Scientific Publications
Scientific publications and exciting articles where PreciPoint products and solutions were successfully used.
Gao, Jia; Ren, Jing; Ye, Hanjie; Chu, Wenhui; Ding, Xuankai; Ding, Lingzhi; Fu, Yongqian
M8 Microscope and Scanner Used in Research on ZIF-8 Sericin Hydrogel for Bone Regeneration Promoting Angiogenesis and Osteogenesis
A recent study used the M8 microscope and scanner to evaluate a novel bone regeneration scaffold. Designing scaffolds with optimal biodegradability, osteogenic potential, and angiogenic properties presents a significant challenge. Thymosin beta 10 (TMSB10), known for its roles in angiogenesis and osteogenic differentiation, faces activity preservation limitations. To address this, researchers engineered ZIF-8 as a carrier for TMSB10 (TMSB10@ZIF-8), integrating it into a self-assembled sericin hydrogel. Testing the composite in a rat cranial defect model revealed successful synthesis of TMSB10@ZIF-8 with an 88.21% encapsulation efficiency. The sustained release of TMSB10 from this composite significantly enhanced tube formation in HUVECs and promoted angiogenesis in the CAM model. Additionally, it notably improved osteogenic differentiation in MC 3 T3-E1 cells. Eight weeks post-implantation, the TMSB10@ZIF-8/Sericin hydrogel group demonstrated substantial bone healing (86.77 ± 8.91%), outperforming controls.
Result: Histological observation of the skulls was conducted using M8 microscope and scanner. The skulls were first decalcified, followed by dehydration using a graded series of ethanol. Subsequently, the samples were cleared in xylene and embedded in paraffin. Tissue slices were then obtained from the central area of each defect and subjected to staining with H&E, Masson\'s trichrome, and Sirius Red for microscopic evaluation. The approach enabled detailed examination and documentation of tissue morphology and composition within the bone defects, providing crucial insights into the efficacy of the TMSB10@ZIF-8/Sericin hydrogel scaffold in promoting bone regeneration.
@article{nokey,
title = {Thymosin beta 10 loaded ZIF-8/sericin hydrogel promoting angiogenesis and osteogenesis for bone regeneration},
author = {Jia Gao and Jing Ren and Hanjie Ye and Wenhui Chu and Xuankai Ding and Lingzhi Ding and Yongqian Fu},
url = {https://www.sciencedirect.com/science/article/pii/S0141813024023675#s0075},
doi = {10.1016/j.ijbiomac.2024.131562},
year = {2024},
date = {2024-05-01},
journal = {International Journal of Biological Macromolecules},
volume = {267},
abstract = {Angiogenesis is pivotal for osteogenesis during bone regeneration. A hydrogel that promotes both angiogenesis and osteogenesis is essential in bone tissue engineering. However, creating scaffolds with the ideal balance of biodegradability, osteogenic, and angiogenic properties poses a challenge. Thymosin beta 10 (TMSB10), known for its dual role in angiogenesis and osteogenesis differentiation, faces limitations due to protein activity preservation. To tackle this issue, ZIF-8 was engineered as a carrier for TMSB10 (TMSB10@ZIF-8), and subsequently integrated into the self-assembled sericin hydrogel. The efficacy of the composite hydrogel in bone repair was assessed using a rat cranial defect model. Characterization of the nanocomposites confirmed the successful synthesis of TMSB10@ZIF-8, with a TMSB10 encapsulation efficiency of 88.21 %. The sustained release of TMSB10 from TMSB10@ZIF-8 has significantly enhanced tube formation in human umbilical vein endothelial cells (HUVECs) in vitro and promoted angiogenesis in the chicken chorioallantoic membrane (CAM) model in vivo. It has markedly improved the osteogenic differentiation ability of MC 3 T3-E1 cells in vitro. 8 weeks post-implantation, the TMSB10@ZIF-8/ Sericin hydrogel group exhibited significant bone healing (86.77 ± 8.91 %), outperforming controls. Thus, the TMSB10@ZIF-8/Sericin hydrogel, leveraging ZIF-8 for TMSB10 delivery, emerges as a promising bone regeneration scaffold with substantial clinical application potential.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Fuentes, Mary Esmeralda; Lu, Xiaoyin; Flores, Natasha M.; Hausmann, Simone; Mazur, Pawel K.
M8 Microscope and Scanner Investigates High-Grade Pancreatic Neuroendocrine Tumors in Mice with MEN1, ATRX, and PTEN Deletion
M8 microscope and scanner was used in the research involving pancreatic neuroendocrine tumors (PanNETs) that are rare yet aggressive malignancies lacking effective therapies. Characterized by extensive heterogeneity, PanNETs often present at advanced stages, resulting in poor prognoses. Research efforts focusing on genomic landscapes have identified recurrent mutations in MEN1, ATRX, DAXX, and PTEN, critical in PanNET pathogenesis. The development of effective therapeutics is hindered by this heterogeneity and limited preclinical models. Notably, MEN1, ATRX, and PTEN deletions in mice mimic PanNET tumorigenesis, offering a promising model for translational research and therapeutic development. Understanding the roles of these mutations and associated pathways holds potential for targeted precision therapies in this challenging disease.
