JCSM rapid communications最新文献

英文中文

A genome wide association study to identify germline copy number variants associated with cancer cachexia: a preliminary analysis 通过基因组全关联研究确定与癌症恶病质相关的种系拷贝数变异：初步分析

JCSM rapid communications

Pub Date : 2024-04-18 DOI: 10.1002/rco2.91

Ashok Narasimhan, Mahalakshmi Kumaran, Ioannis Gioulbasanis, Richard J.E. Skipworth, Oliver F. Bathe, Stein Kaasa, Florian Strasser, Bruno Gagnon, Vickie Baracos, Sambasivarao Damaraju

Background

Cancer cachexia is characterized by severe loss of muscle and fat involving a complex interplay of host–tumour interactions. While much emphasis has been placed on understanding the molecular mechanisms associated with cachexia, understanding the heritable component of cachexia remains less explored. The current study aims to identify copy number variants (CNV) as genetic susceptibility determinants for weight loss in patients with cancer cachexia using genome wide association study (GWAS) approach.

Methods

A total of 174 age-matched patients with oesophagogastric or lung cancer were classified as weight losing (>10% weight loss) or weight stable participants (<2% weight loss). DNA was genotyped using Affymetrix SNP 6.0 arrays to profile CNVs. We tested CNVs with >5% frequency in the population for association with weight loss. Pathway analysis was performed using the genes embedded within CNVs. To understand if the CNVs in the present study are also expressed in skeletal muscle of patients with cachexia, we utilized two publicly available human gene expression datasets to infer the relevance of identified genes in the context of cachexia.

Results

Among the associated CNVs, 5414 CNVs had embedded protein coding genes. Of these, 1583 CNVs were present at >5% frequency. We combined multiple contiguous CNVs within the same genomic region and called them Copy Number Variable Region (CNVR). This led to identifying 896 non-redundant CNV/CNVRs, which encompassed 803 protein coding genes. Genes embedded within CNVs were enriched for several pathways implicated in cachexia and muscle wasting including JAK–STAT signalling, Oncostatin M signalling, Wnt signalling and PI3K-Akt signalling. This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. Further, we show that a subset of CNV/CNVR embedded genes identified in the current study are common with the previously published skeletal muscle gene expression datasets, indicating that expression of CNV/CNVR genes in muscle may have functional consequences in patients with cachexia. These genes include CPT1B, SPON1, LOXL1, NFAT5, RBFOX1, and PCSK6 to name a few.

Conclusions

This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. The data generated will aid in future replication studies in larger cohorts to account for genetic susceptibility to weig

背景癌症恶病质的特点是肌肉和脂肪严重流失，其中涉及宿主与肿瘤之间复杂的相互作用。尽管人们非常重视了解与恶病质相关的分子机制，但对恶病质遗传因素的了解仍然较少。本研究旨在利用全基因组关联研究（GWAS）方法确定拷贝数变异（CNV）作为癌症恶病质患者体重减轻的遗传易感性决定因素。方法共有 174 名年龄匹配的食管胃癌或肺癌患者被分为体重减轻者（体重减轻 10%）和体重稳定者（体重减轻 2%）。使用 Affymetrix SNP 6.0 阵列对 DNA 进行基因分型，以确定 CNV。我们测试了人群中频率为 5%的 CNV 与体重减轻的关系。利用嵌入 CNV 的基因进行了通路分析。为了了解本研究中的 CNV 是否也在恶病质患者的骨骼肌中表达，我们利用两个公开的人类基因表达数据集来推断所发现的基因与恶病质的相关性。结果在相关的 CNV 中，有 5414 个 CNV 嵌入了蛋白质编码基因。其中，1583 个 CNV 的出现频率为 5%。我们将同一基因组区域内多个连续的 CNVs 合并，称其为拷贝数可变区（CNVR）。这样就确定了 896 个非冗余 CNV/CNVR，其中包括 803 个蛋白质编码基因。嵌入 CNVs 的基因富集于与恶病质和肌肉萎缩有关的几个通路，包括 JAK-STAT 信号、Oncostatin M 信号、Wnt 信号和 PI3K-Akt 信号。这是首个将 CNVs 鉴定为癌症恶病质遗传决定因素的 GWAS 原理验证研究。此外，我们还发现，本研究中发现的一部分 CNV/CNVR 嵌入基因与之前发表的骨骼肌基因表达数据集具有共通性，这表明 CNV/CNVR 基因在肌肉中的表达可能会对恶病质患者产生功能性影响。这些基因包括 CPT1B、SPON1、LOXL1、NFAT5、RBFOX1 和 PCSK6 等。结论这是首次将 CNVs 确定为癌症恶病质遗传决定因素的原理性 GWAS 研究。所产生的数据将有助于今后在更大的队列中进行重复研究，以解释癌症恶病质患者体重减轻的遗传易感性。

