Statins in Acute Ischemic Stroke: Mechanisms, Resistance, and Precision Strategies for Neurovascular and Cognitive Protection.

Acute ischemic stroke (AIS) remains a leading cause of mortality and long-term disability globally, with survivors at high risk of recurrent stroke, cardiovascular events, and post-stroke dementia. Statins, while widely used for their lipid-lowering effects, also possess pleiotropic properties, including anti-inflammatory, endothelial-stabilizing, and neuroprotective actions, which may offer added benefit in AIS management. This article synthesizes emerging evidence on statins' dual mechanisms of action and evaluates their role in reducing recurrence, improving survival, and mitigating cognitive decline.

Clinical response to azacitidine in MDS is associated with distinct DNA methylation changes in HSPCs.

Hypomethylating agents are frontline therapies for myelodysplastic neoplasms (MDS), yet clinical responses remain unpredictable. We conducted a phase 2 trial comparing injectable and oral azacitidine (AZA) administered over one or three weeks per four-week cycle, with the primary objective of investigating whether response is linked to in vivo drug incorporation or DNA hypomethylation. Our findings show that injection results in higher drug incorporation, but lower DNA demethylation per cycle, while global DNA methylation levels in mononuclear cells are comparable between responders and non-responders.

Chronic kidney disease prevalence and clinical outcomes in anterior circulation acute ischemic stroke patients with reperfusion therapy: A meta-analysis.

Aim: Chronic Kidney Disease (CKD) is a common comorbidity among acute ischaemic stroke (AIS) patients undergoing reperfusion therapies, including intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT). Acknowledging CKD's prevalence in this cohort and understanding its influence on outcomes is crucial for prognosis and optimizing care. This study aims to determine the prevalence of CKD among anterior circulation AIS (acAIS) patients undergoing reperfusion therapies and to analyse the role of CKD in mediating outcomes.

Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer.

Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/- chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, the latter also being highly stable and clinically relevant regulators of disease.

Association of Lesion Topography with Functional Outcomes in Acute Ischemic Stroke Patients Considered for, or Receiving, Reperfusion Therapy: A Meta-Analysis.

Background: The impact of lesion topography (LT), characterised by the Alberta Stroke Programme Early CT Score (ASPECTS), on outcomes after reperfusion therapy in acute ischemic stroke (AIS) is poorly elucidated. We investigated the prognostic accuracy of ASPECTS-based LT assessment and its association with clinical outcomes in AIS patients considered for reperfusion therapy or receiving intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), or none or both. Methods: Studies were identified from PubMed with additional studies added from Google Scholar.

Short-chain fatty acid concentrations in the incidence and risk-stratification of colorectal cancer: a systematic review and meta-analysis.

Background: The beneficial role of gut microbiota and bacterial metabolites, including short-chain fatty acids (SCFAs), is well recognized, although the available literature around their role in colorectal cancer (CRC) has been inconsistent.

Methods: We performed a systematic review and meta-analysis to examine the associations of fecal SCFA concentrations to the incidence and risk of CRC. Data extraction through Medline, Embase, and Web of Science was carried out from database conception to June 29, 2022.

Role of Neutrophil-Lymphocyte Ratio in the Prognosis of Acute Ischaemic Stroke After Reperfusion Therapy: A Systematic Review and Meta-analysis.

Background: Inflammation may mediate response to acute reperfusion therapy (RT) in acute cerebral ischaemia. Neutrophil-lymphocyte ratio (NLR), an inflammatory biomarker, may play an important role in acute ischaemic stroke (AIS) prognostication.

Objective: This meta-analysis sought to examine the effect of NLR on functional outcomes, mortality and adverse outcomes in AIS patients receiving RT.

Considerations for the selection of tests for SARS-CoV-2 molecular diagnostics.

During the course of 2020, the outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spread rapidly across the world. Clinical diagnostic testing for SARS-Cov-2 infection has relied on the real-time Reverse Transcriptase Polymerase Chain Reaction and is considered the gold standard assay. Commercial vendors and laboratories quickly mobilised to develop diagnostic tests to detect the novel coronavirus, which was fundamentally important in the pandemic response.

Harnessing Liquid Biopsies to Guide Immune Checkpoint Inhibitor Therapy.

Immunotherapy (IO), involving the use of immune checkpoint inhibition, achieves improved response-rates and significant disease-free survival for some cancer patients. Despite these beneficial effects, there is poor predictability of response and substantial rates of innate or acquired resistance, resulting in heterogeneous responses among patients. In addition, patients can develop life-threatening adverse events, and while these generally occur in patients that also show a tumor response, these outcomes are not always congruent.

Role of diabetes in stroke: Recent advances in pathophysiology and clinical management.

The increasing prevalence of diabetes and stroke is a major global public health concern. Specifically, acute stroke patients, with pre-existing diabetes, pose a clinical challenge. It is established that diabetes is associated with a worse prognosis after acute stroke and the various biological factors that mediate poor recovery profiles in diabetic patients is unknown.

Neutrophil-lymphocyte ratio in acute ischemic stroke: Immunopathology, management, and prognosis.

There is an ongoing need for accurate prognostic biomarkers in the milieu of acute ischemic stroke (AIS) receiving reperfusion therapy. Neutrophil-lymphocyte ratio (NLR) has been implicated in emergency medicine and acute stroke setting as an important biomarker in the prognosis of patients. However, there are ongoing questions around its accuracy and translation into clinical practice given suboptimal sensitivity and specificity results, as well as varying thresholds and lack of clarity around which NLR time points are most clinically indicative.

