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Genes Jun 2024Due to its turbulent demographic history, marked by extensive settlement and gene flow from diverse regions of Eurasia, Southeastern Europe (SEE) has consistently served... (Review)
Review
Due to its turbulent demographic history, marked by extensive settlement and gene flow from diverse regions of Eurasia, Southeastern Europe (SEE) has consistently served as a genetic crossroads between East and West and a junction for the migrations that reshaped Europe's population. SEE, including modern Croatian territory, was a crucial passage from the Near East and even more distant regions and human populations in this region, as almost any other European population represents a remarkable genetic mixture. Modern humans have continuously occupied this region since the Upper Paleolithic era, and different (pre)historical events have left a distinctive genetic signature on the historical narrative of this region. Our views of its history have been mostly renewed in the last few decades by extraordinary data obtained from Y-chromosome studies. In recent times, the international research community, bringing together geneticists and archaeologists, has steadily released a growing number of ancient genomes from this region, shedding more light on its complex past population dynamics and shaping the genetic pool in Croatia and this part of Europe.
Topics: Humans; Chromosomes, Human, Y; Croatia; Genetics, Population; Gene Pool; DNA, Ancient; Gene Flow; Human Migration; Male
PubMed: 38927684
DOI: 10.3390/genes15060748 -
Biomedicines May 2024The neurobiological effects of transcranial direct current stimulation (tDCS) have still not been unequivocally clarified. Some studies have suggested that the... (Review)
Review
Neurobiological Effects of Transcranial Direct Current Stimulation over the Inferior Frontal Gyrus: A Systematic Review on Cognitive Enhancement in Healthy and Neurological Adults.
The neurobiological effects of transcranial direct current stimulation (tDCS) have still not been unequivocally clarified. Some studies have suggested that the application of tDCS over the inferior frontal gyrus (IFG) enhances different aspects of cognition in healthy and neurological individuals, exerting neural changes over the target area and its neural surroundings. In this systematic review, randomized sham-controlled trials in healthy and neurological adults were selected through a database search to explore whether tDCS over the IFG combined with cognitive training modulates functional connectivity or neural changes. Twenty studies were finally included, among which twelve measured tDCS effects through functional magnetic resonance (fMRI), two through functional near-infrared spectroscopy (fNIRS), and six through electroencephalography (EEG). Due to the high heterogeneity observed across studies, data were qualitatively described and compared to assess reliability. Overall, studies that combined fMRI and tDCS showed widespread changes in functional connectivity at both local and distant brain regions. The findings also suggested that tDCS may also modulate electrophysiological changes underlying the targeted area. However, these outcomes were not always accompanied by corresponding significant behavioral results. This work raises the question concerning the general efficacy of tDCS, the implications of which extend to the steadily increasing tDCS literature.
PubMed: 38927353
DOI: 10.3390/biomedicines12061146 -
Biology Jun 2024A remarkable new deep-water skate, n. sp., is described based on eight specimens caught during different expeditions to the southern Madagascar Ridge in the...
Description of a Remarkable New Skate Species of Malm, 1877 (Rajiformes, Rajidae) from the Southwestern Indian Ocean: Introducing 3D Modeling as an Innovative Tool for the Visualization of Clasper Characters.
A remarkable new deep-water skate, n. sp., is described based on eight specimens caught during different expeditions to the southern Madagascar Ridge in the southwestern Indian Ocean. The new species differs from all congeners by its remarkably long and acutely angled snout (horizontal preorbital length 17.2-22.6% TL vs. 8.5-11.9% TL and 4.2-6.1 vs. 1.7-3.5 times orbit length, snout angle 65-85° vs. 90-150°). Furthermore, it is apparently endemic to the Madagascar Ridge, distant from the known distribution areas of all congeners. In addition to and , n. sp. is also the only species with plain dorsal coloration. Furthermore, the new species is the only species with an external clasper component dike and, besides , the only one with four dorsal terminal (dt) cartilages. The shape of the accessory terminal 1 (at1) cartilage with four tips is also unique within the genus. A new approach for the visualization of the clasper characters is introduced based on 3D models of all skeletal and external features. This enables a much easier and much more precise interpretation of every single clasper component, of the entire structure, and, in particular, the relationship between external features and skeletal cartilages. A new English translation of the first diagnosis of is provided, along with a revised generic diagnosis and a key to the species of in the Indian Ocean.