{"title":"A genome wide association study to identify germline copy number variants associated with cancer cachexia: a preliminary analysis","authors":"Ashok Narasimhan, Mahalakshmi Kumaran, Ioannis Gioulbasanis, Richard J.E. Skipworth, Oliver F. Bathe, Stein Kaasa, Florian Strasser, Bruno Gagnon, Vickie Baracos, Sambasivarao Damaraju","doi":"10.1002/rco2.91","DOIUrl":"https://doi.org/10.1002/rco2.91","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer cachexia is characterized by severe loss of muscle and fat involving a complex interplay of host–tumour interactions. While much emphasis has been placed on understanding the molecular mechanisms associated with cachexia, understanding the heritable component of cachexia remains less explored. The current study aims to identify copy number variants (CNV) as genetic susceptibility determinants for weight loss in patients with cancer cachexia using genome wide association study (GWAS) approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 174 age-matched patients with oesophagogastric or lung cancer were classified as weight losing (>10% weight loss) or weight stable participants (<2% weight loss). DNA was genotyped using Affymetrix SNP 6.0 arrays to profile CNVs. We tested CNVs with >5% frequency in the population for association with weight loss. Pathway analysis was performed using the genes embedded within CNVs. To understand if the CNVs in the present study are also expressed in skeletal muscle of patients with cachexia, we utilized two publicly available human gene expression datasets to infer the relevance of identified genes in the context of cachexia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the associated CNVs, 5414 CNVs had embedded protein coding genes. Of these, 1583 CNVs were present at >5% frequency. We combined multiple contiguous CNVs within the same genomic region and called them Copy Number Variable Region (CNVR). This led to identifying 896 non-redundant CNV/CNVRs, which encompassed 803 protein coding genes. Genes embedded within CNVs were enriched for several pathways implicated in cachexia and muscle wasting including JAK–STAT signalling, Oncostatin M signalling, Wnt signalling and PI3K-Akt signalling. This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. Further, we show that a subset of CNV/CNVR embedded genes identified in the current study are common with the previously published skeletal muscle gene expression datasets, indicating that expression of CNV/CNVR genes in muscle may have functional consequences in patients with cachexia. These genes include CPT1B, SPON1, LOXL1, NFAT5, RBFOX1, and PCSK6 to name a few.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. The data generated will aid in future replication studies in larger cohorts to account for genetic susceptibility to weig","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 1","pages":"55-65"},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.91","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combined orchiectomy and limb immobilization recapitulate early age-related changes to skeletal muscle in mice 睾丸切除术和肢体固定相结合再现了小鼠骨骼肌早期与年龄有关的变化

JCSM rapid communications

Pub Date : 2024-04-16 DOI: 10.1002/rco2.90

Danielle A. Debruin, Jasmaine Murphy, Dean G. Campelj, Ryan Bagaric, Cara A. Timpani, Craig A. Goodman, Erik D. Hanson, Emma Rybalka, Alan Hayes

Background

Muscle mass and function decline in middle age, ultimately resulting in sarcopenia in the elderly and poor health outcomes, reducing quality of life. There is a lack of cost- and time-effective murine models that recapitulate the physiological changes associated with muscle mass decline to study possible interventions to delay sarcopenia. We aimed to evaluate the effectiveness of combining orchiectomy (ORC) surgery to simulate age-related androgen decline and hindlimb immobilization (IM) in inducing age-related skeletal muscle changes.

Methods

Four-month-old male C57BL/6J mice (n = 10) were subjected to ORC, followed by IM (right hindlimb casting) for 14 days. Upon completion of the casting period, ex vivo muscle contractile function, histology, and various mitochondrial markers were assessed, and results were compared with age-matched controls (CON; n = 8) and middle-aged (MA; 12 ± 1 months, n = 9) animals.