Result: Researchers used the M8 microscope and scanner to identify key genetic alterations in human PanNETs. They analyzed the GENIE v14.1 genomic sequencing database, revealing frequent mutations in MEN1, ATRX, DAXX, and PTEN. Co-occurring mutations in MEN1, PTEN, and ATRX or DAXX suggest their combined loss drives PanNET pathogenesis. Using MAP mutant mice (Men1LoxP/LoxP; AtrxLoxP/LoxP; PtenLoxP/LoxP; Pdx1-CreER), experts induced tumorigenesis and observed robust tumor development resembling intermediate-grade PanNETs with progressive malignancy. RNA sequencing confirmed elevated neuroendocrine and PanNET marker gene expression, aligning with human PanNET biology. Transcriptomic analysis revealed MAP model similarity to human PanNETs, distinct from other mouse models, highlighting its relevance for studying PanNET pathogenesis.
@article{nokey,
title = {Combined deletion of MEN1, ATRX and PTEN triggers development of high-grade pancreatic neuroendocrine tumors in mice},
author = {Mary Esmeralda Fuentes and Xiaoyin Lu and Natasha M. Flores and Simone Hausmann and Pawel K. Mazur},
url = {https://www.nature.com/articles/s41598-024-58874-2},
doi = {10.1038/s41598-024-58874-2},
year = {2024},
date = {2024-04-12},
urldate = {2024-04-12},
journal = {Scientific Reports},
volume = {14},
issue = {1},
abstract = {Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of tumors that exhibit an unpredictable and broad spectrum of clinical presentations and biological aggressiveness. Surgical resection is still the only curative therapeutic option for localized PanNET, but the majority of patients are diagnosed at an advanced and metastatic stage with limited therapeutic options. Key factors limiting the development of new therapeutics are the extensive heterogeneity of PanNETs and the lack of appropriate clinically relevant models. In that context, genomic sequencing of human PanNETs revealed recurrent mutations and structural alterations in several tumor suppressors. Here, we demonstrated that combined loss of MEN1, ATRX, and PTEN, tumor suppressors commonly mutated in human PanNETs, triggers the development of high-grade pancreatic neuroendocrine tumors in mice. Histopathological evaluation and gene expression analyses of the developed tumors confirm the presence of PanNET hallmarks and significant overlap in gene expression patterns found in human disease. Thus, we postulate that the presented novel genetically defined mouse model is the first clinically relevant immunocompetent high-grade PanNET mouse model.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Porth, Isabel
M8 Microscope and Scanner and ViewPoint Software Used to Study Trastuzumab\'s Long-term Effects in HER2-positive Advanced Gastric or Gastroesophageal Adenocarcinoma
A study, conducted with the help of M8 microscope and scanner and ViewPoint software, identified biomarkers distinguishing HER2-positive gastric cancer patients with long-term versus short-term responses to trastuzumab plus chemotherapy. Genetic analyses revealed two non-synonymous mutations in ERBB2, occurring exclusively in long-term responders. However, neither HER2 gene copy number nor other genetic alterations correlated with treatment response. Notably, patients with homogeneous HER2 protein expression had improved progression-free survival on trastuzumab-containing therapy. Evaluating PD-L1, long-term responders exhibited higher PD-L1 combined positive scores, correlating positively with progression-free survival across the cohort. PD-L1 positivity (combined positive score ≥1) was associated with enhanced progression-free survival on trastuzumab-based treatment. Bioinformatics analysis linked increased PD-L1 scores to elevated CD4+ memory T-cell levels. While genetic mutations in ERBB2 were specific to long-term responders, a homogeneous HER2 expression pattern and PD-L1 positivity emerged as potential biomarkers for improved treatment outcomes in HER2-positive gastric cancer, emphasizing the clinical importance of PD-L1 in this setting.
Result: The study used M8 microscope and scanner and ViewPoint software to identify that the PD-L1 combined positive score (CPS) is higher in long-term responders compared to short-term responders, suggesting a potential biomarker for predicting the efficacy of trastuzumab in these patients. The PD-L1 CPS was also positively correlated with progression-free survival (PFS), highlighting its potential as a prognostic marker for better outcomes under trastuzumab-based therapy. The study found that the copy number variations (CNVs) of the HER2 gene (ERBB2) did not significantly distinguish between long-term and short-term responders. However, patients with a homogeneous HER2 expression pattern showed improved PFS, suggesting that the uniformity of HER2 expression might be an important factor in the effectiveness of trastuzumab therapy. The CD4+ memory T-cells were found in higher levels in PD-L1 positive patients. Overall, the thesis suggests that PD-L1 expression and the immune cell landscape, particularly the presence of CD4+ memory T-cells, hold significant potential as indicators for better clinical outcomes in HER2-positive gastric and gastroesophageal junction cancers.
