1,018 results on '"Takaku, K."'
Search Results
2. Inactivation and proteolytic degradation of perforin within lytic granules upon neutralization of acidic pH
- Author
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KATAOKA, T., TOGASHI, K., TAKAYAMA, H., TAKAKU, K., and NAGAI, K.
- Published
- 1997
3. Monetary policy, incomplete asset markets, and welfare in a small open economy
- Author
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Shigeto Kitano and Takaku, K.
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Small open economy, DSGE, Welfare comparison, Incomplete financial market, Ramsey policy, Exchange rate regime ,jel:G15 ,small open economy, DSGE ,welfare comparison, incomplete financial market, Ramsey policy, exchange rate regime ,jel:F3 ,jel:F4 ,jel:F31 ,jel:E44 ,jel:E52 ,jel:E42 ,jel:F41 - Abstract
We develop a small open economy model with capital, sticky prices, and a simple form of financial frictions. We compare welfare levels under three alternative rules: a domestic inflation-based Taylor rule, a CPI inflation-based Taylor rule, and an exchange rate peg. We show that the superiority of an exchange rate peg over a domestic inflation-based Taylor rule becomes more pronounced under incomplete financial asset markets and more severe financial frictions.
- Published
- 2015
4. Unresectable primary hepatic adenosquamous carcinoma successfully treated with systemic and transcatheter hepatic arterial injection chemotherapies followed by conversion surgery: a case report and literature review.
- Author
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Watanabe Y, Osaki A, Kimura K, Yakubo S, Takaku K, Sato M, Hashidate H, Waguri N, and Terai S
- Subjects
- Humans, Immunotherapy, Injections, Middle Aged, Carcinoma, Adenosquamous drug therapy, Carcinoma, Squamous Cell, Liver Neoplasms drug therapy
- Abstract
Background: Primary hepatic adenosquamous carcinoma (ASC) is a type of tumor that has the features of both adenocarcinoma and squamous cell carcinoma (SCC). The prognosis for patients with ASC is poor, as the chemotherapy has been ineffective so far., Case Presentation: Here, we report a case of a 62-year-old male patient who presented with high fever. The tumor marker levels were high, and abdominal dynamic computed tomography showed a liver tumor and distant lymph node metastases. Upon further investigation, needle biopsy of the liver tumor showed a primary hepatic SCC. Because the SCC was unresectable, the patient was treated with tegafur/gimeracil/oteracil (S-1) and transcatheter hepatic arterial injection (TAI) of cisplatin. After chemotherapy, a surgical resection performed on the remaining liver tumor, made the patient cancer-free. After the operation, the liver tumor was confirmed as primary hepatic ASC. Subsequently, the patient was administered postoperative adjuvant chemotherapy, which prevented its recurrence., Conclusions: Due to the lack of an effective treatment for primary hepatic ASC, its prognosis is poor. Here, we suggest that a chemotherapy combination of 5-fluorouracil (S-1) and cisplatin along with conversion surgery might be an effective way for treating primary hepatic ASC. Our experience from this case shall be valuable to clinicians around the world involved in the treatment of primary hepatic ASC., (© 2021. The Author(s).)
- Published
- 2021
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5. Balloon-occluded retrograde transvenous obliteration for gastric varices improves hepatic functional reserve in long-term follow-up.
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Waguri N, Osaki A, Watanabe Y, Matsubara T, Yamazaki S, Yokoyama H, Kimura K, Wakabayashi T, Mito M, Yakubo S, Azumi R, Kohisa J, Takaku K, Sato M, and Furukawa K
- Abstract
Background and Aim: Balloon-occluded retrograde transvenous obliteration (BRTO) has been widely adopted for the management of gastric fundal varices (GVs). There are a few reports that BRTO leads to the improvement of mid-term and long-term hepatic functional reserve (HFR). We retrospectively investigated the long-term effect on HFR and prognosis among patients who had undergone BRTO for GVs., Methods: This single-center, retrospective study included 57successful patients out of 60 patients who underwent BRTO for GVs from December 2005 to September 2018. We examined the indicators of HFR (e.g., encephalopathy and ascites statuses, serum total bilirubin and albumin levels, % prothrombin time, and Child-Pugh and albumin-bilirubin [ALBI] scores) during 3 years of follow-up after BRTO. We analyzed survival using the Kaplan-Meier method and identified the independent prognostic factors via multivariate analyses., Results: GVs disappeared in all patients who were successfully treated by BRTO. At 3 years after BRTO, serum albumin levels were significantly elevated (from 3.3 to 4.0 g/dL, P = 0.008), while Child-Pugh and ALBI scores were significantly decreased (from 7.0 to 5.7, P = 0.043, and from -1.94 to -2.60, P = 0.006, respectively). The median survival time among all patients was 2207 days; the survival rates after BRTO were 87.0% at 1 year, 81.8% at 3 years, 67.3% at 5 years, and 44.1% at 10 years. Multivariate analyses revealed that ascites, hepatic encephalopathy, and malignant neoplasms were independently associated with poor prognosis., Conclusion: BRTO for GVs has a favorable effect on long-term HFR., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
- Published
- 2021
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6. A Rare Case of Recurrent Generalized Peritonitis Caused by Spontaneous Urinary Bladder Rupture after Radiotherapy: A Case Report and Literature Review.
- Author
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Watanabe Y, Yamazaki S, Yokoyama H, Yakubo S, Osaki A, Takaku K, Sato M, Waguri N, and Terai S
- Abstract
Since generalized peritonitis is a fatal disease, accurate diagnosis and treatment are important. In this paper, we report a case of recurrent generalized peritonitis associated with spontaneous urinary bladder rupture (SBR). A 65 year old woman, who underwent radiotherapy 21 years prior, was diagnosed with generalized peritonitis. Although the cause of the generalized peritonitis could not be identified, the patient recovered with conservative treatment in short period. However, recurrent episodes of generalized peritonitis occurred four times. We diagnosed the patient with urinary ascites due to SBR, based on a history of radiotherapy and dysuria. No recurrence of generalized peritonitis had occurred after accurate diagnosis and treatment with long-term bladder catheter placement. Since SBR often occurs as a late complication after radiotherapy, it is difficult to diagnose SBR, which leads to delayed treatment. This case and literature review of similar cases suggest that the information of the following might be helpful in the diagnosis of SBR: (i) history of recurrent generalized peritonitis, (ii) pseudo-renal failure, (iii) history of radiotherapy, (iv) dysuria, and (v) increase or decrease of ascites in a short period. It is important to list SBR in the differential diagnosis by knowing the disease and understanding its clinical features. This case and literature review will serve as a reference for future practices.
- Published
- 2021
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7. A case of Lemierre's syndrome in association with liver abscess without any other metastatic lesions.
- Author
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Iwasaki T, Yamamoto T, Inoue K, and Takaku K
- Subjects
- Adult, Anti-Bacterial Agents therapeutic use, Carbapenems therapeutic use, Disseminated Intravascular Coagulation drug therapy, Disseminated Intravascular Coagulation etiology, Doripenem, Fusobacterium necrophorum isolation & purification, Fusobacterium necrophorum pathogenicity, Humans, Lemierre Syndrome diagnosis, Lemierre Syndrome drug therapy, Liver Abscess diagnosis, Liver Abscess drug therapy, Male, Ofloxacin therapeutic use, Lemierre Syndrome complications, Liver Abscess etiology
- Abstract
Lemierre's syndrome (LS) is characterized by pharyngitis followed by septicemia, internal jugular vein thrombophlebitis, and metastatic embolization in general. LS is commonly caused by Fusobacterium necrophorum. Herein, we present a case of LS with liver abscesses that presented as a sole metastatic lesion. We were not able to diagnose LS until Fusobacterium necrophorum was isolated due to the lack of the common involvement. Doripenem was effective against the pathologic features including the liver abscesses. LS should be taken into consideration when clinicians find liver abscesses following pharyngitis even when the common complications of LS are not detected.
- Published
- 2012
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8. Acute heart failure syndrome associated with snow shoveling.
- Author
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Ito M, Yamamoto T, Takaku K, Tsutsui N, Sasagawa M, Hirono S, Suzuki T, and Kodama M
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- Acute Disease, Aged, Aged, 80 and over, Coronary Angiography, Electrocardiography, Female, Follow-Up Studies, Heart Failure diagnosis, Heart Failure physiopathology, Humans, Male, Syndrome, Tomography, X-Ray Computed, Heart Failure etiology, Physical Exertion, Snow
- Abstract
There have been only a few reports regarding the relation between snow shoveling and acute heart failure syndromes (AHFS). We present a case series of 5 patients who presented with AHFS, all within 5 days after shoveling snow. Although all patients underwent examination at a regular out-patient clinic, no patient had prior signs or symptoms of heart failure. The condition of all patients had gradually deteriorated, with no abrupt onset of dyspnea after shoveling snow. Four of the 5 patients demonstrated a preserved ejection fraction on echocardiography. Snow shoveling may lead to AHFS in patients who are at risk for developing heart failure.
