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Response to “expanding the clinical and Immunogenomic relevance of SAMD1 in hepatocellular carcinoma” 对“扩大SAMD1在肝细胞癌中的临床和免疫基因组相关性”的回应。
IF 11.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-26 DOI: 10.1016/j.metabol.2025.156336
Guo-Qiang Pan, Yu-Chuan Yan, Rui-Zhe Li, Zhao-Ru dong, Tao Li
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引用次数: 0
Best practice recommendations for the diagnosis and management of hypoparathyroidism 甲状旁腺功能减退症的诊断和治疗的最佳实践建议。
IF 10.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-26 DOI: 10.1016/j.metabol.2025.156335
Aliya A. Khan , Dalal S. Ali , John P. Bilezikian , Sigridur Björnsdottir , Michael T. Collins , Natalie E. Cusano , Peter R. Ebeling , Ghada El Haj Fuleihan , Seiji Fukumoto , Andrea Giustina , Stephanie M. Kaiser , Christian A. Koch , Tayyab Khan , Patty Keating , Jian-Min Liu , Christos S. Mantzoros , Michael Mannstadt , Ambrish Mithal , Nancy D. Perrier , Michele Rayes , Maria Luisa Brandi

Background

Hypoparathyroidism (HypoPT) is characterized by low serum calcium due to insufficient parathyroid hormone (PTH). This manuscript builds upon the 2022 international HypoPT guidelines and three systematic reviews, which have been further informed by updated narrative reviews and expert consensus. This paper presents current best practice consensus recommendations for the diagnosis and management of HypoPT.

Methods

An International Panel of Experts updated the previous systematic reviews (SR's), conducted narrative reviews, developed, and subsequently approved these best practice recommendations at the Parathyroid Summit, held as a pre-Endocrine Society meeting in May 2024 (Boston, USA).

Results

Diagnostic criteria for chronic HypoPT require hypocalcemia with inappropriately normal or low PTH levels. Conventional therapy is recommended as first line therapy and includes calcium supplementation, active vitamin D, correction of vitamin D inadequacy and correction of abnormalities in serum magnesium. Monitoring is required to achieve optimal serum calcium while avoiding hyperphosphatemia, hypercalciuria and declines in renal function. Assessment of HypoPT complications is required including skeletal health assessment in postmenopausal women and men over the age of 50 years. Specific strategies are provided for managing HypoPT during pregnancy and lactation as well as in children. PTH replacement with palopegteriparatide has been approved and is an important therapeutic option, especially when conventional therapy is inadequate or not tolerated.

Conclusion

These best practice recommendations provide a framework for HypoPT diagnosis and management, emphasizing individualized care, role of DNA analysis in the diagnosis of nonsurgical HypoPT, and role of PTH or PTH analogue therapy as appropriate. They complement the 2022 international guidelines and incorporate updated therapeutic recommendations from the past 3 years including the positioning of the newly approved molecule palopegteriparatide based on recent clinical trial data and expert consensus.
背景:甲状旁腺功能减退症(HypoPT)的特点是由于甲状旁腺激素(PTH)不足导致血清钙水平降低。本文建立在2022年国际HypoPT指南和三篇系统综述的基础上,这些综述通过更新的叙述性综述和专家共识得到了进一步的信息。本文提出了目前诊断和管理HypoPT的最佳实践共识建议。方法:一个国际专家小组更新了以前的系统评价(SR),进行了叙述性评价,制定并随后在2024年5月(美国波士顿)举行的内分泌学会前会议甲状旁腺峰会上批准了这些最佳实践建议。结果:慢性HypoPT的诊断标准需要低钙伴甲状旁腺激素异常或低水平。常规治疗建议作为一线治疗,包括补钙、活性维生素D、纠正维生素D不足和纠正血清镁异常。监测是必要的,以达到最佳的血清钙,同时避免高磷血症,高钙尿症和肾功能下降。需要对HypoPT并发症进行评估,包括对绝经后妇女和年龄在50岁 以上的男性进行骨骼健康评估。提供了在妊娠和哺乳期以及儿童中管理HypoPT的具体策略。用palopegteriparatide替代PTH已被批准,是一种重要的治疗选择,特别是当常规治疗不足或不能耐受时。结论:这些最佳实践建议为HypoPT的诊断和管理提供了一个框架,强调个性化护理,DNA分析在非手术HypoPT诊断中的作用,以及PTH或PTH类似物治疗的作用。它们补充了2022年国际指南,并纳入了过去3 年更新的治疗建议,包括基于最近临床试验数据和专家共识的新批准的分子palopegteriparatide的定位。
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引用次数: 0
Finerenone in the SGLT2i era: Redundancy or complementarity? SGLT2i时代的精烯酮:冗余还是互补?