@mastersthesis{nokey,
title = {Long-term response to trastuzumab in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma},
author = {Isabel Porth},
url = {https://archiv.ub.uni-heidelberg.de/volltextserver/34645/1/Thesis%20Isabel%20Porth%20final.pdf},
doi = {10.11588/heidok.00034645},
year = {2024},
date = {2024-04-11},
urldate = {2024-04-11},
school = {Heidelberg University Library},
abstract = {Gastric cancer is the fifth most prevalent cancer type, with the fourth highest cancer-related mortality worldwide. Since 2010, the HER2-targeting agent trastuzumab has been approved as a first-line therapy in combination with chemotherapy for HER2-positive advanced/metastatic gastric or gastroesophageal junction cancer. However, despite improvement of overall survival through trastuzumab treatment, the survival remains low with only about one year. However, a subgroup of patients with long-term response to trastuzumab has been observed in small studies and case reports. Genetic alterations and the level of HER2 gene amplification have been proposed to identify patients with trastuzumab long-term response. Despite this, a biomarker for superior response to trastuzumab remains elusive. This study aimed to identify a biomarker that could distinguish between HER2-positive gastric cancer patients with long-term and short-term response to trastuzumab plus chemotherapy. FFPE tumor samples and follow-up data of 19 patients with HER2-positive advanced/metastatic gastric or gastroesophageal junction cancer who underwent trastuzumab-containing therapy were retrospectively collected from four German clinical centers. The patients were divided into long-term (n=7) and short-term responding groups (n=12) according to progression-free survival on trastuzumab-containing therapy (PFS≥12 months vs. PFS<12 months). A comprehensive genetic and gene expression analysis was performed. In addition, established biomarkers HER2, PD-L1 and MSI were analyzed. An automated analysis pipeline was developed to detect genetic alterations such as somatic single nucleotide variants and copy number alterations. The copy number of the HER2 gene, ERBB2, could not distinguish between trastuzumab long-term and short-term response in gastric cancer patients. However, two somatic non-synonymous mutations were detected in ERBB2, and both mutations occurred in patients with long-term response to trastuzumab. Other genetic alterations and the tumor mutational burden were not correlated with response to trastuzumab. The HER2 protein expression pattern was also evaluated, and the results showed that patients with homogeneous HER2 expression pattern had improved progression-free survival on trastuzumab-containing therapy.
Evaluation of the biomarker PD-L1 revealed a higher PD-L1 combined positive score in longterm responding patients, and a positive correlation between PD-L1 combined positive score and PFS in the overall study population. PD-L1 positivity, defined as a combined positive score ≥1, was associated with improved PFS on trastuzumab-based treatment. Furthermore, using bioinformatics methods, increased PD-L1 combined positive scores could be associated with a higher level of CD4+ memory T-cells.
In conclusion, genetic alterations and the tumor mutational burden were not correlated with response to a trastuzumab-containing therapy, while a homogeneous HER2 protein expression pattern and PD-L1 combined positive score were identified as potential biomarkers for improved progression-free survival. The findings highlight the clinical relevance of PD-L1 for the treatment of HER2-positive advanced gastric and gastroesophageal adenocarcinoma.
},
keywords = {M8, ViewPoint},
pubstate = {published},
tppubtype = {mastersthesis}
}
Evaluation of the biomarker PD-L1 revealed a higher PD-L1 combined positive score in longterm responding patients, and a positive correlation between PD-L1 combined positive score and PFS in the overall study population. PD-L1 positivity, defined as a combined positive score ≥1, was associated with improved PFS on trastuzumab-based treatment. Furthermore, using bioinformatics methods, increased PD-L1 combined positive scores could be associated with a higher level of CD4+ memory T-cells.
In conclusion, genetic alterations and the tumor mutational burden were not correlated with response to a trastuzumab-containing therapy, while a homogeneous HER2 protein expression pattern and PD-L1 combined positive score were identified as potential biomarkers for improved progression-free survival. The findings highlight the clinical relevance of PD-L1 for the treatment of HER2-positive advanced gastric and gastroesophageal adenocarcinoma.
