scholarly journals KCNH1 potassium channels are expressed in cervical cytologies from pregnant patients and are regulated by progesterone

Reproduction ◽  
2013 ◽  
Vol 146 (6) ◽  
pp. 615-623 ◽  
Author(s):  
A Ramírez ◽  
L M Hinojosa ◽  
J d J Gonzales ◽  
D Montante-Montes ◽  
B Martínez-Benítez ◽  
...  

Potassium voltage-gated channel, subfamily H (eag-related), member 1 (KCNH1) potassium channels are potential tumour markers and cancer therapeutic targets and are up-regulated by oestrogens and human papilloma virus (HPV) oncogenes. However, the role of KCNH1 in normal tissues is poorly understood, and its expression in pregnancy is unknown. We wondered whether KCNH1 channels are expressed in cervical cells from pregnant patients and whether progesterone (P4) regulates KCNH1. The association with HPV was also investigated. KCNH1 protein expression was studied by immunocytochemistry in liquid-based cervical cytologies; 93 samples were obtained from pregnant patients at different trimesters, and 15 samples were obtained from non-pregnant women (controls). The presence ofHPVwas studied by PCR with direct sequencing and nested multiplex PCR. HeLa cervical cancer cells were transfected with human progesterone receptor-B (PR-B) and treated with P4.KCNH1mRNA expression in these cultures was studied by real-time PCR. KCNH1 protein was detected in 100% of the pregnancy samples and in 26% of the controls. We found 18 pregnant patients infected with HPV and detected 14 types ofHPV. There was no association between the percentage of cells expressing KCNH1 and either the presence or type of HPV. P4induced KCNH1 mRNA and protein expression in cells transfected with human PR-B. No regulation of KCNH1 by P4was observed in non-transfected cells. We show for the first time the expression of an ion channel during human pregnancy at different trimesters and KCNH1 regulation by P4in human cells. These data raise a new research field for KCNH1 channels in human tissues.

2018 ◽  
Vol 2 (XXIII) ◽  
pp. 121-133
Author(s):  
Katarzyna Wojan

This article outlines the original research concept developed and applied by the Voronezh researchers, which brought both quantitative and qualitative results to the field of linguistic comparative research. Their monograph is devoted to the macrotypological unity of the lexical semantics of the languages in Europe. In addition, semantic stratification of Russian and Polish lexis has been analyzed. Their research concept is now known as the “lexical-semantic macrotypological school of Voronezh.” Representatives of this school have created a new research field in theoretical linguistics – a lexical-semantic language macrotypology as a branch of linguistic typology. The monograph has been widely discussed and reviewed in Russia.


Author(s):  
Almaz F. Abdulvaliev

This article presents the conceptual foundations for the formation of a new research field “Judicial Geography”, including the prerequisites for its creation, academic, and theoretical development, both in Russia and abroad. The purpose of the study is to study the possibility of applying geographical methods and means in criminal law, criminal procedure, and in judicial activity in general via the academic direction “Judicial Geography”. The author describes in detail the main elements of judicial geography and its role and significance for such legal sciences, as criminal law, criminal procedure, criminalistics, and criminology among others. The employed research methods allow showing the main vectors of the development of judicial geography, taking into account the previous achievements of Russian and worldwide academics. The author indicates the role and place of judicial geography in the system of legal sciences. This study suggests a concept of using scientific geographical methods in the study of various legal phenomena of a criminal and criminal-procedural nature when considering the idea of building judicial bodies and judicial instances, taking into account geographical and climatic factors. In this regard, the author advises to introduce the special course “Judicial Geography”, which would allow law students to study the specifics of the activities of the judiciary and preliminary investigation authorities from a geographical point of view, as well as to use various geographical methods, including the mapping method, in educational and practical activities. The author concludes that forensic geography may become a new milestone for subsequent scientific research in geography and jurisprudence.


2021 ◽  
Vol 20 ◽  
pp. 153303382199208
Author(s):  
Shufang Wang ◽  
Xinlong Huo

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinhong Qi ◽  
Li Zhou ◽  
Dongqing Li ◽  
Jingyuan Yang ◽  
He Wang ◽  
...  