IF 11.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-26 DOI: 10.1016/j.metabol.2025.156337
Hongyi Chen , Yuying Ma , Qiang Wang
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引用次数: 0
Carboxylic acid metabolism in cancer: Mechanisms, microenvironment interactions, and therapeutic opportunities 癌症中的羧酸代谢:机制、微环境相互作用和治疗机会
IF 10.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-26 DOI: 10.1016/j.metabol.2025.156334
Xiqing Bian , Yue Zhuo , Luo Zhou , Yi Zhun Zhu , Na Li , Jian-Lin Wu
Cancer cells reprogram their metabolism to favor aerobic glycolysis and enhance carboxylic acid metabolism, supporting their energy needs and promoting tumor progression. This review explores the role of carboxylic acids, such as lactate, fatty acids, and amino acids, in cancer through four key pathways: (1) lactate-mediated tumor microenvironment acidification and immune suppression, (2) fatty acid metabolism driving tumorigenesis, (3) amino acid regulation of cancer cell survival, and (4) the crosstalk between these metabolic networks. These pathways contribute to immune evasion, proliferation, and drug resistance by modulating key enzymes, transporters, and signaling mechanisms. Despite their therapeutic potential, targeting carboxylic acid metabolism remains challenging owing to tumor adaptability and metabolic heterogeneity. Future research directions include the development of isoform-specific inhibitors, combination therapies, and precision medicine approaches based on metabolic profiling. Understanding these interconnected pathways may reveal new vulnerabilities for innovative cancer treatments.
癌细胞重新编程其代谢,以支持有氧糖酵解和增强羧酸代谢,支持其能量需求并促进肿瘤进展。本文综述了羧酸,如乳酸,脂肪酸和氨基酸在癌症中的作用,通过四个关键途径:(1)乳酸介导的肿瘤微环境酸化和免疫抑制,(2)脂肪酸代谢驱动肿瘤发生,(3)氨基酸调节癌细胞存活,以及(4)这些代谢网络之间的相互作用。这些途径通过调节关键酶、转运体和信号传导机制促进免疫逃避、增殖和耐药。尽管具有治疗潜力,但由于肿瘤的适应性和代谢异质性,靶向羧酸代谢仍然具有挑战性。未来的研究方向包括开发异构体特异性抑制剂、联合疗法和基于代谢谱的精准医学方法。了解这些相互联系的途径可能会揭示创新癌症治疗的新弱点。
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引用次数: 0
Exosomal miRNAs in muscle-bone crosstalk: Mechanistic links, exercise modulation and implications for sarcopenia, osteoporosis and osteosarcopenia 外泌体mirna在肌-骨相互作用中的作用:机制联系、运动调节和对肌肉减少症、骨质疏松症和骨-骨减少症的影响
IF 10.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-21 DOI: 10.1016/j.metabol.2025.156333
Bo Zhang, Yang Chen, Qiaojie Chen, Haijun Zhang
This review investigates the emerging role of exosomal microRNAs (miRNAs) as pivotal mediators of bidirectional communication between the skeletal muscle and bone tissue, with significant implications for age-related musculoskeletal disorders. In aging populations, sarcopenia often coexists with osteoporosis, forming osteosarcopenia, which markedly increases fracture risk, disability, and mortality. While traditional paradigms emphasize mechanical loading and endocrine pathways, emerging evidence has revealed that exosomes carrying bioactive miRNAs represent a novel class of paracrine factors in the muscle-bone axis. We examined how muscle-derived exosomal miRNAs (miR-34a and miR-27a-3p) influence bone metabolism, while bone-derived exosomal miRNAs (miR-486-5p) modulate muscle physiology. For each miRNA, we identified the target messenger RNAs (mRNAs) and signaling mechanisms. Importantly, exercise has emerged as a potent modulator of this crosstalk, altering exosomal miRNA profiles to promote anabolic outcomes in both tissues. This bidirectional communication contributes to osteosarcopenia pathophysiology, leading us to propose a novel “Exosomal miRNA Regulatory Network” for diagnosis and pathogenesis. Exosomal miRNAs show promise as early biomarkers for subclinical deterioration and therapeutic targets. However, methodological challenges in exosome isolation, incomplete characterization of miRNA networks, and aging complexity must be addressed before clinical implementation.