Tang, Yuan-juan; Zhang, Zhen; Yan, Tong; Chen, Ken; Xu, Guo-fan; Xiong, Shi-qiang; Wu, Dai-qian; Chen, Jie; Jose, Pedro A.; & Jin-juan Fu, Chun-yu Zeng
M8 Microscope and Scanner Explores Irisin’s Impact on Type 1 Diabetic Cardiomyopathy
Research on diabetic cardiomyopathy (DCM) in type 1 diabetes mellitus (T1DM) was conducted with the assistance of an M8 microscope and scanner. Diabetes, particularly type 1 diabetes mellitus (T1DM), presents a significant global health challenge, with diabetic cardiomyopathy (DCM) posing a major threat to patients, characterized by cardiac dysfunction leading to morbidity and mortality. While apoptosis is recognized as a primary mechanism in DCM, recent evidence suggests a role for ferroptosis, a distinct form of cell death involving iron accumulation and lipid peroxidation. Despite emerging links between ferroptosis and DCM, understanding remains limited, especially in T1DM. Training has shown protective effects against DCM, and irisin, a myokine, has been implicated in cardiovascular protection and ferroptosis inhibition in other conditions. Investigating the role of ferroptosis in DCM pathogenesis, particularly in T1DM, and exploring whether irisin mitigates cardiac dysfunction through anti-ferroptotic mechanisms are crucial research aims.
Result: The study revealed lower irisin levels in the heart and serum of STZ-induced T1DM mice. Irisin supplementation improved cardiac function in diabetic cardiomyopathy (DCM) by inhibiting ferroptosis. This was shown by decreased cardiac MDA, restored GSH, and increased SLC7A11/GPX4 expression. The protective effect of irisin was demonstrated to be specific to ferroptosis, as erastin, a ferroptosis inducer, blocked irisin-mediated benefits. Mechanistically, irisin increased SIRT1 and decreased p53 K382 acetylation, leading to reduced p53 levels, upregulation of SLC7A11/GPX4, and ultimately decreasing ferroptosis and protecting cardiomyocytes from high glucose-induced injury.
@article{nokey,
title = {Irisin attenuates type 1 diabetic cardiomyopathy by anti-ferroptosis via SIRT1-mediated deacetylation of p53},
author = {Yuan-juan Tang and Zhen Zhang and Tong Yan and Ken Chen and Guo-fan Xu and Shi-qiang Xiong and Dai-qian Wu and Jie Chen and Pedro A. Jose and Chun-yu Zeng & Jin-juan Fu},
url = {https://cardiab.biomedcentral.com/articles/10.1186/s12933-024-02183-5},
doi = {10.1186/s12933-024-02183-5},
year = {2024},
date = {2024-04-02},
urldate = {2024-04-02},
journal = {Cardiovascular Diabetology},
volume = {23},
issue = {1},
abstract = {Background
Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia–reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known.
Methods and results
T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose.
Conclusion
This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia–reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known.
Methods and results
T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose.
Conclusion
This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.
Wang, Dongxu; Ren, Jing; Li, Jiping; Li, Xiuying; Ying, Jinchi; Jiang, Tiantian; Wang, Zhen; Pan, Zheng; Guo, Qianqian; Li, Chunyi; Zhang, Guokun
M8 Microscope and Scanner Utilized to Explore Deer Antler Stem Cell Conditioned Media\'s Potential in Alleviating Type 1 Diabetes via NF-κB Pathway Inhibition
A study, using the M8 microscope and slide scanner, delved into the impact of Type 1 diabetes mellitus (T1D) on human health. Type 1 diabetes mellitus (T1D) poses a significant threat to human health, primarily due to absolute insulin deficiency, leading to elevated blood glucose levels and potentially life-threatening complications such as liver injury. Mesenchymal stem cell (MSC) transplantation has emerged as a promising treatment for T1D and its associated liver injuries, leveraging the regenerative and immunomodulatory properties of MSCs. The study explored the therapeutic potential of conditioned medium from deer antler stem cells (AnSC-CM) in T1D and diabetic liver injuries. Results indicate that AnSC-CM not only alleviates T1D symptoms but also mitigates T1D-induced liver injury, outperforming bone marrow MSC-conditioned medium (BMSC-CM). Mechanistic insights suggest that the therapeutic effects of AnSC-CM may be mediated through targeting the NF-κB signaling pathway. The research proposes a novel strategy utilizing alternative stem cell conditioned mediums for effective treatment of T1D and associated liver injuries in clinical settings.
Result: Research findings demonstrated that AnSC-CM effectively relieved symptoms associated with T1D, including decreased body weight, elevated blood glucose levels, islet lesions, and diminished insulin secretion. Additionally, AnSC-CM treatment exhibited notable improvements in liver function and the mitigation of T1D-induced liver injury in mice. The therapeutic efficacy of AnSC-CM surpassed that of BMSC-CM. Analysis of underlying mechanisms unveiled significant downregulation of the NF-κB signaling pathway in both pancreatic and liver tissues by AnSC-CM. These results suggest that AnSC-CM\'s therapeutic effects on T1D and associated liver injury induced by STZ may be attributed to its modulation of the NF-κB signaling pathway.
