Pub Date : 2022-11-01DOI: 10.3390/endocrines3040057
J. Aseervatham
14-3-3s are a family of structurally similar proteins that bind to phosphoserine or phosphothreonine residues, forming the central signaling hub that coordinates or integrates various cellular functions, thereby controlling many pathways important in cancer, cell motility, cell death, cytoskeletal remodeling, neuro-degenerative disorders and many more. Their targets are present in all cellular compartments, and when they bind to proteins they alter their subcellular localization, stability, and molecular interactions with other proteins. Changes in environmental conditions that result in altered homeostasis trigger the interaction between 14-3-3 and other proteins to retrieve or rescue homeostasis. In circumstances where these regulatory proteins are dysregulated, it leads to pathological conditions. Therefore, deeper understanding is needed on how 14-3-3 proteins bind, and how these proteins are regulated or modified. This will help to detect disease in early stages or design inhibitors to block certain pathways. Recently, more research has been devoted to identifying the role of MicroRNAs, and long non-coding RNAs, which play an important role in regulating gene expression. Although there are many reviews on the role of 14-3-3 proteins in cancer, they do not provide a holistic view of the changes in the cell, which is the focus of this review. The unique feature of the review is that it not only focuses on how the 14-3-3 subunits associate and dissociate with their binding and regulatory proteins, but also includes the role of micro-RNAs and long non-coding RNAs and how they regulate 14-3-3 isoforms. The highlight of the review is that it focuses on the role of 14-3-3, actin, actin binding proteins and Rho GTPases in cancer, and how this complex is important for cell migration and invasion. Finally, the reader is provided with super-resolution high-clarity images of each subunit of the 14-3-3 protein family, further depicting their distribution in HeLa cells to illustrate their interactions in a cancer cell.
{"title":"Interactions between 14-3-3 Proteins and Actin Cytoskeleton and Its Regulation by microRNAs and Long Non-Coding RNAs in Cancer","authors":"J. Aseervatham","doi":"10.3390/endocrines3040057","DOIUrl":"https://doi.org/10.3390/endocrines3040057","url":null,"abstract":"14-3-3s are a family of structurally similar proteins that bind to phosphoserine or phosphothreonine residues, forming the central signaling hub that coordinates or integrates various cellular functions, thereby controlling many pathways important in cancer, cell motility, cell death, cytoskeletal remodeling, neuro-degenerative disorders and many more. Their targets are present in all cellular compartments, and when they bind to proteins they alter their subcellular localization, stability, and molecular interactions with other proteins. Changes in environmental conditions that result in altered homeostasis trigger the interaction between 14-3-3 and other proteins to retrieve or rescue homeostasis. In circumstances where these regulatory proteins are dysregulated, it leads to pathological conditions. Therefore, deeper understanding is needed on how 14-3-3 proteins bind, and how these proteins are regulated or modified. This will help to detect disease in early stages or design inhibitors to block certain pathways. Recently, more research has been devoted to identifying the role of MicroRNAs, and long non-coding RNAs, which play an important role in regulating gene expression. Although there are many reviews on the role of 14-3-3 proteins in cancer, they do not provide a holistic view of the changes in the cell, which is the focus of this review. The unique feature of the review is that it not only focuses on how the 14-3-3 subunits associate and dissociate with their binding and regulatory proteins, but also includes the role of micro-RNAs and long non-coding RNAs and how they regulate 14-3-3 isoforms. The highlight of the review is that it focuses on the role of 14-3-3, actin, actin binding proteins and Rho GTPases in cancer, and how this complex is important for cell migration and invasion. Finally, the reader is provided with super-resolution high-clarity images of each subunit of the 14-3-3 protein family, further depicting their distribution in HeLa cells to illustrate their interactions in a cancer cell.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41984300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-21DOI: 10.3390/endocrines3040056
R. Okawa, K. Nakano
X-linked hypophosphatemia (XLH) is the most common genetic form of rickets and osteomalacia and is characterized by growth retardation, deformities of the lower limbs, and bone and muscular pain. Spontaneous dental abscesses caused by endodontic infections due to dentin dysplasia are well-known dental manifestations. When dentin affected by microcracks or attrition of the enamel is exposed to oral fluids, oral bacteria are able to invade the hypomineralized dentin and pulp space, leading to pulp necrosis, followed by the formation of a periapical gingival abscess. Without appropriate dental management, this dental manifestation results in early loss of teeth and deterioration in the patient’s quality of life. Early specific dental intervention and oral management in collaboration with medical personnel are strongly recommended for XLH patients. Importantly, dental manifestations sometimes appear before the diagnosis of XLH. Dentists should be alert for this first sign of XLH and refer affected children to a pediatrician for early diagnosis. A humanized monoclonal antibody for FGF23 (burosumab) is a promising new treatment for XLH; however, the effects on the dental manifestations remain to be elucidated. The establishment of fundamental dental therapy to solve dental problems is still underway and is eagerly anticipated.
