Scientific Publications
Scientific publications and exciting articles where PreciPoint products and solutions were successfully used.
Yingying Yang Lu Ding, Zeyu Wang
M8 Microscope and Scanner Used to Study the Pharmacological Impact of QM against PF in COVID -19 Patients
The coronavirus, also known as COVID-19, ravaged the world with its deadly spread in 2019. Pulmonary fibrosis (PF) occurred in severe COVID-19 patients, and signs of PF were found in the anatomical examination of the dead COVID -19 patients. On the treatment front, medical experts used Qimai Feiluoping Decoction (QM), a traditional Chinese medicine (TCM) formula, to improve the syndromes of phlegm-stasis in channels in convalescent COVID-19 patients and recommended it in a rehabilitation program for functional disorders of discharged patients. Researchers studied the pharmacological action of QM against PF from the perspective of imaging, pathological staining, and molecular mechanisms and identified possible active components.
Result: The immunohistochemistry (IHC) staining was performed to analyze the expression of PF-related biomarkers in lung tissues. After staining, the images of each section were acquired through our M8 Microscope and Scanner.
@article{nokey,
title = {Qimai Feiluoping decoction inhibits mitochondrial complex I-mediated oxidative stress to ameliorate bleomycin-induced pulmonary fibrosis},
author = {Lu Ding, Yingying Yang, Zeyu Wang, Hang Su, Yaxin Li, Jing Ma, Tingting Bao, Hongyu Qi, Siyu Song, Jing Li, Jiachao Zhao, Ziyuan Wang, Daqing Zhao, Xiangyan Li, Linhua Zhao, Xiaolin Tong},
url = {https://www.sciencedirect.com/science/article/pii/S094471132300065X},
doi = {S094471132300065X},
year = {2023},
date = {2023-02-11},
urldate = {2023-02-11},
journal = {Elsevier},
volume = {112},
abstract = {Abstract:
“Qimai Feiluoping decoction (QM), a Traditional Chinese Medicine formula, has been included in rehabilitation program for functional disorders of discharged COVID-19 patients. QM has been proved to effectively improve the clinical symptoms and imaging signs of PF in COVID-19 convalescent patients.” },
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
“Qimai Feiluoping decoction (QM), a Traditional Chinese Medicine formula, has been included in rehabilitation program for functional disorders of discharged COVID-19 patients. QM has been proved to effectively improve the clinical symptoms and imaging signs of PF in COVID-19 convalescent patients.”
Capellmann, Sandro; Sonntag, Roland; Schüler, Herdit; Meurer, Steffen K; Gan, Lin; Kauffmann, Marlies; Horn, Katharina; Königs-Werner, Hiltrud; Weiskirchen, Ralf; Liedtke, Christian; Huber, Michael
Fritz Slide Scanner Helps Researchers Understand the Cause of the Transformation of Murine PMCs in Connective Tissue
Researchers used our Fritz slide scanner in a study aimed at understanding the cause of the transformation of murine peritoneum-derived mast cells (PMCs) in connective tissue. Mast cells play a crucial role in both cancer progression and the immune response to infections by viruses and bacteria. They support angiogenesis, degradation of the extracellular matrix, and the transition from epithelial to mesenchymal cells. PMCs, which are mast cells isolated from the peritoneum, were the focus of the study. The goal was to determine why these PMCs were undergoing transformation.
Result: Researchers used our Fritz Slide Scanner equipped with a 40x objective and our MicroPoint software for the microscopic review and interpretation of the MGG-stained MCs. To view or transfer data, researchers used our ViewPoint and ConvertPoint software.
