ReVEAL4D is validated using data from 8 healthy volunteers and 2 patients and compared with compressed sensing technique, L1-SENSE.

Results: Healthy subjects-Compared with 2D phase-contrast MRI (2D-PC), flow quantification from ReVEAL4D shows no significant bias. In contrast, the peak velocity and peak flow rate for L1-SENSE are significantly underestimated. Compared with traditional parallel MRI-based 4D flow imaging, ReVEAL4D demonstrates small but significant biases in net flow and peak flow rate, with no significant bias in peak velocity. All 3 indices are significantly and more markedly underestimated by L1-SENSE. Patients-Flow quantification from ReVEAL4D agrees well with the 2D-PC reference. In contrast, L1-SENSE markedly underestimated peak velocity.

Conclusions: The combination of highly accelerated 5-minute Cartesian acquisition, self-gating, and ReVEAL4D enables whole-heart 4D flow imaging with accurate flow quantification.
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http://dx.doi.org/10.1002/mrm.28491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718421PMC
March 2021

Algebraic reconstruction of 3D spatial EPR images from high numbers of noisy projections: An improved image reconstruction technique for high resolution fast scan EPR imaging.

J Magn Reson 2020 10 25;319:106812. Epub 2020 Aug 25.

Department of Internal Medicine, Division of Cardiovascular Medicine, and the EPR Center, Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Biomedical Engineering and the EPR Center, College of Engineering, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

A novel method for reconstructing 3D spatial EPR images from large numbers of noisy projections was developed that minimizes mean square error between the experimental projections and those from the reconstructed image. The method utilizes raw projection data and zero gradient spectrum to account for EPR line shape and hyperfine structure of the paramagnetic probe without the need for deconvolution techniques that are poorly suited for processing of high noise projections. A numerical phantom was reconstructed for method validation. Reconstruction time for the matrix of 128 voxels and 16,384 noiseless projections was 4.6 min for a single iteration. The algorithm converged quickly, reaching R ~ 0.99975 after the very first iteration. An experimental phantom sample with nitroxyl radical was measured. With 16,384 projections and a field gradient of 8 G/cm, resolutions of 0.4 mm were achieved for a cubical area of 25 × 25 × 25 mm. Reconstruction was sufficiently fast and memory efficient making it suitable for applications with large 3D matrices and fully determined system of equations. The developed algorithm can be used with any gradient distribution and does not require adjustable filter parameters that makes for simple application. A thorough analysis of the strengths and limitations of this method for 3D spatial EPR imaging is provided.
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http://dx.doi.org/10.1016/j.jmr.2020.106812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554188PMC
October 2020

A Chitosan-PLGA based catechin hydrate nanoparticles used in targeting of lungs and cancer treatment.

Saudi J Biol Sci 2020 Sep 20;27(9):2344-2357. Epub 2020 May 20.

Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Gautam Budh Nagar, Greater Noida 201310, India.

Objective: To prepare a novel Chitosan (CS)-coated-PLGA-NPs of catechin hydrate (CTH) and to improve lungs bioavailability via direct nose to lungs-delivery for the comparative assessment of a pulmokinetics study by the first-time UHPLC-MS/MS developed method in the treatment of lungs cancer via anticancer activities on H1299 lung cancer cells.

Material And Methods: PLGA-NPs was prepared by solvent evaporation (double emulsion) method followed by coated with chitosan (CS) and evaluated based on release and permeation of drug, a comparative pulmokinetics study with their anticancer activities on H1299 lung cancer cells.

Results: The particle size, PDI and ZP of the optimized CAT-PLGA-NPs and CS-CAT-PLGA-NPs were determined 124.64 ± 12.09 nm and 150.81 ± 15.91 nm, 0.163 ± 0.03 and 0.306 ± 0.03, -3.94 ± 0.19 mV and 26.01 ± 1.19 mV respectively. Furthermore, higher entrapment efficiency was observed for CS-CAT PLGA NPs. The release pattern of the CS-CAT-PLGA NPs was found to favor the release of entrapped CAT within the cancer microenvironment. CS-CAT-PLGA-NPs exposed on H1299 cancer cells upto 24.0 h was found to be higher cytotoxic as compared to CAT-solution (CAT-S). CS-CAT-PLGA-NPs showed higher apoptosis of cancer cells after their exposure as compared to CAT-S. CS-CTH-PLGA-NPs showed tremendous mucoadhesive-nature as compared to CTH-S and CS-CTH-PLGA NPs by retention time (RT) of 0.589 min, and / of 289.21/109.21 for CTH alongwith RT of 0.613 min and / of 301.21/151.21 was found out for IS (internal standard), i.e. Quercetin). Likewise, for 1-1000 ng mL (linear range) of % accuracy (92.01-99.31%) and %CV (inter & intra-day, i.e. 2.14-3.33%) was determined. The improved C with AUC was observed extremely significant (p < 0.001) via i.n. as compared oral and i.v. in the wistar rat's lungs. The CS-approach was successfully designed and safely delivered CAT to the lungs without causing any risk.

