Paclitaxel Promotes Cell Apoptosis in Uterine Leiomyomas

Pharmacology ◽  
2017 ◽  
Vol 100 (5-6) ◽  
pp. 246-252 ◽  
Author(s):  
Haiping Liu ◽  
Jianye Wang ◽  
Lianbing Sheng ◽  
Yan Zhang ◽  
Ning Tang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Critical Role ◽  
Estradiol Benzoate ◽  
Uterine Leiomyomas ◽  
Health Concern ◽  
Major Health ◽  
Gynecological Tumors ◽  
Dose Limiting Toxicity ◽  
Insight Into ◽  
Apoptosis Level

Uterine leiomyomas are common clinical gynecological tumors, which are a major health concern for many women. In the current study, we aimed to investigate the effect of paclitaxel (PTX) on uterine leiomyomas. A mouse model of uterine leiomyomas was established by estradiol benzoate, followed by treatment with increasing doses of PTX. PTX showed no dose-limiting toxicity that affected the survival of mice, and was able to restore the apoptosis level of uterus tissues of the model mice to normal levels. In this study, we discovered that PTX played a critical role in promoting apoptosis in the mouse model of uterine leiomyomas, which provides a new insight into the therapy of uterine leiomyomas.

scholarly journals COVID-19: A natural phenomena or laboratory-based origin?

2020 ◽  
Author(s):  
Fanila Shahzad ◽  
Md Talat Nasim
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Medical Science ◽  
Health Concern ◽  
The Novel ◽  
Natural Phenomena ◽  
Viral Reservoirs ◽  
Major Health ◽  
Novel Virus ◽  
Novel Coronavirus ◽  
Insight Into

The novel coronavirus, otherwise known as COVID-19 has fast become a major health concern. The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV‐ 2) is the third coronavirus outbreak, following severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses. Since the initial cases of a pneumonia of unknown aetiology, which was later identified as COVID-19 in Wuhan, Hubei province, China, there has been much debate and speculation regarding the origins of this novel virus. This review aims to provide an insight into the origin of SARS-CoV-2 by reflecting on genomic data gathered thus far. Identifying the origins of SARS-CoV-2 can lead to better understanding of hidden viral reservoirs that may exist and pose a threat to society as well as allow greater understanding of the mechanisms by which these viruses have successfully achieved cross species transmission. Greater knowledge in regard to this can lead to the development of strategies which can aid in preventing future outbreaks of this scale. Bangladesh Journal of Medical Science Vol.19(0) 2020 p. p. S 85-S 87

scholarly journals Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vidya C. Sinha ◽  
Amanda L. Rinkenbaugh ◽  
Mingchu Xu ◽  
Xinhui Zhou ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Mouse Model ◽  
Transition State ◽  
Tumor Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Breast Lesions ◽  
Aggressive Tumor ◽  
Insight Into

AbstractThere is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.

scholarly journals Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune regulatory pathways

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Won Jin Ho ◽  
Rossin Erbe ◽  
Ludmila Danilova ◽  
Zaw Phyo ◽  
Emma Bigelow ◽  
...  
Keyword(s):  
Mouse Model ◽  
Primary Tumors ◽  
Regulatory Pathways ◽  
Tumor Microenvironments ◽  
Clinical Responses ◽  
Cellular Pathways ◽  
Autopsy Specimens ◽  
Rapid Autopsy ◽  
Insight Into ◽  
Systemic Therapies

Abstract Background The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed at the metastatic stage, and standard therapies have limited activity with a dismal 5-year survival rate of only 8%. The liver and lung are the most common sites of PDAC metastasis, and each have been differentially associated with prognoses and responses to systemic therapies. A deeper understanding of the molecular and cellular landscape within the tumor microenvironment (TME) metastasis at these different sites is critical to informing future therapeutic strategies against metastatic PDAC. Results By leveraging combined mass cytometry, immunohistochemistry, and RNA sequencing, we identify key regulatory pathways that distinguish the liver and lung TMEs in a preclinical mouse model of metastatic PDAC. We demonstrate that the lung TME generally exhibits higher levels of immune infiltration, immune activation, and pro-immune signaling pathways, whereas multiple immune-suppressive pathways are emphasized in the liver TME. We then perform further validation of these preclinical findings in paired human lung and liver metastatic samples using immunohistochemistry from PDAC rapid autopsy specimens. Finally, in silico validation with transfer learning between our mouse model and TCGA datasets further demonstrates that many of the site-associated features are detectable even in the context of different primary tumors. Conclusions Determining the distinctive immune-suppressive features in multiple liver and lung TME datasets provides further insight into the tissue specificity of molecular and cellular pathways, suggesting a potential mechanism underlying the discordant clinical responses that are often observed in metastatic diseases.

