Jalal Jazayeri - Academia.edu (original) (raw)

Papers by Jalal Jazayeri

Research paper thumbnail of Additional file 11 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

Additional file 11 File S1. A zip archive containing excel files with the most significant pathwa... more Additional file 11 File S1. A zip archive containing excel files with the most significant pathways enrichment results from methylomics analysis including those of Fig. S7B, Table S2 and Table S3. The archive unpacks as five separate folders, each containing the following pathways analysis results. A) All GO enrichments for each cell comparison significant below the adjP =0.001 level. B) All GO enrichments that were uique to a particular cell comparison. C) KEGG enriched pathways for each cell comparison, with analyses performed separately on hypermethyalted (files labelled up) and hyperemethylated (files labelled down) probes. These correspond to the pathways of of Fig. S7B. D) All KEGG enriched pathways from C which were unique to a particular cell comparison. E) All All Reactome enriched pathways for each cell comparison significant below the adjP =0.05 level.

Research paper thumbnail of Additional file 5 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 5:File S4. An excel file containing proteomics results for 243 proteins which ful... more Additional file 5:File S4. An excel file containing proteomics results for 243 proteins which fulfil stringency criteria of t-test p-value of less than 0.05, and a fold change greater than 1.5 by both the protein and peptide approaches from File S2. Related to Fig. 3. Column B shows "red" (more abundant in comparative sample 1) and "blue" (less abundant in sample 1) significantly differential proteins for each pair wise comparison which were later used for "red" and 'blue" WebGestalt pathways enrichment analysis (File S5). Comparisons follow File S2.

Research paper thumbnail of Additional file 4 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 4:File S3. Principal component analysis results for pathways associated with SWAT... more Additional file 4:File S3. Principal component analysis results for pathways associated with SWATH-MS proteomics results.

Research paper thumbnail of Additional file 6 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 6:File S5. WebGestalt pathway mapping excel results file for red and blue protein... more Additional file 6:File S5. WebGestalt pathway mapping excel results file for red and blue proteins from File S4. Related to Fig. 3. (A) WebGestalt Features (GO, KEGG Pathways, Wikipathways, Pathway Commons, Transcription Factors) significant at the adjP≤0.001 level between any 2 comparisons. (B) Features from A, viewed at the adjP

Research paper thumbnail of Additional file 8 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 8:File S7. A zip archive containing time lapse Holo-tomographic video.avi files o... more Additional file 8:File S7. A zip archive containing time lapse Holo-tomographic video.avi files of cells. These images are based upon differences in refractive index [53], and are provided for the dynamic visualization of mitochondria. Prominent visible features include small white lipid droplets and cholesterol-rich mitochondria [21], as well as nuclear membrane and nucleoli. The previously described MIA PaCa-2 cell bleb-like protrusions [34] are apparent as highly dynamic rearrangements of the cytoplasmic membrane, which may contribute to intercellular communication. (A) MP cells. (B) WT cells. (C) DM cells. (D) TM cells.

Research paper thumbnail of Additional file 3 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 3:File S2. An Excel file showing experimental design, normalized ion intensities ... more Additional file 3:File S2. An Excel file showing experimental design, normalized ion intensities for 1330 proteins identified by SWATH-MS proteomics, and six pairwise comparisons between the 4 sample types [1) MP v. WT, 2) MP v. DM, 3) MP v. TM, 4) WT v. DM, 5) WT v. TM, and 6) DM v. TM]. Related to Fig. 3. The first tab contains a detailed descriptive legend. Data are available via ProteomeXchange with identifier PXD014716.