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- 2012
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9. Etiologies of Splenic Venous Hypertension: A Review.
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Tidwell, Jasmine, Thakkar, Bianca, and Wu, George Y.
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GASTRIC varices ,PORTAL hypertension ,HEPATIC portal system ,THERAPEUTICS ,GENETIC disorders ,GASTROINTESTINAL hemorrhage ,PANCREATIC tumors - Published
- 2024
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10. Detour canal, a civil engineering heritage created through historical struggle for water resources, now provides the habitats for a rare freshwater fish.
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Yohei Yamasaki, Hironori Hayashi, Suguru Kubo, Takashi Namiki, and Yuichi Kano
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CIVIL engineering ,WATER supply ,FRESHWATER fishes ,SPECIES diversity ,SPECIES distribution - Abstract
The Ariake catfish, Tachysurus aurantiacus, is a freshwater fish endemic to Kyushu Island, Japan. However, these catfish are now endangered owing to environmental changes. Despite their status, there is scant quantitative research on the Ariake catfish regarding their potential conservation. The Yabe River is a typical catfish habitat situated in the northern part of Kyushu Island (Ariake Area) and has a unique civil engineering heritage, as represented by the so-called 'detour canal'. The canals were created owing to competition by two Domains to divert additional water resources into their own territory for rice cultivation during the Edo Period (1603-1867). To fill the research gap on the Ariake catfish and assess the ecological value of detour canals, in this study, we conducted a survey of local catfish populations and nine environmental parameters that can affect them. We found that the population volume of the Ariake catfish was significantly higher in canals than in ordinary branch rivers. Although the detour canals were not originally constructed for biodiversity conservation, they nonetheless unintentionally provide catfish habitat at present. As these canals represent a remarkable example of a contribution by a civil engineering heritage structure to biodiversity conservation, our study should be used as a potential justification for preserving the canals, as well as conserving the aquatic species that utilise them as vital habitat. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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11. Studying the Effect of the Host Genetic Background of Juvenile Polyposis Development Using Collaborative Cross and Smad4 Knock-Out Mouse Models.
- Author
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Zohud, Osayd, Midlej, Kareem, Lone, Iqbal M., Nashef, Aysar, Abu-Elnaaj, Imad, and Iraqi, Fuad A.
- Subjects
KNOCKOUT mice ,SMAD proteins ,MICE ,K-nearest neighbor classification ,INTESTINAL polyps ,LABORATORY mice ,MACHINE learning ,GENETIC variation - Abstract
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with mutations in genes such as Smad4 and BMPR1A. This study explores the impact of Smad4 knock-out on the development of intestinal polyps using collaborative cross (CC) mice, a genetically diverse model. Our results reveal a significant increase in intestinal polyps in Smad4 knock-out mice across the entire population, emphasizing the broad influence of Smad4 on polyposis. Sex-specific analyses demonstrate higher polyp counts in knock-out males and females compared to their WT counterparts, with distinct correlation patterns. Line-specific effects highlight the nuanced response to Smad4 knock-out, underscoring the importance of genetic variability. Multimorbidity heat maps offer insights into complex relationships between polyp counts, locations, and sizes. Heritability analysis reveals a significant genetic basis for polyp counts and sizes, while machine learning models, including k-nearest neighbors and linear regression, identify key predictors, enhancing our understanding of juvenile polyposis genetics. Overall, this study provides new information on understanding the intricate genetic interplay in the context of Smad4 knock-out, offering valuable insights that could inform the identification of potential therapeutic targets for juvenile polyposis and related diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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12. Gene Function is a Driver of Activin Signaling Pathway Evolution Following Whole-Genome Duplication in Rainbow Trout (Oncorhynchus mykiss).
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Richman, Jasmine A, Davis, Leah R, and Phelps, Michael P
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RAINBOW trout ,CELLULAR signal transduction ,ACTIVIN receptors ,ACTIVIN ,PLANT genomes - Abstract
The genomes of plant and animal species are influenced by ancestral whole-genome duplication (WGD) events, which have profound impacts on the regulation and function of gene networks. To gain insight into the consequences of WGD events, we characterized the sequence conservation and expression patterns of ohnologs in the highly duplicated activin receptor signaling pathway in rainbow trout (RBT). The RBT activin receptor signaling pathway is defined by tissue-specific expression of inhibitors and ligands and broad expression of receptors and Co-Smad signaling molecules. Signaling pathway ligands exhibited shared expression, while inhibitors and Smad signaling molecules primarily express a single dominant ohnolog. Our findings suggest that gene function influences ohnolog evolution following duplication of the activin signaling pathway in RBT. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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13. SMARCA4 Loss and Mutated β-Catenin Induce Proliferative Lesions in the Murine Embryonic Cerebellum.
- Author
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Göbel, Carolin, Schoof, Melanie, Holdhof, Dörthe, Spohn, Michael, and Schüller, Ulrich
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CEREBELLUM ,CEREBRAL cortex ,DNA analysis ,EMBRYOLOGY ,NEURONAL differentiation ,CATENINS ,CEREBELLAR cortex ,WNT signal transduction ,NEURAL stem cells - Abstract
Almost all medulloblastomas (MB) of the Wingless/Int-1 (WNT) type are characterized by hotspotmutations in CTNNB1, and mouse models have convincingly demonstrated the tumor-initiating role of these mutations. Additional alterations in SMARCA4 are detected in ~20% of WNT MB, but their functional role is mostly unknown. We, therefore, amended previously described brain lipid binding protein (Blbp)-cre::Ctnnb1(ex3)fl/wt mice by the introduction of floxed Smarca4 alleles. Unexpectedly, mutated and thereby stabilized ß-catenin on its own induced severe developmental phenotypes in male and female Blbp-cre::Ctnnb1(ex3)fl/wt mice in our hands, including a thinned cerebral cortex, hydrocephalus, missing cerebellar layering, and cell accumulations in the brainstem and cerebellum. An additional loss of SMARCA4 even resulted in prenatal death for most mice. Respective Blbp-cre:: Ctnnb1(ex3)fl/wt::Smarca4fl/rec mutants (male and female) developed large proliferative lesions in the cerebellum evolving from E13.5 to E16.5. Histological and molecular analysis of these lesions by DNA methylation profiling and single-cell RNA sequencing suggested an origin in early undifferentiated SOX2-positive cerebellar progenitors. Furthermore, upregulated WNT signaling, altered actin/cytoskeleton organization, and reduced neuronal differentiation were evident in mutant cells. In vitro, cells harboring alterations in both Ctnnb1 and Smarca4 were negatively selected and did not show tumorigenic potential after transplantation in adult female recipient mice. However, in cerebellar explant cultures, mutant cells displayed significantly increased proliferation, suggesting an important role of the embryonic microenvironment in the development of lesions. Altogether, these results represent an important first step toward the unraveling of tumorigenic mechanisms induced by aberrant WNT signaling and SMARCA4 deficiency. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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14. The clinical relevance of heme detoxification by the macrophage heme oxygenase system.
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Yeudall, Scott, Upchurch, Clint M., and Leitinger, Norbert
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HEME oxygenase ,HEME ,CELL death ,MACROPHAGES ,DISCRETE groups - Abstract
Heme degradation by the heme oxygenase (HMOX) family of enzymes is critical for maintaining homeostasis and limiting heme-induced tissue damage. Macrophages express HMOX1 and 2 and are critical sites of heme degradation in healthy and diseased states. Here we review the functions of the macrophage heme oxygenase system and its clinical relevance in discrete groups of pathologies where heme has been demonstrated to play a driving role. HMOX1 function in macrophages is essential for limiting oxidative tissue damage in both acute and chronic hemolytic disorders. By degrading pro-inflammatory heme and releasing anti-inflammatory molecules such as carbon monoxide, HMOX1 fine-tunes the acute inflammatory response with consequences for disorders of hyperinflammation such as sepsis. We then discuss divergent beneficial and pathological roles for HMOX1 in disorders such as atherosclerosis and metabolic syndrome, where activation of the HMOX system sits at the crossroads of chronic low-grade inflammation and oxidative stress. Finally, we highlight the emerging role for HMOX1 in regulating macrophage cell death via the iron- and oxidationdependent form of cell death, ferroptosis. In summary, the importance of heme clearance by macrophages is an active area of investigation with relevance for therapeutic intervention in a diverse array of human diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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15. Roles of reactive oxygen species in inflammation and cancer.