scholarly journals Environmental Detection and Potential Transmission of Equine Herpesviruses

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 423
Author(s):  
Anisha Dayaram ◽  
Peter A. Seeber ◽  
Alex D. Greenwood
Keyword(s):  
Environmental Samples ◽  
Environmental Stability ◽  
Health Concern ◽  
Viral Dynamics ◽  
Major Health ◽  
Environmental Detection ◽  
Environmental Transmission ◽  
Direct Exposure ◽  
Equine Herpesviruses ◽  
Important Disease

Equine herpesviruses (EHV) are a major health concern for domestic and wild equids and represent one of the most economically important disease agents of horses. Most known EHVs are transmitted directly between individuals as a result of direct exposure to exudates and aerosols. However, accumulating evidence suggests that environmental transmission may play a role including air, water, and fomites. Here, we reviewed studies on environmental stability and transmission of EHVs, which may influence viral dynamics and the use of environmental samples for monitoring EHV shedding.

Why Does He Do It? What Explanations Resonate During Counseling for Women in Understanding Their Partner’s Abuse?

2021 ◽  
pp. 088626052198985
Author(s):  
Sally Marsden ◽  
Cathy Humphreys ◽  
Kelsey Hegarty
Keyword(s):  
Partner Violence ◽  
Research Question ◽  
Critical Role ◽  
Mental Health Research ◽  
Individual Characteristics ◽  
Clinical Group ◽  
Structured Interviews ◽  
Women’S Perceptions ◽  
Ipv Perpetration ◽  
Insight Into

Intimate partner violence (IPV) is a complex and multifaceted problem gaining increasing attention within mental health research and practice. IPV explanations focus on both individual and systemic levels; however, it is increasingly acknowledged that a single level explanation may not be sufficient. The practices of clinical disciplines may, however, still privilege an explanation at one level over another, which will influence how they work with clients. It is likely that one such clinical group, psychologists, may play a critical role in helping victim-survivors to understand and explain their experiences of IPV. However, we were unable to find any studies focusing on women’s perceptions of psychologists’ role in this. Additionally, we know little about women victim-survivors’ perceptions of why their partners use IPV. To address these gaps, the research question for this study was: What explanations resonate during counseling for women in understanding their partner’s abuse? To explore this question, 20 women who had seen psychologists after experiencing IPV participated in semi-structured interviews. The interviews were analyzed using reflexive thematic analysis and three themes constructed from the data. The first two themes, narcissist description was helpful and not all bad all the time, showed that the women found it powerful in their healing processes when psychologists offered the opportunity to discuss their partners individual characteristics as explanations for their use of IPV. The third theme, structural explanations, showed that some of the women also reflected on wider structural contexts. Implications for clinical practice include the potential healing effect when practitioners can move along a continuum of explanation levels, covering both the inner and outer worlds. Implications for research into IPV perpetration are that women hold expertise and insight into individual perpetrators and could make valuable contributions to this field.

scholarly journals Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Hua Yang ◽  
Mengjie Zhang ◽  
Jiahao Shi ◽  
Yunhe Zhou ◽  
Zhipeng Wan ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Mouse Model ◽  
Glutamate Release ◽  
Critical Role ◽  
Conditional Knockout ◽  
Snare Complex ◽  
Extracellular Glutamate ◽  
Glutamate Level

Several studies have associated reduced expression of synaptosomal-associated protein of 25 kDa (SNAP-25) with schizophrenia, yet little is known about its role in the illness. In this paper, a forebrain glutamatergic neuron-specific SNAP-25 knockout mouse model was constructed and studied to explore the possible pathogenetic role of SNAP-25 in schizophrenia. We showed that SNAP-25 conditional knockout (cKO) mice exhibited typical schizophrenia-like phenotype. A significantly elevated extracellular glutamate level was detected in the cerebral cortex of the mouse model. Compared with Ctrls, SNAP-25 was dramatically reduced by about 60% both in cytoplasm and in membrane fractions of cerebral cortex of cKOs, while the other two core members of SNARE complex: Syntaxin-1 (increased ~80%) and Vamp2 (increased ~96%) were significantly increased in cell membrane part. Riluzole, a glutamate release inhibitor, significantly attenuated the locomotor hyperactivity deficits in cKO mice. Our findings provide in vivo functional evidence showing a critical role of SNAP-25 dysfunction on synaptic transmission, which contributes to the developmental of schizophrenia. It is suggested that a SNAP-25 cKO mouse, a valuable model for schizophrenia, could address questions regarding presynaptic alterations that contribute to the etiopathophysiology of SZ and help to consummate the pre- and postsynaptic glutamatergic pathogenesis of the illness.