Conclusion: CS-CTH-PLGA-NPs were showed a significant role (p < 0.001) for the enhancement of lungs-bioavailability and potentially promising approach to treat lung cancers. CS-CTH-PLGA-NPs did not cause any toxicity, it showed safety and have no obvious toxic-effects on the rat's lungs and does not produce any mortality followed by no abnormal findings in the treated-rats.
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http://dx.doi.org/10.1016/j.sjbs.2020.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451615PMC
September 2020

Prospective correction of patient-specific respiratory motion in myocardial T and T mapping.

Magn Reson Med 2021 02 27;85(2):855-867. Epub 2020 Aug 27.

Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA.

Purpose: Respiratory motion in cardiovascular MRI presents a challenging problem with many potential solutions. Current approaches require breath-holds, apply retrospective image registration, or significantly increase scan time by respiratory gating. Myocardial T and T mapping techniques are particularly sensitive to motion as they require multiple source images to be accurately aligned prior to the estimation of tissue relaxation. We propose a patient-specific prospective motion correction (PROCO) strategy that corrects respiratory motion on the fly with the goal of reducing the spatial variation of myocardial parametric mapping techniques.

Methods: A rapid, patient-specific training scan was performed to characterize respiration-induced motion of the heart relative to a diaphragmatic navigator, and a parametric mapping pulse sequence utilized the resulting motion model to prospectively update the scan plane in real-time. Midventricular short-axis T and T maps were acquired under breath-hold or free-breathing conditions with and without PROCO in 7 healthy volunteers and 3 patients. T and T were measured in 6 segments and compared to reference standard breath-hold measurements using Bland-Altman analysis.

Results: PROCO significantly reduced the spatial variation of parametric maps acquired during free-breathing, producing limits of agreement of -47.16 to 30.98 ms (T ) and -1.35 to 4.02 ms (T ), compared to -67.77 to 74.34 ms (T ) and -2.21 to 5.62 ms (T ) for free-breathing acquisition without PROCO.

Conclusion: Patient-specific respiratory PROCO method significantly reduced the spatial variation of myocardial T and T mapping, while allowing for 100% efficient free-breathing acquisitions.
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http://dx.doi.org/10.1002/mrm.28475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506658PMC
February 2021

Optimization of extraction and quantification technique for phenolics content of garlic (Allium sativum): An application for comparative phytochemical evaluation based on cultivar origin.

Biomed Chromatogr 2020 Nov 20;34(11):e4942. Epub 2020 Jul 20.

Department of Pharmacognosy, Faculty of Pharmacy, Federal Urdu University of Arts, Science and Technology, Karachi, Pakistan.

A range of conventional, i.e. maceration, percolation, ultrasonic assisted, Soxhlet and Soxtec extraction (STE), to advanced extraction techniques of accelerated solvent extraction (ASE) was utilized for the first time in order to optimize the extract yield and recovery of phenolics-gallic acid (GA), rutin (RT) and quercetin (QT)-quantified via ultra-high performance liquid chromatography with diode array detector (UHPLC-DAD). The effect of solvents (n-hexane, dichloromethane and methanol) and temperature (60, 80 and 100°C) upon extraction yield, phenolic content and antioxidant activity (DPPH, ABTS and DPPH) was studied, and the method was validated in commercial food samples from Saudi Arabia, China and India. A high extract yield with percentage recovery was observed for STE (1221.10 mg/5 g; 24.42%) and ASE techniques (91.50 mg/1 g; 9.15%) in methanol at 100°C. UHPLC-DAD showed retention times (min) of 0.67, 1.93 and 1.90 for GA, RT and QT, respectively in the shortest runtime of 3 min. The yield for phenolics was higher for STE/ASE (ppm): 15.27/15.29 (GA), 85.24/37.56 (RT) and 52.20/33.40 (QT), respectively. In terms of antioxidant activities, low IC values (μg/ml) of 1.09/1.18 (DPPH), 2.11/5.32 (ABTS) and 4.35/7.88 (phenazine methosulfate-nicotinamide adenine dinucleotide) were observed for STE and ASE, respectively. Multivariate analysis for STE showed a significant (P = 0.000) correlation for extraction type vs. extract yield and phenolics content; however, there was no significance for antioxidant activities vs. extraction type. ASE showed a positive correlation for solvent vs. extraction yield, phenolics and antioxidant activity; however, there was no correlation for extraction yield and DPPH activity. Principal component analysis for STE showed a major variability (52.02%) for extraction yield and phenolics in PC1 followed by PC2 (38.30%) for antioxidant activities. For ASE, PC1 (48.68%) showed a positive correlation for solvent vs. extraction yield and phenolics while PC2 (33.12%) showed a positive correlation for temperature and antioxidant activities. STE and ASE were the optimized extraction techniques for the garlic food sample while a significant effect of solvent and temperature was observed upon extraction yield, phenolics and antioxidant activity.
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http://dx.doi.org/10.1002/bmc.4942DOI Listing
November 2020