{"title":"Dental Manifestations and Oral Management of X-Linked Hypophosphatemia","authors":"R. Okawa, K. Nakano","doi":"10.3390/endocrines3040056","DOIUrl":"https://doi.org/10.3390/endocrines3040056","url":null,"abstract":"X-linked hypophosphatemia (XLH) is the most common genetic form of rickets and osteomalacia and is characterized by growth retardation, deformities of the lower limbs, and bone and muscular pain. Spontaneous dental abscesses caused by endodontic infections due to dentin dysplasia are well-known dental manifestations. When dentin affected by microcracks or attrition of the enamel is exposed to oral fluids, oral bacteria are able to invade the hypomineralized dentin and pulp space, leading to pulp necrosis, followed by the formation of a periapical gingival abscess. Without appropriate dental management, this dental manifestation results in early loss of teeth and deterioration in the patient’s quality of life. Early specific dental intervention and oral management in collaboration with medical personnel are strongly recommended for XLH patients. Importantly, dental manifestations sometimes appear before the diagnosis of XLH. Dentists should be alert for this first sign of XLH and refer affected children to a pediatrician for early diagnosis. A humanized monoclonal antibody for FGF23 (burosumab) is a promising new treatment for XLH; however, the effects on the dental manifestations remain to be elucidated. The establishment of fundamental dental therapy to solve dental problems is still underway and is eagerly anticipated.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46662600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-18DOI: 10.3390/endocrines3040055
M. Ishaq, D. Tran, Cheng Yang, Min Jia Ng, Arlene Kackanattil, Karthik Tata, B. Deans, M. Bleasel, Silvia Vicenzi, Cameron Randall, T. Ahmad, Carmelo Vicario, M. Ronci, M. Zuccarini, R. Ciccarelli, P. Scowen, D. Chellappan, Glenn Jacobson, Alex C. Bissember, Jason A Smith, R. Eri, J. Canales, M. Iglesias, Nuri Guven, V. Caruso
Obesity produces a systemic low-grade inflammation associated with many adverse health conditions and, as we recently learned, with complications of COVID-19. Functional studies in animal models have demonstrated that asperuloside, an iridoid glycoside found in many medicinal plants, has produced promising anti-obesity results. However, the safety profile and the anti-inflammatory properties of asperuloside remain unknown. Here, we confirmed the previously reported anti-obesity properties of asperuloside, and, importantly, we performed toxicity studies assessing cell viability providing a dose reference for future animal experiments. Asperuloside significantly reduced blood levels of leptin and the mRNA levels of orexigenic peptides, such as NPY and AgRP in mice consuming HFD, with no effect on mice eating a standard chow diet. In addition, our results indicate that ASP reduced both hypothalamic and hepatic mRNA levels of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α as well as the blood levels of plasminogen activator inhibitor-1 (PAI-1), which are known to play a major role in the development of insulin resistance and cardiovascular complications. Collectively, our findings suggest that asperuloside is a safe compound for long-term use in animal models and that it reduces the elevated levels of pro-inflammatory cytokines occurring in obesity.