Abstract Background Cell division cycle 25A (CDC25A) is a well-recognized regulator of cell cycle progression and is involved in cancer development. This work focused on the function of CDC25A in cervical cancer cell growth and the molecules involved. Methods A GEO dataset GSE63514 comprising data of cervical squamous cell carcinoma (CSCC) tissues was used to screen the aberrantly expressed genes in cervical cancer. The CDC25A expression in cancer and normal tissues was predicted in the GEPIA database and that in CSCC and normal cells was determined by RT-qPCR and western blot assays. Downregulation of CDC25A was introduced in CSCC cells to explore its function in cell growth and the cell cycle progression. The potential regulators of CDC25A activity and the possible involved signaling were explored. Results CDC25A was predicted to be overexpressed in CSCC, and high expression of CDC25A was observed in CSCC cells. Downregulation of CDC25A in ME180 and C33A cells reduced cell proliferation and blocked cell cycle progression, and it increased cell apoptosis. ALX3 was a positive regulator of CDC25A through transcription promotion. It recruited a histone demethylase, lysine demethylase 2B (KDM2B), to the CDC25A promoter, which enhanced CDC25A expression through demethylation of H3k4me3. Overexpression of ALX3 in cells blocked the inhibitory effects of CDC25A silencing. CDC25A was found as a positive regulator of the PI3K/Akt signaling pathway. Conclusion This study suggested that the ALX3 increased CDC25A expression through KDM2B-mediated demethylation of H3K4me3, which induced proliferation and cell cycle progression of cervical cancer cells.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1138
Author(s):  
Zhe Zhang ◽  
Jiayan Shi ◽  
Edouard C. Nice ◽  
Canhua Huang ◽  
Zheng Shi

Flavonoids are considered as pleiotropic, safe, and readily obtainable molecules. A large number of recent studies have proposed that flavonoids have potential in the treatment of tumors by the modulation of autophagy. In many cases, flavonoids suppress cancer by stimulating excessive autophagy or impairing autophagy flux especially in apoptosis-resistant cancer cells. However, the anti-cancer activity of flavonoids may be attenuated due to the simultaneous induction of protective autophagy. Notably, flavonoids-triggered protective autophagy is becoming a trend for preventing cancer in the clinical setting or for protecting patients from conventional therapeutic side effects in normal tissues. In this review, focusing on the underlying autophagic mechanisms of flavonoids, we hope to provide a new perspective for clinical application of flavonoids in cancer therapy. In addition, we highlight new research ideas for the development of new dosage forms of flavonoids to improve their various pharmacological effects, establishing flavonoids as ideal candidates for cancer prevention and therapy in the clinic.


2021 ◽  
pp. 106689692110120
Author(s):  
Cecilia Lezcano ◽  
Annette M. Müller ◽  
Denise Frosina ◽  
Enmily Hernandez ◽  
Jerica A. Geronimo ◽  
...  

Cancer-testis (CT) antigens were identified by their ability to elicit T- or B-cell immune responses in the autologous host. They are typically expressed in a wide variety of neoplasms and in normal adult tissues are restricted to testicular germ cells. PReferentially expressed Antigen of Melanoma (PRAME) is a member of the family of nonclassical CT antigens being expressed in a few other normal tissues besides testis. Interestingly, knowledge about the protein expression of many CT antigens is still incomplete due to the limited availability of reagents for their immunohistochemical detection. Here, we tested several commercially available serological reagents and identified a monoclonal antibody suitable for the immunohistochemical detection of PRAME in formalin-fixed paraffin-embedded specimens. We also tested a wide array of normal and neoplastic tissues. PRAME protein expression in normal tissues is congruent with original molecular data being present in the testis, and at low levels in the endometrium, adrenal cortex, and adult as well as fetal ovary. In tumors, there is diffuse PRAME immunoreactivity in most metastatic melanomas, myxoid liposarcomas, and synovial sarcomas. Other neoplasms such as seminomas and carcinomas of various origins including endometrial, serous ovarian, mammary ductal, lung, and renal showed an intermediate proportion of cases and variable extent of tumor cells positive for PRAME protein expression. As seen with other CT antigens, hepatocellular and colorectal carcinoma, Leydig cell tumors, mesothelioma, and leiomyosarcoma are poor expressers of PRAME.


