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The extent of microglial heterogeneity in humans remains a central yet poorly explored question in light of the development of therapies targeting this cell type. Here, we investigate the population structure of live microglia purified from human cerebral cortex samples obtained at autopsy and during neurosurgical procedures. Using single cell RNA sequencing, we find that some subsets are enriched for disease-related genes and RNA signatures. We confirm the presence of four of these microglial subpopulations histologically and illustrate the utility of our data by characterizing further microglial cluster 7, enriched for genes depleted in the cortex of individuals with Alzheimer’s disease (AD). Histologically, these cluster 7 microglia are reduced in frequency in AD tissue, and we validate this observation in an independent set of single nucleus data. Thus, our live human microglia identify a range of subtypes, and we prioritize one of these as being altered in AD. Imbalance of microglial phenotypes in the aging brain might underlie their involvement in late onset neurodegenerative diseases. Here we report the population structure of microglia in the aged human brain and the reduction of a particular microglia subset in individuals with Alzheimer’s disease .

With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia—the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative disease. Here, we establish the set of genes that is preferentially expressed by microglia in the aged human brain. This HuMi_Aged gene set captures a unique phenotype, which we confirm at the protein level. Furthermore, we find this gene set to be enriched in susceptibility genes for Alzheimer’s disease and multiple sclerosis, to be increased with advancing age, and to be reduced by the protective APOEε2 haplotype . APOEε4 has no effect. These findings confirm the existence of an aging-related microglial phenotype in the aged human brain and its involvement in the pathological processes associated with brain aging. Aging is associated with various changes in the brain, including transcription alteration. Here, Bradshaw and colleagues describe the transcriptome of aged human cortical microglia, and show age-related gene expression as related to neurodegeneration.

Understanding tumor vasculogenesis is a cornerstone for the inhibition of tumor progression. This study aimed to generate an in vivo breast cancer environment to analyze the patterns of tumor vasculogenesis. Human mesenchymal stem cells (hMSC) and breast cancer MCF-7 cells (MCF-7) were seeded onto a chorioallantoic membrane (CAM) and, after a 7-day incubation, we performed a morphological and immunohistochemical analysis of CAM. hMSC and MCF-7 activated vasculogenesis and hematopoiesis on CAM. They stimulated the development of cord/capillary-like structures (CLS), formed by endothelial-like cells and hematopoietic cells. CLS presented a polygonal pattern, evolving towards a clearly visible plexus. Immunohistochemically, CLS were CD105+/AC133+/Oct3/4+, and the intensity was weak-moderate in the endothelial-like cells (inconstant) and weak in the hematopoietic cells. Tumor and embryonic vasculogenesis share a common paradigm, while CD105, AC133, and Oct3/4 were found to play a role in establishing the vasculogenic and hematopoietic stage.

Fat grafting has gained prominence in reconstructive and aesthetic surgery, necessitating accurate assessment methods for evaluating graft volume retention. This paper reviews various techniques for assessing fat and fat grafts, including their benefits and limitations. Three-dimensional (3D) scanning offers highly accurate, non-invasive volumetric assessments with minimal interference from breathing patterns. Magnetic resonance imaging (MRI) is recognized as the gold standard, providing precise volumetric evaluations and sensitivity to complications like oil cysts and necrosis. Computed tomography (CT) is useful for fat volume assessment but may overestimate retention rates. Ultrasonography presents a reliable, non-invasive method for measuring subcutaneous fat thickness. Other methods, such as digital imaging, histological analysis, and weight estimation, contribute to fat graft quantification. The integration of these methodologies is essential for advancing fat graft assessment, promoting standardized practices, and improving patient outcomes in clinical settings.

Complexity of cell-type composition has created much skepticism surrounding the interpretation of bulk tissue transcriptomic studies. Recent studies have shown that deconvolution algorithms can be applied to computationally estimate cell-type proportions from gene expression data of bulk blood samples, but their performance when applied to brain tissue is unclear. Here, we have generated an immunohistochemistry (IHC) dataset for five major cell-types from brain tissue of 70 individuals, who also have bulk cortical gene expression data. With the IHC data as the benchmark, this resource enables quantitative assessment of deconvolution algorithms for brain tissue. We apply existing deconvolution algorithms to brain tissue by using marker sets derived from human brain single cell and cell-sorted RNA-seq data. We show that these algorithms can indeed produce informative estimates of constituent cell-type proportions. In fact, neuronal subpopulations can also be estimated from bulk brain tissue samples. Further, we show that including the cell-type proportion estimates as confounding factors is important for reducing false associations between Alzheimer's disease phenotypes and gene expression. Lastly, we demonstrate that using more accurate marker sets can substantially improve statistical power in detecting cell-type specific expression quantitative trait loci (eQTLs).

The sural nerve grafting plays a crucial role in the repair of peripheral nerve impairments when tension-free neurorrhaphy is unfeasible. The sural nerve is frequently utilized in sensory and mixed nerve repairs because of its anatomical reliability, sensory characteristics, and low donor site morbidity. This article critically reviews the current knowledge in the field and examines the anatomical and histological features of the sural nerve, along with contemporary harvesting techniques and clinical applications. High-resolution ultrasound (US) is highlighted as a non-invasive, real-time instrument for preoperative preparation, intraoperative mapping, and postoperative assessment. Ultrasonography enhances procedural precision, resulting in superior outcomes and less complications. Given the constraints of sural nerve grafts, alternative solutions such processed allografts and synthetic guidance are being evaluated.