Research paper thumbnail of Serious infections in Rheumatoid Arthritis and strategies for their prevention: A review and discussion of implications for clinical practice

Introduction: Serious infections (SIs) in rheumatoid arthritis (RA) are common and may be life-th... more Introduction: Serious infections (SIs) in rheumatoid arthritis (RA) are common and may be life-threatening or fatal. The goal of this review was to assess the spectrum of SIs in RA, review potential causes for these SIs and to formulate strategies for prevention. Methods: We performed a systematic review that included multiple databases viz. PubMed, Medline, Scopus, and Google Scholar. Search terms used were ‘Rheumatoid Arthritis AND infection’. Searches were limited to the title of articles, human subjects and non-juvenile arthritis and to those articles published in English. Results: In total, 3,324 articles, identified through PubMed, Medline, Scopus and Google Scholar repository were found. After removing duplicates, 825 articles remained for further screening from which 141 articles were selected. These were further assessed and 110 were then excluded because 31 articles were case reports, 35 focused on young subjects (<16 years) and 44 studies focused on non-serious infection. Overall, only 31 studies met our selection criteria. Conclusion: SIs are far more common in RA than in the general population. Corticosteroids are associated with an appreciable increase in SI risk. Most commonly used and currently favored synthetic DMARDs confer a small or no risk, biologic DMARDs confer moderate risk in the first year of therapy and then a diminishing risk thereafter, and higher dose biologic or combination biologic therapy should be avoided since the SI risk is unacceptably high. Undetectable Mannose Binding Lectin (MBL) is a major risk factor for SI in RA, comparable to Prednisolone.

Research paper thumbnail of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Research Square (Research Square), Feb 27, 2020

Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells... more Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results: We demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/Akt activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/Akt activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells. Conclusions: Altogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology.

Research paper thumbnail of Oral Presentations: O-22: Leukaemia Inhibitory Factor (Lif) Antagonist as Novel Candidate for Modulating of Chondroblast Progenitor Cells

Research paper thumbnail of Patient experiences of codesigned rehabilitation interventions in hospitals: a rapid review

BMJ Open, Nov 1, 2022

Background Codesign strengthens partnerships between healthcare workers and patients. It also fac... more Background Codesign strengthens partnerships between healthcare workers and patients. It also facilitates collaborations supporting the development, design and delivery of healthcare services. Prior rehabilitation reviews have focused mainly on the clinical and organisational outcomes of codesign with less focus on the lived experience of rehabilitation patients. Objective To explore patient experiences of codesigned hospital rehabilitation interventions. Design Rapid review and evidence synthesis of the literature. Data sources CINAHL, MEDLINE, Embase and Cochrane were searched from 1 January 2000 to 25 April 2022. Study selection Studies reporting patient experiences of codesigned rehabilitation interventions in hospitals. Results 4156 studies were screened, and 38 full-text studies were assessed for eligibility. Seven studies were included in the final rapid review. Five out of the seven studies involved neurological rehabilitation. All eligible studies used qualitative research methods. The main barriers to codesign were related to staffing and dedicated time allocated to face-to-face patient-therapist interactions. High-quality relationships between patients and their therapists were a facilitator of codesign. Thematic synthesis revealed that codesigned rehabilitation interventions can enable a meaningful experience for patients and facilitate tailoring of treatments to align with individual needs. Personalised rehabilitation increases patient involvement in rehabilitation planning, delivery and decision-making. It also promotes positive feelings of empowerment and hope. Conclusion This rapid review supports the implementation of codesigned rehabilitation interventions to improve patient experiences in hospitals. PROSPERO registration number CRD42021264547.

Research paper thumbnail of Patient experiences of co-designed rehabilitation interventions: protocol for a rapid review

BMJ Open, 2022

Introduction Patient-centred care can be facilitated by co-design, which refers to collaboration ... more Introduction Patient-centred care can be facilitated by co-design, which refers to collaboration between healthcare professionals and consumers in producing and implementing healthcare. Systematic reviews on co-design have mainly focused on the effectiveness of co-produced healthcare interventions. Less attention has been directed towards the experiences of patients in co-designed interventions. This rapid review aims to explore patient experiences of co-designed rehabilitation interventions and inform rehabilitation decision-making. Methods and analysis A rapid review will expedite timely information on co-design experiences for stakeholders. Four electronic databases, including Cochrane CENTRAL, MEDLINE, Embase and CINAHL, will be searched for papers published from 1 January 2000 to 1 January 2022. The Cochrane Risk of Bias tool will be used for randomised trials. Critical appraisal checklists from The Joanna Briggs Institute shall evaluate the risk of bias of non-randomised trials and qualitative studies. A narrative synthesis will be provided for the quantitative studies. Thematic synthesis will be conducted on qualitative findings. The overall strength of the evidence will be measured using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for quantitative investigations and the GRADE-Confidence in Evidence from Reviews of Qualitative Research for qualitative studies. The results will be presented using narrative summaries, identified themes, summary tables, flow charts and quantitative statistical analyses. Ethics and dissemination Ethics approval is not required for the review. The protocol and rapid review will be submitted to an online, open access and peerreviewed journal for publication. The review findings will be rapidly translated to consumers, clinicians, healthcare leaders, organisations, researchers and policy makers via publications, evidence summaries, conferences, workshops, websites, social media and online events. PROSPERO registration number CRD42021264547.