Ethnobotany, ethnopharmacology, phytochemistry, biological activities and toxicity of Pistacia chinensis subsp. integerrima: A comprehensive review.

Phytother Res 2020 Nov 4;34(11):2793-2819. Epub 2020 Jun 4.

Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal Dir (U), Pakistan.

Pistacia chinensis subsp. integerrima (J. L. Stewart ex Brandis) Rech. F. is a valuable medicinal plant used in south Asian communities for the treatment of asthma, diarrhea, diabetes, liver diseases, fever, pain and inflammation. This review critically evaluates the available information on P. integerrima's ethnobotany, ethnopharmacology, phytochemistry, pharmacology and toxicology. Electronic databases such as Google Scholar, PubMed, Springer Link, and so forth, books and theses were used to find relevant information about P. integerrima using keywords such as "Pistacia integerrima," "P. integerrima," "Ethnopharmacology," "Phytochemistry," "Traditional uses". A number of in vitro and in vivo pharmacological activities have been reported; however, the most promising and attractive activity observed was its role in Alzheimer, diabetes, convulsions, cancer, asthma, diabetes, diarrhea and as an immunomodulatory, analgesic and antiinflammatory. In addition, Pistagremic acid exerted anti-Alzheimer's activity based on a hitherto unknown mechanism through interference with the amyloidogenic pathway. Most of the pharmacological activities were linked with traditional uses. A range of compounds have been reported from P. integerrima extracts including triterpenes, volatile oils, flavonoids, fatty acids, phenolic, phytosterols, tannins and oligosaccharides as well as unknown triterpenes and flavonoids. Pistagremic acid, a novel triterpene, was attributed to most of the activities. in vivo toxicological studies in animal suggested a toxic dose of 1,500 mg kg , for its methanolic extract. All reported pharmacological activities were carried out in vitro and a gap in research, that is, preclinical and clinical investigation exists. Its outstanding activity as an antiglycating agent is the most promising and a so far unique activity and needs further evaluation. In-depth research and clinical trials on human subjects in order to investigate P. integerrima pharmacological activity, clinical efficacy and safety are crucial next steps.
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http://dx.doi.org/10.1002/ptr.6720DOI Listing
November 2020

Peripheral symmetrical gangrene due to severe malaria: a case report.

Trop Doct 2020 Jul 21;50(3):251-253. Epub 2020 May 21.

Assistant Professor, Department of Medicine, JNMCH, Aligarh, Uttar Pradesh, India.

We present a patient with severe malaria of seven days' duration who developed an altered sensorium of one day. During hospital admission, peripheral symmetrical gangrene of hands and feet followed, despite normal limb vasculature.
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http://dx.doi.org/10.1177/0049475520925378DOI Listing
July 2020

Assessment of cardiac function, blood flow and myocardial tissue relaxation parameters at 0.35 T.

NMR Biomed 2020 07 4;33(7):e4317. Epub 2020 May 4.

Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio.

