• Title/Summary/Keyword: Brain function

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THE EFFECT OF BONE MORPHOGENETIC PROTEIN 2(BMP2) ON THE GROWTH OF CRANIAL BONE AND EARLY MORPHOGENESIS OF THE CRANIAL SUTURE (Bone Morphogenetic Protein 2 가 두개골 성장 및 두개봉합부의 초기형태발생에 미치는 영향)

  • Jung, Hae-Kyung;Park, Mi-Hyun;Ryoo, Hyun-Mo;Nam, Soon-Hyeun;Kim, Young-Jin;Kim, Hyun-Jung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.2
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    • pp.217-228
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    • 2003
  • Co-ordinate growth of the brain and skull is achieved through a series of tissue interactions between the developing brain, the growing bones of the skull and the sutures that unite the bones. Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of these interactions. Bmp2, one of bone morphogenetic proteins (Bmps), is involved in the regulation of the shapes of individual bones and the relative proportions of the skeleton. Mutations in the homeobox gene Msx2, known as a downstream gene of Bmp, cause Boston-type human craniosynostosis. The phenotype of Dlx5 homozygote mutant mouse presents craniofacial abnormalities including a delayed ossification of calvarial bone. These facts suggest important roles of Bmp2, Msx2 and Dlx5 genes in the cranial bone growth and suture morphogenesis. To elucidate the function of these molecules in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of Bmp2(E15-18), Msx2 and Dlx5 genes in the developing sagittal suture of calvaria during the embryonic stage. Bmp2 mRNA was intensely expressed in the osteogenic fronts and also at the low level in the periosteum of parietal bones during embryonic stage, Msx2 mRNA was intensely expressed in the sutural mesenchyme and mildly expressed in the dura mater during the embryonic stage. Dlx5 mRNA was intensely expressed osteogenic fronts and parietal bones. To further examine the role of Bmp signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of Bmp2-soaked beads onto the osteogenic fronts after 48 hours organ culture resulted in the increase of the tissue thickness and cell number around Bmp2 beads, compared to BSA control beads. In addition Bmp2 induced etopic expressions of Msx2 and Dlx5 genes. On the other hand, overexpression of FGF2 did not induce the expression of Msx2 and Dlx5. Taken together, these data indicate that Bmp2 signaling molecule has a important role in regulating the cranial bone growth and early morphogenesis of cranial suture. We also suggest that Bmp signaling is involved in all the stages of osteogenesis of cranial bones and the maintenance of cranial suture by regulating Msx2 and Dlx5 genes, and that Msx2 and Dlx5 genes are specific transcription factors of Bmp signaling pathway.

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Functional MRI Study of Changes in Brain Activity by Manual Acupuncture at LI11 or ST36 (곡지, 족삼리 침자극이 뇌활성화에 미치는 영향에 대한 뇌기능적 자기공명영상을 이용한 연구)

  • Cho, Seung-Yeon;Jahng, Geon-Ho;Park, Seong-Uk;Jung, Woo-Sang;Moon, Sang-Kwan;Gho, Chang-Nam;Cho, Ki-Ho;Kim, Young-Suk;Bae, Hyung-Sup;Park, Jung-Mi
    • The Journal of Korean Medicine
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    • v.31 no.1
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    • pp.81-92
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    • 2010
  • Objectives: The objective of this study was to assess bra in activation and difference by LI11 or ST36 acupuncture stimulation using functional MRI (fMRI). Methods: A total of 10 healthy right-handed volunteers were studied. LI11 acupuncture and ST36 acupuncture stimulations were applied in order on the left. The block design paradigm of RARARA was used for the task, with R representing rest and A representing stimulation, and each period lasted 30 seconds. fMRI data were analyzed using SPM2. Results: The left LI11 acupuncture stimulation activated both sides of the inferior parietal lobule, the left side of the extra-nuclear, culmen and inferior semi-lunar lobules. On the right side, the nodule and midbrain regions were activated by the left LI11 acupuncture stimulation. The left ST36 acupuncture stimulation activated the right side of the superior frontal gyrus, middle frontal gyrus, superior parietal lobule, inferior semi-lunar lobule and pyramis. On the left side, the sub-gyral, middle temporal gyrus, fusiform gyrus, supramarginal gyrus, extra-nuclear, cingulate gyrus and fastigium regions were activated by the left ST36 acupuncture stimulation. Besides, both sides of the paracentral lobule, inferior parietal lobule, culmen, cerebellar tonsil and midbrain regions were activated. Conclusions: In conclusion, brain signal activation patterns according to acupoints were observed to differ, and ST36 acupuncture stimulation activated more regions than LI11. It is supposed that LI11 and ST36 acupuncture stimulations have an influence on motor function and sensory aphasia, and these stimulations thus represent potential for ocular motor dysfunction, discriminative touch or position sense disorder. Moreover, ST36 acupuncture stimulation activated the cingulate gyrus of the limbic system, so it seems to have an influence over autonomic functions.