Research paper thumbnail of Rapid detection of Clostridium difficile toxins from stool samples using real-time multiplex PCR

Journal of Medical Microbiology, Sep 1, 2013

In this study, a total of 650 stool samples were tested to show that our method is capable of det... more In this study, a total of 650 stool samples were tested to show that our method is capable of detecting four Clostridium difficile genes; tcdA, tcdB, encoding toxin A (TcdA) and toxin B (TcdB), and the binary toxin C. difficile transferase genes (cdtA and/or cdtB) encoding CDT toxin. Besides detecting the targeted C. difficile genes, our method can be used to detect the presence of any inhibitory components in the PCR. This assay, combined with a selective culture medium, such as the chromID TM C. difficile, can be applied directly for screening C. difficile-associated disease. The PCR-based assay developed here is rapid (4 h per 21 stool samples) and accurate in diagnosing C. difficile infection, 100 % assay sensitivity and negative predictive value (NPV) were obtained. However, the assay specificity of 99.1 % and positive predictive value (PPV) of 94.9 % were slightly lower than the optimal value of 100 %. The assay protocol outlined here can be used as a rapid screening tool to assist infection control units and in managing infected patients by reducing the number of patients requiring isolation and extended hospitalization. Rapid detection can prevent unnecessary antibiotic therapy and potentially reduce the spread of infection by emerging hypervirulent C. difficile strains.

Research paper thumbnail of Optimization Transgene Expression of Short Fully Synthesized Lipopeptide- Based Transfection Agent for Non-Viral Gene Delivery Vehicle

Gene therapy using non-viral gene delivery vehicle might be applied for the treatment of viral in... more Gene therapy using non-viral gene delivery vehicle might be applied for the treatment of viral infection, cancer and genetic disorders. However, the most challenging barrier is the low efficiency of transgene expression. Therefore, optimization of transgene expression is very important and critical to be performed before doing extensive evaluation of the transfection agent. Herein, we present transgene expression optimization data of gene encoding luciferase condensed with a series of short fully synthesized lipopeptide on COS7, HeLa and 293T cells. The complex formation, effect of molar ratio, forced sedimentation, incubation period of the DNA-transfection agent complexes were explored on transfection efficiency. Moreover, the enhancement effect in transfection efficiency of polymer PEI as co-transfection agent in DNA-lipopeptide was also investigated. The results show that the complex particles of the DNA-lipopeptide were formed efficiently in the low ionic strength environment (HEPES Glucose Buffer pH 7.4), and the complex was incubated more than 10 hours before it was transfected onto the cells. Depending on the lipopeptide, the DNA-lipopeptide incubation in 24 hours (at 4-6C) resulted an increased up to 2-4-fold in the transgene expression. In addition, polymer PEI enhanced the transfection efficiency of the lipopeptide-mediated gene delivery up to 50-fold compared to control. In summary, short and a linear of fully synthesized lipopeptide-based transfection agent facilitated transgene expression in several mammalian cells by optimizing the DNA-lipopeptide complex formation and transfection condition.

Research paper thumbnail of Additional file 9 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

Additional file 9 Table S2. GO pathways enrichment results. Related to Fig. 7. The top ten GO enr... more Additional file 9 Table S2. GO pathways enrichment results. Related to Fig. 7. The top ten GO enrichments for each cell comparison from Fig. 7. Full results are available in File S1.

