**CANCER SURVIVORSHIP**

#### **Cancer Survivorship**

http://dx.doi.org/10.5772/intechopen.74342 Edited by Dil Afroze

#### **Contributors**

Trinanjan Basu, Nithin Bhaskar, Shazia Ali, Bilal Ahmad Rah, Dil Afroze, Mohd Ishaq Dar, Xiaoqiang Sun, Edda Sciutto, Jacquelynne Cervantes-Torres, Laura Montero-León, Gladis Fragoso, Diana Torres-García, Noé Rodriguez-Rodriguez, Bogdan Cizmarevic, Calin Molnar, Marian Botoncea, Vlad Olimpiu Butiurca, Claudiu Varlam Molnar, Tomas Cianciulli

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**6.4 Summary of reservoir models**

There are other reservoir models described in the literature, e.g. Ennis-King and Paterson (2005) conclude that anisotropy of the reservoir has a strong effect on dissolution trapping, but this is beyond the scope of this book chapter and the reader is encouraged to check current research; this is an active area of research.

The simulation results are very important for CCS assessments and project planning, but it must be emphasized that more experimental research should be conducted, in the laboratory and especially at field scale to evaluate the quality of the model predictions. In addition, it is important to stress the approximative character of these models, real field situations are much more complex, e.g. it is not clear whether Fick's law can describe diffusion in the field or whether very heterogeneous pore structures (for instance in carbonate reservoirs) enhance convection or slow it down.


**Estrogen and Mitochondrial Function in Disease**

**Estrogen and Mitochondrial Function in Disease**

DOI: 10.5772/intechopen.73015

#### Ved P. Mooga, C. Roger White and Samantha Giordano-Mooga Samantha Giordano-Mooga Additional information is available at the end of the chapter

Ved P. Mooga, C. Roger White and

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.73015

#### **Abstract**

Anecdotal and scientific evidence suggest that the sex hormone estrogen provides significant health benefits in women. Women have higher estrogen levels than men. Circulating estrogen reaches its highest level during the reproductive period and steadily declines with the onset of menopause. The role of estrogen and estrogen receptors in both cellular physiology and pathophysiology has been controversial. Estrogen has anti-inflammatory and anti-oxidant effects, which preserve cell viability during cardiovascular incidents, but it enhances disease progression in the context of breast cancer. Estrogen mediates these responses *via* activation of estrogen receptor subtypes located in the cell membrane, nucleus, and mitochondrion. Further, transcription of nuclear and mitochondrial genes by estrogen yields products that play an important role in regulating mitochondrial function. Mitochondria are part of a highly dynamic network and undergo fission and fusion, produce cellular energy, adenosine 5′ triphosphate (ATP), and regulate cell death. Herein, we review the cell and receptor specific effects of estrogen on mitochondrial structure, function, and cell death under normal physiological conditions and in the context of cardiovascular disease, inflammation, neurodegeneration, and cancer. Further research is needed to elucidate the specific role of estrogenic control of mitochondria in health and disease.

**Keywords:** estrogen, mitochondria, aging, menopause, estrogen receptors

#### **1. Introduction**

The term estrogen refers to a family of chemically similar steroid hormones that include estrone, estradiol, and estriol. Estrogens are synthesized primarily by the ovarian follicles [1]. An important rate limiting step in steroid hormone synthesis is the production of pregnenolone in follicular granulosa cells. Cholesterol is transported from the outer to the inner mitochondrial membrane by the steroidogenic acute regulatory (StAR) protein, followed

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

by conversion to pregnenolone by cytochrome P450 side chain cleavage (CYP11A1). Pregnenolone then diffuses to the theca cells where it is converted to androstenedione and then re-routed to the granulosa cells for the aromatase-mediated conversion to estrogen. Androstenedione can also be converted to testosterone. Thus, mitochondria play an important role in estrogen biosynthesis.

