Single-cell analysis of the T-cell receptor repertoire in untreated myeloma patients suggests potential myeloma-reactive CD8+ T-cells are shared between blood and marrow.

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, , microRNAs, and ceRNA Networks: Precision Targeting in Cancer Therapeutics.

The phosphatase and tensin homolog deleted on chromosome 10 () is a well characterised tumour suppressor, playing a critical role in the maintenance of fundamental cellular processes including cell proliferation, migration, metabolism, and survival. Subtle decreases in cellular levels of PTEN result in the development and progression of cancer, hence there is tight regulation of the expression, activity, and cellular half-life of PTEN at the transcriptional, post-transcriptional, and post-translational levels. , the processed pseudogene of , is an important transcriptional and post-transcriptional regulator of expression produces sense and antisense transcripts modulating expression, in conjunction with miRNAs.

Single-cell analysis of the CD8 T-cell compartment in multiple myeloma reveals disease specific changes are chiefly restricted to a CD69 subset suggesting potent cytotoxic effectors exist within the tumor bed.

Multiple myeloma (MM) is an incurable disease of the bone marrow (BM) characterized by the uncontrolled proliferation of neoplastic plasma cells. While CD8+ T cells have an established role in disease control, few studies have focused on these cells within the MM tumor microenvironment (TME). We analyzed CD8+ T cells in the BM and peripheral blood (PB) of untreated patients with MM and non-myeloma controls using flow cytometry, mass cytometry and single-cell RNA sequencing, using several novel bioinformatics workflows.

Evaluating High and Low Heart Rate Variability Response and Neurocognitive Performance in Workers: An Exploratory Study.

Heart rate variability (HRV) has the potential to be a predicting factor of cognitive performance. The present research aimed to explore the differences in neurocognitive performance of workers with high HRV and low HRV. A total of 48 white-collar workers and 53 blue-collar workers were assessed.

Short-chain fatty acids and insulin sensitivity: a systematic review and meta-analysis.

Context: There is substantial evidence that reduced short-chain fatty acids (SCFAs) in the gut are associated with obesity and type 2 diabetes, although findings from clinical interventions that can increase SCFAs are inconsistent.

Objective: This systematic review and meta-analysis aimed to assess the effect of SCFA interventions on fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR).

Data Sources: Relevant articles published up to July 28, 2022, were extracted from PubMed and Embase using the MeSH (Medical Subject Headings) terms of the defined keywords [(short-chain fatty acids) AND (obesity OR diabetes OR insulin sensitivity)] and their synonyms.

Neuropsychological Performance and Cardiac Autonomic Function in Blue- and White-Collar Workers: A Psychometric and Heart Rate Variability Evaluation.

The 21st century has brought a growing and significant focus on performance and health within the workforce, with the aim of improving the health and performance of the blue- and white-collar workforce. The present research investigated heart rate variability (HRV) and psychological performance between blue and white-collar workers to determine if differences were evident. A total of 101 workers ( = 48 white-collar, = 53 blue-collar, aged 19-61 years) underwent a three lead electrocardiogram to obtain HRV data during baseline (10 min) and active (working memory and attention) phases.

Expression Profile of Sphingosine Kinase 1 Isoforms in Human Cancer Tissues and Cells: Importance and Clinical Relevance of the Neglected 1b-Isoform.

Background: Overexpression of sphingosine kinase 1 (SphK1) is casually associated with many types of cancer, and inhibitors of SphK1 sensitize tumors to chemotherapy. SphK1 is expressed as two major isoforms, SphK1a and SphK1b. To date, no information has been reported on the SphK1 isoform expression profile and its clinical relevance.

Pancreatic Transdifferentiation Using β-Cell Transcription Factors for Type 1 Diabetes Treatment.

Type 1 diabetes is a chronic illness in which the native beta (β)-cell population responsible for insulin release has been the subject of autoimmune destruction. This condition requires patients to frequently measure their blood glucose concentration and administer multiple daily exogenous insulin injections accordingly. Current treatments fail to effectively treat the disease without significant side effects, and this has led to the exploration of different approaches for its treatment.