Research paper thumbnail of Additional file 1 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

Additional file 1 Fig. S1. Representative hyperspectral autofluorescence cell images from the mea... more Additional file 1 Fig. S1. Representative hyperspectral autofluorescence cell images from the measurements. Related to Fig. 1. (A) Mean cellular intensity of hyperspectral autofluorescence channel 18 [495 nm(Ex), 700 nm(Em)], which may reflect porphyrin or protein-bound red-shifted flavin emission [46], is significantly affected by PGRMC1-HA phosphorylation status. The table provides Kolmogorov-Smirnov test p values from pair wise comparisons. (B) The ratio of hyperspectral autofluorescence channels 3 [375 nm(Ex), 450 nm(Em)] to channel 12 [435 nm(Ex), 587 nm(Em)] differs significantly between cells. The table follows C. (C) Individual channels #3 and #4 from (B) as listed in Table S1 (left) and the same two channels superimposed (right).

Research paper thumbnail of Additional file 8 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

Additional file 8 Table S1. Spectral channel filters employed for hyperspectral autofluorescence ... more Additional file 8 Table S1. Spectral channel filters employed for hyperspectral autofluorescence imaging. Related to Fig. 1. For further details of this approach see Gosnell et al. [44].

Research paper thumbnail of Additional file 1 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 1:Figure S1. Detailed views of selected pathways identified by WebGestalt analyse... more Additional file 1:Figure S1. Detailed views of selected pathways identified by WebGestalt analyses. Related to Fig. 3. All panels are adapted from File S6. Heat map colors follow Fig. 3. (A) Principal component (PC) analysis of SWATH-MS proteomics results showing distribution of PC1 and PC2. PC1 corresponded to pathways associated with ribosomes and translation, while PC2 corresponded to pathways associated with mRNA splicing processing (see File S3). (B) Proteins associated with PI3K/AKT activity (WebGestalt Database: PC, DB_ID:1648, "Class I PI3K signaling events mediated by AKT") are less abundant in TM cells. (C) F1/F0 ATPase subunits elevated in WT and TM cells. (D) Abundances of proteins associated with protein folding and microtubule function are altered by PGRMC1 phosphorylation status. Proteins detected in any of the following WebGestalt pathways or functions (1–4) or a manual search (5) are mapped against their expression profiles. 1) cellular component chaperoni...

Research paper thumbnail of Additional file 7 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 7:File S6. An excel file with heat map protein IDs and pathways for red vs. blue ... more Additional file 7:File S6. An excel file with heat map protein IDs and pathways for red vs. blue pathways adjP

Research paper thumbnail of Additional file 2 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 2:File S1. A zip archive containing time lapse mp4 movies of migrating cells in s... more Additional file 2:File S1. A zip archive containing time lapse mp4 movies of migrating cells in scratch assays. Related to Fig. 1. Images were taken at 10 min intervals over 36 h and are replayed over 65 s at 9 frames per second (2000x real time). The presented 32.4 MB MP4 files were generated from the original 666 MB (6000x real time) .avi files (length 21 s, frame width x height 1024 × 1024, Data rate/bit rate 287,462 kbps, frame rate 100 fps) by processing in Adobe Premiere Pro 2017 using the following settings: Preset "custom"; Width: 1024; Height 1024; Aspect Square Pixels (1.0); Field Order: progressive; Profile: high; Target Bitrate [Mbps] 4.08; Maximum Bitrate [Mbps] 4.39; 9 fps; No Audio; Output as standard .mp4; Time Interpolation: Frame Sampling; Stream Compatibility: Standard; Variable bit rate, single pass; Number of frames 00:01:04:09. The zip archive contains 4 files with filenames representing cell type and date of measurement (yyyymmdd). (A) A_MP_20170807....

Research paper thumbnail of Non-invasive detection and monitoring of biochemistry in cells and tissues by decomposing autofluorescence

Asia Communications and Photonics Conference 2016, 2016

Hyperspectral imaging based on endogenous contrast provides a new non-invasive method to characte... more Hyperspectral imaging based on endogenous contrast provides a new non-invasive method to characterise cells and tissues. Cellular content and maps of native fluorophores help monitor biological processes, with proper account of intrinsic cellular heterogeneity.