Results

IM combined with ORC induced a 30%–40% decrease in muscle mass across multiple hindlimb muscles (P < 0.0001), with the magnitude of muscle loss comparable with the MA group when corrected for body weight (P < 0.0001). In the IM limb of ORC mice, soleus muscle force significantly decreased when compared with the contralateral limb (P < 0.05) and aged-matched CON group (P < 0.05). The decrements in muscle force and mass present in the IM limb of ORC mice were accompanied by a 70% reduction in the expression of the muscle structural protein dystrophin and various mitochondrial markers, including cytochrome C (−55%), peroxisome proliferator-activated receptor gamma co-activator 1-beta (PGC1-β) (−49%), and cytochrome oxidase IV (COX-IV) (−73%) when compared with CON animals (P < 0.001). Lastly, our model also demonstrated specific fibre-type shifts in fast- and slow-twitch muscles, which mimicked changes in the MA group.

Conclusions

Applying treatments during IM could target acute muscle atrophy in MA adults, while applying them following cast removal in a low-testosterone environment could represent a window for rehabilitation therapeutics.

背景肌肉质量和功能在中年时会下降，最终导致老年人肌肉疏松症和不良的健康状况，降低生活质量。目前缺乏成本低、时间短、效果好的小鼠模型来再现肌肉质量下降的相关生理变化，从而研究延缓肌肉疏松症的可能干预措施。我们旨在评估睾丸切除手术（ORC）模拟与年龄相关的雄激素下降和后肢固定（IM）在诱导与年龄相关的骨骼肌变化方面的有效性。方法对四个月大的雄性 C57BL/6J 小鼠（n = 10）进行睾丸切除手术，然后进行为期 14 天的右后肢固定。铸造期结束后，评估体内外肌肉收缩功能、组织学和各种线粒体标记物，并将结果与年龄匹配的对照组（CON；n = 8）和中年组（MA；12 ± 1 个月，n = 9）动物进行比较。结果 IM 与 ORC 联用会导致后肢多块肌肉的肌肉质量下降 30%-40%（P < 0.0001），根据体重校正后，肌肉损失的程度与 MA 组相当（P < 0.0001）。与对侧肢体（P <0.05）和年龄匹配的CON组（P <0.05）相比，ORC小鼠IM肢体的比目鱼肌力显著下降。与对照组相比，ORC 小鼠肢体肌力和肌肉质量下降的同时，肌肉结构蛋白肌营养不良蛋白和各种线粒体标记物的表达也减少了 70%，其中包括细胞色素 C（-55%）、过氧化物酶体增殖激活受体伽马共激活因子 1-β（PGC1-β）（-49%）和细胞色素氧化酶 IV（COX-IV）（-73%）（P < 0.001）。最后，我们的模型还显示了快慢肌特定纤维类型的变化，这与 MA 组的变化相似。结论在 IM 期间应用治疗方法可针对 MA 成年人的急性肌肉萎缩，而在低睾酮环境中拆除石膏后应用治疗方法可代表康复疗法的一个窗口。

{"title":"Combined orchiectomy and limb immobilization recapitulate early age-related changes to skeletal muscle in mice","authors":"Danielle A. Debruin, Jasmaine Murphy, Dean G. Campelj, Ryan Bagaric, Cara A. Timpani, Craig A. Goodman, Erik D. Hanson, Emma Rybalka, Alan Hayes","doi":"10.1002/rco2.90","DOIUrl":"https://doi.org/10.1002/rco2.90","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle mass and function decline in middle age, ultimately resulting in sarcopenia in the elderly and poor health outcomes, reducing quality of life. There is a lack of cost- and time-effective murine models that recapitulate the physiological changes associated with muscle mass decline to study possible interventions to delay sarcopenia. We aimed to evaluate the effectiveness of combining orchiectomy (ORC) surgery to simulate age-related androgen decline and hindlimb immobilization (IM) in inducing age-related skeletal muscle changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four-month-old male C57BL/6J mice (<i>n =</i> 10) were subjected to ORC, followed by IM (right hindlimb casting) for 14 days. Upon completion of the casting period, ex vivo muscle contractile function, histology, and various mitochondrial markers were assessed, and results were compared with age-matched controls (CON; <i>n</i> = 8) and middle-aged (MA; 12 ± 1 months, <i>n</i> = 9) animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IM combined with ORC induced a 30%–40% decrease in muscle mass across multiple hindlimb muscles (<i>P</i> < 0.0001), with the magnitude of muscle loss comparable with the MA group when corrected for body weight (<i>P</i> < 0.0001). In the IM limb of ORC mice, soleus muscle force significantly decreased when compared with the contralateral limb (<i>P <</i> 0.05) and aged-matched CON group (<i>P <</i> 0.05). The decrements in muscle force and mass present in the IM limb of ORC mice were accompanied by a 70% reduction in the expression of the muscle structural protein dystrophin and various mitochondrial markers, including cytochrome C (−55%), peroxisome proliferator-activated receptor gamma co-activator 1-beta (PGC1-β) (−49%), and cytochrome oxidase IV (COX-IV) (−73%) when compared with CON animals (<i>P</i> < 0.001). Lastly, our model also demonstrated specific fibre-type shifts in fast- and slow-twitch muscles, which mimicked changes in the MA group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Applying treatments during IM could target acute muscle atrophy in MA adults, while applying them following cast removal in a low-testosterone environment could represent a window for rehabilitation therapeutics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 1","pages":"40-54"},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.90","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Betulinic acid ameliorates cast-immobilized skeletal muscle atrophy but not denervation-induced skeletal muscle atrophy 白桦脂酸可改善石膏固定的骨骼肌萎缩，但不能改善去神经诱导的骨骼肌萎缩

