Zhenlong Yu1,+, Xiangge Tian1,+, Yuling Peng1,+, Zheng Sun1, Chao Wang 1, Ning Tang1, Bin Li2, Yuqing Jian2, Wei Wang2,*, Xiaokui Huo1, Xiaochi Ma1,*
*Correspondence: Professor Xiaochi Ma, E-mail: [email protected] (Xiaochi Ma); Professor Wei Wang, E-mail: [email protected] (Wei Wang).
+These authors equally contributed to this work.
Correction:
Unfortunately, the original version of this article1 contained the errors. The band of p-p38 in Figure 1F (SH-SY5Y) was mistakenly uploaded, during the arrangement of the figure panels. The mistake did not affect our results or discussion as the text refers to the correct experimental values. The corrected Figure 1F is provided here. Additionally, an error was also identified in the authors' names, where Yulin Peng's name was mistakenly written as “Yuling Peng”.
We regret any inconvenience this has caused.
Corrected Figure 1F
DOI: 10.1111/jpi.12478Zhenlong Yu1,+, Xiangge Tian1,+, Yuling Peng1,+, Zheng Sun1, Chao Wang 1, Ning Tang1, Bin Li2, Yuqing Jian2, Wei Wang2,*, Xiaokui Huo1, Xiaochi Ma1,**Correspondence:马晓驰教授,电子邮件:[email protected] (马晓驰电子邮件:[email protected] (Xiaochi Ma);王伟教授,电子邮件:[email protected] (Wei Wang):[Correction:Unfortunately, the original version of this article1 contained the errors.图1F(SH-SY5Y)中p-p38的条带在编排时被错误上传。这个错误并不影响我们的结果或讨论,因为文中提到的是正确的实验值。现提供更正后的图 1F。此外,我们还发现了作者姓名中的一处错误,彭玉林的名字被误写为 "Yuling Peng"。
{"title":"Erratum to: Mitochondrial cytochrome P450 (CYP) 1B1 is responsible for melatonin-induced apoptosis in neural cancer cells","authors":"","doi":"10.1111/jpi.12917","DOIUrl":"10.1111/jpi.12917","url":null,"abstract":"<p><b>DOI: 10.1111/jpi.12478</b></p><p>Zhenlong Yu<sup>1,+</sup>, Xiangge Tian<sup>1,+</sup>, Yuling Peng<sup>1,+</sup>, Zheng Sun<sup>1</sup>, Chao Wang <sup>1</sup>, Ning Tang<sup>1</sup>, Bin Li<sup>2</sup>, Yuqing Jian<sup>2</sup>, Wei Wang<sup>2,*</sup>, Xiaokui Huo<sup>1</sup>, Xiaochi Ma<sup>1,*</sup></p><p>*Correspondence: Professor Xiaochi Ma, E-mail: <span>[email protected]</span> (Xiaochi Ma); Professor Wei Wang, E-mail: <span>[email protected]</span> (Wei Wang).</p><p><sup>+</sup>These authors equally contributed to this work.</p><p><b>Correction</b>:</p><p>Unfortunately, the original version of this article<span><sup>1</sup></span> contained the errors. The band of p-p38 in Figure 1F (SH-SY5Y) was mistakenly uploaded, during the arrangement of the figure panels. The mistake did not affect our results or discussion as the text refers to the correct experimental values. The corrected Figure 1F is provided here. Additionally, an error was also identified in the authors' names, where Yulin Peng's name was mistakenly written as “Yuling Peng”.</p><p>We regret any inconvenience this has caused.</p><p><b>Corrected</b> Figure 1F</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12917","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41095240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Han-jun Qin, Si-ying He, Ke Shen, Qing-rong Lin, Yan-jun Hu, Zi-lin Chen, Bin Yu, Nan Jiang
Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM.