{"title":"The Anti-Obesity Compound Asperuloside Reduces Inflammation in the Liver and Hypothalamus of High-Fat-Fed Mice","authors":"M. Ishaq, D. Tran, Cheng Yang, Min Jia Ng, Arlene Kackanattil, Karthik Tata, B. Deans, M. Bleasel, Silvia Vicenzi, Cameron Randall, T. Ahmad, Carmelo Vicario, M. Ronci, M. Zuccarini, R. Ciccarelli, P. Scowen, D. Chellappan, Glenn Jacobson, Alex C. Bissember, Jason A Smith, R. Eri, J. Canales, M. Iglesias, Nuri Guven, V. Caruso","doi":"10.3390/endocrines3040055","DOIUrl":"https://doi.org/10.3390/endocrines3040055","url":null,"abstract":"Obesity produces a systemic low-grade inflammation associated with many adverse health conditions and, as we recently learned, with complications of COVID-19. Functional studies in animal models have demonstrated that asperuloside, an iridoid glycoside found in many medicinal plants, has produced promising anti-obesity results. However, the safety profile and the anti-inflammatory properties of asperuloside remain unknown. Here, we confirmed the previously reported anti-obesity properties of asperuloside, and, importantly, we performed toxicity studies assessing cell viability providing a dose reference for future animal experiments. Asperuloside significantly reduced blood levels of leptin and the mRNA levels of orexigenic peptides, such as NPY and AgRP in mice consuming HFD, with no effect on mice eating a standard chow diet. In addition, our results indicate that ASP reduced both hypothalamic and hepatic mRNA levels of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α as well as the blood levels of plasminogen activator inhibitor-1 (PAI-1), which are known to play a major role in the development of insulin resistance and cardiovascular complications. Collectively, our findings suggest that asperuloside is a safe compound for long-term use in animal models and that it reduces the elevated levels of pro-inflammatory cytokines occurring in obesity.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41771782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-13DOI: 10.3390/endocrines3040054
Toshiyuki Kakinuma, Takahumi Ohkusa, Takumi Shinohara, A. Shimizu, Rora Okamoto, M. Kagimoto, Ayaka Kaneko, Kaoru Kakinuma, K. Yanagida, N. Takeshima, M. Ohwada
Microwave endometrial ablation (MEA) is a minimally invasive treatment for uterine myoma with hypermenorrhea, which can replace conventional hysterectomy. However, cases requiring additional treatment because of postoperative recurrence are often encountered. MEA cauterizes the endometrium and is not recommended for patients who wish to preserve fertility. We present the cases of a patient with myoma-related hypermenorrhea who underwent microwave ablation of the inflowing blood vessels to the uterine myoma under transvaginal ultrasound guidance. A 43-year-old woman was diagnosed with chronic myeloid leukemia and treated with dasatinib 2 years ago. Worsening hypermenorrhea was observed after treatment initiation. Ultrasound and pelvic magnetic resonance imaging revealed a uterine myoma. Therefore, she underwent MEA under transvaginal ultrasound guidance. Visual analog scale evaluation demonstrated considerable improvement in hypermenorrhea and dysmenorrhea; the myoma size showed reduction. The postoperative course was uneventful, and the patient was discharged on the day after surgery. No postoperative complications were observed. This patient is currently undergoing infertility treatment. The microwave ablation of myoma under transvaginal ultrasound guidance can effectively and safely reduce the myoma size. These findings suggest that this method is a novel treatment option for patients with myoma-related hypermenorrhea who wish to preserve their fertility and have children.