Research paper thumbnail of Additional file 11 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

Additional file 11 File S1. A zip archive containing excel files with the most significant pathwa... more Additional file 11 File S1. A zip archive containing excel files with the most significant pathways enrichment results from methylomics analysis including those of Fig. S7B, Table S2 and Table S3. The archive unpacks as five separate folders, each containing the following pathways analysis results. A) All GO enrichments for each cell comparison significant below the adjP =0.001 level. B) All GO enrichments that were uique to a particular cell comparison. C) KEGG enriched pathways for each cell comparison, with analyses performed separately on hypermethyalted (files labelled up) and hyperemethylated (files labelled down) probes. These correspond to the pathways of of Fig. S7B. D) All KEGG enriched pathways from C which were unique to a particular cell comparison. E) All All Reactome enriched pathways for each cell comparison significant below the adjP =0.05 level.

Research paper thumbnail of Additional file 5 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 5:File S4. An excel file containing proteomics results for 243 proteins which ful... more Additional file 5:File S4. An excel file containing proteomics results for 243 proteins which fulfil stringency criteria of t-test p-value of less than 0.05, and a fold change greater than 1.5 by both the protein and peptide approaches from File S2. Related to Fig. 3. Column B shows "red" (more abundant in comparative sample 1) and "blue" (less abundant in sample 1) significantly differential proteins for each pair wise comparison which were later used for "red" and 'blue" WebGestalt pathways enrichment analysis (File S5). Comparisons follow File S2.

Research paper thumbnail of Additional file 4 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 4:File S3. Principal component analysis results for pathways associated with SWAT... more Additional file 4:File S3. Principal component analysis results for pathways associated with SWATH-MS proteomics results.

Research paper thumbnail of Additional file 6 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 6:File S5. WebGestalt pathway mapping excel results file for red and blue protein... more Additional file 6:File S5. WebGestalt pathway mapping excel results file for red and blue proteins from File S4. Related to Fig. 3. (A) WebGestalt Features (GO, KEGG Pathways, Wikipathways, Pathway Commons, Transcription Factors) significant at the adjP≤0.001 level between any 2 comparisons. (B) Features from A, viewed at the adjP

Research paper thumbnail of Additional file 8 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 8:File S7. A zip archive containing time lapse Holo-tomographic video.avi files o... more Additional file 8:File S7. A zip archive containing time lapse Holo-tomographic video.avi files of cells. These images are based upon differences in refractive index [53], and are provided for the dynamic visualization of mitochondria. Prominent visible features include small white lipid droplets and cholesterol-rich mitochondria [21], as well as nuclear membrane and nucleoli. The previously described MIA PaCa-2 cell bleb-like protrusions [34] are apparent as highly dynamic rearrangements of the cytoplasmic membrane, which may contribute to intercellular communication. (A) MP cells. (B) WT cells. (C) DM cells. (D) TM cells.

Research paper thumbnail of Additional file 3 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 3:File S2. An Excel file showing experimental design, normalized ion intensities ... more Additional file 3:File S2. An Excel file showing experimental design, normalized ion intensities for 1330 proteins identified by SWATH-MS proteomics, and six pairwise comparisons between the 4 sample types [1) MP v. WT, 2) MP v. DM, 3) MP v. TM, 4) WT v. DM, 5) WT v. TM, and 6) DM v. TM]. Related to Fig. 3. The first tab contains a detailed descriptive legend. Data are available via ProteomeXchange with identifier PXD014716.

Research paper thumbnail of Serious infections in Rheumatoid Arthritis and strategies for their prevention: A review and discussion of implications for clinical practice