{"title":"Melatonin, a potentially effective drug for the treatment of infected bone nonunion","authors":"Han-jun Qin, Si-ying He, Ke Shen, Qing-rong Lin, Yan-jun Hu, Zi-lin Chen, Bin Yu, Nan Jiang","doi":"10.1111/jpi.12914","DOIUrl":"10.1111/jpi.12914","url":null,"abstract":"<p>Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of <i>Staphylococcus aureus</i>. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41095328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuan Shao, Yun Yang, Yanlei Liu, Yongqing Wang, Yangyu Zhao, Xin Yu, Juan Liu, Yu-Xia Li, Yan-Ling Wang
Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre-eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T0) synthesis, reduced estradiol (E2), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E2 as well as elevated T0 synthesis in PE placentas. Administration of the T0 analog testosterone propionate (TP; 2 mg/kg/day) to pregnant mice from E7.5 onwards resulted in PE-like symptoms, along with elevated T0 production and reduced E2 and melatonin production. Notably, supplementation with melatonin (10 mg/kg/day) in TP-treated mice had detrimental effects on fetal and placental development and compromised hormone synthesis. Importantly, E2, but not T0, actively enhanced melatonin synthetase AANAT expression and melatonin production in primary human trophoblast (PHT) cells through GPER1-PKA-CREB signaling pathway. On the other hand, melatonin suppressed the level of estrogen synthetase aromatase while promoting the expressions of androgen synthetic enzymes including 17β-HSD3 and 3β-HSD1 in PHT cells. These findings reveal an orchestrated feedback mechanism that maintains homeostasis of placental sex hormones and melatonin. It is implied that abnormal elevation of T0 synthesis likely serves as the primary cause of placental endocrine disturbances associated with PE. The suppression of melatonin may represent an adaptive strategy to correct the imbalance in sex hormone levels within preeclamptic placentas. The findings of this study offer novel evidence that identifies potential targets for the development of innovative therapeutic strategies for PE.
{"title":"Orchestrated feedback regulation between melatonin and sex hormones involving GPER1-PKA-CREB signaling in the placenta","authors":"Xuan Shao, Yun Yang, Yanlei Liu, Yongqing Wang, Yangyu Zhao, Xin Yu, Juan Liu, Yu-Xia Li, Yan-Ling Wang","doi":"10.1111/jpi.12913","DOIUrl":"10.1111/jpi.12913","url":null,"abstract":"<p>Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre-eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T<sub>0</sub>) synthesis, reduced estradiol (E<sub>2</sub>), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E<sub>2</sub> as well as elevated T<sub>0</sub> synthesis in PE placentas. Administration of the T<sub>0</sub> analog testosterone propionate (TP; 2 mg/kg/day) to pregnant mice from E7.5 onwards resulted in PE-like symptoms, along with elevated T<sub>0</sub> production and reduced E<sub>2</sub> and melatonin production. Notably, supplementation with melatonin (10 mg/kg/day) in TP-treated mice had detrimental effects on fetal and placental development and compromised hormone synthesis. Importantly, E<sub>2</sub>, but not T<sub>0</sub>, actively enhanced melatonin synthetase AANAT expression and melatonin production in primary human trophoblast (PHT) cells through GPER1-PKA-CREB signaling pathway. On the other hand, melatonin suppressed the level of estrogen synthetase aromatase while promoting the expressions of androgen synthetic enzymes including 17β-HSD3 and 3β-HSD1 in PHT cells. These findings reveal an orchestrated feedback mechanism that maintains homeostasis of placental sex hormones and melatonin. It is implied that abnormal elevation of T<sub>0</sub> synthesis likely serves as the primary cause of placental endocrine disturbances associated with PE. The suppression of melatonin may represent an adaptive strategy to correct the imbalance in sex hormone levels within preeclamptic placentas. The findings of this study offer novel evidence that identifies potential targets for the development of innovative therapeutic strategies for PE.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
After publication of the paper “Melatonin ameliorates PM2.5-induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis” by Jinjin Jiang et al. it was noticed that the paper contains error in Figure 4D and Figure 6D. During the assembly of certain figure panel of this article showing representative immunoblot, Ac-SOD2 and GPADH (Figure 4D) and GAPDH (Figure 6D) were presented incorrectly, due to unintended duplication mistake. Using the original source data, the rectified version of the incorrectly presented panel of Figure 4D and Figure 6D were generated and is shown below. Here we provided the revised Figure 4 and Figure 6. The authors apologize for the oversight and declare that the correction does not affect the description, interpretation, or conclusions detailed in the original manuscript.