本文综述了外泌体microRNAs (miRNAs)作为骨骼肌和骨组织之间双向通讯的关键介质的新作用,对年龄相关的肌肉骨骼疾病具有重要意义。在老年人群中,骨骼肌减少症常与骨质疏松症共存,形成骨骨骼肌减少症,显著增加骨折风险、残疾和死亡率。虽然传统的范式强调机械负荷和内分泌途径,但新出现的证据表明,携带生物活性mirna的外泌体代表了肌肉-骨轴中一类新的旁分泌因子。我们研究了肌源性外泌体miRNAs (miR-34a和miR-27a-3p)如何影响骨代谢,而骨源性外泌体miRNAs (miR-486-5p)如何调节肌肉生理。对于每个miRNA,我们确定了目标信使rna (mrna)和信号传导机制。重要的是,运动已成为这种串扰的有效调节剂,改变外泌体miRNA谱,促进两种组织的合成代谢结果。这种双向交流有助于骨骼肌减少症的病理生理,因此我们提出了一种新的“外泌体miRNA调节网络”来诊断和发病。外泌体mirna有望成为亚临床恶化和治疗靶点的早期生物标志物。然而,在临床应用之前,必须解决外泌体分离、miRNA网络不完整表征和衰老复杂性方面的方法学挑战。
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引用次数: 0
The bone-heart axis: A crucial dialogue in cardiovascular disease 骨-心轴:心血管疾病的关键对话。
IF 10.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-19 DOI: 10.1016/j.metabol.2025.156332
Ying Liu , Qi Yao , Jiabin Yu, Yadan Zhang, Yang Xiao, Nan Zhang, Qi-Zhu Tang
Cardiovascular diseases (CVDs), the leading cause of global mortality, are now understood to be profoundly influenced by the endocrine regulatory functions of the skeletal system. Emerging evidence suggests that osteocrine factors, including fibroblast growth factor-23 (FGF23), lipocalin-2 (LCN2), Dickkopf-1 (DKK1), myeloid-derived growth factor (MYDGF), osteocalcin (OCN), and sclerostin (SOST), establish bidirectional regulatory networks with the cardiovascular system, termed the “bone-heart axis”. This axis regulates critical pathological processes, including mineral metabolism, vascular calcification, and myocardial energy homeostasis. Dysregulation of this crosstalk accelerates the progression of atherosclerosis (AS), heart failure (HF), and other CVDs. Therefore, current research necessitates a paradigm shift from univariate analyses to elucidating the spatiotemporal dynamics of interorgan communication, thereby facilitating the development of precision therapeutic strategies for integrated skeletal and cardiovascular protection.
心血管疾病(cvd),全球死亡的主要原因,现在被理解为深刻地影响骨骼系统的内分泌调节功能。新出现的证据表明,骨分泌因子,包括成纤维细胞生长因子-23 (FGF23)、脂钙素-2 (LCN2)、Dickkopf-1 (DKK1)、髓源性生长因子(MYDGF)、骨钙素(OCN)和硬化蛋白(SOST),与心血管系统建立了双向调节网络,称为“骨-心轴”。这条轴调节关键的病理过程,包括矿物质代谢、血管钙化和心肌能量稳态。这种串扰的失调加速了动脉粥样硬化(AS)、心力衰竭(HF)和其他心血管疾病的进展。因此,当前的研究需要从单变量分析转向阐明器官间通讯的时空动态,从而促进骨骼和心血管综合保护的精确治疗策略的发展。
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引用次数: 0
Glycine as a conditionally essential amino acid and its relationship to l-serine 甘氨酸作为一种条件必需氨基酸及其与l-丝氨酸的关系
IF 10.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-15 DOI: 10.1016/j.metabol.2025.156330
Milan Holeček
Glycine is a conditionally essential amino acid obtained from food and synthesized in the body, primarily from l-serine. Glycine deficiency has been reported due to inadequate protein intake, malnutrition, late gestation, diabetes, insulin resistance, and increased exposure to xenobiotics. Because of the close links in glycine and l-serine metabolism mediated by serine hydroxymethyltransferase (SHMT), decreased concentrations of both amino acids coincide in most glycine-deficient states. The consequence is a widespread impact on metabolism, including altered synthesis of glutathione, collagen, nucleotides, and one‑carbon units, impaired antioxidant defense, cytoprotection, conjugation, and neurotransmission and increased levels of homocysteine and deoxysphingolipids. It can, therefore, be assumed that, rather than glycine alone, its coadministration with l-serine is more appropriate in glycine-deficient conditions. Replacing a part of the glycine with l-serine should avoid (i) glycine flux through SHMT towards l-serine associated with the loss of methylenetetrahydrofolate, a substance essential for methylation reactions, and (ii) ammonia formation due to glycine flux through the glycine cleavage system. Unfortunately, studies comparing the effects of separate administration of glycine and its coadministration with l-serine do not exist. Well-controlled studies in subjects without glycine deficit are required to examine the potential benefits of high doses of glycine as a pharmaconutrient.