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Yu, Yunfei, Liu, Shengzhuo, Yang, Luchen, Song, Pan, Liu, Zhenghuan, Liu, Xiaoyang, Yan, Xin, and Dong, Qiang
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REACTIVE oxygen species ,ONCOLOGY ,CHIMERIC antigen receptors ,INFLAMMATION ,IMMUNE checkpoint proteins ,CANCER vaccines - Abstract
Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions in ROS equilibrium span various diseases, and current insights suggest a dual role for ROS in tumorigenesis and the immune response within cancer. This review rigorously examines ROS production and its role in normal cells, elucidating the subsequent regulatory network in inflammation and cancer. Comprehensive synthesis details the documented impacts of ROS on diverse immune cells. Exploring the intricate relationship between ROS and cancer immunity, we highlight its influence on existing immunotherapies, including immune checkpoint blockade, chimeric antigen receptors, and cancer vaccines. Additionally, we underscore the promising prospects of utilizing ROS and targeting ROS modulators as novel immunotherapeutic interventions for cancer. This review discusses the complex interplay between ROS, inflammation, and tumorigenesis, emphasizing the multifaceted functions of ROS in both physiological and pathological conditions. It also underscores the potential implications of ROS in cancer immunotherapy and suggests future research directions, including the development of targeted therapies and precision oncology approaches. In summary, this review emphasizes the significance of understanding ROS‐mediated mechanisms for advancing cancer therapy and developing personalized treatments. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps.
- Author
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Sonoshita M, Takaku K, Oshima M, Sugihara K, and Taketo MM
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- Actins biosynthesis, Adenomatous Polyposis Coli enzymology, Adenomatous Polyposis Coli metabolism, Adenomatous Polyposis Coli pathology, Animals, Antigens, CD34 biosynthesis, Antigens, Differentiation biosynthesis, Cyclooxygenase 2, Endothelium, Vascular cytology, Endothelium, Vascular enzymology, Endothelium, Vascular metabolism, Fibroblasts enzymology, Fibroblasts metabolism, Humans, Immunohistochemistry, Intestinal Polyps pathology, Macrophages enzymology, Macrophages metabolism, Membrane Proteins, Mice, Mice, Knockout, Stromal Cells enzymology, Stromal Cells metabolism, Vimentin biosynthesis, Intestinal Polyps enzymology, Isoenzymes biosynthesis, Prostaglandin-Endoperoxide Synthases biosynthesis
- Abstract
Cyclooxygenase-2 (COX-2), the inducible COX isozyme, plays a key role in intestinal tumorigenesis. We have demonstrated recently that COX-2 protein is induced in the polyp stroma near the intestinal luminal surface in the Apc(Delta716) mouse, a model for human familial adenomatous polyposis, and stimulate tumor angiogenesis. However, the precise cell types that express COX-2 are still to be determined. By immunohistochemical analysis, here we show that the majority of COX-2-expressing cells in the intestinal polyps of Apc(Delta716) mice are fibroblasts and endothelial cells. Furthermore, the COX-2-expressing cells in human familial adenomatous polyposis polyps are also fibroblasts and endothelial cells. In contrast, bone marrow-derived cells such as macrophages and leukocytes express little COX-2 protein in the intestinal polyps. These results clearly indicate that fibroblasts and endothelial cells play important roles in polyp expansion by expressing COX-2, resulting in tumor angiogenesis.
- Published
- 2002
17. Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene.
- Author
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Sun J, Hoshino H, Takaku K, Nakajima O, Muto A, Suzuki H, Tashiro S, Takahashi S, Shibahara S, Alam J, Taketo MM, Yamamoto M, and Igarashi K
- Subjects
- 3T3 Cells, Animals, Base Sequence, Basic-Leucine Zipper Transcription Factors, Cell Line, DNA Primers, DNA Probes, Fanconi Anemia Complementation Group Proteins, Heme Oxygenase-1, Humans, Membrane Proteins, Mice, Mice, Knockout, Polymerase Chain Reaction, Transcription Factors deficiency, Transcription Factors genetics, Transfection, Enhancer Elements, Genetic, Gene Expression Regulation, Enzymologic, Heme Oxygenase (Decyclizing) genetics, Transcription Factors metabolism
- Abstract
Heme oxygenase-1 (HO-1) protects cells from various insults including oxidative stress. Transcriptional activators, including the Nrf2/Maf heterodimer, have been the focus of studies on the inducible expression of ho-1. Here we show that a heme-binding factor, Bach1, is a critical physiological repressor of ho-1. Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo, while heme abrogated this repressor function of Bach1 by inhibiting its binding to the ho-1 enhancers. Gene targeting experiments in mice revealed that, in the absence of Bach1, ho-1 became expressed constitutively at high levels in various tissues under normal physiological conditions. By analyzing bach1/nrf2 compound-deficient mice, we documented antagonistic activities of Bach1 and Nrf2 in several tissues. Chromatin immunoprecipitation revealed that small Maf proteins participate in both repression and activation of ho-1. Thus, regulation of ho-1 involves a direct sensing of heme levels by Bach1 (by analogy to lac repressor sensitivity to lactose), generating a simple feedback loop whereby the substrate effects repressor-activator antagonism.
- Published
- 2002
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18. No effects of Smad2 (madh2) null mutation on malignant progression of intestinal polyps in Apc(delta716) knockout mice.
- Author
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Takaku K, Wrana JL, Robertson EJ, and Taketo MM
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- Animals, Disease Progression, Female, Heterozygote, Intestinal Polyps pathology, Loss of Heterozygosity, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Polymerase Chain Reaction, Smad2 Protein, DNA-Binding Proteins genetics, Genes, APC, Intestinal Polyps genetics, Trans-Activators genetics
- Abstract
The loss of heterozygosity (LOH) in human chromosome 18q21 is found at high frequencies in advanced pancreatic and colorectal cancers. Several candidate tumor suppressor genes, such as SMAD2, SMAD4, and DCC, are located in this region. The homologues of these genes in the mouse are also clustered on chromosome 18. Mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis, and we earlier constructed a mouse model for familial adenomatous polyposis, Apc(delta716). Although human APC is located on chromosome 5q, mouse Apc is on chromosome 18, 30 cM proximal to the Dcc-Smad4-Smad2 locus. Taking advantage of this fact, we constructed previously a cis-compound Apc(delta716) Smad4 mutant, the intestinal polyps of which progress to very invasive adenocarcinomas. To determine whether Smad2 mutations play similar roles in malignant progression, here we constructed compound mutant mice carrying Apc and Smad2 knockouts in the cis configuration. In contrast to the cis-compound Apc(delta716) Smad4 heterozygotes, the polyps in the cis-compound Apc(delta716) Smad2 heterozygotes showed no difference in the number, size, or histopathology from the polyps in the simple Apc(delta716) heterozygotes. These results suggest that, on human chromosome 18q21, the SMAD4 LOH plays a more significant role, and SMAD2 LOH is insufficient to cause malignant progression of colonic polyps.
- Published
- 2002
19. Cyclooxygenase 2- and prostaglandin E(2) receptor EP(2)-dependent angiogenesis in Apc(Delta716) mouse intestinal polyps.
- Author
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Seno H, Oshima M, Ishikawa TO, Oshima H, Takaku K, Chiba T, Narumiya S, and Taketo MM
- Subjects
- Adenocarcinoma blood supply, Adenocarcinoma genetics, Adenocarcinoma metabolism, Adenocarcinoma pathology, Adenoma blood supply, Adenoma genetics, Adenoma metabolism, Adenoma pathology, Animals, Cyclooxygenase 2, Endothelial Growth Factors biosynthesis, Fibroblast Growth Factor 2 biosynthesis, Gene Expression, Intestinal Polyps genetics, Intestinal Polyps metabolism, Intestinal Polyps pathology, Isoenzymes biosynthesis, Isoenzymes genetics, Lymphokines biosynthesis, Mice, Mice, Knockout, Neovascularization, Pathologic enzymology, Neovascularization, Pathologic genetics, Prostaglandin-Endoperoxide Synthases biosynthesis, Prostaglandin-Endoperoxide Synthases genetics, Receptors, Prostaglandin E biosynthesis, Receptors, Prostaglandin E genetics, Receptors, Prostaglandin E, EP2 Subtype, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Intestinal Polyps blood supply, Isoenzymes physiology, Neovascularization, Pathologic metabolism, Prostaglandin-Endoperoxide Synthases physiology, Receptors, Prostaglandin E physiology
- Abstract
To investigate angiogenesis during intestinal polyp development, we determined the microvessel density (MVD) in polyps of Apc knockout (Apc(Delta716)) mice, a model for human familial adenomatous polyposis. We scored MVD also in several compound mutants carrying Apc(Delta716), namely, mice with an additional mutation in Smad4, in which the polyps progress into invasive adenocarcinomas; mice with a cyclooxygenase (COX)-2 gene (Ptgs2) mutation, in which adenoma growth is suppressed; and mice with prostaglandin E(2) EP receptor gene mutations. In both simple Apc(Delta716) and compound Apc(Delta716) Smad4 mutants, MVD increased in a polyp size-dependent manner only in the polyps expanded beyond a threshold of about 1 mm in diameter. These results indicate that tumor angiogenesis is stimulated only after tumors grow to a certain size, and this angiogenic switch is common to both benign adenomas and malignant adenocarcinomas. In Apc(Delta716) polyposis attenuated by the COX-2 gene mutation, in contrast, MVD did not increase even in polyps larger than 1 mm. The same phenomenon was observed in the compound mutant mice with Apc(Delta716) and the EP(2) receptor gene mutations, but not in other EP compound mutants. We also immunohistochemically studied COX-2 and angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor. Interestingly, expression of these proteins was also increased in polyps larger than 1 mm. These results suggest that, in both benign and malignant mouse intestinal tumors, stromal expression of COX-2 results in elevated prostaglandin E(2) levels that stimulate cell surface receptor EP(2), followed by induction of vascular endothelial growth factor that causes tumor angiogenesis.