A low field strength (B0) system could increase cardiac MRI availability for patients otherwise contraindicated at higher field. Lower equipment costs could also broaden cardiac MR accessibility. The current study investigated the feasibility of cardiac function with steady-state free precession and flow assessment with phase contrast (PC) cine images at 0.35 T, and evaluated differences in myocardial relaxation times using quantitative T1, T2 and T2* maps by comparison with 1.5 and 3 T results in a small cohort of six healthy volunteers. Signal-to-noise ratio (SNR) differences across systems were characterized with proton density-weighted spin echo phantom data. SNR at 0.35 T was lower by factors of 5.5 and 15.0 compared with the 1.5 and 3 T systems used in this study. All cine images at 0.35 T scored 3 or greater on a five-point image quality scale. Normalized blood-myocardium contrast in cine images, left ventricular volumes (end diastolic volume, end systolic volume) and function (ejection fraction and stroke volume) measures at 0.35 T matched 1.5 and 3 T results. Phase-to-noise ratio in 0.35 T PC images (11.7 ± 1.9) was lower than 1.5 T (18.7 ± 5.2) and 3 T (44.9 ± 16.5). Peak velocity and stroke volume determined from PC images were similar across systems. Myocardial T1 increased (564 ± 13 ms at 0.35 T, 955 ± 19 ms at 1.5 T and 1200 ± 35 ms at 3 T) while T2 (59 ± 4 ms at 0.35 T, 49 ± 3 ms at 1.5 T and 40 ± 2 ms at 3 T) and T2* (42 ± 8 ms at 0.35 T, 33 ± 6 ms at 1.5 T and 24 ± 3 ms at 3 T) decreased with increasing B0. Despite SNR deficits, cardiovascular function, flow assessment and myocardial relaxation parameter mapping is feasible at 0.35 T using standard cardiovascular imaging sequences.
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http://dx.doi.org/10.1002/nbm.4317DOI Listing
July 2020

Patient-Adaptive Magnetic Resonance Oximetry: Comparison With Invasive Catheter Measurement of Blood Oxygen Saturation in Patients With Cardiovascular Disease.

J Magn Reson Imaging 2020 11 1;52(5):1449-1459. Epub 2020 May 1.

Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.

Background: The current standard method to measure intracardiac oxygen (O ) saturation is by invasive catheterization. Accurate noninvasive blood O saturation by MRI could potentially reduce the duration and risk of invasive diagnostic procedures.

Purpose: To noninvasively determine blood oxygen saturation in the heart with MRI and compare the accuracy with catheter measurements.

Study Type: Prospective.

Subjects: Thirty-two patients referred for right heart catheterization (RHC) and five healthy subjects.

Field Strength/sequence: T2-prepared single-shot balanced steady-state free-precession at 1.5T.

Assessment: MR signals in venous and arterial blood, hematocrit, and arterial O saturation from a pulse oximeter were jointly processed to fit the Luz-Meiboom model and estimate blood O saturation in the right heart. Interstudy reproducibility was evaluated in volunteers and patients. Interobserver reproducibility among three readers was assessed using data from volunteers and 10 patients. Accuracy of MR oximetry was compared to RHC in all patients.

Statistical Tests: Coefficient of variation, intraclass correlation coefficient, Bland-Altman analysis, Pearson's correlation.

Results: The coefficient of variation for interstudy reproducibility of O saturation was 2.6% on average in volunteers and 3.2% in patients. Interobserver reproducibility among three observers yielded intraclass correlation coefficients of 0.81 and 0.87 respectively for RV and MPA O saturation. O saturation (y = 0.85x + 0.13, R = 0.78) and (a-v)O difference (y = 0.71x + 0.90, R = 0.69) by MR and RHC were significantly correlated (N = 32, P < 0.05 in both cases) in patients. MR slightly overestimated O saturation compared to RHC with 2% ± 5% bias and limits of agreement between -7% and 12%.

Data Conclusion: MR oximetry is repeatable and reproducible. Good agreement was shown between MR and catheter venous O saturation and (a-v)O difference in a cohort whose venous O ranged from abnormally low to high levels, with most values in the normal physiological range.

Level Of Evidence: 2.

Technical Efficacy Stage: 2.
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http://dx.doi.org/10.1002/jmri.27179DOI Listing
November 2020

A comparative pulmonary pharmacokinetic study of budesonide using polymeric nanoparticles targeted to the lungs in treatment of asthma.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):749-762

Nanomedicine Lab, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, Hamdard Nagar, New Delhi, India.

Budesonide (BUD) exhibits a very low bioavailability to lungs which makes it less favourable as an inhalational dosage form. Developed-Nanoparticles (NPs) [coated with chitosan (CS)] i.e. BUD-NPs are intended to enhance lungs-BUD bioavailability, aerosolization, lungs deposition as well as pharmacokinetic profile for BUD-NPs. BUD-NPs were developed through single-emulsification-solvent-evaporation technique. Characterisation of BUD-NPs was done for particle size, zeta potential, size distribution, encapsulation efficiency, and drug-release. A particle size (196.4 ± 10.05 nm) with smooth and spherical shape alongwith zeta potential (11.8 ± 0.91 mV) and drug-content (44.64 ± 2.91 µg/mg) was observed. Ultra-high-performance-liquid-chromatography-mass spectroscopy (UHPLC-MS/MS) study was successfully applied for comparative effects of BUD-NPs lungs bioavailability via major delivery routes, and their biological effects. The NPs i.e. BUD-NPs revealed more bioavailability and lung deposition in animal model as compared to oral (3.0-times-higher) and i.v. (2.0-times-higher). BUD 0.75 min and 431.61/323.16 whereas Fluticasone (IS) 1.16 min and 501.42/313.31 , elution time and transition respectively. The CS-approach was successfully designed and safely delivered BUD to the lungs without causing any risk. BUD-NPs did not cause any toxicity, it showed safety and have no obvious toxic-effects on the rat's lungs and does not produce any mortality followed by no abnormal findings in the treated-rats.
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http://dx.doi.org/10.1080/21691401.2020.1748640DOI Listing
December 2020