@article{nokey,
title = {Transformation of primary murine peritoneal mast cells by constitutive KIT activation as a result of lost Cdkn2a/Arf expression},
author = {Sandro Capellmann and Roland Sonntag and Herdit Schüler and Steffen K Meurer and Lin Gan and Marlies Kauffmann and Katharina Horn and Hiltrud Königs-Werner and Ralf Weiskirchen and Christian Liedtke and Michael Huber},
url = {https://www.biorxiv.org/content/10.1101/2023.01.24.525344v1.full},
doi = {10.1101/2023.01.24.525344},
year = {2023},
date = {2023-01-24},
journal = {bioRxiv},
abstract = {Mast cells (MCs) are immune cells of the myeloid lineage distributed in tissues throughout the body. Phenotypically, they are a heterogeneous group characterized by different protease repertoires stored in secretory granules and differential presence of receptors. To adequately address aspects of MC biology either primary MCs isolated from human or mouse tissue or different human MC lines, like HMC-1.1 and -1.2, or rodent MC lines like L138.8A or RBL-2H3 are frequently used. Nevertheless, cellular systems to study MC functions are very limited. We have generated a murine connective tissue-like MC line, termed PMC-306, derived from primary peritoneal MCs (PMCs), which spontaneously transformed. We analyzed PMC-306 cells regarding MC surface receptor expression, effector functions and respective signaling pathways, and found that the cells reacted very similar to primary wildtype (WT) PMCs. In this regard, stimulation with MAS-related G-protein-coupled receptor member B2 (MRGPRB2) ligands induced respective signaling and effector functions. Furthermore, PMC-306 cells revealed significantly accelerated cell cycle progression, which however was still dependent on IL-3 and stem cell factor (SCF). Phenotypically, PMC-306 cells adopted an immature connective tissue-like MCs appearance. The reason for immortalization most likely is the loss of the two critical cell cycle regulators Cdkn2a/INK4A and Arf/p19, respectively. The loss of Cdkn2a and Arf expression could be mimicked in primary bone marrow-derived mast cells (BMMCs) by SCF supplementation strongly arguing for an involvement of KIT activation in the transformation process. Hence, this new cell line might be a useful tool to study further aspects of PMC function and to address tumorigenic processes associated with MC leukemia.},
keywords = {Fritz, ViewPoint},
pubstate = {published},
tppubtype = {article}
}
Dabel, Jennifer; Schneider, Florian; Wistuba, Joachim; Kliesch, Sabine; Schlatt, Stefan; Neuhaus, Nina
Our Microscope and ViewPoint in Use for Research in Fertility Feasibility in Transwomen
The study aimed to evaluate the feasibility of fertility preservation in pre-pubertal individuals undergoing gender-affirming hormone therapy. The established method of cryopreservation of immature testicular tissue, containing a population of diploid spermatogonia, is utilized as a means of preserving the spermatogenic potential of these individuals. A retrospective analysis of testicular tissue from 25 selected subjects was performed, who received a comparable hormonal regimen utilizing cyproterone acetate and estrogens.
Result: For the analysis of tissue and measurement of germ cells, the researchers used our digital microscope equipped with a 60x objective. Researchers analyzed two independent MAGE A4-stained tissue sections. The samples were then viewed using ViewPoint software, which was used to identify and count all MAGE A4-positive and -negative spermatogonia within each sample.
@article{nokey,
title = {New perspectives on fertility in transwomen with regard to spermatogonial stem cells},
author = {Jennifer Dabel and Florian Schneider and Joachim Wistuba and Sabine Kliesch and Stefan Schlatt and Nina Neuhaus},
url = {https://raf.bioscientifica.com/view/journals/raf/4/1/RAF-22-0022.xml},
doi = {10.1530/RAF-22-0022},
year = {2023},
date = {2023-01-18},
journal = {Reproduction and Fertility},
volume = {4},
issue = {1},
abstract = {Objective
Germ cells of transwomen are affected by gender-affirming hormone therapy (GAHT). Fertility will be lost after surgical intervention; thereby, fertility preservation becomes an increasingly imortant topic. This study investigated if the absolute number of spermatogonia in transwomen is comparable at the time of gender-affirming surgery (GAS) to that in pre-pubertal boys.
Methods
We carried out a retrospective study of testicular tissues from 25 selected subjects, which had undergone a comparable sex hormone therapy regimen using cyproterone acetate (10 or 12.5 mg) and estrogens. As controls, testicular biopsies of five cisgender adult men (aged 35–48 years) and five pre-/pubertal boys (5–14 years) were included. Testicular tissues were immunohistochemically stained for MAGE A4-positive cells, the most advanced germ cell type. The number of spermatogonia per area was assessed. Clinical values and serum hormone values for FSH, LH, testosterone, free testosterone, estradiol and prolactin were determined on the day of GAS for correlation analyses.
Results
Round spermatids were the most advanced germ cell type in 3 subjects, 5 had an arrest at spermatocyte stage, while 17 showed a spermatogonial arrest. On average, testicular tissues of transwomen contained 25.15 spermatogonia/mm3, a number that was significantly reduced compared to the two control groups (P < 0.01, adult 80.65 spermatogonia/mm3 and pre-/pubertal boys 78.55 spermatogonia/mm3). Linear regression analysis revealed that testes with higher weight and high LH contained more spermatogonia.