Expressional Analysis of Superoxide Dismutase in Olive Flounder (Paralichthys olivaceus) against Viral Hemorrhagic Septicemia Virus Infection (Viral hemorrhagic septicemia virus (VHSV) 감염에 대한 넙치 superoxide dismutase(Of-SOD)의 발현분석)

  • Lee, Young Mee;Kim, Jung-Eun;Noh, Jae Koo;Kim, Hyun Chul;Park, Choul-Ji;Park, Jong-Won;Kim, Kyung-Kil;Lee, Jeong-Ho
    • Journal of Life Science
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    • v.24 no.12
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    • pp.1371-1377
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    • 2014
  • Superoxide dismutase is a family of important antioxidant metalloenzymes and catalyzes the dismutation of toxic superoxide anions into dioxygen and hydrogen peroxide. A recent study identified the partial superoxide dismutase (SOD) gene in olive flounder (Paralichthys olivaceus). The same study reported that it strongly induced benzo[a]pyrene and that it was an indicator of aquatic oxidative stress responses. However, its transcriptional response against viral infection has not been investigated. In the present study, the spatial and temporal expression profiles were analyzed to investigate the function of Of-SOD in the antiviral response. The Of-SOD transcripts were ubiquitously detected at various levels in diverse tissues in a real-time PCR. The expression of Of-SOD was significantly higher in the muscles, liver, and brain but extremely low in the stomach and spleen. Following a VHSV challenge, the expression of Of-SOD increased within 3 h in the kidneys and decreased to the original level 2 days postchallenge. In muscle, liver, and brain, Of-SOD mRNA was similarly up-regulated at 3-6 h postchallenge and then decreased to the basal level. Although the expression pattern and induction time differed slightly depending on the tissue, the transcript of Of-SOD consistently increased in the acute infection response, but the expression was low in the chronic response. The expression of Of-SOD was induced after the VHSV infection, and Of-SOD was probably involved in the immune response against the viral challenge. These results suggest that SOD may play important roles in the immune defense system of P. olivaceus and perhaps contribute to the protective effects against oxidative stress in olive flounder.

Clinical Application of Compressed Spectral Array During Deep Hypothermia (초저체온하 대동맥수술 환자에서 완전 순환차단의 안전한 체온 및 기간에 대한 연구 - 뇌파 Compressed Spectral Array의 임상적 응용 -)