Anxiety Linked to COVID-19: A Systematic Review Comparing Anxiety Rates in Different Populations.

The COVID-19 pandemic has incited a rise in anxiety, with uncertainty regarding the specific impacts and risk factors across multiple populations. A qualitative systematic review was conducted to investigate the prevalence and associations of anxiety in different sample populations in relation to the COVID-19 pandemic. Four databases were utilised in the search (Medline, EMBASE, CINAHL, and PsycINFO).

Manipulating cellular microRNAs and analyzing high-dimensional gene expression data using machine learning workflows.

MicroRNAs (miRNAs) are elements of the gene regulatory network and manipulating their abundance is essential toward elucidating their role in patho-physiological conditions. We present a detailed workflow that identifies important miRNAs using a machine learning algorithm. We then provide optimized techniques to validate the identified miRNAs through over-expression/loss-of-function studies.

Studying the Oncosuppressive Functions of PTENP1 as a ceRNA.

PTENP1 is a processed pseudogene of the tumour suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). It functions posttranscriptionally to regulate PTEN by acting as a sponge for microRNAs that target PTEN. PTENP1 therefore functions as a competitive endogenous RNA (ceRNA), competing with PTEN for binding of microRNAs (miRNA) and thereby modulating PTEN cellular abundance.

Use of a Hybrid Adeno-Associated Viral Vector Transposon System to Deliver the Insulin Gene to Diabetic NOD Mice.

Previously, we used a lentiviral vector to deliver furin-cleavable human insulin () to the livers in several animal models of diabetes using intervallic infusion in full flow occlusion (FFO), with resultant reversal of diabetes, restoration of glucose tolerance and pancreatic transdifferentiation (PT), due to the expression of beta (β)-cell transcription factors (β-TFs). The present study aimed to determine whether we could similarly reverse diabetes in the non-obese diabetic (NOD) mouse using an adeno-associated viral vector (AAV) to deliver - ± the β-TF to the livers of diabetic mice. The traditional AAV8, which provides episomal expression, and the hybrid AAV8/ that results in transgene integration were used.

Electroencephalographic prediction of global and domain specific cognitive performance of clinically active Australian Nurses.

Objective: To investigate the relationship between EEG activity and the global and domain specific cognitive performance of healthy nurses, and determine the predictive capabilities of these relationships.

Approach: Sixty-four nurses were recruited for the present study, and data from 61 were utilised in the present analysis. Global and domain specific cognitive performance of each participant was assessed psychometrically using the Mini-mental state exam and the Cognistat, and a 32-lead monopolar EEG was recorded during a resting baseline phase and an active phase in which participants completed the Stroop test.

Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19.

The world is currently experiencing the worst health pandemic since the Spanish flu in 1918-the COVID-19 pandemic-caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the world's third wake-up call this century. In 2003 and 2012, the world experienced two major coronavirus outbreaks, SARS-CoV-1 and Middle East Respiratory syndrome coronavirus (MERS-CoV), causing major respiratory tract infections.

Inverse relationship between oligoclonal expanded CD69- TTE and CD69+ TTE cells in bone marrow of multiple myeloma patients.

CD8+CD57+ terminal effector T (TTE) cells are a component of marrow-infiltrating lymphocytes and may contribute to the altered immune responses in multiple myeloma (MM) patients. We analyzed TTE cells in the bone marrow (BM) and peripheral blood (PB) of age-matched controls and patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), and newly diagnosed (ND) MM using flow cytometry, mass cytometry, and FlowSOM clustering. TTE cells are heterogeneous in all subjects, with BM containing both CD69- and CD69+ subsets, while only CD69- cells are found in PB.

Toward Systems Pathology for PTEN Diagnostics.

Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus and Proteus-like syndromes, as well as autism spectrum disorder. Studies have shown an increase in the risk of developing specific cancer types in the presence of a germline mutation. Furthermore, outside of the familial setting, somatic variants of occur in numerous malignancies.