PubMed: 38927285
DOI: 10.3390/biology13060405 -
Biomolecules May 2024Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea.... (Review)
Review
Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists of almost 2000 different species of bacteria, forming a bioreactor fueled by dietary micronutrients to produce bioreactive compounds, which are absorbed by our body and signal to distant organs. Studies have shown that the Western diet, with fewer short-chain fatty acids (SCFAs), can alter the gut microbiome composition and cause the host's epigenetic reprogramming. Additionally, overproduction of HS from the gut microbiome due to changes in diet patterns can further activate pro-inflammatory signaling pathways in UC. This review discusses how the Western diet affects the microbiome's function and alters the host's physiological homeostasis and susceptibility to UC. This article also covers the epidemiology, prognosis, pathophysiology, and current treatment strategies for UC, and how they are linked to colorectal cancer.
Topics: Humans; Gastrointestinal Microbiome; Colitis, Ulcerative; Colorectal Neoplasms; Epigenesis, Genetic; Diet, Western; Animals
PubMed: 38927037
DOI: 10.3390/biom14060633 -
Journal of Medical Case Reports Jun 2024Testicular metastasis from malignant solid tumors is extremely rare. It is usually found by chance during autopsy or pathological examination of testicular specimens....
BACKGROUND
Testicular metastasis from malignant solid tumors is extremely rare. It is usually found by chance during autopsy or pathological examination of testicular specimens. Therefore, we consider it necessary to report our patient's case of testicular metastasis from colon cancer.
CASE PRESENTATION
We report a 61-year-old Han Chinese male patient who presented to our clinic with progressive painless swelling of the right testicle for 2 years. Positron emission tomography-computed tomography scans showed increased 18F-fluorodeoxyglucose metabolism in the right testicle, possibly owing to distant metastasis. His previous medical history suggested that he had undergone laparoscopic-assisted right hemicolectomy for ascending colon cancer 4 years ago. Considering the ascending colon cancer metastasis to the right testicle, we performed a right radical testicular resection through an inguinal approach. Postoperative histological examination showed intestinal metastatic adenocarcinoma.
CONCLUSION
Colon cancer metastasis to the testes is uncommon. The clinical and imaging manifestations of this tumor are nonspecific, so the diagnosis relies on postoperative pathology. If testicular metastasis is found, treatment principles for advanced colon cancer should be followed.
Topics: Humans; Male; Testicular Neoplasms; Colonic Neoplasms; Middle Aged; Adenocarcinoma; Positron Emission Tomography Computed Tomography; Colectomy; Orchiectomy; Colon, Ascending; Fluorodeoxyglucose F18
PubMed: 38926771
DOI: 10.1186/s13256-024-04587-z -
Advances in Simulation (London, England) Jun 2024Evaluating the impact of simulation-based education (SBE) has prioritised demonstrating a causal link to improved patient outcomes. Recent calls herald a move away from...
BACKGROUND
Evaluating the impact of simulation-based education (SBE) has prioritised demonstrating a causal link to improved patient outcomes. Recent calls herald a move away from looking for causation to understanding 'what else happened'. Inspired by Shorrock's varieties of human work from patient safety literature, this study draws on the concept of work-as-done versus work-as-imagined. Applying this to SBE recognises that some training impacts will be unexpected, and the realities of training will never be quite as imagined. This study takes a critical realist stance to explore the experience and consequences, intended and unintended, of the internal medicine training (IMT) simulation programme in Scotland, to better understand 'training-as-done'.
METHODS
Critical realism accepts that there is a reality to uncover but acknowledges that our knowledge of reality is inevitably our construction and cannot be truly objective. The IMT simulation programme involves three courses over a 3-year period: a 3-day boot camp, a skills day and a 2-day registrar-ready course. Following ethical approval, interviews were conducted with trainees who had completed all courses, as well as faculty and stakeholders both immersed in and distant from course delivery. Interviews were audio-recorded, transcribed verbatim and analysed using critical realist analysis, influenced by Shorrock's proxies for work-as-done.
RESULTS
Between July and December 2023, 24 interviews were conducted with ten trainees, eight faculty members and six stakeholders. Data described proxies for training-as-done within three broad categories: design, experience and impact. Proxies for training design included training-as-prescribed, training-as-desired and training-as-prioritised which compete to produce training-as-standardised. Experience included training-as-anticipated with pre-simulation anxiety and training-as-unintended with the valued opportunity for social comparison as well as a sense of identity and social cohesion. The impact reached beyond the individual trainee with faculty development and inspiration for other training ventures.
CONCLUSION
Our findings highlight unintended consequences of SBE such as social comparison and feeling 'valued as a trainee, valued as a person'. It sheds light on the fear of simulation, reinforcing the importance of psychological safety. A critical realist approach illuminated the 'bigger picture', revealing insights and underlying mechanisms that allow this study to present a new framework for conceptualising training evaluation.
PubMed: 38926742
DOI: 10.1186/s41077-024-00299-y -
Cell Death Discovery Jun 2024Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it...
Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8 T cell infiltration and better prognoses in ICC patients. Mechanistically, β-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, β-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic β-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or β-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.