- Published
- 2002
20. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice.
- Author
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Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F, Narumiya S, Oshima M, and Taketo MM
- Subjects
- Adenoma genetics, Adenoma pathology, Adenomatous Polyposis Coli pathology, Animals, Cyclooxygenase 2, Dinoprostone metabolism, Endothelial Growth Factors genetics, Homozygote, Isoenzymes genetics, Lymphokines genetics, Mice, Mice, Knockout, Prostaglandin-Endoperoxide Synthases genetics, Receptors, Prostaglandin genetics, Receptors, Prostaglandin metabolism, Receptors, Prostaglandin E metabolism, Receptors, Prostaglandin E, EP1 Subtype, Receptors, Prostaglandin E, EP2 Subtype, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli physiopathology, Isoenzymes metabolism, Prostaglandin-Endoperoxide Synthases metabolism, Receptors, Prostaglandin E genetics
- Abstract
Arachidonic acid is metabolized to prostaglandin H(2) (PGH(2)) by cyclooxygenase (COX). COX-2, the inducible COX isozyme, has a key role in intestinal polyposis. Among the metabolites of PGH(2), PGE(2) is implicated in tumorigenesis because its level is markedly elevated in tissues of intestinal adenoma and colon cancer. Here we show that homozygous deletion of the gene encoding a cell-surface receptor of PGE(2), EP2, causes decreases in number and size of intestinal polyps in Apc(Delta 716) mice (a mouse model for human familial adenomatous polyposis). This effect is similar to that of COX-2 gene disruption. We also show that COX-2 expression is boosted by PGE(2) through the EP2 receptor via a positive feedback loop. Homozygous gene knockout for other PGE(2) receptors, EP1 or EP3, did not affect intestinal polyp formation in Apc(Delta 716) mice. We conclude that EP2 is the major receptor mediating the PGE2 signal generated by COX-2 upregulation in intestinal polyposis, and that increased cellular cAMP stimulates expression of more COX-2 and vascular endothelial growth factor in the polyp stroma.
- Published
- 2001
- Full Text
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21. A mutant Escherichia coli tyrosyl-tRNA synthetase utilizes the unnatural amino acid azatyrosine more efficiently than tyrosine.
- Author
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Hamano-Takaku F, Iwama T, Saito-Yano S, Takaku K, Monden Y, Kitabatake M, Soll D, and Nishimura S
- Subjects
- Alanine analogs & derivatives, Base Sequence, DNA Primers, Genes, Bacterial, Models, Molecular, Mutagenesis, Plasmids, Protein Conformation, Tyrosine-tRNA Ligase chemistry, Tyrosine-tRNA Ligase genetics, Alanine metabolism, Escherichia coli enzymology, Tyrosine metabolism, Tyrosine-tRNA Ligase metabolism
- Abstract
Alloproteins, proteins that contain unnatural amino acids, have immense potential in biotechnology and medicine. Although various approaches for alloprotein production exist, there is no satisfactory method to produce large quantities of alloproteins containing unnatural amino acids in specific positions. The tyrosine analogue azatyrosine, l-beta-(5-hydroxy-2-pyridyl)-alanine, can convert the ras-transformed phenotype to normal phenotype, presumably by its incorporation into cellular proteins. This provided the stimulus for isolation of a mutant tyrosyl-tRNA synthetase (TyrRS) capable of charging azatyrosine to tRNA. A plasmid library of randomly mutated Escherichia coli tyrS (encoding TyrRS) was made by polymerase chain reaction techniques. The desired TyrRS mutants were selected by screening for in vivo azatyrosine incorporation of E. coli cells transformed with the mutant tyrS plasmids. One of the clones thus isolated, R-6-A-7, showed a 17-fold higher in vivo activity for azatyrosine incorporation than wild-type TyrRS. The mutant tyrS gene contained a single point mutation resulting in replacement of phenylalanine by serine at position 130 in the protein. Structural modeling revealed that position 130 is located close to Asp(182), which directly interacts with tyrosyladenylate. Kinetic analysis of aminoacyl-tRNA formation by the wild-type and mutated F130S TyrRS enzymes showed that the specificity for azatyrosine, measured by the ratios of k(cat)/K(m) for tyrosine and the analogue, increased from 17 to 36 as a result of the F130S mutation. Thus, the high discrimination against azatyrosine is significantly reduced in the mutant enzyme. These results suggest that utilization of F130S TyrRS for in vivo protein biosynthesis may lead to efficient production of azatyrosine-containing alloproteins.
- Published
- 2000
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22. Suppression of intestinal polyposis in Apc(delta 716) knockout mice by an additional mutation in the cytosolic phospholipase A(2) gene.
- Author
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Takaku K, Sonoshita M, Sasaki N, Uozumi N, Doi Y, Shimizu T, and Taketo MM
- Subjects
- Animals, Base Sequence, DNA Primers, Intestinal Polyps enzymology, Intestinal Polyps pathology, Mice, Mice, Knockout, RNA, Messenger genetics, Cytosol enzymology, Genes, APC, Mutation, Phospholipases A genetics
- Abstract
Arachidonic acid is a precursor for biosynthesis of eicosanoids, including prostaglandins, thromboxanes, leukotrienes, and lipoxins. Cytosolic phospholipase A(2) (cPLA(2)) plays a key role in the release of arachidonic acid as the substrate of cyclooxygenase-1 (COX-1) or COX-2. We found that the level of cPLA(2) mRNA was markedly elevated in the polyps and correlated with the polyp size in the small intestine of the Apc(delta)(716) knockout mouse, a model for human familial adenomatous polyposis. To determine the role of cPLA(2) in intestinal tumorigenesis, we then introduced a cPLA(2) gene mutation into Apc(delta)(716) mice. In the compound mutant mice, the size of the small intestinal polyps was reduced significantly, although the numbers remained unchanged. These results provide direct genetic evidence that cPLA(2) plays a key role in the expansion of polyps in the small intestine rather than in the initiation process. In contrast, colonic polyps were not affected in either size or number. Interestingly, group X sPLA(2) was constitutively expressed in the colon at much higher levels than in the small intestine. These results suggest that in the colon, group X sPLA(2) supplies arachidonic acid in both the normal epithelium and the polyps even in the absence of cPLA(2).
- Published
- 2000
- Full Text
- View/download PDF
23. Gastric and duodenal polyps in Smad4 (Dpc4) knockout mice.
- Author
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Takaku K, Miyoshi H, Matsunaga A, Oshima M, Sasaki N, and Taketo MM
- Subjects
- Animals, DNA-Binding Proteins deficiency, DNA-Binding Proteins metabolism, Duodenal Neoplasms pathology, Genes, Tumor Suppressor, Heterozygote, Humans, Intestinal Polyps pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Polyps pathology, Smad4 Protein, Stomach Neoplasms pathology, Trans-Activators deficiency, Trans-Activators metabolism, DNA-Binding Proteins genetics, Duodenal Neoplasms genetics, Intestinal Polyps genetics, Polyps genetics, Stomach Neoplasms genetics, Trans-Activators genetics
- Abstract
The SMAD4 (DPC4) gene was initially isolated as a candidate tumor suppressor from the convergent site of homozygous deletions on 18q in a panel of pancreatic carcinoma cell lines. It encodes a common cytoplasmic signaling molecule shared by the transforming growth factor-beta, activin, and bone morphogenic pathways. We recently inactivated its mouse homologue Smad4 and demonstrated its role in the malignant progression of benign adenomas to invasive adenocarcinomas by analyzing mice with Apc and Smad4 compound mutations. Although simple Smad4 homozygotes were embryonically lethal, the heterozygotes were fertile and appeared normal up to the age of 1 year. Upon further investigation, however, they have developed inflammatory polyps in the glandular stomach and duodenum. By PCR genotyping and immunohistochemical staining, the wild-type Smad4 allele has been lost in the polyp epithelial cells, ie., loss of heterozygosity. On the other hand, we have not found any mutations in such genes as K-Ras, H-Ras, N-Ras, p53, or PTEN. Histologically, the polyps are similar to human juvenile polyps showing moderate stromal cell proliferation and infiltrations by eosinophils and plasma cells. In addition, foci of adenocarcinoma with signet ring cells are also found. These results are consistent with a recent report that germ-line SMAD4 mutations are found in a subset of familial juvenile polyposis.
- Published
- 1999
24. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene.
