• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.4867-4871
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• 2012

Cervical cancer is a leading cause of morbidity and mortality in women worldwide. Although the human papillomavirus (HPV) is considered the major causative agent of cervical cancer, yet the viral infection alone is not sufficient for cancer progression. The etiopathogenesis of cervical cancer is indeed complex; a precise understanding of the complex cellular/molecular mechanisms underlying the initiation, progression and/or prevention of the uterine cervix is therefore essential. Autophagy is emerging as an important biological mechanism in targeting human cancers, including cervical cancer. Furthermore, autophagy, a process of cytoplasm and cellular organelle degradation in lysosomes, has been implicated in homeostasis. Autophagic flux may vary depending on the cell/tissue type, thereby altering cell fate under stress conditions leading to cell survival and/or cell death. Autophagy may in turn govern tumor metastasis and subsequent carcinogenesis. Inflammation is a known hallmark of cancer. Vascular insufficiency in tumors, including cervical tissue, leads to depletion of glucose and/or oxygen perturbing the osmotic mileu causing extracellular acidosis in the tumor microenvironment that may eventually result in autophagy. Thus, targeted manipulation of complex autophagic signaling may prove to be an innovative strategy in identification of clinically relevant biomarkers in cervical cancer in the near future.

• Animal cells and systems
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• 제4권4호
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• pp.347-352
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• 2000

Programmed cell death, apoptosis, is a mechanism to maintain tissue homeostasis. Although the apoptotic process in rodent mammary tissues has been known to occur at the onset of involution, little is known about programmed cell death in the bovine tissues. Therefore, the purpose of this study was to investigate the molecular and cellular basis of apoptotic process in bovine mammary cells. Mammary tissues were obtained at different lactational and involurional stages. By apoptosis in situ endlabeling assay, apoptotic cells were found around the acinar celt lining in regressing bovine mammary tissues. The apoptosis-related genes bel-2 and bax were detected throughout involution by Northern blotting assay. The level of bax mRNA was dominantly expressed during involution. On the other hand, the bel-2 RNA transcripts were constantly expressed by 14 of post-lactation and declined thereafter. The expression of the testosterone-repressed prostate message-2 (TRPM-2) RNA transcripts, a marker for tissue remodeling, was increased as involution progressed. TNF a, were induced the DNA fragmentation and enhanced the expression of bax mRNA. In addition, milk protein secretion and amino acid uptake were decreased in mammary acinar culture treated with TNF $\alpha$. These results indicate that bovine mammary cells undergo apoptotic process after the cessation of milking and that TNF $\alpha$ may trigger apoptosis in lactating bovine mammary acini.

• BMB Reports
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• 제56권8호
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• pp.417-425
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• 2023

In various organisms, the Hippo signaling pathway has been identified as a master regulator of organ size determination and tissue homeostasis. The Hippo signaling coordinates embryonic development, tissue regeneration and differentiation, through regulating cell proliferation and survival. The YAP and TAZ (YAP/TAZ) act as core transducers of the Hippo pathway, and they are tightly and exquisitely regulated in response to various intrinsic and extrinsic stimuli. Abnormal regulation or genetic variation of the Hippo pathway causes a wide range of human diseases, including cancer. Recent studies have revealed that Hippo signaling plays a pivotal role in the immune system and cancer immunity. Due to pathophysiological importance, the emerging role of Hippo signaling in blood cell differentiation, known as hematopoiesis, is receiving much attention. A number of elegant studies using a genetically engineered mouse (GEM) model have shed light on the mechanistic and physiological insights into the Hippo pathway in the regulation of hematopoiesis. Here, we briefly review the function of Hippo signaling in the regulation of hematopoiesis and immune cell differentiation.

• IMMUNE NETWORK
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• 제16권5호
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• pp.281-285
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• 2016

CD4⁺ regulatory T cells (Tregs) are essential for normal immune surveillance, and their dysfunction can lead to the development of autoimmune diseases, such as type-1 diabetes (T1D). T1D is a T cell-mediated autoimmune disease characterized by islet b cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Tregs play a critical role in the development of T1D and participate in peripheral tolerance. Pluripotent stem cells (PSCs) can be utilized to obtain a renewable source of healthy Tregs to treat T1D as they have the ability to produce almost all cell types in the body, including Tregs. However, the right conditions for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) remain undefined, especially molecular mechanisms that direct differentiation of such Tregs. Auto Ag-specific PSC-Tregs can be programmed to be tissue-associated and infiltrate to local inflamed tissue (e.g., islets) to suppress autoimmune responses after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. Developing auto Ag-specific PSC-Tregs can reduce overall immunosuppression after adoptive transfer by accumulating inflamed islets, which drives forward the use of therapeutic PSC-Tregs for cell-based therapies in T1D.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.12.1-12.14
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• 2018