{"title":"Corrigendum to “melatonin ameliorates PM2.5-induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis”","authors":"","doi":"10.1111/jpi.12915","DOIUrl":"10.1111/jpi.12915","url":null,"abstract":"<p>After publication of the paper “Melatonin ameliorates PM<sub>2.5</sub>-induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis” by Jinjin Jiang et al. it was noticed that the paper contains error in Figure 4D and Figure 6D. During the assembly of certain figure panel of this article showing representative immunoblot, Ac-SOD2 and GPADH (Figure 4D) and GAPDH (Figure 6D) were presented incorrectly, due to unintended duplication mistake. Using the original source data, the rectified version of the incorrectly presented panel of Figure 4D and Figure 6D were generated and is shown below. Here we provided the revised Figure 4 and Figure 6. The authors apologize for the oversight and declare that the correction does not affect the description, interpretation, or conclusions detailed in the original manuscript.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinho Kim, Wei Li, Jingjing Wang, Sergei V. Baranov, Brianna E. Heath, Jiaoying Jia, Yalikun Suofu, Oxana V. Baranova, Xiaomin Wang, Timothy M. Larkin, William R. Lariviere, Diane L. Carlisle, Robert M. Friedlander
Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating melatonin levels. Melatonin is a potent antioxidant and exogenous melatonin treatment is neuroprotective in experimental HD models. In neurons, melatonin is exclusively synthesized in the mitochondrial matrix. Thus, we investigated the integrity of melatonin biosynthesis pathways in pineal and extrapineal brain areas in human HD brain samples, in the R6/2 mouse model of HD and in full-length mutant huntingtin knock-in cells. Aralkylamine N-acetyltransferase (AANAT) is the rate-limiting step enzyme in the melatonin biosynthetic pathway. We found that AANAT expression is significantly decreased in the pineal gland and the striatum of HD patients compared to normal controls. In the R6/2 mouse forebrain, AANAT protein expression was decreased in synaptosomal, but not nonsynaptosomal, mitochondria and was associated with decreased synaptosomal melatonin levels compared to wild type mice. We also demonstrate sequestration of AANAT in mutant-huntingtin protein aggregates likely resulting in decreased AANAT bioavailability. Paradoxically, AANAT mRNA expression is increased in tissues where AANAT protein expression is decreased, suggesting a potential feedback loop that is, ultimately unsuccessful. In conclusion, we demonstrate that pineal, extrapineal, and synaptosomal melatonin levels are compromised in the brains of HD patients and R6/2 mice due, at least in part, to protein aggregation.