Introduction: Serious infections (SIs) in rheumatoid arthritis (RA) are common and may be life-th... more Introduction: Serious infections (SIs) in rheumatoid arthritis (RA) are common and may be life-threatening or fatal. The goal of this review was to assess the spectrum of SIs in RA, review potential causes for these SIs and to formulate strategies for prevention. Methods: We performed a systematic review that included multiple databases viz. PubMed, Medline, Scopus, and Google Scholar. Search terms used were ‘Rheumatoid Arthritis AND infection’. Searches were limited to the title of articles, human subjects and non-juvenile arthritis and to those articles published in English. Results: In total, 3,324 articles, identified through PubMed, Medline, Scopus and Google Scholar repository were found. After removing duplicates, 825 articles remained for further screening from which 141 articles were selected. These were further assessed and 110 were then excluded because 31 articles were case reports, 35 focused on young subjects (<16 years) and 44 studies focused on non-serious infection. Overall, only 31 studies met our selection criteria. Conclusion: SIs are far more common in RA than in the general population. Corticosteroids are associated with an appreciable increase in SI risk. Most commonly used and currently favored synthetic DMARDs confer a small or no risk, biologic DMARDs confer moderate risk in the first year of therapy and then a diminishing risk thereafter, and higher dose biologic or combination biologic therapy should be avoided since the SI risk is unacceptably high. Undetectable Mannose Binding Lectin (MBL) is a major risk factor for SI in RA, comparable to Prednisolone.

Research paper thumbnail of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Research Square (Research Square), Feb 27, 2020

Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells... more Background: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results: We demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/Akt activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/Akt activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells. Conclusions: Altogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology.

Research paper thumbnail of Oral Presentations: O-22: Leukaemia Inhibitory Factor (Lif) Antagonist as Novel Candidate for Modulating of Chondroblast Progenitor Cells

Research paper thumbnail of Patient experiences of codesigned rehabilitation interventions in hospitals: a rapid review

BMJ Open, Nov 1, 2022

Background Codesign strengthens partnerships between healthcare workers and patients. It also fac... more Background Codesign strengthens partnerships between healthcare workers and patients. It also facilitates collaborations supporting the development, design and delivery of healthcare services. Prior rehabilitation reviews have focused mainly on the clinical and organisational outcomes of codesign with less focus on the lived experience of rehabilitation patients. Objective To explore patient experiences of codesigned hospital rehabilitation interventions. Design Rapid review and evidence synthesis of the literature. Data sources CINAHL, MEDLINE, Embase and Cochrane were searched from 1 January 2000 to 25 April 2022. Study selection Studies reporting patient experiences of codesigned rehabilitation interventions in hospitals. Results 4156 studies were screened, and 38 full-text studies were assessed for eligibility. Seven studies were included in the final rapid review. Five out of the seven studies involved neurological rehabilitation. All eligible studies used qualitative research methods. The main barriers to codesign were related to staffing and dedicated time allocated to face-to-face patient-therapist interactions. High-quality relationships between patients and their therapists were a facilitator of codesign. Thematic synthesis revealed that codesigned rehabilitation interventions can enable a meaningful experience for patients and facilitate tailoring of treatments to align with individual needs. Personalised rehabilitation increases patient involvement in rehabilitation planning, delivery and decision-making. It also promotes positive feelings of empowerment and hope. Conclusion This rapid review supports the implementation of codesigned rehabilitation interventions to improve patient experiences in hospitals. PROSPERO registration number CRD42021264547.

Research paper thumbnail of Patient experiences of co-designed rehabilitation interventions: protocol for a rapid review

BMJ Open, 2022

Introduction Patient-centred care can be facilitated by co-design, which refers to collaboration ... more Introduction Patient-centred care can be facilitated by co-design, which refers to collaboration between healthcare professionals and consumers in producing and implementing healthcare. Systematic reviews on co-design have mainly focused on the effectiveness of co-produced healthcare interventions. Less attention has been directed towards the experiences of patients in co-designed interventions. This rapid review aims to explore patient experiences of co-designed rehabilitation interventions and inform rehabilitation decision-making. Methods and analysis A rapid review will expedite timely information on co-design experiences for stakeholders. Four electronic databases, including Cochrane CENTRAL, MEDLINE, Embase and CINAHL, will be searched for papers published from 1 January 2000 to 1 January 2022. The Cochrane Risk of Bias tool will be used for randomised trials. Critical appraisal checklists from The Joanna Briggs Institute shall evaluate the risk of bias of non-randomised trials and qualitative studies. A narrative synthesis will be provided for the quantitative studies. Thematic synthesis will be conducted on qualitative findings. The overall strength of the evidence will be measured using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for quantitative investigations and the GRADE-Confidence in Evidence from Reviews of Qualitative Research for qualitative studies. The results will be presented using narrative summaries, identified themes, summary tables, flow charts and quantitative statistical analyses. Ethics and dissemination Ethics approval is not required for the review. The protocol and rapid review will be submitted to an online, open access and peerreviewed journal for publication. The review findings will be rapidly translated to consumers, clinicians, healthcare leaders, organisations, researchers and policy makers via publications, evidence summaries, conferences, workshops, websites, social media and online events. PROSPERO registration number CRD42021264547.