Conclusion
Irrespective of treatment dose or duration, spermatogenesis was impaired. Spermatogonial numbers were significantly reduced in transwomen compared to the control groups.
Lay summary
When transwomen go through treatment to confirm their gender, their germ cells are affected. They lose their fertility after surgery, so fertility preservation becomes an important topic. We carried out a study looking at tissue from testes of 25 people who had been through the same sex hormone therapy until surgery. Blood samples were also taken. As controls, samples were taken from the testes of cisgender boys and adult men. On average, the samples from the testes of transwomen contained a smaller number of early sperm cells compared to the two control groups. Regardless of the dose or length of hormone treatment, the fertility of transwomen was significantly reduced so that counseling about fertility preservation should be offered before hormone therapy.},
keywords = {Fritz, ViewPoint},
pubstate = {published},
tppubtype = {article}
}
Germ cells of transwomen are affected by gender-affirming hormone therapy (GAHT). Fertility will be lost after surgical intervention; thereby, fertility preservation becomes an increasingly imortant topic. This study investigated if the absolute number of spermatogonia in transwomen is comparable at the time of gender-affirming surgery (GAS) to that in pre-pubertal boys.
Methods
We carried out a retrospective study of testicular tissues from 25 selected subjects, which had undergone a comparable sex hormone therapy regimen using cyproterone acetate (10 or 12.5 mg) and estrogens. As controls, testicular biopsies of five cisgender adult men (aged 35–48 years) and five pre-/pubertal boys (5–14 years) were included. Testicular tissues were immunohistochemically stained for MAGE A4-positive cells, the most advanced germ cell type. The number of spermatogonia per area was assessed. Clinical values and serum hormone values for FSH, LH, testosterone, free testosterone, estradiol and prolactin were determined on the day of GAS for correlation analyses.
Results
Round spermatids were the most advanced germ cell type in 3 subjects, 5 had an arrest at spermatocyte stage, while 17 showed a spermatogonial arrest. On average, testicular tissues of transwomen contained 25.15 spermatogonia/mm3, a number that was significantly reduced compared to the two control groups (P < 0.01, adult 80.65 spermatogonia/mm3 and pre-/pubertal boys 78.55 spermatogonia/mm3). Linear regression analysis revealed that testes with higher weight and high LH contained more spermatogonia.
Conclusion
Irrespective of treatment dose or duration, spermatogenesis was impaired. Spermatogonial numbers were significantly reduced in transwomen compared to the control groups.
Lay summary
When transwomen go through treatment to confirm their gender, their germ cells are affected. They lose their fertility after surgery, so fertility preservation becomes an important topic. We carried out a study looking at tissue from testes of 25 people who had been through the same sex hormone therapy until surgery. Blood samples were also taken. As controls, samples were taken from the testes of cisgender boys and adult men. On average, the samples from the testes of transwomen contained a smaller number of early sperm cells compared to the two control groups. Regardless of the dose or length of hormone treatment, the fertility of transwomen was significantly reduced so that counseling about fertility preservation should be offered before hormone therapy.
Salmah Aalmri Kholoud Alwosaibai, Miral Mashhour
M8 Microscope and Scanner and ViewPoint Software Unlocks PD-L1 Expression Activities in Ovarian Cancer Dynamics
Researchers investigated the potential of immune checkpoint inhibitors, specifically PD-L1 inhibitors, in treating ovarian cancer with the help of M8 microscope and scanner and ViewPoint software. Surprisingly, they found high PD-L1 expressions in 47.8% of ovarian cancer samples, spanning various epithelial ovarian cancer types. Contrary to expectations, high PD-L1 expression wasn\'t linked to poor prognosis. Additionally, 81% of ovarian cancer samples exhibited TILs expressing both CD8 and CD4, significantly correlating with elevated PD-L1 levels. Furthermore, high PD-L1 expression was associated with stem cell markers CD44 and LGR5, hinting at a connection between immune response, stem cells, and ovarian cancer. PD-L1 overexpression, especially in serous ovarian carcinomas, didn\'t impact overall survival rates. This finding underscores the intricate interplay between PD-L1, TILs, and cancer stem cells, suggesting that inhibiting PD-L1 with immune checkpoint inhibitors might curtail the stem cell population linked to cancer recurrence.