{"title":"Biosynthesis of neuroprotective melatonin is dysregulated in Huntington's disease","authors":"Jinho Kim, Wei Li, Jingjing Wang, Sergei V. Baranov, Brianna E. Heath, Jiaoying Jia, Yalikun Suofu, Oxana V. Baranova, Xiaomin Wang, Timothy M. Larkin, William R. Lariviere, Diane L. Carlisle, Robert M. Friedlander","doi":"10.1111/jpi.12909","DOIUrl":"10.1111/jpi.12909","url":null,"abstract":"<p>Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating melatonin levels. Melatonin is a potent antioxidant and exogenous melatonin treatment is neuroprotective in experimental HD models. In neurons, melatonin is exclusively synthesized in the mitochondrial matrix. Thus, we investigated the integrity of melatonin biosynthesis pathways in pineal and extrapineal brain areas in human HD brain samples, in the R6/2 mouse model of HD and in full-length mutant huntingtin knock-in cells. Aralkylamine N-acetyltransferase (AANAT) is the rate-limiting step enzyme in the melatonin biosynthetic pathway. We found that AANAT expression is significantly decreased in the pineal gland and the striatum of HD patients compared to normal controls. In the R6/2 mouse forebrain, AANAT protein expression was decreased in synaptosomal, but not nonsynaptosomal, mitochondria and was associated with decreased synaptosomal melatonin levels compared to wild type mice. We also demonstrate sequestration of AANAT in mutant-huntingtin protein aggregates likely resulting in decreased AANAT bioavailability. Paradoxically, <i>AANAT</i> mRNA expression is increased in tissues where AANAT protein expression is decreased, suggesting a potential feedback loop that is, ultimately unsuccessful. In conclusion, we demonstrate that pineal, extrapineal, and synaptosomal melatonin levels are compromised in the brains of HD patients and R6/2 mice due, at least in part, to protein aggregation.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
José Fernández-Martínez, Yolanda Ramírez-Casas, Paula Aranda-Martínez, Alba López-Rodríguez, Ramy K. A. Sayed, Germaine Escames, Darío Acuña-Castroviejo
Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in Bmal1 clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible Bmal1 knockout mice (iMS-Bmal1−/−) were examined by phenotypic tests and light and electron microscopy. Our results revealed a disruption of the normal activity/rest rhythm, a drop in skeletal muscle function and mass, and increased frailty in male and female iMS-Bmal1−/− animals compared to controls. A reduction in muscle fiber size and increased collagenous tissue were also detected, accompanied by reduced mitochondrial oxidative capacity and a compensatory shift towards a more oxidative fiber type. Electron microscopy further supports mitochondrial impairment in mutant mice. Melatonin and exercise ameliorated the damage caused by loss of Bmal1 in mutant mice, except for mitochondrial damage, which was worsened by the latter. Thus, iMS-Bmal1−/− mice let us to identify Bmal1 deficiency as the responsible for the appearance of sarcopenia in the gastrocnemius muscle. Moreover, the results support the exercise and melatonin as therapeutic tools to counteract sarcopenia, by a mechanism that does not require the presence of Bmal1.
{"title":"iMS-Bmal1−/− mice show evident signs of sarcopenia that are counteracted by exercise and melatonin therapies","authors":"José Fernández-Martínez, Yolanda Ramírez-Casas, Paula Aranda-Martínez, Alba López-Rodríguez, Ramy K. A. Sayed, Germaine Escames, Darío Acuña-Castroviejo","doi":"10.1111/jpi.12912","DOIUrl":"10.1111/jpi.12912","url":null,"abstract":"<p>Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in <i>Bmal1</i> clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible <i>Bmal1</i> knockout mice (iMS-<i>Bmal1</i><sup><i>−/−</i></sup>) were examined by phenotypic tests and light and electron microscopy. Our results revealed a disruption of the normal activity/rest rhythm, a drop in skeletal muscle function and mass, and increased frailty in male and female iMS-<i>Bmal1<sup>−/−</sup></i> animals compared to controls. A reduction in muscle fiber size and increased collagenous tissue were also detected, accompanied by reduced mitochondrial oxidative capacity and a compensatory shift towards a more oxidative fiber type. Electron microscopy further supports mitochondrial impairment in mutant mice. Melatonin and exercise ameliorated the damage caused by loss of <i>Bmal1</i> in mutant mice, except for mitochondrial damage, which was worsened by the latter. Thus, iMS-<i>Bmal1<sup>−/−</sup></i> mice let us to identify <i>Bmal1</i> deficiency as the responsible for the appearance of sarcopenia in the gastrocnemius muscle. Moreover, the results support the exercise and melatonin as therapeutic tools to counteract sarcopenia, by a mechanism that does not require the presence of <i>Bmal1</i>.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10276830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Filippo Gagliardi, Pierfrancesco De Domenico, Enrico Garbin, Silvia Snider, Pietro Mortini
Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.