Studies utilizing ERα and ERβ knockout (KO) mice have provided insight into the function of each receptor type. Male and female ERα KO mice are infertile, while ERβ KO mice are fertile but produce small litters [12–14]. These studies highlight the importance of estrogen in the

Estrogen and Mitochondrial Function in Disease http://dx.doi.org/10.5772/intechopen.73015 465

ERα and ERβ are also found on the membranes of cellular organelles, including the endoplasmic reticulum and the mitochondrion, where they mediate various cellular functions. Localization to mitochondria was first confirmed using radioligand binding methods in mitochondria isolated from rat uterus and later by immunocytochemistry in rat pancreatic acinar cells [16]. MALDI-TOF mass spectrometry studies have shown that mitochondrial ERs are identical to ERs located in the nucleus [17]. ERβ is the predominant mitochondrial receptor in most tissues: for example ovary, uterus, spermatocytes, cerebral and hippocampal neurons, cardiomyocytes, and endothelial cells [17, 18]. In contrast, the identification of mitochondrial ERα has been limited to the uterus, ovary, and the MCF-7 breast cancer cell line [18]. The presence of ERs on mitochondria and estrogen responsive elements on the mitochondrial DNA suggests a role for estrogen in regulating the structure and/or function

Estrogen also binds to a GPER on the plasma membrane. GPER specifically binds to estradiol and mediates numerous responses including cell proliferation, vasodilation, and regulation of glucose metabolism by non-genomic mechanisms [20]. GPER has also been localized to intracellular sites. In the endoplasmic reticulum, GPER activation induces calcium release and activation of the phosphoinositide 3-kinase (PI3K)-*Akt* pathway, which induces cell proliferation [21, 22]. While GPER is not associated with the mitochondria, its regulation of cellular calcium handling indirectly impacts mitochondrial function and mitochondrial-induced cell death [22, 23]. Calcium uptake by mitochondria results in the opening of the mitochondrial permeability transition pore (mPTP) and induction of the intrinsic cell death pathway. GPERspecific agonist G1 binding to GPER has been shown to attenuate these responses in a rodent model of ischemia/reperfusion (I/R) by preventing endoplasmic reticulum calcium release [23]. ER-X is an additional estrogen receptor type that is associated with the cell membrane. This novel receptor shares sequence homology with ERα and ERβ, which is expressed primarily in the brain during development and becomes re-expressed in response to ischemic brain injury [24]. While little is known regarding the function of ER-X, some data suggest that

The mitochondria are classically described as the powerhouse of the cell by virtue of its ability to generate ATP. Physiological processes underlying mitochondrial bioenergetics and respiration have been previously reviewed [25]. Under aerobic conditions, mitochondria utilize electron transport and a protomotive force to produce ~36 ATP molecules for every glucose molecule. Reducing equivalents produced by the Krebs cycle (NADH and FADH2

are accepted by the respiratory chain at Complex I (NADH Dehydrogenase) and Complex

)

development of reproductive systems of both sexes [14, 15].

of the organelle [19].

it exerts a cytoprotective role in the brain [24].

**3. Mitochondrial function**

Estrogen serves a major role in determining female secondary sex characteristics during development and in regulating the estrous cycle.  Estrogen levels oscillate during the estrous cycle. They are lowest during menstruation, steadily rise during the follicular stage and reach a maximal level during ovulation. If a woman becomes pregnant, estrogen levels will remain high, but if fertilization does not occur, hormone levels decline during the luteal phase. Following the luteal phase, menstruation occurs, and the cycle resumes. As estrogen levels fluctuate during the estrous cycle, mitochondria alter the production of pregnenolone accordingly.

Estrogen is a pleiotropic hormone that exerts its effects *via* both transcriptional and nongenomic mechanisms. In addition to regulating reproductive function, estrogen exerts numerous cytoprotective effects. With respect to atherosclerosis, estrogen regulates levels of circulating lipids by stimulating the formation of high density lipoprotein (HDL) and decreasing expression of low density lipoprotein (LDL) [2]. It exerts antioxidant and anti-inflammatory effects by preventing the oxidation of LDL, inhibiting the expression of endothelial cell adhesion molecules and stimulating nitric oxide formation [3]. As discussed in this chapter, differential responses to estrogen are due to activation of different receptor subtypes. Recent studies also suggest that many of the protective responses to estrogen are related to the ability of the hormone to maintain normal mitochondrial function. Mitochondrial localization of estrogen receptors has been shown to regulate mitochondrial gene expression. In this manner, estrogen plays an important role in the supporting mitochondrial respiration and adenosine 5′ triphosphate (ATP) production, reducing reactive oxygen species (ROS) formation and inhibiting activation of mitochondrial cell death pathways. The goal of this chapter is to discuss mechanisms by which estrogen regulates mitochondrial signaling and function under normal physiological conditions and in the context of disease.


**5. Research limitations and future studies**

This study was carried out in Zimbabwe, a developing country that was grappling with political and economic challenges. These challenges could have had an impact on how the research participants perceive the whole relationship between domestic tourism and sustainable tourism development. This might make generalisation of the results to other countries difficult limiting the study to Zimbabwe and other developing countries going through similar political and economic challenges.