Result: Anti-CD8 (clone 4B11) mouse monoclonal antibody and Anti-CD4 (clone 4B12) mouse monoclonal antibody were used with a dilution ratio of 1:100 for tumor-infiltrating lymphocytes. The subsequent immunoreactivity was observed using M8 digital microscope and scanner. The specimen was further imaged and analyzed using ViewPoint Virtual Slide Viewing Software.
@article{nokeyo,
title = {PD-L1 is highly expressed in ovarian cancer and associated with cancer stem cells populations expressing CD44 and other stem cell markers},
author = {Kholoud Alwosaibai, Salmah Aalmri, Miral Mashhour, Salim Ghandorah, Abdulraheem Alshangiti, Faisal Azam, Waleed Selwi, Lubna Gharaibeh, Yasser Alatawi, Zainab Alruwaii & Hashem O. Alsaab },
url = {https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10404-x},
doi = {10.1186/s12885-022-10404-x},
issn = {1471-2407},
year = {2023},
date = {2023-01-05},
journal = {BMC Cancer},
number = {13},
pages = {16},
abstract = {Background
Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer.
Methods
A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients’ medical record to investigate the association with PD-L1, TILs, and stem cells expressions.
Results
We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5.
Conclusions
PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer.
Methods
A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients’ medical record to investigate the association with PD-L1, TILs, and stem cells expressions.
Results
We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5.
Conclusions
PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.
Patrizia Moser Aleksandrs Krigers, Helga Fritsch; Freyschlag, Christian F.
M8 Microscope and Scanner Helps Understand the Role of Connexin-43 and Ki67 in Mon-glial Central Nervous System Tumors
Intercellular communication mediated by gap junctions plays an important role in the exchange of small molecules and ions, which not only serve to maintain homeostasis but also affect cell proliferation and differentiation. The protein connexin-43 (Cx43) is involved in the formation of these gap junctional channels and hemichannels. To better understand this, researchers examined the expression of Cx43 and Ki67 in formalin-fixed, paraffin-embedded samples of human brain metastases, meningiomas and neurinomas using immunohistochemistry. To comprehensively understand the functions of connexin-43 and Ki67 within non-glial central nervous system tumors, researchers used PreciPoint’s M8 digital microscope and scanner.
Result: Researchers used our M8 Microscope and Scanner in multiple instances. M8 Microscope and Scanner 200x magnification helped researchers to understand why metastases from NSCLC did not express Cx43 as opposed to the affected cortex. Additionally, samples under M8 showed that the cellular nuclei remain unstained.
@article{nokey,
title = {The relationship between connexin-43 expression and Ki67 in non-glial central nervous system tumors},
author = {Aleksandrs Krigers, Patrizia Moser, Helga Fritsch, Matthias Demetz, Johannes Kerschbaumer, Konstantin R. Brawanski, Claudius Thomé and Christian F. Freyschlag},
url = {https://journals.sagepub.com/doi/full/10.1177/03936155221143138},
doi = {10.1177/03936155221143138},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Sage Journals},
volume = {38},
issue = {1},
abstract = {“Background
Advanced intercellular communication is a known oncogenic factor. In the central nervous system, Connexin-43 (Cx43) forms this junctional networking. Moreover, it correlates with the proliferation rate, and thus behavior, of gliomas. We assessed the expression of Cx43 and its relationship to Ki67 in other common central nervous system tumors.
…
Results
A total of 14 metastases of different extracerebral carcinomas, 6 meningiomas, and 10 neurinomas were evaluated. Five (36%) metastases and 5 (31%) meningiomas/neurinomas showed minor expression, whereas 6 (43%) metastases and 2 (13%) meningiomas/neurinomas showed no Cx43 expression at all. In 3 (21%) metastases and 9 (56%) meningiomas/neurinomas, moderate or strong expression of Cx43 was identified. The higher expression of Cx43 in meningiomas and neurinomas directly correlated with Ki67, r = 0.53 (P = 0.034). For metastases no significant correlation was found. Mitotic index in meningiomas/neurinomas correlated with Ki67 expression, r = 0.74 (P < 0.001), but did not show statistically significant correlation with Cx43 expression in these tumors.
Conclusions
The expression of Cx43 as a marker of cell-to-cell networking exposed a significant correlation with the Ki67-defined proliferation index in case of primary central nervous system neuroectodermal neoplasms. However, it does not seem to play a comparable role in metastases with extracerebral origin.”