PubMed: 38926350
DOI: 10.1038/s41420-024-02079-z -
Cell Reports Jun 2024The intricate interplay between resident cells and the extracellular matrix (ECM) profoundly influences cancer progression. In triple-negative breast cancer (TNBC), ECM...
The intricate interplay between resident cells and the extracellular matrix (ECM) profoundly influences cancer progression. In triple-negative breast cancer (TNBC), ECM architecture evolves due to the enrichment of lysyl oxidase, fibronectin, and collagen, promoting distant metastasis. Here we uncover a pivotal transcription regulatory mechanism involving the epigenetic regulator UBR7 and histone methyltransferase EZH2 in regulating transforming growth factor (TGF)-β/Smad signaling, affecting the expression of ECM genes. UBR7 loss leads to a dramatic reduction in facultative heterochromatin mark H3K27me3, activating ECM genes. UBR7 plays a crucial role in matrix deposition in adherent cancer cells and spheroids, altering collagen content and lysyl oxidase activity, directly affecting matrix stiffness and invasiveness. These findings are further validated in vivo in mice models and TNBC patients, where reduced UBR7 levels are accompanied by increased ECM component expression and activity, leading to fibrosis-mediated matrix stiffness. Thus, UBR7 is a master regulator of matrix stiffening, influencing the metastatic potential of TNBC.
PubMed: 38923455
DOI: 10.1016/j.celrep.2024.114394 -
Cancer Reports (Hoboken, N.J.) Jun 2024Liver metastasis of CRC is still the main cause of poor prognosis in patients with CRC. Previous studies have suggested that serpin family C member 1(SERPINC1) is...
BACKGROUND
Liver metastasis of CRC is still the main cause of poor prognosis in patients with CRC. Previous studies have suggested that serpin family C member 1(SERPINC1) is involved in the development of a variety of tumours, but its effect on colorectal cancer progression has been poorly elucidated.
METHODS
Based on the GEO database, this study identifies the core gene SERPINC1 associated with liver metastasis in CRC. We used transcriptomic data and immunohistochemical staining to explore the expression of SERPINC1 in normal, cancer, and liver metastases tissue from CRC patients. Clinical data obtained from our hospital were used to explore the impact of SERPINC1 on the prognosis of colon cancer patients. Mechanistically, the biological functions exerted by SERPINC1 in CRC were predicted by bioinformatics, and the results were validated by the results of the experiments in vitro. Cell lines with knockdown of SERPINC1 were performed a series assay such as trans well, CCK-8 and colony formation assay to explore the relationship between SERPINC1 and proliferation and metastasis of CRC cells. Finally, the effect of SERPINC1 on the sensitivity of colon cancer patients to immune checkpoint therapy was evaluated.
RESULTS
In CRC liver metastatic tissues, we found significantly high expression of SERPINC1. Briefly, 212 CRC cohorts showed that SERPINC1 was significantly associated with TNM stage and plasma CA19-9 and CEA in CRC patients. Univariate and multivariate Cox demonstrated that SERPINC1 was significantly associated with 5-year survival after radical surgery for colorectal cancer (p < 0.001). Bioinformatics predicted that SERPINC1 affects metastasis of colon cancer through epithelial-mesenchymal transition (EMT). Colony formation assay and CCK-8 assay showed that SERPINC1 promotes malignant proliferation of CRC cells, trans well assay showed that SERPINC1 promotes distant migratory behaviour of CRC cells and protein blotting assay showed that SERPINC1 may promote migration by promoting the TGF-β1-mediated EMT of CRC cells. In addition, several immunotherapy cohorts also reflected that the expression of SERPINC1 reduced the sensitivity of CRC patients to immune checkpoint therapy.
CONCLUSION
Our study identified SERPINC1 as a novel liver metastasis-associated gene in CRC. Targeting SERPINC1 may be a novel therapeutic strategy for patients with liver metastases from CRC.
Topics: Humans; Epithelial-Mesenchymal Transition; Prognosis; Liver Neoplasms; Male; Disease Progression; Colonic Neoplasms; Female; Biomarkers, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Middle Aged; Cell Line, Tumor; Cell Movement; Immune Checkpoint Inhibitors; Colorectal Neoplasms
PubMed: 38923313
DOI: 10.1002/cnr2.2079 -
Toxins May 2024As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to...
As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.
Topics: Humans; Muscle Spasticity; Male; Female; Retrospective Studies; Middle Aged; Urinary Bladder, Overactive; Adult; Spinal Cord Injuries; Multiple Sclerosis; Neuromuscular Agents; Botulinum Toxins, Type A; Urinary Bladder, Neurogenic; Aged; Injections, Intramuscular; Treatment Outcome
PubMed: 38922146
DOI: 10.3390/toxins16060252