@article{nokey,
title = {Conditioned Media from Deer Antler Stem Cells Effectively Alleviate Type 1 Diabetes Mellitus Possibly via Inhibiting the NF-κB Signaling Pathway},
author = {Dongxu Wang and Jing Ren and Jiping Li and Xiuying Li and Jinchi Ying and Tiantian Jiang and Zhen Wang and Zheng Pan and Qianqian Guo and Chunyi Li and Guokun Zhang},
url = {https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903096/htm},
year = {2024},
date = {2024-03-11},
journal = {Front. Biosci. (Landmark Ed)},
volume = {29},
issue = {3},
abstract = {Background: Type 1 diabetes mellitus (T1D) represents a severe threat to human health. Persistent hyperglycemia and dyslipidemia can lead to damaged liver function, while effective interventions for these complications are currently lacking. Deer antler stem cells (AnSCs), a novel type of adult stem cells, significantly reduced liver injury, which was speculated to be achieved through the paracrine pathway. Methods: In this study, AnSC-conditioned medium (AnSC-CM) was used to treat C57BL/6 mice with T1D symptoms induced by streptozotocin (STZ). The therapeutic effects of AnSC-CM on T1D were evaluated, and the underlying mechanism was investigated. Results: It was shown that AnSC-CM alleviated the T1D symptom: decreased body weight, increased blood glucose levels and islet lesions, and reduced insulin secretion. Moreover, AnSC-CM treatment improved liver function and mitigated liver injury in T1D mice. Impressively, the therapeutic effects of AnSC-CM on T1D were better than those of bone marrow mesenchymal stem cell-CM (BMSC-CM). The mechanistic study revealed that AnSC-CM significantly downregulated the NF-κB signaling pathway in both pancreatic and liver tissues. Conclusions: Therapeutic effects of AnSC-CM on STZ-induced T1D and liver injury may be achieved through targeting the NF-κB signaling pathway.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Hansen,; E.,; Wang,; M.,; Rolling,; C.,; & Holaska,; M., J.
PreciPoint Slide Scanning Microscope Unveils the Invasive Phenotype of MCF7 Cells under Emerin Deficiency
Using PreciPoint’s slide scanning microscope, researchers investigated how cancer cells migrate through blood vessels during metastasis. They observed that cancer cells adapt to pass through narrow gaps in the endothelium by altering their nuclei, which become more deformable. The study focused on the role of emerin protein in this process. Researchers found that invasive breast cancer cells, which have lower levels of emerin, exhibit smaller and misshapen nuclei compared to non-cancerous cells. This reduction in emerin was associated with higher rates of metastasis. To validate their hypothesis, the researchers manipulated emerin levels in noninvasive MCF7 cells and observed similar changes in nucleus size and shape, leading to impaired cell migration. This effect was consistent when emerin levels were reduced in invasive breast cancer cells. Furthermore, the analysis of breast cancer patient samples revealed a negative correlation between emerin expression and cancer invasiveness, suggesting its potential as a biomarker for tumor progression. The findings indicate that emerin loss plays a crucial role in promoting invasive transformation, highlighting its significance in cancer metastasis.
Result: To investigate how reducing emerin levels affects MCF7 cells, researchers created various MCF7 cell lines. These cell lines were engineered to produce one of three distinct emerin shRNA sequences labeled as A, B, or C, alongside a control group that expressed a scrambled shRNA sequence obtained from Genecopoeia. Immunohistochemistry and tissue microarray analyses were conducted on these cell lines. For the tissue microarray analysis, tissue microarrays underwent deparaffinization and rehydration procedures. Following additional tissue treatments, images were captured utilizing the Precipoint slide scanning microscope.
@article{nokey,
title = {Emerin deficiency drives MCF7 cells to an invasive phenotype},
author = {Hansen and E. and Wang and M. and Rolling and C. and & Holaska and J. M.},
url = {https://www.biorxiv.org/content/10.1101/2024.02.21.581379v2.full.pdf
https://www.biorxiv.org/content/10.1101/2024.02.21.581379v2},
doi = {10.1101/2024.02.21.581379},
year = {2024},
date = {2024-02-24},
journal = {Cold Spring Harbor Laboratory},
abstract = {During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer cells showed similar results. Supporting the clinical relevance of emerin reduction in cancer progression, our analysis of 192 breast cancer patient samples showed emerin expression inversely correlates with cancer invasiveness. We conclude emerin loss is an important driver of invasive transformation and has utility as a biomarker for tumor progression.