},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Advanced intercellular communication is a known oncogenic factor. In the central nervous system, Connexin-43 (Cx43) forms this junctional networking. Moreover, it correlates with the proliferation rate, and thus behavior, of gliomas. We assessed the expression of Cx43 and its relationship to Ki67 in other common central nervous system tumors.
…
Results
A total of 14 metastases of different extracerebral carcinomas, 6 meningiomas, and 10 neurinomas were evaluated. Five (36%) metastases and 5 (31%) meningiomas/neurinomas showed minor expression, whereas 6 (43%) metastases and 2 (13%) meningiomas/neurinomas showed no Cx43 expression at all. In 3 (21%) metastases and 9 (56%) meningiomas/neurinomas, moderate or strong expression of Cx43 was identified. The higher expression of Cx43 in meningiomas and neurinomas directly correlated with Ki67, r = 0.53 (P = 0.034). For metastases no significant correlation was found. Mitotic index in meningiomas/neurinomas correlated with Ki67 expression, r = 0.74 (P < 0.001), but did not show statistically significant correlation with Cx43 expression in these tumors.
Conclusions
The expression of Cx43 as a marker of cell-to-cell networking exposed a significant correlation with the Ki67-defined proliferation index in case of primary central nervous system neuroectodermal neoplasms. However, it does not seem to play a comparable role in metastases with extracerebral origin.”
Kono, Yosuke; Yokota, Shigefumi; Fukushi, Isato; Arima, Yosuke; Onimaru, Hiroshi; Okazaki, Shuntaro; Takeda, Kotaro; Yazawa, Itaru; Yoshizawa, Masashi; Hasebe, Yohei; Koizumi, Keiichi; Pokorski, Mieczyslaw; Toda, Takako; Sugita, Kanji; Okada, Yasumasa
Digital microscope and M8 slidescanner in use in brain research
As the control element and processing unit for information, the brain is one of the most important organs in humans. Because it is so complex, many processes in the brain are still unexplored. In their scientific report “Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow”, published in the scientific journal Nature, Yosuke Kono et al. investigate the structural and functional connection of the dorsomedial hypothalamus, an area in the forebrain, and the ventral medulla, which is located in the rhomboid brain. Here, the structures of rat brains were studied as a model organism. Measurements were made by tractography, a method to visualize particle fluxes in the cells by color, and by voltage-dependent dyes, which can visualize the membrane potential in the neurons by color. Our M8 microscope was used to scan the tissue sections on which the tractography was subsequently performed.
Result: Our M8 microscope was used to scan the tissue sections on which tractography was subsequently performed.
@article{nokey,
title = {Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow},
author = {Yosuke Kono and Shigefumi Yokota and Isato Fukushi and Yosuke Arima and Hiroshi Onimaru and Shuntaro Okazaki and Kotaro Takeda and Itaru Yazawa and Masashi Yoshizawa and Yohei Hasebe and Keiichi Koizumi and Mieczyslaw Pokorski and Takako Toda and Kanji Sugita and Yasumasa Okada },
url = {https://www.nature.com/articles/s41598-020-70234-4},
doi = {10.1038/s41598-020-70234-4},
year = {2022},
date = {2022-08-07},
journal = {Scientific Reports},
volume = {10},
issue = {13325},
abstract = {Psychological stress activates the hypothalamus, augments the sympathetic nervous output, and elevates blood pressure via excitation of the ventral medullary cardiovascular regions. However, anatomical and functional connectivity from the hypothalamus to the ventral medullary cardiovascular regions has not been fully elucidated. We investigated this issue by tract-tracing and functional imaging in rats. Retrograde tracing revealed the rostral ventrolateral medulla was innervated by neurons in the ipsilateral dorsomedial hypothalamus (DMH). Anterograde tracing showed DMH neurons projected to the ventral medullary cardiovascular regions with axon terminals in contiguity with tyrosine hydroxylase-immunoreactive neurons. By voltage-sensitive dye imaging, dynamics of ventral medullary activation evoked by electrical stimulation of the DMH were analyzed in the diencephalon-lower brainstem-spinal cord preparation of rats. Although the activation of the ventral medulla induced by single pulse stimulation of the DMH was brief, tetanic stimulation caused activation of the DMH sustained into the post-stimulus phase, resulting in delayed recovery. We suggest that prolonged excitation of the DMH, which is triggered by tetanic electrical stimulation and could also be triggered by psychological stress in a real life, induces further prolonged excitation of the medullary cardiovascular networks, and could contribute to the pathological elevation of blood pressure. The connectivity from the DMH to the medullary cardiovascular networks serves as a chronological amplifer of stress-induced sympathetic excitation. This notion will be the anatomical and pathophysiological basis to understand the mechanisms of stress-induced sustained augmentation of sympathetic activity.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Mowday, Alexandra M.; Dubois, Ludwig J.; Kubiak, Aleksandra M.; Chan-Hyams, Jasmine V. E.; Guise, Christopher P.; Ashoorzadeh, Amir; Lambin, Philippe; Ackerley, David F.; Smaill, Jeff B.; Minton, Nigel P.; Theys, Jan; Patterson, Adam V.