  • 장병철;유선국
    • Journal of Chest Surgery
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    • v.30 no.8
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    • pp.752-759
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    • 1997
  • Profound hypothermia protects . cerebral function during total circulatory arrest(TCA) in the surgical treatment of a variety of cardiac and aortic diseases. Despite its importance, there is no ideal technique to monitor the brain injury from ischemia. Since 1994, we have developed compressed spectral array(CSA) of electroencephalography(EEG) and monitored cerebral activity to reduce ischemic injury. The purposes of this study are to analyse the efficacy of CSA and to establish objective criteria to consistently identify the safe level of temperature and arrest time. We studied 6 patients with aortic dissection(AD, n=3) or aortic arch aneurysm(n=3, ruptured in 2). Body temperatures from rectum and esophagus and the EEG were monitored continuously during cooling and rewarming period. TCA with cerebral ischemia was performed in 3 patients and TCA with selective cerebral perfusion was performed in 3 patients. Total ischemic time was 30, 36 and 56 minutes respectively for TCA group and selective perfusion time was 41, 56 and 92 minutes respectively for selective perfusion group. The rectal temperatures for flat EEG were between 16.1 and 22. $1^{\circ}C$ (mean: 18.4 $\pm$ 2.0): the esophageal temperatures between 12.7 and $16.4^{\circ}C$ (mean $14.7\pm1.6).$ The temperatures at which EEG reappeared $5~15.4^{\circ}C$ for esophagus. There was no neurological defic t and no surgical mortality in this series. In summary, the electrical cerebral activity Teappeared within 23 minutes at the temperature less than $16^{\circ}C$ for rectum. It seemed that $15^{\circ}C$ of esophageal temperature was not safe for 20 minutes of TCA and continuous monitoring the EEG with CSA to identify the electrocerebral silence was useful.

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Variation of Lactate Dehydrogenase Isozymes in Angelfish (Pterophyllum scalare) according to Acute Environmental Change (급격한 환경변화에 대한 angelfish (Pterophyllum scalare) 젖산탈수소효소 동위효소의 변화)

  • An, Chang-Su;Cho, Sung-Kyu;Yum, Jung-Joo
    • Journal of Life Science
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    • v.20 no.3
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    • pp.416-423
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    • 2010
  • In this study, the properties and gene expression of the lactate dehydrogenase (EC 1.1.1.27, LDH) isozyme were studied in angelfish (Pterophyllum scalare) - known for their adaptation to the low oxygen environment of the tropics - which were acclimated to acute temperature change ($27{\pm}0.5{\rightarrow}18{\pm}0.5^{\circ}C$) and dissolved oxygen (DO) change ($6{\pm}1{\rightarrow}18\;ppm$) for 2 hours. The properties of the LDH isozymes were confirmed in the native-polyacrylamide gel electrophoresis, Western blot analysis and enzyme activity measurement. Liver- and eye-specific Ldh-C gene were expressed in liver, eye and brain tissues. Through Western blot analysis, the LDH $A_4$ isozyme was shown to have a more cathodal mobility relative to the $B_4$ isozyme. In the liver tissue, the LDH $A_4$ isozyme increased with temperature drop while the $B_4$ isozyme decreased. The LDH $A_4$ and $C_4$ isozymes increased with DO increment, while the $B_4$ isozyme decreased. In the eye tissue, the LDH $A_4$ and B4 isozymse increased with temperature drop while the $B_4$ isozyme decreased. The LDH $A_4$ and $B_4$ isozymes increased with DO increment, but the $C_4$ isozyme and isozymes including the subunit C decreased. In the heart tissue, LDH activity increased with DO increment, as well as the LDH $B_4$ isozyme. In the brain tissue, the LDH $A_4$ and $B_4$ isozymes increased with temperature drop. The LDH $B_4$ isozyme increased with DO increment. Accordingly, since the liver- and eye-specific Ldh-C are influenced by changes in DO and the LDH $B_4$ and $C_4$ isozymes are relatively controlled in the liver and eye tissues, the $C_4$ isozyme can be considered to have a lactate oxidase function.

Recent Advancement in the Stem Cell Biology (Stem Cell Biology, 최근의 진보)