Osteoporosis develops with high prevalence in both postmenopausal women and hypogonadal men. Osteoporosis results in significant morbidity, but no cure has been established. Mesenchymal stem cells (MSCs) critically contribute to bone homeostasis and possess potent immunomodulatory/anti-inflammatory capability. Here, we investigated the therapeutic efficacy of using an infusion of MSCs to treat sex hormone-deficient bone loss and its underlying mechanisms. In particular, we compared the impacts of MSC cytotherapy in the two genders with the aim of examining potential gender differences. Using the gonadectomy (GNX) model, we confirmed that the osteoporotic phenotypes were substantially consistent between female and male mice. Importantly, systemic MSC transplantation (MSCT) not only rescued trabecular bone loss in GNX mice but also restored cortical bone mass and bone quality. Unexpectedly, no differences were detected between the genders. Furthermore, MSCT demonstrated an equal efficiency in rectifying the bone remodeling balance in both genders of GNX animals, as proven by the comparable recovery of bone formation and parallel normalization of bone resorption. Mechanistically, using green fluorescent protein (GFP)-based cell-tracing, we demonstrated rapid engraftment but poor inhabitation of donor MSCs in the GNX recipient bone marrow of each gender. Alternatively, MSCT uniformly reduced the $CD3^+T$-cell population and suppressed the serum levels of inflammatory cytokines in reversing female and male GNX osteoporosis, which was attributed to the ability of the MSC to induce T-cell apoptosis. Immunosuppression in the microenvironment eventually led to functional recovery of endogenous MSCs, which resulted in restored osteogenesis and normalized behavior to modulate osteoclastogenesis. Collectively, these data revealed recipient sexually monomorphic responses to MSC therapy in gonadal steroid deficiency-induced osteoporosis via immunosuppression/anti-inflammation and resident stem cell recovery.

• Molecules and Cells
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• 제40권4호
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• pp.243-253
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• 2017

Eukaryotic cilia are organelles that project from the surface of cells to fulfill motility and sensory functions. In vertebrates, the functions of both motile and immotile cilia are critical for embryonic development and adult tissue homeostasis. Importantly, a multitude of human diseases is caused by abnormal cilia biogenesis and functions which rely on the compartmentalization of the cilium and the maintenance of its protein composition. The transition zone (TZ) is a specialized ciliary domain present at the base of the cilium and is part of a gate that controls protein entry and exit from this organelle. The relevance of the TZ is highlighted by the fact that several of its components are coded by ciliopathy genes. Here we review recent developments in the study of TZ proteomes, the mapping of individual components to the TZ structure and the establishment of the TZ as a lipid gate.

• Biomolecules & Therapeutics
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• 제12권4호
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• pp.202-208
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• 2004

Diabetes mellitus is a complex metabolic derangement with hyperglycaemia being the most characteristic symptom of diabetes. Hyperglycaemia can be caused by an increase in the rate of glucose production by the liver or by a decrease in the rate of glucose use by peripheral tissues. Impaired glucose transport is one of the major factors contributing to insulin resistance in type 2 diabetic patients. The ability of insulin to mediate tissue glucose uptake is a critical step in maintaining glucose homeostasis and in clearing the post-prandial glucose load. Glucose transport is mediated by specific carriers called glucose transporters (GLUTs). In this article, the functional importance and molecular mechanisms of insulin-induced glucose transport and development of hypoglycaemic agents which increase glucose transport are reviewed.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.268.2-269
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• 2003

Prostaglandins (PGs) and NO (nitric oxide) are important elements to keep homeostasis and host defense system in human beings. When PGs and NO are overproduced by cyclooxygenase-2(COX-2) and inducible nitric oxide synthase (iNOS), respectively, they can cause chronic inflammation, tissue damage, and carcinogenesis. On this line, we are interested in finding agents that can inhibit the production of PGs and NO from natural products for devloping anti-inflammatory and cancer chemopreventive agents. (omitted)

• BMB Reports
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• 제41권1호
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• pp.11-22
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• 2008

Apoptosis (programmed cell death) is a cellular self-destruction mechanism that is essential for a variety of biological events, such as developmental sculpturing, tissue homeostasis, and the removal of unwanted cells. Mitochondria play a crucial role in regulating cell death. $Ca^{2+}$ has long been recognized as a participant in apoptotic pathways. Mitochondria are known to modulate and synchronize $Ca^{2+}$ signaling. Massive accumulation of $Ca^{2+}$ in the mitochondria leads to apoptosis. The $Ca^{2+}$ dynamics of ER and mitochondria appear to be modulated by the Bcl-2 family proteins, key factors involved in apoptosis. The number and morphology of mitochondria are precisely controlled through mitochondrial fusion and fission process by numerous mitochondria-shaping proteins. Mitochondrial fission accompanies apoptotic cell death and appears to be important for progression of the apoptotic pathway. Here, we highlight and discuss the role of mitochondrial calcium handling and mitochondrial fusion and fission machinery in apoptosis.

• 셀메드
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• 제7권1호
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• pp.3.1-3.2
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• 2017

The efficient removal of dead cells is an evolutionarily conserved process essential for homeostasis in multicellular organisms. The phagocytosis involves a series of steps that ultimately leads the detection of apoptotic cell by the phagocytes and the subsequent engulfment and degradation of corpse. The uptake of apoptotic cells by phagocytes not only removes debris from tissues but also generates an anti-inflammatory signal that blocks tissue inflammation. Conversely, impaired clearance of dead cells can cause loss of immune tolerance and the development of various inflammation-associated diseases such as autoimmunity, but can also affect cancer development. This review will discuss current understanding of the molecular mechanism of apoptotic cell phagocytosis and how they may be related to human diseases.