Advancing Cancer Treatment: The M8 Microscope in Investigating Tumor-Proximate Gene Therapeutics via Clostridia
Today, medicine offers a wide variety of approaches to the treatment of cancer. Some of them are already used as standard, others are still in research, but are quite promising. In their study, Mowday et al. describe one of these research approaches in which the bacterium Clostridium sporogenes is used to effect a cure. In “Use of an optimized enzyme/prodrug combination for Clostridia directed enzyme prodrug therapy induces a significant growth delay in necrotic tumors” the bacterium is cultivated in the direct environment of the tumor tissue and is supposed to produce a therapeutic gene there. This is possible because the tumor tissue forms a nutrient environment that is selective for Clostridium sporogenes and thus promotes growth.
Result: Our digital microscope was used for the scanning tumor tissue sections that were stained with hematoxylin eosin or Gram-twort.
@mastersthesis{nokey,
title = {Use of an optimised enzyme/prodrug combination for Clostridia directed enzyme prodrug therapy induces a significant growth delay in necrotic tumours},
author = {Alexandra M. Mowday and Ludwig J. Dubois and Aleksandra M. Kubiak and Jasmine V. E. Chan-Hyams and Christopher P. Guise and Amir Ashoorzadeh and Philippe Lambin and David F. Ackerley and Jeff B. Smaill and Nigel P. Minton and Jan Theys and Adam V. Patterson },
url = {https://www.nature.com/articles/s41417-021-00296-7},
doi = {10.1038/s41417-021-00296-7},
year = {2021},
date = {2021-02-08},
journal = {Cancer Gene Therapy},
volume = {29},
pages = {178-188},
abstract = {Necrosis is a typical histological feature of solid tumours that provides a selective environment for growth of the nonpathogenic anaerobic bacterium Clostridium sporogenes. Modest anti-tumour activity as a single agent encouraged the use of C. sporogenes as a vector to express therapeutic genes selectively in tumour tissue, a concept termed Clostridium Directed Enzyme Prodrug Therapy (CDEPT). Here, we examine the ability of a recently identified Neisseria meningitidis type I nitroreductase (NmeNTR) to metabolise the prodrug PR-104A in an in vivo model of CDEPT. Human HCT116 colon cancer cells stably over-expressing NmeNTR demonstrated significant sensitivity to PR-104A, the imaging agent EF5, and several nitro(hetero)cyclic anti-infective compounds. Chemical induction of necrosis in human H1299 xenografts by the vascular disrupting agent vadimezan promoted colonisation by NmeNTR-expressing C. sporogenes, and efficacy studies demonstrated moderate but significant anti-tumour activity of spores when compared to untreated controls. Inclusion of the pre-prodrug PR-104 into the treatment schedule provided significant additional activity, indicating proof-of-principle. Successful preclinical evaluation of a transferable gene that enables metabolism of both PET imaging agents (for vector visualisation) and prodrugs (for conditional enhancement of efficacy) is an important step towards the prospect of CDEPT entering clinical evaluation.},
keywords = {M8},
pubstate = {published},
tppubtype = {mastersthesis}
}
Klatt, Wybke; Wallner, Susanne; Brochhausen, Christoph; Stolwijk, Judith A.; Schreml, Stephan
Decoding Skin Tumors: Proton-Sensing G-Protein Coupled Receptors and the Vital Role of the M8 Microscope
The cases of skin cancer in Germany had been rising since the last few decades and regarding a report of the health insurance company TK, every third diagnosed tumor is a skin tumor. Because of that, continuous medical research is important to understand the mechanism of tumor proliferation. This interesting topic is also investigated in the scientific paper of Klatt W., Wallner S., Brochhausen C. et al. „Expression profiles of proton‑sensing G‑protein coupled receptors in common skin tumors “. In this research, our microscope M8 was used for whole slide scanning of immunohistochemically stained tissue.