},
keywords = {Fritz, M8},
pubstate = {published},
tppubtype = {article}
}
Yu, Jing; Gao, Boyuan; Li, Danning; Li, Shuang; Chiang, Vincent L.; Li, Wei; Zhou, Chenguang
M8 Microscope Reveals PtrLBD39 Overexpression Hinders Primary and Secondary Growth in Populus Trichocarpa
Researchers used M8 microscope and scanner to investigate the mechanisms underlying primary and secondary growth in trees, crucial for height and stem diameter increments, respectively, which are essential for woody biomass production. They discovered PtrLBD39, a transcription factor highly specific to stem phloem in Populus trichocarpa. Through ectopic expression of PtrLBD39 in P. trichocarpa, researchers observed a significant retardation in both primary and secondary growth. Their comprehensive analysis, including RNA-seq, ChIP-seq, and weighted gene co-expression network analysis (WGCNA), unveiled PtrLBD39\'s role in regulating transcription factors associated with vascular tissue development, wood formation, hormonal signaling, and enzymes responsible for wood components. This regulatory function resulted in growth inhibition, reduced fibrocyte secondary cell wall thickness, and diminished wood production. The study suggests that PtrLBD39 acts as a repressor, affecting both primary and secondary growth when ectopically expressed in P. trichocarpa.
Result: The stem segments, after treatment, underwent cutting into 10-micrometer sections and staining with solutions containing 5% Safranin O, 1.25% Fast Green, and 0.1% Toluidine Blue. Subsequently, micrographs of the stem sections were obtained using an M8 digital microscope and scanner. The findings of the study suggest that PtrLBD39 functions as a suppressor, impacting both primary and secondary growth upon its ectopic expression in P. trichocarpa.
@article{nokey_27,
title = {Ectopic Expression of PtrLBD39 Retarded Primary and Secondary Growth in Populus trichocarpa},
author = {Jing Yu and Boyuan Gao and Danning Li and Shuang Li and Vincent L. Chiang and Wei Li and Chenguang Zhou},
url = {https://doi.org/10.3390/ijms25042205},
doi = {10.3390/ijms25042205},
year = {2024},
date = {2024-02-12},
urldate = {2024-02-12},
journal = {International Journal of Molecular Sciences},
volume = {25},
issue = {4},
abstract = {Primary and secondary growth of trees are needed for increments in plant height and stem diameter, respectively, affecting the production of woody biomass for applications in timber, pulp/paper, and related biomaterials. These two types of growth are believed to be both regulated by distinct transcription factor (TF)-mediated regulatory pathways. Notably, we identified PtrLBD39, a highly stem phloem-specific TF in Populus trichocarpa and found that the ectopic expression of PtrLBD39 in P. trichocarpa markedly retarded both primary and secondary growth. In these overexpressing plants, the RNA-seq, ChIP-seq, and weighted gene co-expression network analysis (WGCNA) revealed that PtrLBD39 directly or indirectly regulates TFs governing vascular tissue development, wood formation, hormonal signaling pathways, and enzymes responsible for wood components. This regulation led to growth inhibition, decreased fibrocyte secondary cell wall thickness, and reduced wood production. Therefore, our study indicates that, following ectopic expression in P. trichocarpa, PtrLBD39 functions as a repressor influencing both primary and secondary growth.
},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Rusche,; D.,; Englert,; N.,; Runz,; M.,; Hetjens,; S.,; Langner,; C.,; Gaiser,; T.,; & Weis,; C.-A.,
M8 Microscope and Scanner Assists Researchers in Exploring the Challenges of Detecting Tumor Budding in Colorectal Carcinoma Histology
In colorectal carcinoma (CRC) research, the M8 microscope and scanner played a pivotal role in a study aimed at predicting post-surgery treatment requirements by discerning crucial tumor features within whole slide images of solid tumors. Addressing this challenge with a small CRC dataset, researchers explored two distinct approaches. Firstly, a conventional tile-level training method was examined, incorporating various data augmentation techniques to counter the memorization effect in a noisy label setting. Secondly, a multi-instance learning (MIL) approach at the case level was explored, adapting data augmentation to prevent over-fitting in the context of limited data. The tile-level strategy proved ineffective due to a scarcity of informative image tiles per case, while the MIL approach, coupled with post-feature vector creation data augmentation, successfully predicted nodal status based on expert-derived budding scores for these cases.
Result: The dataset consisted of 29 whole slide images (WSIs), including 21 for tumors, one each for high-grade and low-grade intra-epithelial neoplasia (IEN), five for ulcerative colitis, and one for healthy tissue. The entire tissue sections were scanned and saved in the .svs format for further analysis using the M8 microscope and scanner. The study demonstrated the effectiveness of the MIL method in identifying predictive factors such as tumor budding, even within the constraints of a limited dataset size by incorporating data augmentation techniques.