Thus, recommended that similar studies be done in other developing countries that do not share similar economic and political challenges with Zimbabwe. It would also be interesting if similar studies are done in developed countries to see if the results will be comparable.

*Tourism*


**Leaching Kinetics of Valuable Metals**

Editor

**Stefano Ubaldini**

MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin

*Editor* Stefano Ubaldini Consiglio Nazionale delle Ricerche (CNR)—Istituto di Geologia Ambientale e Geoingegneria (IGAG) Italy

*Editorial Office* MDPI St. Alban-Anlage 66 4052 Basel, Switzerland

This is a reprint of articles from the Special Issue published online in the open access journal *Metals* (ISSN 2075-4701) (available at: https://www.mdpi.com/journal/metals/special issues/leaching kinetics valuable metals).

For citation purposes, cite each article independently as indicated on the article page online and as indicated below:

LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. *Journal Name* **Year**, *Volume Number*, Page Range.

**ISBN 978-3-0365-0548-0 (Hbk) ISBN 978-3-0365-0549-7 (PDF)**

© 2021 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications.

The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND.


**11. Acknowledgments**

The author would like to thank Prof. Tang Tongyi (Ph.D. supervisor of the author) of Tsinghua University for his guidance in the investigation of the algorithm, as well as Profs. Zhang Zhonghua and Zhang Deshi of the NIM and Prof. Yang Fusheng of Tsinghua University for their guidance. Appreciation also goes to Mr. Wang Lei of the NIM for his work in the construction of the equipment, as well as Ms. Li Min, Ms. Liu Lijuan, and Mr. Zhou Hao for their contributions to the project. Special thanks to Dr. Eddy So of the National Research Council of Canada for his valuable advice.


**5.8 Privatization of public open spaces**

These places they use are safe, monitored, clean and convenient in order to meet their demands, as well as free from the unwanted urban crowds. The major similarity between these projects is their claim to bring the public and private realms together. The perceptions of urban residents about the "publicness" of the urban space also have an important part in the formation of these projects. The ways in which the urban middle classes think about different parts of the city elevates the demand for the lifestyle offered by such projects and thereby encourage the investment to the construction of privatized public spaces.

### **6. Conclusion**

*Landscape Reclamation - Rising From What's Left*

*Extreme densities (Sahabiye Neighborhood) (2018) [51].*

their investments.

**Figure 4.**

**5.5 Transparency**

been declared as renewal area.

**5.6 The regions have seen a mission developer**

neighborhood would not be halted by private investors.

**5.7 The deterioration of urban open space system**

make the system inadequate with new typology.

attractiveness, investors believe that will not be able to get the economic value of

Due to the controversial structures of renewal projects, decision makers and practitioners do not tend to be transparent in order to reduce public reaction and are trying to implement them in a hastily. The developers and designers of these projects are usually government-dependent and have the power to advance the system rapidly. The interviews conducted in the fields, usually until the last moment, it was seen that the people do not have any information that their neighborhoods have

It was understood that the people living in the neighborhood obtained the information about the project from the visuals held in the negotiation process after the implementation decision and from the visuals displayed around the project area.

These areas have become an attraction for new investments. This entrepreneurial role is significant in the sense that the situation of severe disinvestment in the

These projects, which take place on the urban green system, harm the integrity of the system after the transformation in the area (**Figure 5**). These areas, which mostly serve the integrity of gardens and parks and open, semi-open green space,

Another aspect of these constructed spaces is the way, in which the open spaces are used within these projects. Increasingly, the shopping malls and the other facilities are constructed with the functional open spaces around the buildings. Some of these are in the form of parks landscaped with exotic plants and benches, some others are designed as small plazas with marble pavements. In the beginning, these open spaces were just a part of the architecture of the projects. However, in the course of time, they turned into extensions of shopping malls and recreational facilities. Increasingly, the previously mentioned claim of providing a desirable public space to the residents and customers of the projects has evolved into a new form through the "public events" organized by the managements of these newly constructed projects.

**30**

The urban landscape is a complex structure which is a result of the interaction between human and his environment. It also involves a social dimension, a cultural dimension, and an economic dimension. Therefore, they inherit communities' values, beliefs, and symbolic meanings occurring and changing in the course of the time. They change as the communities change, the lifestyles change, and the global economy changes. The urban renewal or revitalization is related with not only the old or the other buildings and the environment or rent but also with the collective memory, symbolic meanings embedded to buildings and structures, and the values attached to the space for centuries by the people living in the area.