Result: Our digital scanner was not only used for generating the scans as also for analyzing the pictures with our viewer-software Viewpoint. We are proud that our product could support this research.
@article{nokey,
title = {Expression profiles of proton‑sensing G‑protein coupled receptors in common skin tumors},
author = {Wybke Klatt and Susanne Wallner and Christoph Brochhausen and Judith A. Stolwijk and Stephan Schreml},
url = {https://www.nature.com/articles/s41598-020-71700-9},
doi = {10.1038/s41598-020-71700-9},
year = {2020},
date = {2020-09-18},
urldate = {2020-09-18},
journal = {Scientific Reports},
volume = {10},
issue = {15327},
abstract = {The proton-sensing GPCRs (pH-GPCRs) GPR4 (GPR19), TDAG8 (GPR65, T-cell death associated gene 8), OGR1 (GPR68, ovarian cancer GPCR1), and G2A (GPR132, G2 accumulation protein) are involved in sensing and transducing changes in extracellular pH (pHe). Extracellular acidification is a central hallmark of solid cancer. pH-GPCR function has been associated with cancer cell proliferation, adhesion, migration and metastasis, as well as with modulation of the immune system. Little is known about the expression levels and role of pH-GPCRs in skin cancer. To better understand the functions of pH-GPCRs in skin cancer in vivo, we examined the expression-profiles of GPR4, TDAG8, OGR1 and G2A in four common skin tumors, i.e. squamous cell carcinoma (SCC), malignant melanoma (MM), compound nevus cell nevi (NCN), basal cell carcinoma (BCC). We performed immunohistochemistry and immunofluorescence staining on paraffin-embedded tissue samples acquired from patients suffering from SCC, MM, NCN or BCC. We show the expression of pH-GPCRs in four common skin cancers. Different expression patterns in the investigated skin cancer types indicate that the different pH-GPCRs may have distinct functions in tumor progression and serve as novel therapeutic targets.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Seo, Jincheol; Park, Junghyung; Kim, Keonwoo; Won, Jinyoung; Yeo, Hyeon-Gu; Jin, Yeung Bae; Koo, Bon-Sang; Lim, Kyung Seob; Jeong, Kang-Jin; Kang, Philyong; Lee, Hwal-Yong; Choi, Won Seok; Baek, Seung Ho; Jeon, Chang-Yeop; Hong, Jung-Joo; Huh, Jae-Won; Kim, Young-Hyun; Park, Sang Je; Kim, Sun-Uk; Lee, Dong-Seok; Lee, Youngjeon
Researching Parkinson\'s disease using the M8 digital microscope and slide scanner
As the second most common neurodegenerative disease and 200000 deaths in 2018, Parkinson’s is one of the most insidious diseases of the 21st century. Research on the disease is ongoing throughout for better diagnoses and treatment options. Jincheol Seo et al, in their Research Article “Chronic Infiltration of T Lymphocytes into the Brain in a Non-human Primate Model of Parkinson’s Disease”of the Neuroscience of the IBR (International Brain Research Organization), describe the influence of T lymphocytes on the degeneration of neurons in the brain. As a model organism, the studies were conducted in Macaca fascicularis, Javanese monkeys.
Result: Tissue sections of the brain were immunohistochemically stained and scanned with our M8.
