CCL2/CCR2 Signalling in Mesenchymal Stem/Progenitor Cell Recruitment and Fracture Healing in Mice.

Macrophage efferocytosis (clearance of apoptotic cells) is crucial for tissue homeostasis and wound repair, where macrophages secrete factors that promote resolution of inflammation and regenerative signalling. This study examined the role of efferocytic macrophage-associated CCL2 secretion, its influence on mesenchymal stem/progenitor cell (MSPC) chemotaxis, and in vivo cell recruitment using Ccr2 (KO) mice with disrupted CCL2 receptor signalling in two regenerative models: ossicle implants and ulnar stress fractures. Single cell RNA sequencing and PCR validation indicated that efferocytosis of various apoptotic cells at bone injury sites (osteoblasts, pre-osteoblasts, MSPC) upregulated CCL2.

Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations.

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

A phase II trial of larotrectinib in tumors with NTRK fusions or extremes of NTRK mRNA overexpression identified by comprehensive genomic profiling.

Background: TRK-inhibitors have demonstrated efficacy across several cancers with NTRK fusions. Their activity in cancers with NTRK overexpression remains unclear.

Methods: This trial enrolled patients with advanced cancers harboring NTRK fusions or extreme mRNA overexpression, defined as NTRK1/2/3 expression by RNA profiling >5 SDs for a given cancer type.

Efficacy and mechanisms of curcumin in the treatment of osteoarthritis: A scoping review.

Osteoarthritis (OA) is a degenerative joint disease that primarily affects the elderly worldwide. It is characterized by local inflammation, which can be targeted therapeutically using natural anti-inflammatory compounds such as curcumin. This scoping review explores the therapeutic effects and mechanisms of curcumin in OA management.

Clinical characteristics and survival outcomes in patients with pulmonary sarcomatoid carcinoma: a multicenter retrospective study.

Purpose: The clinicopathologic features, mutational status, immunohistochemical markers, and prognosis of Pulmonary sarcomatoid carcinoma (PSC) remain uncertain.

Methods: This study included 81 PSC and 337 lung adenocarcinomas (LUAD). Progression-free survival (PFS), overall survival (OS), and other clinical data were examined.

Multimodal tumor suppression by METTL3 gene knockdown in melanoma and colon cancer cells.

METTL3, an m6A methyltransferase, is integral to the regulation of messenger RNA (mRNA) biogenesis, degradation, and translation through the N6-methyladenosine (m6A) modification. Alterations in m6A homeostasis have been implicated in the development, progression, invasion, and metastasis of certain cancers. The present research aims to examine the consequences of METTL3 knockdown using short hairpin RNA (shRNA) on the proliferation and invasive capabilities of human colorectal and melanoma cancer cell lines.

Brazilin alleviates acute lung injury via inhibition of ferroptosis through the SIRT3/GPX4 pathway.

Ferroptosis is a novel type of programmed cell death dependent on iron and is characterized by the accumulation of lipid peroxides, which is involved in acute lung injury (ALI). Brazilin, an organic compound known for its potent antioxidant and anti-inflammatory properties, has not been thoroughly studied for its potential impact on lipopolysaccharide (LPS)-induced ALI. Here, we found that pretreatment of brazilin mitigated LPS-induced lung injury and inflammation by inhibiting mitochondrial oxidative stress and ferroptosis, both in vivo and in vitro.

Microglia heterogeneity during neuroinflammation and neurodegeneration in the mouse retina.

Microglia play important roles in maintaining homeostasis and immunoreactive defense in the central nervous system including retina. To accomplish such a wide range of functions, microglia are highly heterogeneous. Dark microglia (DM) were recently identified by electron microscopy (EM).

Histopathological Examination of 404 Sleeve Gastrectomy Specimens at a Large UK Center and Systematic Review of the Published Literature.

Background: Laparoscopic sleeve gastrectomy (LSG) specimens are histologically analyzed to identify incidental pathologies. However, no guidelines recommend routine histology. This study evaluates the clinical utility of LSG sample analysis and if incidental diagnoses have a significant clinical impact.

Microbial Dynamics in COVID-19: Unraveling the Impact of Human Microbiome on Disease Susceptibility and Therapeutic Strategies.