- Author
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Harada N, Tamai Y, Ishikawa T, Sauer B, Takaku K, Oshima M, and Taketo MM
- Subjects
- Animals, Colonic Neoplasms genetics, Disease Models, Animal, Gene Targeting methods, Genes, Dominant, Integrases genetics, Intestinal Neoplasms genetics, Intestinal Polyps pathology, Mice, Mice, Knockout, Mutation, Proto-Oncogene Proteins genetics, Recombination, Genetic, Signal Transduction genetics, Stem Cells, Wnt Proteins, beta Catenin, Cytoskeletal Proteins genetics, Intestinal Polyps genetics, Trans-Activators, Viral Proteins, Zebrafish Proteins
- Abstract
Ectopic expression of certain Wnt genes in mouse mammary tissue is tumorigenic, and mutations that stabilize beta-catenin are found in various human cancers including colorectal cancer. To determine the role of stabilized beta-catenin in intestinal tumorigenesis in mice, we constructed by embryonic stem (ES) cell-mediated homologous recombination, a mutant beta-catenin allele whose exon 3 was sandwiched by loxP sequences. When the germline heterozygotes were crossed with mice expressing Cre recombinase in the intestines, the serines and threonine encoded by exon 3 and to be phosphorylated by glycogen synthase kinase 3beta (GSK3beta) were deleted in the offspring intestines, which caused adenomatous intestinal polyps resembling those in Apc(Delta716) knockout mice. Some nascent microadenomas were also found in the colon. These results present experimental genetic evidence that activation of the Wnt signaling pathway can cause intestinal and colonic tumors.
- Published
- 1999
- Full Text
- View/download PDF
25. Colonic hamartoma development by anomalous duplication in Cdx2 knockout mice.
- Author
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Tamai Y, Nakajima R, Ishikawa T, Takaku K, Seldin MF, and Taketo MM
- Subjects
- Animals, CDX2 Transcription Factor, Cecal Diseases genetics, Cecal Diseases pathology, Chorionic Villi pathology, Chromosome Mapping, Colonic Diseases embryology, Colonic Diseases pathology, Epithelium metabolism, Hamartoma embryology, Hamartoma pathology, Homeodomain Proteins metabolism, Lac Operon, Mice, Mice, Knockout, Trans-Activators, Colonic Diseases genetics, Hamartoma genetics, Homeodomain Proteins genetics
- Abstract
To determine the biological role of caudal-like homeobox gene CDX2, we constructed knockout mice in which its mouse homologue Cdx2 was inactivated by homologous recombination, placing a bacterial lacZ gene under the control of the Cdx2 promoter. Although the homozygous mutants died in utero around implantation, the heterozygotes were viable and fertile and expressed lacZ in the caudal region in early embryos and in the gut tissues in adults. The heterozygotes developed cecal and colonic villi by anteriorization and formed hamartomatous polyps in the proximal colon. The hamartoma started to develop at 11.5 days of gestation as an outpocket of the gut epithelium, which ceased to express the remaining Cdx2 allele. The outpocket then expanded as a partially duplicated gut but was contained as a hamartoma after birth. In adult mice, these hamartomas grew very slowly and took a benign course. None of them progressed into invasive adenocarcinomas, even at 1.5 years of age. Whereas the cecal and colonic villi expressed lacZ, the hamartoma epithelium did not, nor did it express Cdx2 mRNA from the wild-type allele. However, genomic DNA analysis of the polyp epithelium did not show a loss of heterozygosity of the Cdx2 gene, suggesting a mechanism of biallelic Cdx2 inactivation other than loss of heterozygosity. These results indicate that the Cdx2 haploin-sufficiency caused cecal and colonic villi, whereas the biallelic inactivation of Cdx2 triggered anomalous duplications of the embryonic gut epithelium, which were contained as hamartomas after birth.
- Published
- 1999
26. Size- and invasion-dependent increase in cyclooxygenase 2 levels in human colorectal carcinomas.
- Author
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Fujita T, Matsui M, Takaku K, Uetake H, Ichikawa W, Taketo MM, and Sugihara K
- Subjects
- Adult, Aged, Aged, 80 and over, Base Sequence, Colorectal Neoplasms pathology, Colorectal Neoplasms prevention & control, Cyclooxygenase 1, Female, Humans, Isoenzymes genetics, Male, Membrane Proteins, Middle Aged, Molecular Sequence Data, Neoplasm Invasiveness, Prostaglandin-Endoperoxide Synthases genetics, Colorectal Neoplasms enzymology, Cyclooxygenase Inhibitors therapeutic use, Isoenzymes biosynthesis, Prostaglandin-Endoperoxide Synthases biosynthesis
- Abstract
Nonsteroidal anti-inflammatory drugs reduce the incidence and mortality of colorectal carcinoma. Their chemopreventive effects appear to be due to inhibition of cyclooxygenase (COX)-2. Here, we have studied the relationship between the COX-2 mRNA levels and pathological characteristics in 43 primary colorectal carcinomas. COX-2 levels were significantly higher in tumors with larger sizes and in those with deeper invasions but were not correlated with whether the patients had metastasis or not. These results suggest that larger carcinomas produce more COX-2 to support their own growth and that COX-2 inhibitors may be effective agents of carcinoma growth suppression.
- Published
- 1998
27. Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes.
- Author
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Takaku K, Oshima M, Miyoshi H, Matsui M, Seldin MF, and Taketo MM
- Subjects
- Adenocarcinoma chemistry, Adenocarcinoma pathology, Adenomatous Polyposis Coli pathology, Animals, Chromosome Deletion, Colonic Neoplasms chemistry, Colonic Neoplasms pathology, Crosses, Genetic, Disease Progression, Duodenal Neoplasms chemistry, Duodenal Neoplasms pathology, Heterozygote, Homozygote, Humans, Intestinal Polyps chemistry, Intestinal Polyps genetics, Intestinal Polyps pathology, Intestine, Small, Loss of Heterozygosity, Mice, Mice, Knockout, Neoplasm Invasiveness, Smad4 Protein, Trans-Activators analysis, Tumor Cells, Cultured, Adenocarcinoma genetics, Adenomatous Polyposis Coli genetics, Colonic Neoplasms genetics, DNA-Binding Proteins, Genes, APC physiology, Genes, Tumor Suppressor physiology, Trans-Activators genetics
- Abstract
The DPC4 (SMAD4) gene plays a key role in the TGFbeta signaling pathway. We inactivated its mouse homolog Dpc4 (Smad4). The homozygous mutants were embryonic lethal, whereas the heterozygotes showed no abnormality. We then introduced the Dpc4 mutation into the Apc(delta716) knockout mice, a model for human familial adenomatous polyposis. Because both Apc and Dpc4 are located on chromosome 18, we constructed compound heterozygotes carrying both mutations on the same chromosome by meiotic recombination. In such mice, intestinal polyps developed into more malignant tumors than those in the simple Apc(delta716) heterozygotes, showing an extensive stromal cell proliferation, submucosal invasion, cell type heterogeneity, and in vivo transplantability. These results indicate that mutations in DPC4 (SMAD4) play a significant role in the malignant progression of colorectal tumors.
- Published
- 1998
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28. Early embryonic lethality caused by targeted disruption of the mouse selenocysteine tRNA gene (Trsp).
- Author
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Bösl MR, Takaku K, Oshima M, Nishimura S, and Taketo MM
- Subjects
- Animals, Blastocyst cytology, Blastocyst physiology, Crosses, Genetic, Female, Gene Dosage, Glutathione Peroxidase biosynthesis, Heterozygote, Homozygote, Kidney enzymology, Liver enzymology, Male, Mice, Mice, Knockout, Polymerase Chain Reaction, Pregnancy, Recombination, Genetic, Stem Cells, Chromosome Mapping, Genes, Lethal, RNA, Transfer, Amino Acid-Specific genetics
- Abstract
Selenoprotein biosynthesis is mediated by tRNASec, which inserts selenocysteine at UGA codons in a complex, context-specific manner. This opal suppressor serves in the conversion of serine to selenocysteine as well. The mouse tRNASec gene (Trsp) maps to a proximal segment of chromosome 7. We constructed mice carrying a targeted deletion of the Trsp gene. The heterozygous mutants were viable, fertile, and appeared normal. Although the level of tRNASec was reduced to about 50%-80% of the wild type in most organs, one of the selenoproteins, glutathione peroxidase, remained unaffected in the levels of its mRNA, protein, and enzyme activity, indicating that the haploid amount of tRNASec is not limiting in its biosynthesis. In contrast, the homozygous mutants died shortly after implantation, and the embryos were resorbed before 6.5 days post coitum. When the preimplantation embryos were placed in culture, however, the trophoectoderm cells showed outgrowths and the inner cell mass cells of the homozygous embryos were able to proliferate. These results indicate that Trsp expression is essential for early development of the embryo, and its lack causes peri-implantation lethality. However, the lethality does not appear to be due to a cell-autonomous function of tRNASec.
- Published
- 1997
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- View/download PDF
29. Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene.