In Turkish metropolitan cities, similarly to Kayseri city, the most significant renewal projects of the past decade have been increasingly in the form of "project based" in terms of their size and cost. Urban renewal projects' main aims are to improve the social mix, to improve the environment, as well as the quality of life of inhabitants and city dwellers, to promote rehabilitation of complex urban structures, to preserve the valuable and unique fabric of the selected areas, to control-reverse the deterioration of specific urban zones (i.e. residential, commercial, etc.), to restructure economic activities located in the urban fabric, to sustain urban landscape. These are a very important issue in terms of the renewal process. Social goals may be the main focus in the context of a national policy for combining urban social fabric and larger social structure. Although sustainable development goals such as improved living conditions, existing structural equipment and risk

prevention and protection are never ignored, they are rarely the main focus. Targets should also include:

However, as in many countries and in our country, there can be discrepancies in the theory and post-practice. The economic development should also be encouraged, especially in an era where the world order is designed by competitiveness; however, it should not be the primary goal and the considerations should not be separated from its role as a public entity. In addition, historical urban housing areas are no longer seen as "common public assets" and thus designated renewal areas are not viewed as society's common cultural capital.

**33**

**Author details**

Neşe Yılmaz Bakır

provided the original work is properly cited.

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

City and Regional Planning Department, Erciyes University, Kayseri, Turkey

*Project-Based Urban Renewal and Transformation of Urban Landscape in Turkey*

*DOI: http://dx.doi.org/10.5772/intechopen.84391*

*Project-Based Urban Renewal and Transformation of Urban Landscape in Turkey DOI: http://dx.doi.org/10.5772/intechopen.84391*


*4.1. Mesocotyl Elongation Varied among Culture Conditions*

The elongation of mesocotyl was influenced by various environmental factors, such as light, temperature, moisture [28,29]. Thus, rice mesocotyl elongation were varied among di fferent culture media, such as soil [26], sand [17], water [30]. In our study, mesocotyl length ranged from 0 to 3.99 cm under water culture, which was close to 0-5.05 cm in a previous study [17]. While, the mesocotyl length under 6 cm sand culture ranged from 0 to 4.88 cm, which di ffered from the previous result ranging from 0 to 2.05 cm under 5 cm sand culture [17]. Moreover, more than half of the 208 accessions had mesocotyl length longer than 1 cm under water culture. However, Wu et al. (2015) reported that only 10.5% accessions had mesocotyl length longer than 1 cm under water culture [17]. It is probably that the diverse results were mainly caused by di fferent genotypes. Previous studies suggested that under varied sowing depths of soil cover, mesocotyl length was promoted by the depth in soil culture [11,18,26]. Lee et al. (1999) also reported that mesocotyl length under 3-cm sowing depth was shorter than that under 5-cm sowing depth [31]. Similarly, our results showed that mesocotyl length had a large variation among sowing depth, with an order of 6 cm > 4 cm >2 cm in soil. These results indicated that the variation of mesocotyl length existed in varied culture media and sowing depths.


*Article* **Comparison between Subsequent Irradiation and Co-Irradiation into SIMP Steel**

**Yong Wang 1,\*, Tongmin Zhang 2, Qing Liao 3, Junyuan Yang 3, Weigang Gu 1, Yongfei Ren 1, Zheng Jia 1 and Bingsheng Li 3,4,\***

**Abstract:** A modern Chinese ferritic/martensitic steel SIMP, is a new perspective nuclear structural material for the spallation target in accelerator driven sub-critical system. In this work, aimed at exploring the radiation resistance properties of this material, we investigate the differences between simultaneous Fe and He ions irradiation and He implantation of SIMP steel pre-irradiated by Fe self-ions. The irradiations were performed at 300 ◦C. The radiation-induced hardening was evaluated by nano-indentation, while the lattice disorder was investigated by transmission electron microscopy. Clear differences were found in the material microstructure after the two kinds of the ion irradiation performed. Helium cavities were observed in the co-irradiated SIMP steel, but not the case of He implantation with Fe pre-irradiation. In the same time, the size and density of Frank loops were different in the two different irradiation conditions. The reason for the different observed lattice disorders is discussed.

**Keywords:** martensitic steel; Fe and He irradiation; microstructure