Research paper thumbnail of Rapid detection of Clostridium difficile toxins from stool samples using real-time multiplex PCR

Journal of Medical Microbiology, Sep 1, 2013

In this study, a total of 650 stool samples were tested to show that our method is capable of det... more In this study, a total of 650 stool samples were tested to show that our method is capable of detecting four Clostridium difficile genes; tcdA, tcdB, encoding toxin A (TcdA) and toxin B (TcdB), and the binary toxin C. difficile transferase genes (cdtA and/or cdtB) encoding CDT toxin. Besides detecting the targeted C. difficile genes, our method can be used to detect the presence of any inhibitory components in the PCR. This assay, combined with a selective culture medium, such as the chromID TM C. difficile, can be applied directly for screening C. difficile-associated disease. The PCR-based assay developed here is rapid (4 h per 21 stool samples) and accurate in diagnosing C. difficile infection, 100 % assay sensitivity and negative predictive value (NPV) were obtained. However, the assay specificity of 99.1 % and positive predictive value (PPV) of 94.9 % were slightly lower than the optimal value of 100 %. The assay protocol outlined here can be used as a rapid screening tool to assist infection control units and in managing infected patients by reducing the number of patients requiring isolation and extended hospitalization. Rapid detection can prevent unnecessary antibiotic therapy and potentially reduce the spread of infection by emerging hypervirulent C. difficile strains.

Research paper thumbnail of Optimization Transgene Expression of Short Fully Synthesized Lipopeptide- Based Transfection Agent for Non-Viral Gene Delivery Vehicle

Gene therapy using non-viral gene delivery vehicle might be applied for the treatment of viral in... more Gene therapy using non-viral gene delivery vehicle might be applied for the treatment of viral infection, cancer and genetic disorders. However, the most challenging barrier is the low efficiency of transgene expression. Therefore, optimization of transgene expression is very important and critical to be performed before doing extensive evaluation of the transfection agent. Herein, we present transgene expression optimization data of gene encoding luciferase condensed with a series of short fully synthesized lipopeptide on COS7, HeLa and 293T cells. The complex formation, effect of molar ratio, forced sedimentation, incubation period of the DNA-transfection agent complexes were explored on transfection efficiency. Moreover, the enhancement effect in transfection efficiency of polymer PEI as co-transfection agent in DNA-lipopeptide was also investigated. The results show that the complex particles of the DNA-lipopeptide were formed efficiently in the low ionic strength environment (HEPES Glucose Buffer pH 7.4), and the complex was incubated more than 10 hours before it was transfected onto the cells. Depending on the lipopeptide, the DNA-lipopeptide incubation in 24 hours (at 4-6C) resulted an increased up to 2-4-fold in the transgene expression. In addition, polymer PEI enhanced the transfection efficiency of the lipopeptide-mediated gene delivery up to 50-fold compared to control. In summary, short and a linear of fully synthesized lipopeptide-based transfection agent facilitated transgene expression in several mammalian cells by optimizing the DNA-lipopeptide complex formation and transfection condition.

Research paper thumbnail of Additional file 9 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

Additional file 9 Table S2. GO pathways enrichment results. Related to Fig. 7. The top ten GO enr... more Additional file 9 Table S2. GO pathways enrichment results. Related to Fig. 7. The top ten GO enrichments for each cell comparison from Fig. 7. Full results are available in File S1.