Background: Overexpression of chloride intracellular channel protein 1 (CLIC1) in tumor cells has been confirmed, but it has received less attention in the tumor blood vessel endothelium. Aim: The assessment of CLIC1 expression in ccRCC tumor blood vessels and its relationship with TNM parameters and tumor cell CLIC1 expression. Methods: CLIC1 immunostaining in ccRCC was evaluated in 50 cases in both malignant cells and tumor blood vessels (CLIC1 microvessel density-CLIC1-MVD) and was correlated with TNM staging parameters. Results: CLIC1-MVD was observed in approximately 65% of cases, and CLIC1 co-localization in both tumor and endothelial cells was observed in 59% of cases. ccRCC was classified into four groups (Classes 0–3) based on the percentage of positive tumor cells, with each group including sub-groups defined by CLIC1 expression in the endothelium. Class 3 (60–100% positive tumor cells) had the highest CLIC1-MVD, with an impact on T and M parameters (p value = 0.007 for T, and p value = 0.006 for M). For cases with CLIC1 intracellular translocation, there was a strong correlation between CLIC1-MVD and M (p value < 0.001). Conclusions: Co-expression of ccRCC tumor and endothelial cells promotes tumor progression and metastasis and should be investigated further as a potential therapeutic target for ccRCC and other human malignancies.

Angiogenesis plays a pivotal role in tumor development. Although microvessel density (MVD) is the most common method used for evaluation of angiogenesis, it has several limitations. Our aim was to evaluate MVD and microvessel proliferation (MVP) in a series of invasive breast carcinomas and analyze whether angiogenesis is influenced by the molecular phenotype of each tumor. We examined vascular proliferation using double immunohistochemistry (CD34/Ki67) in a series of 54 invasive breast carcinomas and compared the results with standard MVD, molecular subtypes and other classical parameters. Increased MVD and MVP values were recorded in basal-like subtype, but only the MVP value reached significance among this group of patients (p=0.0001). For all cases combined, increased MVP was significantly correlated with negative estrogen receptor (ER) status (p=0.010) and higher histological grade (p=0.002). MVP more accurately reflects the state of angiogenesis in breast cancer, compared with standard MVD. Vascular proliferation was associated with aggressive tumor features, indicating its contribution to tumor progression. The strong association between vascular proliferation and basal-like tumors suggests that this marker can be used for stratification of patients who might benefit from therapies targeting angiogenesis.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) characterized by complement dysregulation, leading to microvascular thrombosis and multi-organ injury. TMAs are defined by thrombocytopenia, microangiopathic hemolytic anemia and organ dysfunction caused by small-vessel thrombosis. Unlike thrombotic thrombocytopenic purpura, which results from severe ADAMTS13 deficiency, aHUS is driven by uncontrolled activation of the alternative complement pathway. While the kidneys are most frequently affected, other vital organs can also be involved. Genetic susceptibility contributes significantly to disease risk, but a trigger such as infection, pregnancy or autoimmune disease is usually required. Diagnosis is challenging due to overlapping features with other TMAs and relies on exclusion and complement testing. C5 inhibitors, such as eculizumab and ravulizumab, have revolutionized treatment but necessitate prophylactic vaccination and ongoing clinical surveillance. While these therapies provide effective disease control, discontinuing treatment remains complex, especially in patients with complement gene mutations. New therapies targeting various points in the complement cascade are under investigation and may offer safer, more cost-effective options. Progress in genetic profiling and biomarker discovery is essential for earlier diagnosis, individualized therapy and relapse prevention. This review highlights recent advances in the understanding of aHUS pathophysiology, clinical features and evolving therapeutic strategies aimed at improving patient outcomes.

Background: Subclinical atherosclerosis is a “silent” cardiovascular disease that can be devastating when combined with other illnesses. Its presence may affect therapy responses but can potentially worsen hematological malignancies due to most chemotherapy regimens’ cardiovascular adverse effects. Thus, cardiovascular risk factor (CVRF) assessment is required before chemotherapy. Unfortunately, this rarely happens. Aim: we aim to examine the impact of CVRFs on hemodynamic parameters of acute leukemia (AL) patients before chemotherapy. Methods: Overall, 45 AL patients and 26 controls were included. Intima-media thickness (IMT), ankle brachial index (ABI), pulse wave velocity (PWV), and functional cardiac parameters were used. CVRFs were found in 26 AL patients (36.6%), while 19 AL (26.8%) patients lacked CVRFs. CVRFs were also found in 26 controls (36.6%). Results: Left ventricular ejection fraction (LVEF) significantly decreased for patients with CVRFs (59.26 ± 5.62) compared to those without CVRFs (64.05 ± 7.43, p < 0.05). Hypertensive and diabetic patients had a significantly higher left IMT (mm) of 0.92 ± 0.01 compared to those without them (0.76 ± 0.03, p < 0.05). Patients with acute myeloid leukemia (AML) with CVRFs had a significantly higher PWV (m/s) of 8.4 ± 0.12 compared to those without CVRFs (6.87 ± 0.66) (p < 0.05). Conclusions: AL and cardiovascular risk factors interacted before chemotherapy. To decrease cardiotoxicity, AL patients need cardiovascular risk assessment. Subclinical atherosclerosis and echocardiography help chemotherapy patients to choose a treatment regimen, predict long-term outcomes, and predict cardiovascular issues.