- Author
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Matsui M, Oshima M, Oshima H, Takaku K, Maruyama T, Yodoi J, and Taketo MM
- Subjects
- Animals, Blastocyst cytology, Cell Division, Decidua, Female, Gene Targeting, Genes physiology, Homozygote, Mice, Mice, Knockout, Organ Culture Techniques, Phenotype, Blastocyst physiology, Embryonic and Fetal Development genetics, Thioredoxins genetics
- Abstract
Thioredoxins belong to a widely distributed group of small proteins with strong reducing activities mediated by a consensus redox-active dithiol (Cys-Gly-Pro-Cys). Thioredoxin was first isolated as a hydrogen donor for enzymatic synthesis of deoxyribonucleotides by ribonucleotide reductase in Escherichia coli. Recent studies have revealed a variety of roles that thioredoxin plays in transcription, growth control, and immune function. In this report, we describe the phenotype of mice carrying a targeted disruption of the thioredoxin gene (Txn). Heterozygotes are viable, fertile, and appear normal. In contrast, homozygous mutants die shortly after implantation, and the concepti were resorbed prior to gastrulation. When preimplantation embryos were placed in culture, the inner cell mass cells of the homozygous embryos failed to proliferate. These results indicate that Txn expression is essential for early differentiation and morphogenesis of the mouse embryo.
- Published
- 1996
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- View/download PDF
30. Screening for specific inhibitors of phagocytosis of thioglycollate-elicited macrophages.
- Author
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Magae J, Nagi T, Takaku K, Kataoka T, Koshino H, Uramoto M, and Nagai K
- Subjects
- Actinomyces immunology, Animals, Female, In Vitro Techniques, Macrophages immunology, Mice, Mice, Inbred C3H, Macrophages drug effects, Phagocytosis drug effects, Thioglycolates pharmacology
- Abstract
Phagocytosis is one of the basic and characteristic properties of macrophages. We screened metabolites of Actinomyces for low molecular weight substances that selectively inhibited phagocytosis of dried yeast but not pinocytosis of neutral red by thioglycollate-elicited peritoneal macrophages. Inhibitors of actin filament organization, protein kinases, respiration, and lipid synthesis selectively inhibited phagocytosis, and blockers of proton gradients selectively inhibited pinocytosis. This suggests that these functions are differently regulated. We applied this system to screening of metabolites of Actinomyces, and identified mycotrienin, piericidin, and genistein as selective inhibitors of phagocytosis.
- Published
- 1994
- Full Text
- View/download PDF
31. TGF-β signaling in health, disease, and therapeutics.
- Author
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Deng, Ziqin, Fan, Tao, Xiao, Chu, Tian, He, Zheng, Yujia, Li, Chunxiang, and He, Jie
- Published
- 2024
- Full Text
- View/download PDF
32. Mesenchyme instructs growth while epithelium directs branching in the mouse mammary gland.
- Author
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Qiang Lan, Trela, Ewelina, Lindström, Riitta, Satta, Jyoti Prabha, Kaczyńska, Beata, Christensen, Mona M., Holzenberger, Martin, Jernvall, Jukka, and Mikkola, Marja L.
- Published
- 2024
- Full Text
- View/download PDF
33. Insights into the Multifaceted Roles of Thioredoxin-1 System: Exploring Knockout Murine Models.
- Author
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Shcholok, Tetiana and Eftekharpour, Eftekhar
- Subjects
OXIDATION-reduction reaction ,PROTEOMICS ,THIOREDOXIN ,REACTIVE oxygen species ,CELL communication ,CYSTEINE - Abstract
Simple Summary: This article reviews the biological importance of the Thioredoxin-1 system in different cells and organs. Redox balance, defined by an equilibrium between oxidized and reduced molecules, is crucial for proper cellular functions in health. Disruption of this balance may lead to cell death. Oxidation and reduction of cysteine residues in key signaling molecules changes their structural conformation and function. Thioredoxin-1 is a key regulatory protein that is used as a buffer to maintain the proteins in their optimal shape. In this review, we specifically focus on transgenic animal models related to the Thioredoxin-1 system. This review aims to showcase the specific roles of the Thioredoxin-1 system in maintaining balance in various organs and cell types. Redox balance is increasingly identified as a major player in cellular signaling. A fundamentally simple reaction of oxidation and reduction of cysteine residues in cellular proteins is the central concept in this complex regulatory mode of protein function. Oxidation of key cysteine residues occurs at the physiological levels of reactive oxygen species (ROS), but they are reduced by a supply of thiol antioxidant molecules including glutathione, glutaredoxin, and thioredoxin. While these molecules show complex compensatory roles in experimental conditions, transgenic animal models provide a comprehensive picture to pinpoint the role of each antioxidant. In this review, we have specifically focused on the available literature on thioredoxin-1 system transgenic models that include thioredoxin and thioredoxin reductase proteins. As the identification of thioredoxin protein targets is technically challenging, the true contribution of this system in maintaining cellular balance remains unidentified, including the role of this system in the brain. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
34. Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution.
- Author
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Hong, Yuhang, Boiti, Alessandra, Vallone, Daniela, and Foulkes, Nicholas S.
- Subjects
REACTIVE oxygen species ,GENETIC transcription regulation ,OXIDATIVE stress ,CELL physiology ,CELL communication ,HOMEOSTASIS - Abstract
Since the evolution of the aerobic metabolism, reactive oxygen species (ROS) have represented significant challenges to diverse life forms. In recent decades, increasing knowledge has revealed a dual role for ROS in cell physiology, showing they serve as a major source of cellular damage while also functioning as important signaling molecules in various biological processes. Our understanding of ROS homeostasis and ROS-mediated cellular signaling pathways has presumed that they are ancient and highly conserved mechanisms shared by most organisms. However, emerging evidence highlights the complexity and plasticity of ROS signaling, particularly in animals that have evolved in extreme environments. In this review, we focus on ROS generation, antioxidative systems and the main signaling pathways that are influenced by ROS. In addition, we discuss ROS's responsive transcription regulation and how it may have been shaped over the course of evolution. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. Fusobacterium nucleatum bacteremia complicated with intracranial Porphyromonas gingivalis and HSV-1 infection: a case report and literature review.
- Author
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Wang, Sumei, Tian, Yaqiong, Wu, Yujing, Yu, Zhen, Zhang, Jinjuan, Zhang, Jiandong, and Liu, Shuye
- Subjects
PORPHYROMONAS gingivalis infections ,LITERATURE reviews ,HUMAN herpesvirus 1 ,NUCLEOTIDE sequencing ,FUSOBACTERIUM - Abstract
Background: Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection. Case presentation: A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged. Conclusion: To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
36. Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy.
- Author
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Hu, Dian, Zhang, Zerui, Luo, Xiangyuan, Li, Siwen, Jiang, Junqing, Zhang, Jiaqian, Wu, Zhangfan, Wang, Yijun, Sun, Mengyu, Chen, Xiaoping, Zhang, Bixiang, Xu, Xiao, Wang, Shuai, Xu, Shengjun, Wang, Yufei, Huang, Wenjie, and Xia, Limin
- Subjects
TRANSCRIPTION factors ,TARGETED drug delivery ,LEUCINE zippers ,TUMOR microenvironment ,OXIDATIVE stress - Abstract
Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
37. Monogenic Disorders of ROS Production and the Primary Anti-Oxidative Defense.
- Author
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Grüning, Nana-Maria and Ralser, Markus
- Subjects
HOMEOSTASIS ,HEART block ,REACTIVE oxygen species ,NICOTINAMIDE adenine dinucleotide phosphate ,DEFENSE mechanisms (Psychology) ,OXIDATIVE stress ,METABOLIC disorders - Abstract
Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the cellular anti-oxidant defense mechanisms, plays a critical role in the pathogenesis of various human diseases. Redox metabolism, comprising a network of enzymes and genes, serves as a crucial regulator of ROS levels and maintains cellular homeostasis. This review provides an overview of the most important human genes encoding for proteins involved in ROS generation, ROS detoxification, and production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), and the genetic disorders that lead to dysregulation of these vital processes. Insights gained from studies on inherited monogenic metabolic diseases provide valuable basic understanding of redox metabolism and signaling, and they also help to unravel the underlying pathomechanisms that contribute to prevalent chronic disorders like cardiovascular disease, neurodegeneration, and cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
38. Public investment as a growth driver for a commodity-exporting economy: Sizing up the fiscal-monetary involvement.
- Author
-
Shvets, Serhii
- Subjects
PUBLIC investments ,FISCAL policy ,ECONOMIES of scale ,ECONOMIC indicators ,PUBLIC debts ,PUBLIC finance ,SOVEREIGN wealth funds - Abstract
The study presents a solution to maximize public investment as a growth driver for commodity-exporting economies. The solution is to compensate for the low efficiency of public investment by drawing on internal and external factors within an active fiscal and monetary policy framework. For this, the paper introduces a quantitative model that implements a golden rule of public finance in a resource boom backed by a sovereign wealth fund under an active monetary policy stance. The modeling results show that mobilizing windfall resource revenues to finance increased public investment can limit a crowding-out effect through proper resource allocation and change the sectoral structure in favor of the final goods sector. As confirmed by the sensitivity analysis, the low efficiency of public investment can be partially offset by a less restrictive monetary policy response to fiscal dominance, but this leads to excessive volatility in financial indicators. However, if the public debt burden is an issue due to a more robust fiscal dominance regime, a higher tax rate on exported raw materials can be used to maintain sustainability. By developing a policy goals domain, the paper initiates a discussion that can direct policy recommendations toward a promising growth path by maximizing the public investment driver in the complex policy environment of fiscal-monetary interaction. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections.