{"title":"Myoma with Hypermenorrhea Treated with Ultrasound-Guided Microwave Ablation of the Inflowing Blood Vessels to the Uterine Myoma: A Case","authors":"Toshiyuki Kakinuma, Takahumi Ohkusa, Takumi Shinohara, A. Shimizu, Rora Okamoto, M. Kagimoto, Ayaka Kaneko, Kaoru Kakinuma, K. Yanagida, N. Takeshima, M. Ohwada","doi":"10.3390/endocrines3040054","DOIUrl":"https://doi.org/10.3390/endocrines3040054","url":null,"abstract":"Microwave endometrial ablation (MEA) is a minimally invasive treatment for uterine myoma with hypermenorrhea, which can replace conventional hysterectomy. However, cases requiring additional treatment because of postoperative recurrence are often encountered. MEA cauterizes the endometrium and is not recommended for patients who wish to preserve fertility. We present the cases of a patient with myoma-related hypermenorrhea who underwent microwave ablation of the inflowing blood vessels to the uterine myoma under transvaginal ultrasound guidance. A 43-year-old woman was diagnosed with chronic myeloid leukemia and treated with dasatinib 2 years ago. Worsening hypermenorrhea was observed after treatment initiation. Ultrasound and pelvic magnetic resonance imaging revealed a uterine myoma. Therefore, she underwent MEA under transvaginal ultrasound guidance. Visual analog scale evaluation demonstrated considerable improvement in hypermenorrhea and dysmenorrhea; the myoma size showed reduction. The postoperative course was uneventful, and the patient was discharged on the day after surgery. No postoperative complications were observed. This patient is currently undergoing infertility treatment. The microwave ablation of myoma under transvaginal ultrasound guidance can effectively and safely reduce the myoma size. These findings suggest that this method is a novel treatment option for patients with myoma-related hypermenorrhea who wish to preserve their fertility and have children.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48773216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-11DOI: 10.3390/endocrines3040053
R. Cannarella, S. La Vignera, R. Condorelli, A. Calogero
BACKGROUND. Several studies have already investigated the relationship between IGF1 and semen parameters. However, clinical studies rarely concluded on the existence of a relationship between IGF1 and the sperm number, and whether the IGF1 serum levels have a practical value in the diagnostic work-up of patients with oligozoospermia is still unclear. OBJECTIVE. Molecular evidence reported that IGF1 and FSH belongs to the same molecular pathway. The aim of this study is to assess whether insulin-like growth factor-1 (IGF1)/follicle-stimulating hormone (FSH) ratio has an impact on testicular function and, specifically, on sperm number and testicular volume in a cohort of unselected men. METHODS. This is a cross-sectional study on 59 patients who attended the Seminology laboratory of the Division of Endocrinology of the University of Catania (Catania, Italy) for semen analysis. Data were analyzed to evaluate the relationships between IGF1 or IGF1/FSH ratio and sperm concentration, total sperm count (TSC), and testicular volume (TV). We also evaluated the occurrence of any difference in IGF1 and FSH serum levels and the IGF1/FSH ratio in patients with oligozoospermia and those with a TSC > 39 million/ejaculate. MAIN RESULTS AND ROLE OF CHANGE. Patients had a mean age of 31.0 ± 8.5 years. The mean FSH and IGF1 levels were 3.95 ± 2.55 mIU/mL and 232.59 ± 65.13 ng/mL, respectively. IGF1 serum levels did not correlate with sperm concentration, TSC, and TV. The IGF1/FSH ratio showed a positive correlation with sperm concentration (r = 0.408; p = 0.004), TSC (r = 0.468; p = 0.001), and TV (0.463; p = 0.002). Patients with oligozoospermia (Group 1, 23.7%, n = 14) had a significant lower IGF1/FSH ratio (57.9 ± 9.5 vs. 94.1 ± 8.7; p = 0.03) compared to those with TSC > 39 million/ejaculate (Group 2, 76.3%, n = 45). They did not differ significantly for neither IGF1 nor FSH serum levels. CONCLUSION. We found a positive correlation between the IGF1/FSH ratio and sperm concentration, TSC and TV. Furthermore, patients with oligozoospermia showed a significantly lower ratio compared to those with a normal TSC, while neither IGF1 nor FSH differed significantly in the two groups. Our results may reflect the existence of a molecular pathway to which IGF1 and FSH belongs. However, further studies are needed.