甘氨酸是一种条件必需氨基酸,从食物中获得,并在体内合成,主要由l-丝氨酸合成。据报道,甘氨酸缺乏症是由于蛋白质摄入不足、营养不良、妊娠晚期、糖尿病、胰岛素抵抗和接触外源性药物增加所致。由于丝氨酸羟甲基转移酶(SHMT)介导的甘氨酸和l-丝氨酸代谢的密切联系,在大多数甘氨酸缺乏状态下,这两种氨基酸的浓度下降是一致的。其结果是对代谢的广泛影响,包括谷胱甘肽、胶原蛋白、核苷酸和一碳单位的合成改变,抗氧化防御、细胞保护、结合和神经传递受损,同型半胱氨酸和脱氧鞘脂水平升高。因此,可以假设,在甘氨酸缺乏的情况下,与l-丝氨酸共同施用比单独使用甘氨酸更合适。用l-丝氨酸代替部分甘氨酸可以避免(i)甘氨酸通过SHMT流向l-丝氨酸,这与甲基化反应所必需的亚甲基四氢叶酸的损失有关,以及(ii)由于甘氨酸通过甘氨酸裂解系统通量而形成氨。不幸的是,没有研究比较单独给药甘氨酸和与l-丝氨酸共给药的效果。需要在没有甘氨酸缺乏的受试者中进行良好的对照研究,以检验高剂量甘氨酸作为药物营养素的潜在益处。
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引用次数: 0
Expanding the clinical and immunogenomic relevance of SAMD1 in hepatocellular carcinoma 扩大SAMD1在肝细胞癌中的临床和免疫基因组相关性。
IF 11.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-14 DOI: 10.1016/j.metabol.2025.156331
Valbert Oliveira Costa Filho , Pedro Robson Costa Passos
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引用次数: 0
NIPSNAP1 and NIPSNAP2 facilitate healthy aging independent of mitophagy NIPSNAP1和NIPSNAP2促进独立于线粒体自噬的健康衰老。
IF 10.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-13 DOI: 10.1016/j.metabol.2025.156324
Jian Lv , Junmei Wang , Qin Chen , Qianhua Zhong , Hongchao Zhan , Qiuxiao Guo , Jiajie Li , Ningning Guo , Yu Fang , Jingjing Tong , Zhihua Wang
Mitochondrial dysfunction is a hallmark of aging and has been implicated in aging-related diseases. NIPSNAP1 and NIPSNAP2 are functionally redundant homologs involved in mitochondrial quality control, yet their roles in healthy aging and longevity remain unclear. Here, we generated a Nipsnap1/2 double knockout (DKO) mouse line and examined its impacts on mitochondrial physiology and natural aging. We demonstrated that the loss of Nipsnap1/2 impaired mitochondrial function and enhanced glycolysis activity, but it did not affect mitophagy despite the significant accumulation of Parkin. Compared with wild-type mice, DKO mice exhibited reduced body weight, deteriorated muscle strength, and pronounced fragility at 24 months of age. Moreover, Nipsnap1/2 depletion exacerbates aging-associated fibrosis and inflammation in the heart, liver and kidney. RNA-seq revealed a pro-aging transcriptome reprogramming toward energy exhaustion in DKO mice, eventually leading to cachexia-like adverse metabolic remodeling. Our findings demonstrate an anti-aging role of NIPSNAP1/2 via the surveillance of mitochondrial health.