  • Harn, Chang-Yawl
    • Journal of Plant Biotechnology
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    • v.33 no.3
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    • pp.195-207
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    • 2006
  • Stem cells are the primordial, initial cells which usually divide asymmetrically giving rise to on the one hand self-renewals and on the other hand progenitor cells with potential for differentiation. Zygote (fertilized egg), with totipotency, deserves the top-ranking stem cell - he totipotent stem cell (TSC). Both the ICM (inner cell mass) taken from the 6 days-old human blastocyst and ESC (embryonic stem cell) derived from the in vitro cultured ICM have slightly less potency for differentiation than the zygote, and are termed pluripotent stem cells. Stem cells in the tissues and organs of fetus, infant, and adult have highly reduced potency and committed to produce only progenitor cells for particular tissues. These tissue-specific stem cells are called multipotent stem cells. These tissue-specific/committed multipotent stem cells, when placed in altered environment other than their original niche, can yield cells characteristic of the altered environment. These findings are certainly of potential interest from the clinical, therapeutic perspective. The controversial terminology 'somatic stem cell plasticity' coined by the stem cell community seems to have been proved true. Followings are some of the recent knowledges related to the stem cell. Just as the tissues of our body have their own multipotent stem cells, cancerous tumor has undifferentiated cells known as cancer stem cell (CSC). Each time CSC cleaves, it makes two daughter cells with different fate. One is endowed with immortality, the remarkable ability to divide indefinitely, while the other progeny cell divides occasionally but lives forever. In the cancer tumor, CSC is minority being as few as 3-5% of the tumor mass but it is the culprit behind the tumor-malignancy, metastasis, and recurrence of cancer. CSC is like a master print. As long as the original exists, copies can be made and the disease can persist. If the CSC is destroyed, cancer tumor can't grow. In the decades-long cancer therapy, efforts were focused on the reducing of the bulk of cancerous growth. How cancer therapy is changing to destroy the origin of tumor, the CSC. The next generation of treatments should be to recognize and target the root cause of cancerous growth, the CSC, rather than the reducing of the bulk of tumor, Now the strategy is to find a way to identify and isolate the stem cells. The surfaces of normal as well as the cancer stem cells are studded with proteins. In leukaemia stem cell, for example, protein CD 34 is identified. In the new treatment of cancer disease it is needed to look for protein unique to the CSC. Blocking the stem cell's source of nutrients might be another effective strategy. The mystery of sternness of stem cells has begun to be deciphered. ESC can replicate indefinitely and yet retains the potential to turn into any kind of differentiated cells. Polycomb group protein such as Suz 12 repress most of the regulatory genes which, activated, are turned to be developmental genes. These protein molecules keep the ESC in an undifferentiated state. Many of the regulator genes silenced by polycomb proteins are also occupied by such ESC transcription factors as Oct 4, Sox 2, and Nanog. Both polycomb and transcription factor proteins seem to cooperate to keep the ESC in an undifferentiated state, pluripotent, and self-renewable. A normal prion protein (PrP) is found throughout the body from blood to the brain. Prion diseases such as mad cow disease (bovine spongiform encephalopathy) are caused when a normal prion protein misfolds to give rise to PrP$^{SC}$ and assault brain tissue. Why has human body kept such a deadly and enigmatic protein? Although our body has preserved the prion protein, prion diseases are of rare occurrence. Deadly prion diseases have been intensively studied, but normal prion problems are not. Very few facts on the benefit of prion proteins have been known so far. It was found that PrP was hugely expressed on the stem cell surface of bone marrow and on the cells of neural progenitor, PrP seems to have some function in cell maturation and facilitate the division of stem cells and their self-renewal. PrP also might help guide the decision of neural progenitor cell to become a neuron.

Does the Gut Microbiota Regulate a Cognitive Function? (장내미생물과 인지기능은 서로 연관되어 있는가?)

  • Choi, Jeonghyun;Jin, Yunho;Kim, Joo-Heon;Hong, Yonggeun
    • Journal of Life Science
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    • v.29 no.6
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    • pp.747-753
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    • 2019
  • Cognitive decline is characterized by reduced long-/short-term memory and attention span, and increased depression and anxiety. Such decline is associated with various degenerative brain disorders, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The increases in elderly populations suffering from cognitive decline create social problems and impose economic burdens, and also pose safety threats; all of these problems have been extensively researched over the past several decades. Possible causes of cognitive decline include metabolic and hormone imbalance, infection, medication abuse, and neuronal changes associated with aging. However, no treatment for cognitive decline is available. In neurodegenerative diseases, changes in the gut microbiota and gut metabolites can alter molecular expression and neurobehavioral symptoms. Changes in the gut microbiota affect memory loss in AD via the downregulation of NMDA receptor expression and increased glutamate levels. Furthermore, the use of probiotics resulted in neurological improvement in an AD model. PD and gut microbiota dysbiosis are linked directly. This interrelationship affected the development of constipation, a secondary symptom in PD. In a PD model, the administration of probiotics prevented neuron death by increasing butyrate levels. Dysfunction of the blood-brain barrier (BBB) has been identified in AD and PD. Increased BBB permeability is also associated with gut microbiota dysbiosis, which led to the destruction of microtubules via systemic inflammation. Notably, metabolites of the gut microbiota may trigger either the development or attenuation of neurodegenerative disease. Here, we discuss the correlation between cognitive decline and the gut microbiota.