{"title":"The IGF1/FSH Ratio Correlates with Sperm Count and Testicular Volume","authors":"R. Cannarella, S. La Vignera, R. Condorelli, A. Calogero","doi":"10.3390/endocrines3040053","DOIUrl":"https://doi.org/10.3390/endocrines3040053","url":null,"abstract":"BACKGROUND. Several studies have already investigated the relationship between IGF1 and semen parameters. However, clinical studies rarely concluded on the existence of a relationship between IGF1 and the sperm number, and whether the IGF1 serum levels have a practical value in the diagnostic work-up of patients with oligozoospermia is still unclear. OBJECTIVE. Molecular evidence reported that IGF1 and FSH belongs to the same molecular pathway. The aim of this study is to assess whether insulin-like growth factor-1 (IGF1)/follicle-stimulating hormone (FSH) ratio has an impact on testicular function and, specifically, on sperm number and testicular volume in a cohort of unselected men. METHODS. This is a cross-sectional study on 59 patients who attended the Seminology laboratory of the Division of Endocrinology of the University of Catania (Catania, Italy) for semen analysis. Data were analyzed to evaluate the relationships between IGF1 or IGF1/FSH ratio and sperm concentration, total sperm count (TSC), and testicular volume (TV). We also evaluated the occurrence of any difference in IGF1 and FSH serum levels and the IGF1/FSH ratio in patients with oligozoospermia and those with a TSC > 39 million/ejaculate. MAIN RESULTS AND ROLE OF CHANGE. Patients had a mean age of 31.0 ± 8.5 years. The mean FSH and IGF1 levels were 3.95 ± 2.55 mIU/mL and 232.59 ± 65.13 ng/mL, respectively. IGF1 serum levels did not correlate with sperm concentration, TSC, and TV. The IGF1/FSH ratio showed a positive correlation with sperm concentration (r = 0.408; p = 0.004), TSC (r = 0.468; p = 0.001), and TV (0.463; p = 0.002). Patients with oligozoospermia (Group 1, 23.7%, n = 14) had a significant lower IGF1/FSH ratio (57.9 ± 9.5 vs. 94.1 ± 8.7; p = 0.03) compared to those with TSC > 39 million/ejaculate (Group 2, 76.3%, n = 45). They did not differ significantly for neither IGF1 nor FSH serum levels. CONCLUSION. We found a positive correlation between the IGF1/FSH ratio and sperm concentration, TSC and TV. Furthermore, patients with oligozoospermia showed a significantly lower ratio compared to those with a normal TSC, while neither IGF1 nor FSH differed significantly in the two groups. Our results may reflect the existence of a molecular pathway to which IGF1 and FSH belongs. However, further studies are needed.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49566689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-07DOI: 10.3390/endocrines3040051
M. Draznin, S. Kanungo
The inception of pediatric endocrinology in the United States began little less than a century ago, but it has grown as a subspecialty field since the 1950s [...]