A comparative permeation evaluation of a novel 5-Fluorocuracil nanoemulsion-gel by topically applied in the different excised rat, goat, and cow skin.

Saudi J Biol Sci 2020 Apr 3;27(4):1024-1040. Epub 2020 Mar 3.

Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Aim Of The Study: 5-Fluorouracil (5-FU) can't be given orally because of very low bioavailability and produces serious adverse effects. Therefore, the main objective of this research is to develop, evaluate, and comparative effects by different nanoformulations of topical application on chemoprevention of skin cancer in different types of skin.

Material And Methods: Castor oil (oil), Transcutol HP (surfactant), and Polyethylene glycol (PEG)-400 (co-surfactant) have taken on the basis of nonionic property and highest nanoemulsion (NE)-region. Aqueous micro titration method with ultra-sonication method (based on high energy) was used for the preparation of 5-FU-NE. Optimized-5-FU-NE was stable thermodynamically, and their characterizations was performed on the basis of globule size, zeta potential, refractive index, and viscosity. Optimized-NE has been converted into 5-FU-NE-Gel with the help of Carbopol® 934 and also performed their permeation studies in the different skins (cow, goat, and rat, ) using Logan transdermal diffusion cell (DHC-6T). Optimized-5-FU-NE and 5-FU-NE-Gel were evaluated cytotoxic studies () on the melanoma cell lines.

Results: The permeation of 5-FU from 5-FU-NE-Gel nanoformulation for rat skin model was 1.56 times higher than the 5-FU-NE and 12.51 times higher than the 5-FU-S for the cow and goat skin model. The values of steady state flux and permeability coefficient for 5-FU-NE-Gel of rat skin were higher i.e. 12.0244 ± 1.12 µgcmh and 1.2024 ± 0.073 × 10 µg cmh, respectively. Optimized-5-FU-NE and 5-FU-NE-Gel nanoformulation were found to be physically stable. SK-MEL-5 cancer cells have showed the results based on cytotoxicity studies () that 5-FU as Optimized-5-FU-NE-Gel is much more efficacious than 5-FU-NE followed by free 5-FU. Localization of 5-FU from 5-FU-NE-Gel was higher with higher permeation in rat skin.

Conclusion: 5-FU-NE-Gel is found to be for the better to treatment of cutaneous malignancies. It can be developed 5-FU-NE-Gel could be a promising vehicle for the skin cancer chemoprevention.
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http://dx.doi.org/10.1016/j.sjbs.2020.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105695PMC
April 2020

Iron and prebiotic fortified flour improves the immune function of iron deficient women of childbearing age.

Pak J Pharm Sci 2020 Jan;33(1(Supplementary)):253-261

University Institute of Diet and Nutritional Sciences, The University of Lahore, Islamabad Campus, Islamabad, Pakistan.

Micronutrient deficiencies (MNDs) are common worldwide, in both developing as well as developed countries. MNDs such as Iron Deficiency not only compromise the nutritional status of individuals but can also put them at an increased risk of developing various other diseases by negatively affecting their immunity. The objective of the current research was to determine the effects of prebiotics and iron fortificants on various immunoglobulins among iron deficient women belonging to childbearing age. To serve the purpose, a total of seventy five iron deficient women were selected and randomly divided into one control and four treatment groups. Accordingly, different types of fortified wheat flour were prepared, based on varying dosage of prebiotics and iron fortificants, to be fed to anemic women on daily basis for three months. Two iron salts (FeSO and NaFeEDTA) and two prebiotics (Galacto oligosaccharides and Inulin) were used to fortify wheat flour during the trials. Overnight fasted women were asked to give blood samples on monthly basis, up to three months. Four types of Immunoglobulins including IgA, IgE, IgG and IgM were determined at baseline, 30th, 60th and 90th day of trials using their respective protocols. The results of the study indicated that a statistically significant declining trend for IgA, IgE, IgG and IgM was present among the treatment groups (P-value < 0.05), compared to the control group. The study concluded that provision of iron and prebiotic fortified flour improved the immune function of iron deficient women.
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January 2020
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