- Author
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Daskou, Maria, Fotooh Abadi, Leila, Gain, Chandrima, Wong, Michael, Sharma, Eashan, Kombe Kombe, Arnaud John, Nanduri, Ravikanth, and Kelesidis, Theodoros
- Subjects
NUCLEAR factor E2 related factor ,VIRUS diseases ,RESPIRATORY infections ,RESPIRATORY syncytial virus ,VIRAL replication ,PORCINE reproductive & respiratory syndrome - Abstract
In humans, acute and chronic respiratory infections caused by viruses are associated with considerable morbidity and mortality. Respiratory viruses infect airway epithelial cells and induce oxidative stress, yet the exact pathogenesis remains unclear. Oxidative stress activates the transcription factor NRF2, which plays a key role in alleviating redox-induced cellular injury. The transcriptional activation of NRF2 has been reported to affect both viral replication and associated inflammation pathways. There is complex bidirectional crosstalk between virus replication and the NRF2 pathway because virus replication directly or indirectly regulates NRF2 expression, and NRF2 activation can reversely hamper viral replication and viral spread across cells and tissues. In this review, we discuss the complex role of the NRF2 pathway in the regulation of the pathogenesis of the main respiratory viruses, including coronaviruses, influenza viruses, respiratory syncytial virus (RSV), and rhinoviruses. We also summarize the scientific evidence regarding the effects of the known NRF2 agonists that can be utilized to alter the NRF2 pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. Targeting the Metabolic Paradigms in Cancer and Diabetes.
- Author
-
Bosso, Mira, Haddad, Dania, Al Madhoun, Ashraf, and Al-Mulla, Fahd
- Subjects
TYPE 2 diabetes ,DIABETES ,LIPOIC acid ,OXIDATIVE phosphorylation ,INSULIN resistance - Abstract
Dysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 diabetes (T2D), focusing specifically on the contrasting roles of oxidative phosphorylation (OXPHOS) and glycolysis as primary energy-generating pathways within cells. Building on earlier research, we explore how a shift towards one pathway over the other serves as a foundational aspect in the development of cancer and T2D. Unlike previous reviews, we posit that this shift may occur in seemingly opposing yet complementary directions, akin to the Yin and Yang concept. These metabolic fluctuations reveal an intricate network of underlying defective signaling pathways, orchestrating the pathogenesis and progression of each disease. The Warburg phenomenon, characterized by the prevalence of aerobic glycolysis over minimal to no OXPHOS, emerges as the predominant metabolic phenotype in cancer. Conversely, in T2D, the prevailing metabolic paradigm has traditionally been perceived in terms of discrete irregularities rather than an OXPHOS-to-glycolysis shift. Throughout T2D pathogenesis, OXPHOS remains consistently heightened due to chronic hyperglycemia or hyperinsulinemia. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, featuring differential tissue-specific alterations that affect OXPHOS. Recent findings suggest that addressing the metabolic imbalance in both cancer and diabetes could offer an effective treatment strategy. Numerous pharmaceutical and nutritional modalities exhibiting therapeutic effects in both conditions ultimately modulate the OXPHOS–glycolysis axis. Noteworthy nutritional adjuncts, such as alpha-lipoic acid, flavonoids, and glutamine, demonstrate the ability to reprogram metabolism, exerting anti-tumor and anti-diabetic effects. Similarly, pharmacological agents like metformin exhibit therapeutic efficacy in both T2D and cancer. This review discusses the molecular mechanisms underlying these metabolic shifts and explores promising therapeutic strategies aimed at reversing the metabolic imbalance in both disease scenarios. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?
- Author
-
Glorieux, Christophe, Enríquez, Cinthya, González, Constanza, Aguirre-Martínez, Gabriela, and Buc Calderon, Pedro
- Subjects
NUCLEAR factor E2 related factor ,CANCER stem cells ,LINCRNA - Abstract
Physiological concentrations of reactive oxygen species (ROS) play vital roles in various normal cellular processes, whereas excessive ROS generation is central to disease pathogenesis. The nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor that regulates the cellular antioxidant systems in response to oxidative stress by governing the expression of genes encoding antioxidant enzymes that shield cells from diverse oxidative alterations. NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) have been the focus of numerous investigations in elucidating whether NRF2 suppresses tumor promotion or conversely exerts pro-oncogenic effects. NRF2 has been found to participate in various pathological processes, including dysregulated cell proliferation, metabolic remodeling, and resistance to apoptosis. Herein, this review article will examine the intriguing role of phase separation in activating the NRF2 transcriptional activity and explore the NRF2 dual impacts on tumor immunology, cancer stem cells, metastasis, and long non-coding RNAs (LncRNAs). Taken together, this review aims to discuss the NRF2 multifaceted roles in both cancer prevention and promotion while also addressing the advantages, disadvantages, and limitations associated with modulating NRF2 therapeutically in cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
42. The Damping of Effect Pre-excitation for Inrush Currents of 3-Phase Induction Motor
- Author
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TAKAKU, K., primary and AMANO, H., additional
- Published
- 1972
- Full Text
- View/download PDF
43. Metabolite itaconate in host immunoregulation and defense.
- Author
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Yang, Wenchang, Wang, Yaxin, Tao, Kaixiong, and Li, Ruidong
- Abstract
Metabolic states greatly influence functioning and differentiation of immune cells. Regulating the metabolism of immune cells can effectively modulate the host immune response. Itaconate, an intermediate metabolite derived from the tricarboxylic acid (TCA) cycle of immune cells, is produced through the decarboxylation of cis-aconitate by cis-aconitate decarboxylase in the mitochondria. The gene encoding cis-aconitate decarboxylase is known as immune response gene 1 (IRG1). In response to external proinflammatory stimulation, macrophages exhibit high IRG1 expression. IRG1/itaconate inhibits succinate dehydrogenase activity, thus influencing the metabolic status of macrophages. Therefore, itaconate serves as a link between macrophage metabolism, oxidative stress, and immune response, ultimately regulating macrophage function. Studies have demonstrated that itaconate acts on various signaling pathways, including Keap1-nuclear factor E2-related factor 2-ARE pathways, ATF3–IκBζ axis, and the stimulator of interferon genes (STING) pathway to exert antiinflammatory and antioxidant effects. Furthermore, several studies have reported that itaconate affects cancer occurrence and development through diverse signaling pathways. In this paper, we provide a comprehensive review of the role IRG1/itaconate and its derivatives in the regulation of macrophage metabolism and functions. By furthering our understanding of itaconate, we intend to shed light on its potential for treating inflammatory diseases and offer new insights in this field. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model, cellular platform, and clinical human data.
- Author
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Zohud, Osayd, Lone, Iqbal M., Nashef, Aysar, and Iraqi, Fuad A.
- Published
- 2023
- Full Text
- View/download PDF
45. Colorectal Cancer Liver Metastasis—State-of-the-Art and Future Perspectives.
- Author
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Ruivo, Ana, Oliveira, Rui Caetano, Silva-Vaz, Pedro, and Tralhão, José Guilherme
- Subjects
COMPUTER software ,ADJUVANT chemotherapy ,IMMUNE checkpoint inhibitors ,LIVER ,OPERATIVE surgery ,PATIENT selection ,CANCER chemotherapy ,METASTASIS ,INDIVIDUALIZED medicine ,IMMUNE system ,COLORECTAL cancer ,TREATMENT effectiveness ,MOLECULAR biology ,RISK assessment ,DIAGNOSTIC imaging ,SURGICAL margin ,HEALTH care teams ,GENETIC markers ,BODY fluid examination ,TUMOR markers ,COMBINED modality therapy ,HISTOLOGY ,IMMUNOTHERAPY ,ALGORITHMS ,ABLATION techniques - Abstract
The current management of colorectal cancer liver metastasis (CRCLM) patients involves a multidisciplinary approach, with surgical resection remaining the primary curative option. The advances in liver surgery have improved outcomes, enabling more patients to undergo surgery successfully. In addition, the development of imaging software has improved the preoperative planning and patient selection for surgery and other interventions. Systemic therapies, such as targeted therapies and immunotherapies, have enhanced the chances of complete resection. Targeted agents, in combination with chemotherapy, have shown efficacy in downstaging tumors and increasing resectability. The algorithm approach for these patients continues to evolve, driven by a deeper understanding of the underlying biology. Personalized medicine, guided by molecular profiling and the potential of liquid biopsies in this field, may lead to more tailored treatment strategies. A greater understanding of the immune microenvironment in CRLM may unlock the potential for immune checkpoint inhibitors and novel immunotherapies to become more prominent in the treatment landscape. This review explores the current state-of-the-art treatment of CRCLM and discusses promising future perspectives. [ABSTRACT FROM AUTHOR]
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- 2023
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46. Wnt/β-Catenin-Signaling Modulates Megakaryopoiesis at the Megakaryocyte-Erythrocyte Progenitor Stage in the Hematopoietic System.