{"title":"Special Issue “Genetics in Pediatric Endocrinology”","authors":"M. Draznin, S. Kanungo","doi":"10.3390/endocrines3040051","DOIUrl":"https://doi.org/10.3390/endocrines3040051","url":null,"abstract":"The inception of pediatric endocrinology in the United States began little less than a century ago, but it has grown as a subspecialty field since the 1950s [...]","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42416627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-07DOI: 10.3390/endocrines3040052
C. Koliaki, N. Katsilambros
Conventional hypocaloric diets, providing continuous energy restriction, are considered to be the cornerstone of dietary management of obesity. Although energy-restricted diets are overall safe, healthy, and modestly effective, their long-term adherence is difficult to accomplish. Intermittent fasting and ketogenic diets have emerged as attractive alternative dietary options for weight loss and improvement in cardiometabolic risk. Intermittent fasting is a unique dietary pattern characterized by periods of eating alternated with periods of fasting. Ketogenic diets are very low in carbohydrate, modest in protein, and high in fat. Several systematic reviews and meta-analyses of randomized controlled trials (RCTs) have reported beneficial but short-lived effects of intermittent fasting and ketogenic diets on various obesity-related health outcomes. Although for both diets, the current evidence is promising and steadily evolving, whether they are better than traditional calorie-restricted diets, whether they can safely lead to sustained weight loss and overall health benefits, and their effects on body composition, weight loss maintenance, energy intake and expenditure, diet quality, and cardiometabolic risk factors are still not unequivocally proven. The aim of the present review is to summarize the current state of evidence regarding the effects of these two popular modern diets, namely intermittent fasting and ketogenic diets. We describe the rationale and characteristics of different dietary protocols, we analyze the major mechanisms explaining their weight loss and cardiometabolic effects, and we provide a concise update on their effects on body weight and cardiometabolic risk factors, focusing on meta-analyses of RCTs. We also discuss knowledge gaps in the field of these diets, and we indicate directions for future research.
{"title":"Are the Modern Diets for the Treatment of Obesity Better than the Classical Ones?","authors":"C. Koliaki, N. Katsilambros","doi":"10.3390/endocrines3040052","DOIUrl":"https://doi.org/10.3390/endocrines3040052","url":null,"abstract":"Conventional hypocaloric diets, providing continuous energy restriction, are considered to be the cornerstone of dietary management of obesity. Although energy-restricted diets are overall safe, healthy, and modestly effective, their long-term adherence is difficult to accomplish. Intermittent fasting and ketogenic diets have emerged as attractive alternative dietary options for weight loss and improvement in cardiometabolic risk. Intermittent fasting is a unique dietary pattern characterized by periods of eating alternated with periods of fasting. Ketogenic diets are very low in carbohydrate, modest in protein, and high in fat. Several systematic reviews and meta-analyses of randomized controlled trials (RCTs) have reported beneficial but short-lived effects of intermittent fasting and ketogenic diets on various obesity-related health outcomes. Although for both diets, the current evidence is promising and steadily evolving, whether they are better than traditional calorie-restricted diets, whether they can safely lead to sustained weight loss and overall health benefits, and their effects on body composition, weight loss maintenance, energy intake and expenditure, diet quality, and cardiometabolic risk factors are still not unequivocally proven. The aim of the present review is to summarize the current state of evidence regarding the effects of these two popular modern diets, namely intermittent fasting and ketogenic diets. We describe the rationale and characteristics of different dietary protocols, we analyze the major mechanisms explaining their weight loss and cardiometabolic effects, and we provide a concise update on their effects on body weight and cardiometabolic risk factors, focusing on meta-analyses of RCTs. We also discuss knowledge gaps in the field of these diets, and we indicate directions for future research.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48976478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.3390/endocrines3040049
A. Perri, D. Lofaro, S. Bossio, L. Maltese, I. Casaburi, L. Tucci, S. La Vignera, A. Aversa, S. Aquila, V. Rago
Metabolic reprogramming is an emerging hallmark of cancer, involving the overexpression of metabolism-related proteins, such as glucose and monocarboxylate transporters and intracellular glycolytic enzymes. The biology of testicular germ cell tumors (TGCTs) is very complex, and although their metabolic profile has been scantily explored, some authors have recently reported that the metabolic rewiring of cancer cells resulted in an association with aggressive clinicopathological characteristics. In this study we have investigated, by immunohistochemical analysis, the expression of key proteins sustaining the hyperglycolytic phenotype in pure seminoma (SE, nr. 35), pure embryonal carcinoma (EC, nr. 17) tissues samples, and normal testes (nr. 5). GLUT1, CD44, PFK-1, MCT1, MCT4, LDH-A, and PDH resulted in more expression in EC cells compared to SE cells. TOM20 was more expressed in SE than in EC. GLUT1, MCT1, and MCT4 expression showed a statistically significant association with SE histology, while for EC, the association resulted in being significant only for GLUT1 and MCT4. Finally, we observed that EC resulted as negative for p53, suggesting that the GLUT1 and MTC overexpression observed in EC could be also attributed to p53 downregulation. In conclusion, our findings evidenced that EC exhibits a higher expression of markers of active aerobic glycolysis compared to SE, suggesting that the aggressive phenotype is associated with a higher glycolytic rate. These data corroborate the emerging evidence on the involvement of metabolic reprogramming in testicular malignancies as well, highlighting that the metabolic players should be explored in the future as promising therapeutic targets.