Mass Cytometry Discovers Two Discrete Subsets of CD39Treg Which Discriminate MGUS From Multiple Myeloma.

Multiple Myeloma (MM) is preceded by the clinically stable condition monoclonal gammopathy of undetermined significance (MGUS). Critical immune events that discriminate MGUS from newly diagnosed MM (ND)MM patients remain unknown, but may involve changes in the regulatory T cell (Treg) compartment that favor myeloma growth. To address this possibility, we used mass cytometry and the unsupervised clustering algorithm Flow self-organizing map (FlowSOM) to interrogate the distribution of multiple subsets within CD25CD127Treg in matched bone marrow (BM) and peripheral blood (PB) of MGUS and NDMM patients.

Expansion of Murine MSC Impairs Transcription Factor-Induced Differentiation into Pancreatic -Cells.

Combinatorial gene and cell therapy as a means of generating surrogate -cells has been investigated for the treatment of type 1 diabetes (T1D) for a number of years with varying success. One of the limitations of current cell therapies for T1D is the inability to generate sufficient quantities of functional transplantable insulin-producing cells. Due to their impressive immunomodulatory properties, in addition to their ease of expansion and genetic modification , mesenchymal stem cells (MSCs) are an attractive alternative source of adult stem cells for regenerative medicine.

Heart Rate Variability as a Biomarker for Predicting Stroke, Post-stroke Complications and Functionality.

Background: Heart rate variability (HRV) is a non-invasive measure of the function of the autonomic nervous system, and its dynamic nature may provide a means through which stroke and its associated complications may be predicted, monitored, and managed.

Objective: The objective of this review is to identify and provide a critique on the most recent uses of HRV in stroke diagnosis/management and highlight areas that warrant further research.

Methods: The MEDLINE, CINAHL, and OVID MEDLINE databases were canvassed using a systematic search strategy, for articles investigating the use of HRV in stroke diagnosis and management.

Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases.

Cardiovascular disease (CVD) is the leading cause of death in the world and our approach to the control and management of CVD mortality is limited. Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects.

Partial pancreatic transdifferentiation of primary human hepatocytes in the livers of a humanised mouse model.

Background: Gene therapy is one treatment that may ultimately cure type 1 diabetes. We have previously shown that the introduction of furin-cleavable human insulin (INS-FUR) to the livers in several animal models of diabetes resulted in the reversal of diabetes and partial pancreatic transdifferentiation of liver cells. The present study investigated whether streptozotocin-diabetes could be reversed in FRG mice in which chimeric mouse-human livers can readily be established and, in addition, whether pancreatic transdifferentiation occurred in the engrafted human hepatocytes.

PTEN/PTENP1: 'Regulating the regulator of RTK-dependent PI3K/Akt signalling', new targets for cancer therapy.

Regulation of the PI-3 kinase (PI3K)/Akt signalling pathway is essential for maintaining the integrity of fundamental cellular processes, cell growth, survival, death and metabolism, and dysregulation of this pathway is implicated in the development and progression of cancers. Receptor tyrosine kinases (RTKs) are major upstream regulators of PI3K/Akt signalling. The phosphatase and tensin homologue (PTEN), a well characterised tumour suppressor, is a prime antagonist of PI3K and therefore a negative regulator of this pathway.

The analysis of novel microRNA mimic sequences in cancer cells reveals lack of specificity in stem-loop RT-qPCR-based microRNA detection.

Objective: MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity.

"Dicing and Splicing" Sphingosine Kinase and Relevance to Cancer.

Sphingosine kinase (SphK) is a lipid enzyme that maintains cellular lipid homeostasis. Two SphK isozymes, SphK1 and SphK2, are expressed from different chromosomes and several variant isoforms are expressed from each of the isozymes, allowing for the multi-faceted biological diversity of SphK activity. Historically, SphK1 is mainly associated with oncogenicity, however in reality, both SphK1 and SphK2 isozymes possess oncogenic properties and are recognized therapeutic targets.