@article{nokey,
title = {Unraveling a Histopathological Needle-in-Haystack Problem: Exploring the Challenges of Detecting Tumor Budding in Colorectal Carcinoma Histology},
author = {Rusche and D. and Englert and N. and Runz and M. and Hetjens and S. and Langner and C. and Gaiser and T. and & Weis and C.-A.},
url = {https://www.mdpi.com/2076-3417/14/2/949/pdf?version=1706061826},
doi = {10.3390/app14020949},
year = {2024},
date = {2024-01-22},
journal = {Applied Sciences},
volume = {14},
issue = {2},
pages = {949},
abstract = {Background: In this study focusing on colorectal carcinoma (CRC), we address the imperative task of predicting post-surgery treatment needs by identifying crucial tumor features within whole slide images of solid tumors, analogous to locating a needle in a histological haystack. We evaluate two approaches to address this challenge using a small CRC dataset. Methods: First, we explore a conventional tile-level training approach, testing various data augmentation methods to mitigate the memorization effect in a noisy label setting. Second, we examine a multi-instance learning (MIL) approach at the case level, adapting data augmentation techniques to prevent over-fitting in the limited data set context. Results: The tile-level approach proves ineffective due to the limited number of informative image tiles per case. Conversely, the MIL approach demonstrates success for the small dataset when coupled with post-feature vector creation data augmentation techniques. In this setting, the MIL model accurately predicts nodal status corresponding to expert-based budding scores for these cases. Conclusions: This study incorporates data augmentation techniques into a MIL approach, highlighting the effectiveness of the MIL method in detecting predictive factors such as tumor budding, despite the constraints of a limited dataset size.
},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Stallmeyer,; B.,; Bühlmann,; C.,; Stakaitis,; R.,; Dicke,; A.-K.,; Ghieh,; F.,; Meier,; L.,; Zoch,; A.,; MacLeod,; M., D.; Steingröver,; J.,; Okutman,; Ö.,; Fietz,; D.,; Pilatz,; A.,; Escamilla,; R., A.; Xavier,; M.,; Ruckert,; C.,; Persio,; D., S.; Neuhaus,; N.,; Gurbuz,; S., A.; Şalvarci,; A.,; Tüttelmann, …; F.,
O8 Oil Microscope and Scanner Reveals Inherited Defects of piRNA Biogenesis Leading to Transposon De-Repression, Impaired Spermatogenesis, and Human Male Infertility
In an exploration of the genetic intricacies underlying piRNA dysfunction in humans, researchers leveraged the O8 oil digital microscope and slide scanner. The study delved into the critical functions of Piwi-interacting RNAs (piRNAs) in transposon silencing, germ cell maturation, and male fertility. Examining 39 infertile men with biallelic variants in 14 piRNA pathway genes, including novel candidates like PIWIL1 and GTSF1, the research uncovered distinct testicular phenotypes, ranging from complete germ cell loss to the production of abnormal spermatozoa. Notably, impaired piRNA biogenesis in spermatogonia led to transposon de-silencing, validated by elevated LINE1 expression. The study also revealed co-dependencies within the human piRNA pathway, as the abolished expression of both encoded proteins and additional piRNA factors contributed to spermatogenic failure. These findings establish the disrupted piRNA pathway as a significant cause of human infertility, providing crucial insights into transposon silencing in male germ cells.
Result: Testicular biopsies from individuals in the MERGE cohort and control subjects were acquired through testicular sperm extraction (TESE) procedures or histological assessment. These biopsies were fixed in Bouin’s solution overnight, followed by multiple processes. A the end, the processed slides were examined and documented using the O8 oil digital microscope and scanner. The study unveiled intricate co-dependencies within the human piRNA pathway. The study also demonstrated that the absence of expression in both the encoded proteins and additional piRNA factors played a significant role in contributing to spermatogenic failure.
@article{nokey,
title = {Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility},
author = {Stallmeyer and B. and Bühlmann and C. and Stakaitis and R. and Dicke and A.-K. and Ghieh and F. and Meier and L. and Zoch and A. and MacLeod and D. M. and Steingröver and J. and Okutman and Ö. and Fietz and D. and Pilatz and A. and Escamilla and A. R. and Xavier and M. and Ruckert and C. and Persio and S. D. and Neuhaus and N. and Gurbuz and A. S. and Şalvarci and A. and … Tüttelmann and F.},
url = {https://assets.researchsquare.com/files/rs-3710476/v1/14e3a3fa-f9d8-4572-9b1b-9857f92be1bf.pdf?c=1705956027
https://www.researchsquare.com/article/rs-3710476/v1},
doi = {10.21203/rs.3.rs-3710476/v1},
year = {2024},
date = {2024-01-09},
journal = {Research Square Platform LLC.},
abstract = {Piwi-interacting RNAs (piRNAs) are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, and DDX4 as novel disease genes. The testicular phenotypes repeatedly differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal spermatozoa. LINE1 expression in spermatogonia links impaired piRNA biogenesis to transposon de-silencing and serves to classify variants as functionally relevant. Furthermore, an abolished expression of not only the encoded proteins but also of additional piRNA factors reveals co-dependencies within the human pathway. These results establish the disrupted piRNA pathway as a major cause of human spermatogenic failure and provide insights into transposon silencing in human male germ cells.