2021 ◽  
Vol 11 (10) ◽  
pp. 2081-2086
Author(s):  
Bin Qiu ◽  
Hui Zhong ◽  
Shenqiu Ming ◽  
Chunxia Zhu

Abnormal LncRNA HOTAIR level is correlated with various cancers and miR-761 can inhibit cancers. LncRNA HOTAIR targets miR-761 by StarBase 2.0 analysis. Our study investigated whether LncRNA HOTAIR can affect cervical cancer cells by regulating miR-761. The control group (NC group), LncRNA HOTAIR group and LncRNA HOTAIR + miR-761 Mimics group were set up to measure LncRNA HOTAIR and miR-761 level by qRT-PCR. Dual fluorescein reporter assay assessed whether miR-761 binds LncRNA HOTAIR. Western blot was used to measure Cyclin D1, Bcl-2 and Tubulin expression and clone formation assay was to assess cell proliferation and Annexin VFITC/PI staining was to detect cell apoptosis. Compared with normal tissues, LncRNA HOTAIR level was significantly higher in cervical cancer tissues, while miR-761 was lower (P < 0.01). LncRNA HOTAIR targets miR-761. Compared with NC group, CyclinD1 and Bcl-2 in LncRNA HOTAIR group were significantly increased (P < 0.01), which were significantly lower in LncRNA HOTAIR + miR-761 Mimics group (P < 0.05). Compared to NC group, miR-761 in LncRNA HOTAIR group was significantly reduced (P < 0.01) and elevated by miR-761 Mimics. In addition, compared to NC group, the number of cell clones in LncRNA HOTAIR group was increased, cell proliferation was increased, and number of apoptotic cells was decreased, which were all reversed in the LncRNA HOTAIR + miR-761 Mimics group. LncRNA HOTAIR targets miR-761, promotes cell proliferation and reduces cell apoptosis. miR-761 mimics can partially prevent the effects of LncRNA HOTAIR.


2016 ◽  
Vol 838-839 ◽  
pp. 34-40
Author(s):  
Hidehiro Yoshida ◽  
Koji Morita ◽  
Byung Nam Kim ◽  
Koji Matsui ◽  
Yuichi Ikuhara ◽  
...  

Superplasticity in fine-grained oxide ceramics has been generally elucidated on the basis of their experimental strain rate-flow stress relationship and phenomenological analysis of cavity nucleation and growth. It has been widely accepted that the high temperature superplastic flow and failure in ceramics is significantly influenced by the atomic structure and chemistry of grain boundaries. Such phenomenon cannot be explained based on the classical phenomenological analysis. Our research group has therefore proposed to establish a new research field, grain boundary plasticity, to describe the superplastic deformation related to the grain boundary atomic structure. This paper aims to point out the importance of the atomistic analysis of grain boundary to develop new superplastic ceramics.


2018 ◽  
Vol 36 (4) ◽  
pp. 337-352
Author(s):  
Nicole Baron ◽  
Zegeye Cherenet

Purpose Resilience has recently attracted widespread interest in the field of urban planning and theory. However, the research that has been conducted on urban resilience in Africa has major theoretical and methodological gaps. This can lead to problems when designing and implementing resilience strategies there. Understanding African perspectives can be a way of tackling these. The paper aims to discuss these issues. Design/methodology/approach Using the example of Addis Ababa, Ethiopia, this paper analyses expert interviews based on a grounded theory approach. The goal is to explore locally specific perceptions of and pathways to urban resilience. By comparing these findings to those reported in the existing literature, differences and overlaps are identified. Findings This study provides evidence for the existence of locally specific perceptions of and pathways to urban resilience. Furthermore, it identifies urban development pathways such as complete urban makeover (tabula rasa) and complete negation of change (resistance). Research limitations/implications Because this study uses Addis Ababa as a singular case and expert interviews as method, it rather represents an initial attempt at exploring a new research field than claiming generalisability. Its quality and significance lie in its discursive approach and theory formation. Practical implications This exemplary study from Ethiopia demonstrates that a regionally specific understanding of urban resilience is valuable for the design and implementation of urban resilience strategies. Originality/value This study offers unique insights into urban resilience from an African perspective and into the manifestation of urban resilience in Addis Ababa.


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