线粒体功能障碍是衰老的标志,并与衰老相关疾病有关。NIPSNAP1和NIPSNAP2是参与线粒体质量控制的功能冗余同源物,但它们在健康衰老和长寿中的作用尚不清楚。在这里,我们产生了Nipsnap1/2双敲除(DKO)小鼠系,并研究了其对线粒体生理和自然衰老的影响。我们证明Nipsnap1/2的缺失损害了线粒体功能并增强了糖酵解活性,但它不影响线粒体自噬,尽管Parkin显著积累。与野生型小鼠相比,DKO小鼠在24 月龄时表现出体重减轻、肌肉力量恶化和明显的脆弱性。此外,Nipsnap1/2缺失加剧了心脏、肝脏和肾脏中与衰老相关的纤维化和炎症。RNA-seq揭示了DKO小鼠的促衰老转录组重编程,最终导致恶病质样的不良代谢重塑。我们的研究结果通过监测线粒体健康证明了NIPSNAP1/2的抗衰老作用。
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引用次数: 0
USP48 protects against myocardial ischemia-reperfusion injury by stabilizing and upregulating CNN1 in type 1 diabetes mice USP48通过稳定和上调1型糖尿病小鼠CNN1来保护心肌缺血-再灌注损伤
IF 10.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-06-11 DOI: 10.1016/j.metabol.2025.156326
Jia-Bao Su , Guo Chen , Qing-Yi Sun , Xiao Fu , Li-Xue Wu , Hong-Bo Qiu , Zhuo-Lin Lv , Jin-Yi Hu , Yao Wang , You-Yi Zhuang , Hai-Jian Sun , Qing-Bo Lu , Ji-Ru Zhang , Xue-Xue Zhu
Ubiquitin-specific protease 48 (USP48) plays an important role in the regulation of DNA repair and immune signaling in health and diseases. Nonetheless, its implication in the development of diabetes-accelerated myocardial ischemia/reperfusion (I/R) injury (MI/RI) has yet to be clarified. Diabetic mice were constructed by streptozotocin (STZ) injection, and MI/RI was then induced by coronary artery occlusion and reperfusion. H9c2 cells were exposed to high glucose (HG) for 24 h, followed by hypoxia/reoxygenation (H/R) for 4 and 2 h, respectively. USP48 protein and mRNA levels were downregulated in MI/RI mice or H/R-exposed cardiomyocytes, but were unexpectedly upregulated in diabetic mice following MI/RI and H9c2 cells exposed to HG and H/R. Cardiac-specific deficiency of USP48 worsened cardiac dysfunction, increased post-ischemic infarction size, promoted mitochondrial damage in myocardial cells, accelerated cardiomyocyte inflammation, oxidative stress, and apoptosis in diabetic mice. Conversely, such pathological conditions were ameliorated by cardiac-specific overexpression of USP48. Proteomics and experimental validation showed that USP48 stabilized and upregulated calponin 1 (CNN1) to confer cardioprotection, since silencing CNN1 minimized the benefits of USP48 in diabetes-aggravated cardiomyocyte injury. RNA sequencing and experimental data demonstrated that the USP48/CNN1 axis inhibited the release of CXC motif chemokine ligand 1 (CXCL1) and CXCL2 through inactivating the ERK1/2 pathway. Eventually, blockade of CXCL1/2 with specific antibodies protected against diabetes-exacerbated MI/RI, akin to USP48 overexpression. Together, these results highlight USP48 as a potential therapeutic target for managing diabetes-aggravated MI/RI by regulating the CNN1/ERK1/2/CXCL1/2 signaling pathway.
泛素特异性蛋白酶48 (USP48)在健康和疾病的DNA修复和免疫信号调控中发挥重要作用。尽管如此,其在糖尿病-加速心肌缺血/再灌注(I/R)损伤(MI/RI)发展中的意义尚未明确。采用链脲佐菌素(STZ)构建糖尿病小鼠,冠脉闭塞再灌注诱导心肌梗死/再灌注。H9c2细胞暴露于高糖(HG) 24 h,然后分别缺氧/再氧化(h /R) 4 h和2 h。USP48蛋白和mRNA水平在MI/RI小鼠或H/R暴露的心肌细胞中下调,但在MI/RI和H9c2细胞暴露于HG和H/R后,糖尿病小鼠中USP48蛋白和mRNA水平意外上调。在糖尿病小鼠中,心脏特异性USP48缺乏会加重心功能障碍,增加缺血梗死后的大小,促进心肌细胞线粒体损伤,加速心肌细胞炎症、氧化应激和凋亡。相反,心脏特异性的USP48过表达会改善这种病理状况。蛋白质组学和实验验证表明,USP48稳定和上调钙钙蛋白1 (CNN1),从而赋予心脏保护作用,因为沉默CNN1使USP48在糖尿病加重的心肌细胞损伤中的益处最小化。RNA测序和实验数据表明,USP48/CNN1轴通过失活ERK1/2通路抑制CXC基序趋化因子配体1 (CXCL1)和CXCL2的释放。最终,特异性抗体阻断CXCL1/2可防止糖尿病加重的MI/RI,类似于USP48过表达。总之,这些结果强调了USP48是通过调节CNN1/ erk1 /CXCL1/2信号通路来控制糖尿病加重的MI/RI的潜在治疗靶点。
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引用次数: 0
期刊
Metabolism: clinical and experimental
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