},
keywords = {O8},
pubstate = {published},
tppubtype = {article}
}
Shi,; H.,; Yuan,; X.,; Liu,; G.,; & Fan,; W.,
M8 Digital Microscope and Slide Scanning Used for Enhanced Histological Analysis of Wound Tissue
Utilizing the M8 microscope and scanner, this study harnessed the power of bioinformatics and machine learning to scrutinize microarray data sourced from the Gene Expression Omnibus (GEO) database, pinpointing crucial genes linked to Diabetic Foot Ulcers (DFU). The investigation employed GSE68183 and GSE80178 datasets as the training set, employing advanced techniques such as LASSO and SVM-RFE machine learning models through the glmnet and e1071 packages, respectively. Model validation ensued using both the training set and an independent validation set (GSE134431). Subsequent enrichment analyses, encompassing GSEA and GSVA, were applied to the identified genes. Immune functional and immune-related analyses were conducted to unravel the biological significance. The study culminated in a validation phase, employing immunohistochemistry (IHC) to corroborate the significance of the identified model genes.
Result: After preservation in 4% paraformaldehyde for 48 hours, the wound tissue underwent conventional paraffin embedding and sectioning procedures. Subsequently, staining procedures were employed, including hematoxylin and eosin, along with Masson’s trichrome stain, to enhance visualization of tissue characteristics. The stained tissues were meticulously scrutinized using a state-of-the-art M8 digital microscope and slide scanning device, ensuring precise and detailed examination of the histological features.
@article{nokey,
title = {Identifying and Validating GSTM5 as an Immunogenic Gene in Diabetic Foot Ulcer Using Bioinformatics and Machine Learning},
author = {Shi and H. and Yuan and X. and Liu and G. and & Fan and W.},
url = {https://www.tandfonline.com/doi/full/10.2147/JIR.S442388},
doi = {10.2147/JIR.S442388},
year = {2023},
date = {2023-12-19},
journal = {Journal of Inflammation Research},
volume = {16},
pages = {6241-6256},
abstract = {Background
A diabetic foot ulcer (DFU) is a serious, long-term condition associated with a significant risk of disability and mortality. However, research on its biomarkers is still limited. This study utilizes bioinformatics and machine learning methods to identify immune-related biomarkers for DFU and validates them through external datasets and animal experiments.
Methods
This study used bioinformatics and machine learning to analyze microarray data from the Gene Expression Omnibus (GEO) database to identify key genes associated with DFU. Animal experiments were conducted to validate these findings. This research employs the datasets GSE68183 and GSE80178 retrieved from the GEO database as the training dataset for building a gene machine learning model, and after conducting differential analysis on the data, this study used package glmnet and package e1071 to construct LASSO and SVM-RFE machine learning models, respectively. Subsequently, we validated the model using the training set and validation set (GSE134431). We conducted enrichment analysis, including GSEA and GSVA, on the model genes. We also performed immune functional analysis and immune-related analysis on the model genes. Finally, we conducted immunohistochemistry (IHC) validation on the model genes.
Results
This study identifies GSTM5 as a potential immune-related key target in DFU using machine learning and bioinformatics methods. Subsequent validation through external datasets and IHC experiments also confirms GSTM5 as a critical biomarker for DFU. The gene may be associated with T cells regulatory (Tregs) and T cells follicular helper, and it influences the NF-κB, GnRH, and MAPK signaling pathway.
Conclusion
This study identified and validated GSTM5 as a biomarker for DFU. This finding may potentially provide a target for immune therapy for DFU.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
A diabetic foot ulcer (DFU) is a serious, long-term condition associated with a significant risk of disability and mortality. However, research on its biomarkers is still limited. This study utilizes bioinformatics and machine learning methods to identify immune-related biomarkers for DFU and validates them through external datasets and animal experiments.
Methods
This study used bioinformatics and machine learning to analyze microarray data from the Gene Expression Omnibus (GEO) database to identify key genes associated with DFU. Animal experiments were conducted to validate these findings. This research employs the datasets GSE68183 and GSE80178 retrieved from the GEO database as the training dataset for building a gene machine learning model, and after conducting differential analysis on the data, this study used package glmnet and package e1071 to construct LASSO and SVM-RFE machine learning models, respectively. Subsequently, we validated the model using the training set and validation set (GSE134431). We conducted enrichment analysis, including GSEA and GSVA, on the model genes. We also performed immune functional analysis and immune-related analysis on the model genes. Finally, we conducted immunohistochemistry (IHC) validation on the model genes.
Results
This study identifies GSTM5 as a potential immune-related key target in DFU using machine learning and bioinformatics methods. Subsequent validation through external datasets and IHC experiments also confirms GSTM5 as a critical biomarker for DFU. The gene may be associated with T cells regulatory (Tregs) and T cells follicular helper, and it influences the NF-κB, GnRH, and MAPK signaling pathway.
Conclusion
This study identified and validated GSTM5 as a biomarker for DFU. This finding may potentially provide a target for immune therapy for DFU.