{"title":"Different Expression Patterns of Metabolic Reprogramming Proteins in Testicular Germ Cell Cancer","authors":"A. Perri, D. Lofaro, S. Bossio, L. Maltese, I. Casaburi, L. Tucci, S. La Vignera, A. Aversa, S. Aquila, V. Rago","doi":"10.3390/endocrines3040049","DOIUrl":"https://doi.org/10.3390/endocrines3040049","url":null,"abstract":"Metabolic reprogramming is an emerging hallmark of cancer, involving the overexpression of metabolism-related proteins, such as glucose and monocarboxylate transporters and intracellular glycolytic enzymes. The biology of testicular germ cell tumors (TGCTs) is very complex, and although their metabolic profile has been scantily explored, some authors have recently reported that the metabolic rewiring of cancer cells resulted in an association with aggressive clinicopathological characteristics. In this study we have investigated, by immunohistochemical analysis, the expression of key proteins sustaining the hyperglycolytic phenotype in pure seminoma (SE, nr. 35), pure embryonal carcinoma (EC, nr. 17) tissues samples, and normal testes (nr. 5). GLUT1, CD44, PFK-1, MCT1, MCT4, LDH-A, and PDH resulted in more expression in EC cells compared to SE cells. TOM20 was more expressed in SE than in EC. GLUT1, MCT1, and MCT4 expression showed a statistically significant association with SE histology, while for EC, the association resulted in being significant only for GLUT1 and MCT4. Finally, we observed that EC resulted as negative for p53, suggesting that the GLUT1 and MTC overexpression observed in EC could be also attributed to p53 downregulation. In conclusion, our findings evidenced that EC exhibits a higher expression of markers of active aerobic glycolysis compared to SE, suggesting that the aggressive phenotype is associated with a higher glycolytic rate. These data corroborate the emerging evidence on the involvement of metabolic reprogramming in testicular malignancies as well, highlighting that the metabolic players should be explored in the future as promising therapeutic targets.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46607153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-08DOI: 10.3390/endocrines3030047
Y. Imanishi, T. Shoji, M. Emoto
X-linked hypophosphatemia (XLH) is a rare inherited disorder involving elevated levels of fibroblast growth factor (FGF) 23, and is caused by loss-of-function mutations in the PHEX gene. FGF23 induces renal phosphate wasting and suppresses the activation of vitamin D, resulting in defective bone mineralization and rachitic changes in the growth plate and osteomalacia. Conventional treatment with combinations of oral inorganic phosphate and active vitamin D analogs enhances bone calcification, but the efficacy of conventional treatment is insufficient for adult XLH patients to achieve an acceptable quality of life. Burosumab, a fully human monoclonal anti-FGF23 antibody, binds and inhibits FGF23, correcting hypophosphatemia and hypovitaminosis D. This review describes a typical adult with XLH and summarizes the results of clinical trials of burosumab in adults with XLH.