Keyhole Imaging Combined Phase Contrast MR Angiography Technique (Keyhole Imaging기법을 적용한 위상대조도 자기공명 혈관조영기법)

  • Lee, D.H.;Hong, C.P.;Han, B.S.;Lee, M.W.
    • Journal of Biomedical Engineering Research
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    • v.33 no.2
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    • pp.72-77
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    • 2012
  • Phase Contrast MR Angiography(PC MRA) is excellent MRA technique for measuring the velocity of vessels in the human body. PC MRA need to at least four images for angiogram reconstruction and it caused longer scan time. Therefore, we used keyhole imaging combined PC MRA to reduce the scan time. However, keyhole imaging can lead the erroneous effects as loss of phase information or frequency discontinuous. In this study, we applied the keyhole imaging combined 2D PC MRA for improving the temporal resolution and also measured the velocity to evaluate the accuracy of phase information. We used 0.32T MRI scanner(Magfinder II, Scimedix, Korea). Using the 2D PC MRA pulse sequence, the vascular images for a human brain targeted on the Superior Sagittal Sinus(SSS) were obtained. We applied tukey window function for keyhole images to minimize the ringing artifact and erroneous factors that are induced frequency discontinuous and phase information loss. We also applied zero-padded algorithm to peripheral missing k-space lines to compare keyhole imaging results and the artifact power(AP) value was measured on the complex difference images to validate the image quality. Consider as based on our results, heavy image distortions and artifacts were shown until using at least 50% keyhole factor. Using above the 50% keyhole factors are shown well reconstructed and matched for magnitude images and velocity information measurements. In conclusion, we confirmed the image quality and velocity information of keyhole technique combined 2D PC MRA. Especially, measured velocity information through the keyhole imaging combination was similar to the velocity information of full sampled k-space image despite of frequency discontinuous and phase information loss in the keyhole imaging reconstruction process. Consequently, the keyhole imaging combined 2D PC MRA will give some clinical usefulness and advantages as improving the temporal resolution and measuring the velocity information via selecting the appropriate keyhole factor at low tesla MRI system.

Amplitude and phase analysis of the brain Evoked Potential about performing a task related to visual stimulus using Empirical mode decomposition (경험적 모드 분해를 이용한 시각자극 관련 과제수행에 대한 뇌 유발전위 진폭과 위상 변화 분석)

  • Lee, ByuckJin;Yoo, Sun-Kook
    • Science of Emotion and Sensibility
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    • v.18 no.1
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    • pp.15-26
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    • 2015
  • In this paper, amplitude and phase difference patterns for theta and alpha bands of the Evoked Potential(EP) in relation to perform a task at visual stimulus were analyzed using the Empirical mode decomposition(EMD). The EMD is applied to decompose EP signals with task-related sub-frequency band signals. Intrinsic mode function was implied in Hilbert transform and instantaneous amplitude and phase differences of theta and alpha were derived from Hilbert transformed EP. In a task status, large amplitude for both bands was observed at P2, N2, and P3 points as well as maximum phase difference was observed at N1 and P2. We confirmed that both bands are associated with a task at visual stimulus, and less associated with fixation. The proposed method enhances the time and frequency resolution in comparison with band-pass filter method which observed different phase results according to conditions.

Overview of Transforming Growth Factor β Superfamily Involvement in Glioblastoma Initiation and Progression

  • Nana, Andre Wendindonde;Yang, Pei-Ming;Lin, Hung-Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.6813-6823
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    • 2015
  • Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.