Research paper thumbnail of Additional file 1 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

Additional file 1 Fig. S1. Representative hyperspectral autofluorescence cell images from the mea... more Additional file 1 Fig. S1. Representative hyperspectral autofluorescence cell images from the measurements. Related to Fig. 1. (A) Mean cellular intensity of hyperspectral autofluorescence channel 18 [495 nm(Ex), 700 nm(Em)], which may reflect porphyrin or protein-bound red-shifted flavin emission [46], is significantly affected by PGRMC1-HA phosphorylation status. The table provides Kolmogorov-Smirnov test p values from pair wise comparisons. (B) The ratio of hyperspectral autofluorescence channels 3 [375 nm(Ex), 450 nm(Em)] to channel 12 [435 nm(Ex), 587 nm(Em)] differs significantly between cells. The table follows C. (C) Individual channels #3 and #4 from (B) as listed in Table S1 (left) and the same two channels superimposed (right).

Research paper thumbnail of Additional file 8 of PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

Additional file 8 Table S1. Spectral channel filters employed for hyperspectral autofluorescence ... more Additional file 8 Table S1. Spectral channel filters employed for hyperspectral autofluorescence imaging. Related to Fig. 1. For further details of this approach see Gosnell et al. [44].

Research paper thumbnail of Additional file 1 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 1:Figure S1. Detailed views of selected pathways identified by WebGestalt analyse... more Additional file 1:Figure S1. Detailed views of selected pathways identified by WebGestalt analyses. Related to Fig. 3. All panels are adapted from File S6. Heat map colors follow Fig. 3. (A) Principal component (PC) analysis of SWATH-MS proteomics results showing distribution of PC1 and PC2. PC1 corresponded to pathways associated with ribosomes and translation, while PC2 corresponded to pathways associated with mRNA splicing processing (see File S3). (B) Proteins associated with PI3K/AKT activity (WebGestalt Database: PC, DB_ID:1648, "Class I PI3K signaling events mediated by AKT") are less abundant in TM cells. (C) F1/F0 ATPase subunits elevated in WT and TM cells. (D) Abundances of proteins associated with protein folding and microtubule function are altered by PGRMC1 phosphorylation status. Proteins detected in any of the following WebGestalt pathways or functions (1–4) or a manual search (5) are mapped against their expression profiles. 1) cellular component chaperoni...

Research paper thumbnail of Additional file 7 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 7:File S6. An excel file with heat map protein IDs and pathways for red vs. blue ... more Additional file 7:File S6. An excel file with heat map protein IDs and pathways for red vs. blue pathways adjP

Research paper thumbnail of Additional file 2 of PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Additional file 2:File S1. A zip archive containing time lapse mp4 movies of migrating cells in s... more Additional file 2:File S1. A zip archive containing time lapse mp4 movies of migrating cells in scratch assays. Related to Fig. 1. Images were taken at 10 min intervals over 36 h and are replayed over 65 s at 9 frames per second (2000x real time). The presented 32.4 MB MP4 files were generated from the original 666 MB (6000x real time) .avi files (length 21 s, frame width x height 1024 × 1024, Data rate/bit rate 287,462 kbps, frame rate 100 fps) by processing in Adobe Premiere Pro 2017 using the following settings: Preset "custom"; Width: 1024; Height 1024; Aspect Square Pixels (1.0); Field Order: progressive; Profile: high; Target Bitrate [Mbps] 4.08; Maximum Bitrate [Mbps] 4.39; 9 fps; No Audio; Output as standard .mp4; Time Interpolation: Frame Sampling; Stream Compatibility: Standard; Variable bit rate, single pass; Number of frames 00:01:04:09. The zip archive contains 4 files with filenames representing cell type and date of measurement (yyyymmdd). (A) A_MP_20170807....

Research paper thumbnail of Non-invasive detection and monitoring of biochemistry in cells and tissues by decomposing autofluorescence

Asia Communications and Photonics Conference 2016, 2016

Hyperspectral imaging based on endogenous contrast provides a new non-invasive method to characte... more Hyperspectral imaging based on endogenous contrast provides a new non-invasive method to characterise cells and tissues. Cellular content and maps of native fluorophores help monitor biological processes, with proper account of intrinsic cellular heterogeneity.