This review explores the bidirectional relationship between the human microbiome and SARS-CoV-2 infection, elucidating its implications for COVID-19 susceptibility, severity, and therapeutic strategies. Metagenomic analyses reveal notable alterations in microbiome composition associated with SARS-CoV-2 infection, impacting disease severity and clinical outcomes. Dysbiosis within the respiratory, gastrointestinal, oral, and skin microbiomes exacerbates COVID-19 pathology through immune dysregulation and inflammatory pathways.

Guided monocyte fate to FRβ/CD163 S1 macrophage antagonises atopic dermatitis via fibroblastic matrices in mouse hypodermis.

Macrophages are versatile myeloid leukocytes with flexible cellular states to perform diverse tissue functions beyond immunity. This plasticity is however often hijacked by diseases to promote pathology. Scanning kinetics of macrophage states by single-cell transcriptomics and flow cytometry, we observed atopic dermatitis drastically exhausted a resident subtype S1.

Co-Treatment with Cranberry and Vitamin-C Mitigates Reproductive Toxicities Induced by Phenobarbital in Male Rats.

Background/aims: Phenobarbital (PB), commonly used for epilepsy management, is associated with testicular dysfunction after prolonged use. This study aimed to evaluate the ameliorative effects of cranberry (CB) and vitamin C (Vit-C) on PB-induced reproductive toxicity in rats.

Methods: Forty male Wistar rats were divided into five groups.

Therapeutic Effect of Mesenchymal Stem Cells and Olive Leaf Extract Against Cytotoxicity Induced by Streptozotocin in Gestational Diabetes Rats.

Background/aims: Gestational Diabetes Mellitus (GDM), a prevalent complication in pregnancy, is characterized by the Diabetes Association as diabetes diagnosed in the second or third trimester, often remaining asymptomatic. This study investigates the intricate effects of Streptozotocin on pregnant rats, unraveling its impact on Gestational Type 2 Diabetes (GTD). The research delves into the potential therapeutic roles of mesenchymal stem cells (MSCs) and olive leaf extract (OLE) in mitigating the consequences of Streptozotocin-induced pancreatic impairment.

A Systematic Review of the Molecular Mechanisms Involved in the Association Between PCOS and Endometrial and Ovarian Cancers.

Polycystic ovary syndrome (PCOS), a major cause of female infertility, affects 4%-20% of reproductive-age women. Metabolic and hormonal alterations are key features of PCOS, potentially raising the risk of endometrial (EC) and ovarian (OVCA) cancers. This systematic review aims to summarise the proposed molecular mechanisms involved in the association between PCOS and EC or OVCA.

Hyperbaric Oxygen Therapy Improved Neovascularisation Following Limb Ischaemia-The Role of ROS Mitigation.

Hyperbaric oxygen (HBO) therapy has emerged as a potential treatment, shown to enhance blood flow and angiogenesis. However, specific effects and mechanisms of HBO on limb ischaemia responding to a hypoxic environment remain largely unknown. We aimed to investigate the therapeutic potential of HBO in the treatment of limb ischaemia.

Single-Cell RNA-Seq Reveals Injuries in Aortic Dissection and Identifies PDGF Signalling Pathway as a Potential Therapeutic Target.

Aortic dissection (AD) represents a critical condition characterised by a tear in the inner lining of the aorta, leading to the leakage of blood into the layers of the aortic wall, posing a significant risk to life. However, the pathogenesis is unclear. In this study, scRNA-seq was applied to cells derived from aortas of both AD and non-AD donors (control) to unveil the cellular landscape.

Multi-Night Electroencephalography Reveals Positive Association Between Sleep Efficiency and Hippocampal Subfield and Entorhinal Cortex Volumes in Healthy Aging.

Age-related atrophy of the human hippocampus and the enthorinal cortex starts accelerating at around age 60. Due to the contributions of these regions to many cognitive functions seamlessly used in everyday life, this can heavily impact the lives of elderly people. The hippocampus is not a unitary structure, and mechanisms of its age-related decline appear to differentially affect its subfields.

Myeloperoxidase and Thyrotropin-Releasing Hormone Within Leukaemia Stem Cells Increased Chemosensitivity in Acute Myeloid Leukaemia.