{"title":"Complications and Treatments in Adult X-Linked Hypophosphatemia","authors":"Y. Imanishi, T. Shoji, M. Emoto","doi":"10.3390/endocrines3030047","DOIUrl":"https://doi.org/10.3390/endocrines3030047","url":null,"abstract":"X-linked hypophosphatemia (XLH) is a rare inherited disorder involving elevated levels of fibroblast growth factor (FGF) 23, and is caused by loss-of-function mutations in the PHEX gene. FGF23 induces renal phosphate wasting and suppresses the activation of vitamin D, resulting in defective bone mineralization and rachitic changes in the growth plate and osteomalacia. Conventional treatment with combinations of oral inorganic phosphate and active vitamin D analogs enhances bone calcification, but the efficacy of conventional treatment is insufficient for adult XLH patients to achieve an acceptable quality of life. Burosumab, a fully human monoclonal anti-FGF23 antibody, binds and inhibits FGF23, correcting hypophosphatemia and hypovitaminosis D. This review describes a typical adult with XLH and summarizes the results of clinical trials of burosumab in adults with XLH.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43187774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-05DOI: 10.3390/endocrines3030046
Claudia Leanza, L. Mongioì, R. Cannarella, S. La Vignera, R. Condorelli, A. Calogero
The spread of severe acute respiratory syndrome—Coronavirus 2 (SARS-CoV-2) around the world has rapidly sparked the interest of the scientific community to discover its implications in human health. Many studies have suggested that SARS-CoV-2 is directly or indirectly involved in the male reproductive tract impairment. Some evidence supports the possible role of the virus in male infertility. Therefore, this review aims to summarize the relationship between the male urogenital tract, male fertility, and the gonadal hormone profile. The testis is one of the organs with the highest expression of the angiotensin-converting enzyme (ACE) 2-receptor that allows the virus to penetrate human cells. Orchitis is a possible clinical manifestation of COVID-19 and testicular damage has been found on autopsy in the testes of patients who died from the disease. SARS-CoV-2 infection can compromise the blood-testis barrier, favoring testicular damage and the production of anti-sperm autoantibodies. Some studies have detected the presence of SARS-CoV-2 in semen and a high percentage of patients with COVID-19 have altered sperm parameters compared to controls. Finally, lower testosterone levels, higher luteinizing hormone (LH) levels, and decreased follicle-stimulating (FSH)/LH and testosterone/LH ratios suggest primary testicular damage. In conclusion, further studies are needed to evaluate the exact mechanisms by which SARS-CoV-2 affects the male reproductive system and fertility and to evaluate the reversibility of its long-term effects.
{"title":"The Possible Role of SARS-CoV-2 in Male Fertility: A Narrative Review","authors":"Claudia Leanza, L. Mongioì, R. Cannarella, S. La Vignera, R. Condorelli, A. Calogero","doi":"10.3390/endocrines3030046","DOIUrl":"https://doi.org/10.3390/endocrines3030046","url":null,"abstract":"The spread of severe acute respiratory syndrome—Coronavirus 2 (SARS-CoV-2) around the world has rapidly sparked the interest of the scientific community to discover its implications in human health. Many studies have suggested that SARS-CoV-2 is directly or indirectly involved in the male reproductive tract impairment. Some evidence supports the possible role of the virus in male infertility. Therefore, this review aims to summarize the relationship between the male urogenital tract, male fertility, and the gonadal hormone profile. The testis is one of the organs with the highest expression of the angiotensin-converting enzyme (ACE) 2-receptor that allows the virus to penetrate human cells. Orchitis is a possible clinical manifestation of COVID-19 and testicular damage has been found on autopsy in the testes of patients who died from the disease. SARS-CoV-2 infection can compromise the blood-testis barrier, favoring testicular damage and the production of anti-sperm autoantibodies. Some studies have detected the presence of SARS-CoV-2 in semen and a high percentage of patients with COVID-19 have altered sperm parameters compared to controls. Finally, lower testosterone levels, higher luteinizing hormone (LH) levels, and decreased follicle-stimulating (FSH)/LH and testosterone/LH ratios suggest primary testicular damage. In conclusion, further studies are needed to evaluate the exact mechanisms by which SARS-CoV-2 affects the male reproductive system and fertility and to evaluate the reversibility of its long-term effects.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45762475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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