Cytotoxic CD8+ T cells and tissue resident memory cells in colorectal cancer based on microsatellite instability and BRAF status.

Background: Recent studies in non-colorectal malignancy have associated T resident memory (T) cells with improved patient survival. It is unknown if T plays a role in colorectal cancer (CRC).

Aim: To examine the potential role of T cells in providing immunogenicity in CRC stratified by microsatellite instability (MSI) and BRAF status.

Rate of dissemination and prognosis in early and advanced stage colorectal cancer based on microsatellite instability status: systematic review and meta-analysis.

Introduction: For the past two decades, microsatellite instability (MSI) has been reported as a robust clinical biomarker associated with survival advantage attributed to its immunogenicity. However, MSI is also associated with high-risk adverse pathological features (poorly differentiated, mucinous, signet cell, higher grade) and exhibits a double-edged sword phenomenon. We performed a systematic review and meta-analysis to evaluate the rate of dissemination and the prognosis of early and advanced stage colorectal cancer based on MSI status.

Micro RNA Expression after Ingestion of Fucoidan; A Clinical Study.

Fucoidans are a class of fucose-rich sulfated polysaccharides derived from brown macroalgae that exert a range of biological activities in vitro and in vivo. To generate an unbiased assessment of pathways and processes affected by fucoidan, a placebo-controlled double-blind pilot study was performed in healthy volunteers. Blood samples were taken immediately before and 24 h after ingestion of a single dose of 1 g of fucoidan (UPF) or placebo.

Association Between Microsatellite Instability Status and Peri-Operative Release of Circulating Tumour Cells in Colorectal Cancer.

Microsatellite instability (MSI) in colorectal cancer (CRC) is a marker of immunogenicity and is associated with an increased abundance of tumour infiltrating lymphocytes (TILs). In this subgroup of colorectal cancer, it is unknown if these characteristics translate into a measurable difference in circulating tumour cell (CTC) release into peripheral circulation. This is the first study to compare MSI status with the prevalence of circulating CTCs in the peri-operative colorectal surgery setting.

CEP55 is a determinant of cell fate during perturbed mitosis in breast cancer.

The centrosomal protein, CEP55, is a key regulator of cytokinesis, and its overexpression is linked to genomic instability, a hallmark of cancer. However, the mechanism by which it mediates genomic instability remains elusive. Here, we showed that CEP55 overexpression/knockdown impacts survival of aneuploid cells.

Oncogenic BRAF mutation induces DNA methylation changes in a murine model for human serrated colorectal neoplasia.

Colorectal cancer is a major cause of cancer death and approximately 20% arises within serrated polyps, which are under-recognized and poorly understood. Human serrated colorectal polyps frequently exhibit both oncogenic BRAF mutation and widespread DNA methylation changes, which are important in silencing genes restraining neoplastic progression. Here, we investigated whether in vivo induction of mutant Braf is sufficient to result in coordinated promoter methylation changes for multiple cancer-related genes.

Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3.

Dynamic remodelling of the extracellular matrix (ECM) is a key feature of cancer progression. Enzymes that modify the ECM, such as matrix metalloproteinases (MMPs), have long been recognised as important targets of anticancer therapy. Inflammatory cytokines are known to play a key role in regulating protease expression in cancer.

The Potential Value of Immunotherapy in Colorectal Cancers: Review of the Evidence for Programmed Death-1 Inhibitor Therapy.

Colorectal cancers (CRCs) have been identified as potential targets for immunotherapy with programmed cell death (PD)-1 inhibitors. English-language publications from MedLine and Embase that evaluated PD-1/PD ligand 1 (PD-L1) in the CRC tumor microenvironment and clinical trials that assessed PD-1 inhibitors were included. Sixteen abstracts were screened.

Heterogeneity of miR-10b expression in circulating tumor cells.

Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as 'liquid biopsy' to aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient.

Biobank classification in an Australian setting.

In 2011, Watson and Barnes proposed a schema for classifying biobanks into 3 groups (mono-, oligo-, and poly-user), primarily based upon biospecimen access policies. We used results from a recent comprehensive survey of cancer biobanks in New South Wales, Australia to assess the applicability of this biobank classification schema in an Australian setting. Cancer biobanks were identified using publically available data, and by consulting with research managers.

Predictive and prognostic value of circulating tumor cell detection in lung cancer: a clinician's perspective.

There is increasing evidence for the use of circulating tumor cells (CTCs) as a "liquid biopsy" for early detection of lung cancer recurrence, prognosticating disease and monitoring treatment response. Further, CTC molecular analysis and interrogation of single cells hold significant potential in providing insights into tumor biology and the metastatic process. Ongoing research will likely see the translation of CTCs as a prognostic and predictive biomarker in both small cell, and non-small cell, lung cancer to routine clinical practice.

The CIMP Phenotype in BRAF Mutant Serrated Polyps from a Prospective Colonoscopy Patient Cohort.

Colorectal cancers arising via the serrated pathway are often associated with BRAF V600E mutation, CpG island methylator phenotype (CIMP), and microsatellite instability. Previous studies have shown a strong association between BRAF V600E mutation and serrated polyps. This study aims to evaluate CIMP status of all the serrated polyp subtypes and its association with functionally important genes such as MLH1, p16, and IGFBP7.