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Yalcin, Burak H., Macas, Jadranka, Wiercinska, Eliza, Harter, Patrick N., Fawaz, Malak, Schmachtel, Tessa, Ghiro, Ilaria, Bieniek, Ewa, Kosanovic, Djuro, Thom, Sonja, Fruttiger, Marcus, Taketo, Makoto M., Schermuly, Ralph T., Rieger, Michael A., Plate, Karl H., Bonig, Halvard, and Liebner, Stefan
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HEMATOPOIETIC system ,BLOOD cells ,RUNX proteins ,PLATELET-derived growth factor ,HEMATOPOIETIC stem cells ,WNT signal transduction ,ERYTHROCYTES ,BONE marrow - Abstract
The bone marrow (BM) hematopoietic system (HS) gives rise to blood cells originating from hematopoietic stem cells (HSCs), including megakaryocytes (MKs) and red blood cells (erythrocytes; RBCs). Many steps of the cell-fate decision remain to be elucidated, being important for cancer treatment. To explore the role of Wnt/β-catenin for MK and RBC differentiation, we activated β-catenin signaling in platelet-derived growth factor b (Pdgfb)-expressing cells of the HS using a Cre-lox approach (Ctnnb1
BM-GOF ). FACS analysis revealed that Pdgfb is mainly expressed by megakaryocytic progenitors (MKPs), MKs and platelets. Recombination resulted in a lethal phenotype in mutants (Ctnnb1BM-GOFwt/fl , Ctnnb1BM-GOFfl/fl ) 3 weeks after tamoxifen injection, showing an increase in MKs in the BM and spleen, but no pronounced anemia despite reduced erythrocyte counts. BM transplantation (BMT) of Ctnnb1BM-GOF BM into lethally irradiated wildtype recipients (BMT-Ctnnb1BM-GOF ) confirmed the megakaryocytic, but not the lethal phenotype. CFU-MK assays in vitro with BM cells of Ctnnb1BM-GOF mice supported MK skewing at the expense of erythroid colonies. Molecularly, the runt-related transcription factor 1 (RUNX1) mRNA, known to suppress erythropoiesis, was upregulated in Ctnnb1BM-GOF BM cells. In conclusion, β-catenin activation plays a key role in cell-fate decision favoring MK development at the expense of erythroid production. [ABSTRACT FROM AUTHOR]- Published
- 2023
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47. Host Genetic Background Effect on Body Weight Changes Influenced by Heterozygous Smad 4 Knockout Using Collaborative Cross Mouse Population.
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Qahaz, Nayrouz, Lone, Iqbal M., Khadija, Aya, Ghnaim, Aya, Zohud, Osayd, Nun, Nadav Ben, Nashef, Aysar, Abu El-Naaj, Imad, and Iraqi, Fuad A.
- Subjects
KNOCKOUT mice ,MICE ,BODY weight ,MACHINE learning ,WEIGHT gain ,LABORATORY mice ,LOGISTIC regression analysis - Abstract
Obesity and its attendant conditions have become major health problems worldwide, and obesity is currently ranked as the fifth most common cause of death globally. Complex environmental and genetic factors are causes of the current obesity epidemic. Diet, lifestyle, chemical exposure, and other confounding factors are difficult to manage in humans. The mice model is helpful in researching genetic BW gain because genetic and environmental risk factors can be controlled in mice. Studies in mouse strains with various genetic backgrounds and established genetic structures provide unparalleled opportunities to find and analyze trait-related genomic loci. In this study, we used the Collaborative Cross (CC), a large panel of recombinant inbred mouse strains, to present a predictive study using heterozygous Smad4 knockout profiles of CC mice to understand and effectively identify predispositions to body weight gain. Male C57Bl/6J Smad4+/− mice were mated with female mice from 10 different CC lines to create F1 mice (Smad4+/−x CC). Body weight (BW) was measured weekly until week 16 and then monthly until the end of the study (week 48). The heritability (H2) of the assessed traits was estimated and presented. Comparative analysis of various machine learning algorithms for predicting the BW changes and genotype of mice was conducted. Our data showed that the body weight records of F1 mice with different CC lines differed between wild-type and mutant Smad4 mice during the experiment. Genetic background affects weight gain and some lines gained more weight in the presence of heterozygous Smad4 knockout, while others gained less, but, in general, the mutation caused overweight mice, except for a few lines. In both control and mutant groups, female %BW had a higher heritability (H2) value than males. Additionally, both sexes with wild-type genotypes showed higher heritability values than the mutant group. Logistic regression provides the most accurate mouse genotype predictions using machine learning. We plan to validate the proposed method on more CC lines and mice per line to expand the literature on machine learning for BW prediction. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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48. MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists.
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Espinosa-Gil, Sergio, Ivanova, Saska, Alari-Pahissa, Elisenda, Denizli, Melek, Villafranca-Magdalena, Beatriz, Viñas-Casas, Maria, Bolinaga-Ayala, Idoia, Gámez-García, Andrés, Faundez-Vidiella, Claudia, Colas, Eva, Lopez-Botet, Miguel, Zorzano, Antonio, and Lizcano, José Miguel
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- 2023
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49. "Alphabet" Selenoproteins: Their Characteristics and Physiological Roles.
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Dogaru, Carmen Beatrice, Muscurel, Corina, Duță, Carmen, and Stoian, Irina
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SELENOPROTEINS ,IMMUNOREGULATION ,ENDOCRINE glands ,ENDOPLASMIC reticulum - Abstract
Selenium (Se) is a metalloid that is recognized as one of the vital trace elements in our body and plays multiple biological roles, largely mediated by proteins containing selenium—selenoproteins. Selenoproteins mainly have oxidoreductase functions but are also involved in many different molecular signaling pathways, physiological roles, and complex pathogenic processes (including, for example, teratogenesis, neurodegenerative, immuno-inflammatory, and obesity development). All of the selenoproteins contain one selenocysteine (Sec) residue, with only one notable exception, the selenoprotein P (SELENOP), which has 10 Sec residues. Although these mechanisms have been studied intensely and in detail, the characteristics and functions of many selenoproteins remain unknown. This review is dedicated to the recent data describing the identity and the functions of several selenoproteins that are less known than glutathione peroxidases (Gpxs), iodothyronine deiodinases (DIO), thioredoxin reductases (TRxRs), and methionine sulfoxide reductases (Msrs) and which are named after alphabetical letters (i.e., F, H, I, K, M, N, O, P, R, S, T, V, W). These "alphabet" selenoproteins are involved in a wide range of physiological and pathogenetic processes such as antioxidant defense, anti-inflammation, anti-apoptosis, regulation of immune response, regulation of oxidative stress, endoplasmic reticulum (ER) stress, immune and inflammatory response, and toxin antagonism. In selenium deficiency, the "alphabet" selenoproteins are affected hierarchically, both with respect to the particular selenoprotein and the tissue of expression, as the brain or endocrine glands are hardly affected by Se deficiency due to their equipment with LRP2 or LRP8. [ABSTRACT FROM AUTHOR]
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- 2023
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50. Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage.
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Gaili Yan, Xiangyu Zhang, Hongmin Li, Yan Guo, Yong, V. Wee, and Mengzhou Xue
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CEREBRAL hemorrhage ,CANNABIDIOL ,CANNABINOIDS ,NEUROBEHAVIORAL disorders ,OXIDATIVE stress ,FREE radical scavengers ,ANTIOXIDANTS - Abstract
Intracerebral hemorrhage (ICH) is a subtype of stroke with a high mortality rate. Oxidative stress cascades play an important role in brain injury after ICH. Cannabidiol, a major non-psychotropic phytocannabinoids, has drawn increasing interest in recent years as a potential therapeutic intervention for various neuropsychiatric disorders. Here we provide a comprehensive review of the potential therapeutic effects of cannabidiol in countering oxidative stress resulting from ICH. The review elaborates on the various sources of oxidative stress post-ICH, including mitochondrial dysfunction, excitotoxicity, iron toxicity, inflammation, and also highlights cannabidiol's ability to inhibit ROS/RNS generation from these sources. The article also delves into cannabidiol's role in promoting ROS/RNS scavenging through the Nrf2/ARE pathway, detailing both extranuclear and intranuclear regulatory mechanisms. Overall, the review underscores cannabidiol's promising antioxidant effects in the context of ICH and suggests its potential as a therapeutic option. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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