{"title":"Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification","authors":"Filippo Gagliardi, Pierfrancesco De Domenico, Enrico Garbin, Silvia Snider, Pietro Mortini","doi":"10.1111/jpi.12910","DOIUrl":"10.1111/jpi.12910","url":null,"abstract":"<p>Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (<i>n</i> = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (<i>n</i> = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (<i>n</i> = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, <i>p</i> = .02), while GCTs and HGG histology well predicted PD (OR: 13, <i>p</i> = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huo X, Wang C, Yu Z, Peng Y, Wang S, Feng S, Zhang S, Tian X, Sun C, Liu K, Deng S, Ma X. Human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential. J Pineal Res. 2017;62(4):12390. https://doi.org/10.1111/jpi.12390
In Figure 10B, the C-casp3 bands of PC3 cells and Bax bands of U118 cells were accidentally wrongly used during the figure preparation. The corrected figures are provided below.
This corrected figure does not change the conclusions of this study. This correction does not modify the data interpretation of the original article. We apologize for this error.
Huo X, Wang C, Yu Z, Peng Y, Wang S, Feng S, Zhang S, Tian X, Sun C, Liu K, Deng S, Ma X. Human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells:对治疗潜力的影响。J Pineal Res. 2017;62(4):12390。https://doi.org/10.1111/jpi.12390In 图10B中,PC3细胞的C-casp3条带和U118细胞的Bax条带在制图过程中被意外错用。更正后的图表如下。此更正不会修改原文的数据解释。我们对此错误深表歉意。
{"title":"Correction to human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential","authors":"","doi":"10.1111/jpi.12911","DOIUrl":"10.1111/jpi.12911","url":null,"abstract":"<p>Huo X, Wang C, Yu Z, Peng Y, Wang S, Feng S, Zhang S, Tian X, Sun C, Liu K, Deng S, Ma X. Human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential. <i>J Pineal Res</i>. 2017;62(4):12390. https://doi.org/10.1111/jpi.12390</p><p>In Figure 10B, the C-casp3 bands of PC3 cells and Bax bands of U118 cells were accidentally wrongly used during the figure preparation. The corrected figures are provided below.</p><p>This corrected figure does not change the conclusions of this study. This correction does not modify the data interpretation of the original article. We apologize for this error.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12911","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia Méndez, Fernando Corvalan, Diego Halabi, Pamela Ehrenfeld, Rodrigo Maldonado, Karina Vergara, Maria Seron-Ferre, Claudia Torres-Farfan
During gestation, the developing fetus relies on precise maternal circadian signals for optimal growth and preparation for extrauterine life. These signals regulate the daily delivery of oxygen, nutrients, hormones, and other biophysical factors while synchronizing fetal rhythms with the external photoperiod. However, modern lifestyle factors such as light pollution and shift work can induce gestational chronodisruption, leading to the desynchronization of maternal and fetal circadian rhythms. Such disruptions have been associated with adverse effects on cardiovascular, neurodevelopmental, metabolic, and endocrine functions in the fetus, increasing the susceptibility to noncommunicable diseases (NCDs) in adult life. This aligns with the Developmental Origins of Health and Disease theory, suggesting that early-life exposures can significantly influence health outcomes later in life. The consequences of gestational chronodisruption also extend into adulthood. Environmental factors like diet and stress can exacerbate the adverse effects of these disruptions, underscoring the importance of maintaining a healthy circadian rhythm across the lifespan to prevent NCDs and mitigate the impact of gestational chronodisruption on aging. Research efforts are currently aimed at identifying potential interventions to prevent or mitigate the effects of gestational chronodisruption. Melatonin supplementation during pregnancy emerges as a promising intervention, although further investigation is required to fully understand the precise mechanisms involved and to develop effective strategies for promoting health and preventing NCDs in individuals affected by gestational chronodisruption.