@mastersthesis{nokey,
title = {Chronic Infiltration of T Lymphocytes into the Brain in a Non-human Primate Model of Parkinson’s Disease},
author = {Jincheol Seo and Junghyung Park and Keonwoo Kim and Jinyoung Won and Hyeon-Gu Yeo and Yeung Bae Jin and Bon-Sang Koo and Kyung Seob Lim and Kang-Jin Jeong and Philyong Kang and Hwal-Yong Lee and Won Seok Choi and Seung Ho Baek and Chang-Yeop Jeon and Jung-Joo Hong and Jae-Won Huh and Young-Hyun Kim and Sang Je Park and Sun-Uk Kim and Dong-Seok Lee and Youngjeon Lee},
url = {https://www.sciencedirect.com/science/article/pii/S0306452220300737?via%3Dihub},
doi = {10.1016/j.neuroscience.2020.01.043},
year = {2020},
date = {2020-04-01},
journal = {Neuroscience},
volume = {431},
pages = {73-85},
abstract = {Study of interactions between the nervous system and immunity offers insights into the pathogenesis of Parkinson’s disease (PD) and potential therapeutic strategies for neurodegenerative diseases. Studies on rodents have revealed regulatory mechanisms of microglial activation and T lymphocyte recruitment in PD. However, the mechanisms underlying chronic T lymphocyte infiltration into the brain after 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) injection into a non-human primate (NHP) model of PD remain unknown. This study aimed to investigate changes in serum RANTES (regulated on activation, normal T cell expression and secretion) and analyze the chronic infiltration of T lymphocytes into the brain and microglia activation in NHPs at 48 weeks post-MPTP administration. We found selective and local chronic infiltration of CD4+ and CD8+ T lymphocytes, loss of dopaminergic neurons, dopamine transporter expression, chronic normalization of RANTES in the peripheral blood, and altered microglial morphology at 48 weeks after MPTP injection. This study confirms the involvement of CD4+ and CD8+ T lymphocyte infiltration in MPTP-induced NHP models of PD. Additionally, we corroborated previous findings regarding the mechanisms of T lymphocyte-induced neurodegeneration. The findings of chronic infiltration of T lymphocytes in our NHP model of PD provide novel insights into PD pathogenesis and the development of preventive and therapeutic agents.},
keywords = {M8},
pubstate = {published},
tppubtype = {mastersthesis}
}
Heckmann, L; Langenstroth-Röwer, D; Wistuba, J; Portela, J M D; van Pelt, A M M; Redmann, K; Stukenborg, J B; Schlatt, S; Neuhaus, N
Digital microscope and M8 slidescanner in use for reproductive medicine research
Reproductive medicine is an important scientific topic, as it can offer help in cases of unwanted childlessness. In the study of Heckmann et al. „The initial maturation status of marmoset testicular tissues has an impact on germ cell maintenance and somatic cell response in tissue fragment culture”, our microscope helped to generate scans of testicular tissue to make certain types of cell morphologies visible.
Result: Our digital microscope was used for scanning the cell structures that were colored immunohistochemical and have a direct impact on the fertility of an individual. We are proud that our microscope is part of this paper and hope that it will also find use in some following research.
@article{nokey,
title = {The initial maturation status of marmoset testicular tissues has an impact on germ cell maintenance and somatic cell response in tissue fragment culture},
author = {L Heckmann and D Langenstroth-Röwer and J Wistuba and J M D Portela and A M M van Pelt and K Redmann and J B Stukenborg and S Schlatt and N Neuhaus },
url = {https://academic.oup.com/molehr/article/26/6/374/5814289?login=false},
doi = {10.1093/molehr/gaaa024},
year = {2020},
date = {2020-04-01},
urldate = {2020-04-01},
journal = {Molecular Human Reproduction},
volume = {26},
issue = {6},
pages = {374-388},
abstract = {Successful in vitro spermatogenesis was reported using immature mouse testicular tissues in a fragment culture approach, raising hopes that this method could also be applied for fertility preservation in humans. Although maintaining immature human testicular tissue fragments in culture is feasible for an extended period, it remains unknown whether germ cell survival and the somatic cell response depend on the differentiation status of the tissue. Employing the marmoset monkey (Callithrix jacchus), we aimed to assess whether the maturation status of prepubertal and peri-/pubertal testicular tissues influence the outcome of testis fragment culture. Testicular tissue fragments from 4- and 8-month-old (n =3, each) marmosets were cultured and evaluated after 0, 7, 14, 28, and 42 days. Immunohistochemistry was performed for identification and quantification of germ cells (melanoma-associated antigen 4) and Sertoli cell maturation status (anti-Müllerian hormone: AMH). During testis fragment culture, spermatogonial numbers were significantly reduced (P <0.05) in the 4- but not 8-month-old monkeys, at Day 0 versus Day 42 of culture. Moreover, while Sertoli cells from 4-month-old monkeys maintained an immature phenotype (i.e. AMH expression) during culture, AMH expression was regained in two of the 8-month-old monkeys. Interestingly, the progression of differentiation to the later meiotic stage was solely observed in one 8-month-old marmoset, which was at an intermediate state regarding germ cell content, with gonocytes as well as spermatocytes present, as well as Sertoli cell maturation status. Although species-specific differences might influence the outcome of testis fragment experiments in vitro, our study demonstrated that the developmental status of the testicular tissues needs to be considered as it seems to be decisive for germ cell maintenance, somatic cell response and possibly the differentiation potential.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}