scholarly journals Possible Crosstalk of the Immune Cells within the Lung and Mediastinal Fat-Associated Lymphoid Clusters in the Acute Inflammatory Lung Asthma-Like Mouse Model

2021 ◽  
Vol 22 (13) ◽  
pp. 6878
Author(s):  
Yaser Hosny Ali Elewa ◽  
Mahmoud Mansour Abd Elwakil ◽  
Osamu Ichii ◽  
Teppei Nakamura ◽  
Sherif Kh. A. Mohamed ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Cells ◽  
Phosphate Buffer ◽  
Respiratory Diseases ◽  
Critical Role ◽  
Goblet Cells ◽  
Vehicle Group ◽  
Natural Helper ◽  
B And T Lymphocytes ◽  
Intranasal Instillation

Recently, we clarified the function of mediastinal fat-associated lymphoid clusters (MFALCs) in the progression of several respiratory diseases. However, their role has not yet been identified in the lung asthmatic condition. Hence, we compared the immune cells in lung and MFALCs of C57BL/6N mice on days 3 and 7 following intranasal instillation of either papain (papain group “PG”) or phosphate buffer saline (PBS) (vehicle group “VG”). The PG showed significantly prominent MFALCs, numerous goblet cells (GCs), and higher index ratios of different immune cells (macrophages, natural helper cells (NHC), B- and T-lymphocytes) within the MFALCs and lung than in the VG on both days 3 and 7. Interestingly, a tendency of decreased size of MFALCs and a significant reduction in the number of GCs and immune cells were observed within the MFALCs and lung in the PG on day 7 than on day 3. Furthermore, the quantitative parameters of these immune cells in MFALCs were significantly and positively correlated with the size of MFALCs and immune cells in the lung. This suggested that the possible crosstalk between immune cells within MFALCs and the lung could play a critical role in the progression and recovery of the acute inflammatory lung asthma.

scholarly journals MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3026
Author(s):  
Hyuk Moon ◽  
Simon-Weonsang Ro
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Erk Signaling ◽  
Health Concern ◽  
Alternative Mechanism ◽  
Major Health ◽  
Activating Mutations ◽  
Genetic Events

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.

scholarly journals Experimentally Approaching the ICU: Monitoring Outcome-Based Responses in the Two-Hit Mouse Model of Posttraumatic Sepsis

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Susanne Drechsler ◽  
Katrin M. Weixelbaumer ◽  
Heinz Redl ◽  
Martijn van Griensven ◽  
Soheyl Bahrami ◽  
...  
Keyword(s):  
Mouse Model ◽  
Femur Fracture ◽  
Cecal Ligation ◽  
Blood Sampling ◽  
Cecal Ligation And Puncture ◽  
Organ Function ◽  
Daily Monitoring ◽  
Circulating Cells ◽  
Facial Vein ◽  
Insight Into

To simulate and monitor the evolution of posttraumatic sepsis in mice, we combined a two-hit model of trauma/hemorrhage (TH) followed by polymicrobial sepsis with repetitive blood sampling. Anesthetized mice underwent femur fracture/sublethal hemorrhage and cecal ligation and puncture (CLP) 48 h later. To monitor outcome-dependent changes in circulating cells/biomarkers, mice were sampled daily (facial vein) for 7 days and retrospectively divided into either dead (DIE) or surviving (SUR) by post-CLP day 7. Prior to CLP, AST was 3-fold higher in DIE, while all other post-TH changes were similar between groups. There was a significant post-CLP intergroup separation. In SUR, RBC and Hb were lower, platelets and neutrophils higher, and lymphocytes mixed compared to DIE. In DIE, all organ function markers except glucose (decrease) were few folds higher compared to SUR. In summary, the combination of daily monitoring with an adequate two-hit model simulates the ICU setting, allows insight into outcome-based responses, and can identify biomarkers indicative of death in the acute posttraumatic sepsis in mice.

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