{"title":"From gestational chronodisruption to noncommunicable diseases: Pathophysiological mechanisms of programming of adult diseases, and the potential therapeutic role of melatonin","authors":"Natalia Méndez, Fernando Corvalan, Diego Halabi, Pamela Ehrenfeld, Rodrigo Maldonado, Karina Vergara, Maria Seron-Ferre, Claudia Torres-Farfan","doi":"10.1111/jpi.12908","DOIUrl":"10.1111/jpi.12908","url":null,"abstract":"<p>During gestation, the developing fetus relies on precise maternal circadian signals for optimal growth and preparation for extrauterine life. These signals regulate the daily delivery of oxygen, nutrients, hormones, and other biophysical factors while synchronizing fetal rhythms with the external photoperiod. However, modern lifestyle factors such as light pollution and shift work can induce gestational chronodisruption, leading to the desynchronization of maternal and fetal circadian rhythms. Such disruptions have been associated with adverse effects on cardiovascular, neurodevelopmental, metabolic, and endocrine functions in the fetus, increasing the susceptibility to noncommunicable diseases (NCDs) in adult life. This aligns with the Developmental Origins of Health and Disease theory, suggesting that early-life exposures can significantly influence health outcomes later in life. The consequences of gestational chronodisruption also extend into adulthood. Environmental factors like diet and stress can exacerbate the adverse effects of these disruptions, underscoring the importance of maintaining a healthy circadian rhythm across the lifespan to prevent NCDs and mitigate the impact of gestational chronodisruption on aging. Research efforts are currently aimed at identifying potential interventions to prevent or mitigate the effects of gestational chronodisruption. Melatonin supplementation during pregnancy emerges as a promising intervention, although further investigation is required to fully understand the precise mechanisms involved and to develop effective strategies for promoting health and preventing NCDs in individuals affected by gestational chronodisruption.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10122625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In 1992, a paper reported that the melatonin content of the rat duodenum was 24 000 ± 2000 pg/g tissue (range: 4000–100 000 pg/g) while the pineal melatonin content was 580 000 ± 36 000 pg/g. The data has been used for the last 30 years to infer that the gut produces 400 hundred times more melatonin than the pineal gland and that it is the source of plasma melatonin during the daytime. No-one has ever challenged the statement. In this review, evidence is summarised from the literature that pinealectomy eliminates melatonin from the circulation and that studies to the contrary have relied upon poorly validated immunoassays that overstate the levels. Similarly studies that have reported increases in plasma melatonin following tryptophan administration failed to account for cross reactivity of tryptophan and its metabolites in immunoassays. The most extraordinary observation from the literature is that in those studies that have measured melatonin in the gut since 1992, the tissue content is vastly lower than the original report, even when the methodology used could be overestimating the melatonin content due to cross reactivity. Using the more contemporary results we can calculate that rather than a 400:1 ratio of duodenum: pineal melatonin, a ratio of 0.05–0.19: 1 is likely. The gut is not a major extra-pineal source of melatonin; indeed it may well not produce any.
{"title":"The mammalian gastro-intestinal tract is a NOT a major extra-pineal source of melatonin","authors":"David J. Kennaway","doi":"10.1111/jpi.12906","DOIUrl":"10.1111/jpi.12906","url":null,"abstract":"<p>In 1992, a paper reported that the melatonin content of the rat duodenum was 24 000 ± 2000 pg/g tissue (range: 4000–100 000 pg/g) while the pineal melatonin content was 580 000 ± 36 000 pg/g. The data has been used for the last 30 years to infer that the gut produces 400 hundred times more melatonin than the pineal gland and that it is the source of plasma melatonin during the daytime. No-one has ever challenged the statement. In this review, evidence is summarised from the literature that pinealectomy eliminates melatonin from the circulation and that studies to the contrary have relied upon poorly validated immunoassays that overstate the levels. Similarly studies that have reported increases in plasma melatonin following tryptophan administration failed to account for cross reactivity of tryptophan and its metabolites in immunoassays. The most extraordinary observation from the literature is that in those studies that have measured melatonin in the gut since 1992, the tissue content is vastly lower than the original report, even when the methodology used could be overestimating the melatonin content due to cross reactivity. Using the more contemporary results we can calculate that rather than a 400:1 ratio of duodenum: pineal melatonin, a ratio of 0.05–0.19: 1 is likely. The gut is not a major extra-pineal source of melatonin; indeed it may well not produce any.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10142390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}