Leukaemia stem cells (LSCs) are major contributors to chemoresistance in acute myeloid leukaemia (AML). Identifying potential biomarkers within LSCs that can predict chemosensitivity in AML is key. This prospective study involved 20 consecutive de novo AML patients who underwent '7 + 3' induction therapy.

Diagnostic Values of Fine Needle Aspiration Cytology and Frozen Section in Management of Parotid Tumors.

This study aims to investigate the diagnostic values of fine needle aspiration cytology (FNAC) and frozen section (FS) in evaluating parotid gland masses subjected to parotidectomy. A retrospective analysis of data from 274 patients who underwent parotidectomy for parotid gland masses was performed at the Department of Otolaryngology of the University Hospital between 2013 and 2019. We compared the preoperative FNAC and intraoperative FS records with the definitive histopathological diagnoses obtained from the surgical resection specimens.

NanoCMSer: a consensus molecular subtype stratification tool for fresh-frozen and paraffin-embedded colorectal cancer samples.

Colorectal cancer (CRC) is a significant contributor to cancer-related mortality, emphasizing the need for advanced biomarkers to guide treatment. As part of an international consortium, we previously categorized CRCs into four consensus molecular subtypes (CMS1-CMS4), showing promise for outcome prediction. To facilitate clinical integration of CMS classification in settings where formalin-fixed paraffin-embedded (FFPE) samples are routinely used, we developed NanoCMSer, a NanoString-based CMS classifier using 55 genes.

Understanding Cognitive Aging Through White Matter: A Fixel-Based Analysis.

Diffusion-weighted imaging (DWI) has been frequently used to examine age-related deterioration of white matter microstructure and its relationship to cognitive decline. However, typical tensor-based analytical approaches are often difficult to interpret due to the challenge of decomposing and (mis)interpreting the impact of crossing fibers within a voxel. We hypothesized that a novel analytical approach capable of resolving fiber-specific changes within each voxel (i.

The Spatial Distribution of Brain Metastasis Is Determined by the Heterogeneity of the Brain Microenvironment.

It is now understood that brain metastases do not occur randomly but have distinct spatial patterns depending on the origin of the cancer. According to the "seed and soil" hypothesis, the final colonization of metastatic cells is the result of their adaptation to the altered environment. To investigate the most favorable microenvironment for brain metastasis, we analyzed neuroimaging data from 177 patients with breast cancer brain metastasis and 548 patients with lung cancer brain metastasis to create a replicable probabilistic map of metastatic locations.

Part II. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?

Creatine monohydrate supplementation (CrM) is a safe and effective intervention for improving certain aspects of sport, exercise performance, and health across the lifespan. Despite its evidence-based pedigree, several questions and misconceptions about CrM remain. To initially address some of these concerns, our group published a narrative review in 2021 discussing the scientific evidence as to whether CrM leads to water retention and fat accumulation, is a steroid, causes hair loss, dehydration or muscle cramping, adversely affects renal and liver function, and if CrM is safe and/or effective for children, adolescents, biological females, and older adults.

Among the Masses: Multiple Left Atrial Undifferentiated Pleomorphic Sarcomas.

Undifferentiated pleomorphic sarcoma, an exceedingly rare and aggressive primary cardiac tumor arising from mesenchymal stem cells, is associated with poor prognosis and high mortality despite adequate treatment. A 52-year-old female presented with a 2-month history of angina and dyspnea on exertion. Her clinical history included severe acute respiratory syndrome coronavirus 2 myocarditis and iron deficiency anemia.

Waldenström Macroglobulinemia-Induced Cardiac Amyloid Light Chain Amyloidosis.

Waldenström macroglobulinemia is a rare cancer of plasma cells characterized by the excessive production of immunoglobulin M (IgM). IgM-associated systemic amyloid light chain (AL) amyloidosis is a rare complication of Waldenström macroglobulinemia, characterized by the misfolding of lambda light chains that deposit in various organs, including the heart. We describe a case of progressive nonischemic cardiomyopathy secondary to Waldenström macroglobulinemia and IgM-associated AL amyloidosis that was refractory to medical therapy and highlight the challenges in diagnosis and management.