JCSM rapid communications

Pub Date : 2024-04-01 DOI: 10.1002/rco2.89

Yuki Enoki, Yuki Kanezaki, Isamu Takahata, Kazuaki Taguchi, Kazuaki Matsumoto

Background

Terpenoids have gained attention as therapeutic agents for skeletal muscle atrophy owing to their various physiological activities. In this study, we screened four terpenoids for their therapeutic potential against muscle atrophy in cultured cells and evaluated the effectiveness of betulinic acid in two disuse muscle atrophy models.

Methods

C2C12 cells were used as the skeletal muscle model in cell culture experiments. Betulinic acid (100 mg/kg, twice daily) was administered to two different mouse models of muscle atrophy (established using the sciatic denervation and casting methods) for 7 days.

Results

In myotube experiments, the mRNA expression of atrogin-1 and myostatin was significantly suppressed by betulinic and ursolic acids (P < 0.05). In the differentiation phase of C2C12 myotubes, the mRNA expression levels of myoD and myogenin were significantly increased by betulinic acid (P < 0.05). In addition, apelin and irisin were also significantly increased by betulinic acid (P < 0.05 and 0.01, respectively). Consequently, betulinic acid was administered to the aforementioned muscle atrophy models. Betulinic acid did not inhibit the decrease in skeletal muscle weight observed in the denervation model. However, it significantly inhibited the decrease in tibialis anterior (TA) and extensor digitorum longus (EDL) weights and grip strength observed in the cast-immobilized skeletal muscle atrophy model (TA: Cast + Veh vs. Cast + Bet = 42.6 ± 1.0 vs. 46.0 ± 0.8 mg, P < 0.01; EDL: Cast + Veh vs. Cast + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg, P < 0.01; grip strength: Cast + Veh vs. Cast + Bet = 222 ± 4.8 vs. 245 ± 3.6 g, P < 0.05). In addition, betulinic acid administration partially inhibited the decrease in skeletal muscle cross-sectional area.

Conclusions

Betulinic acid alleviated muscle atrophy in the cast model of muscle atrophy and has therapeutic potential for the treatment of immobilized disuse skeletal muscle atrophy.

背景萜类化合物具有多种生理活性，因此作为骨骼肌萎缩的治疗药物已受到关注。本研究筛选了四种萜类化合物在培养细胞中对肌肉萎缩的治疗潜力，并评估了白桦脂酸在两种废用性肌肉萎缩模型中的有效性。方法在细胞培养实验中使用 C2C12 细胞作为骨骼肌模型。给两种不同的肌肉萎缩小鼠模型（使用坐骨神经去神经和铸造法建立）注射白桦脂酸（100 毫克/千克，每天两次），为期 7 天。结果在肌管实验中，白桦脂酸和熊果酸显著抑制了atrogin-1和myostatin的mRNA表达（P< 0.05）。在 C2C12 肌管的分化阶段，桦木酸可明显提高 myoD 和 myogenin 的 mRNA 表达水平（P < 0.05）。此外，凋亡素和鸢尾素也在白桦脂酸的作用下明显增加（P分别为0.05和0.01）。因此，将白桦脂酸用于上述肌肉萎缩模型。白桦脂酸不能抑制去神经模型中观察到的骨骼肌重量的减少。然而，白桦脂酸却能明显抑制在石膏固定骨骼肌萎缩模型中观察到的胫骨前肌（TA）和趾长伸肌（EDL）重量和握力的下降（TA：Cast + Veh vs. EDL：Cast + Bet = 42.6 ± 2.5 ± 2.5）。铸塑 + Bet = 42.6 ± 1.0 vs. 46.0 ± 0.8 mg，P < 0.01；EDL：铸塑 + Veh vs. 铸塑 + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg，P < 0.01；握力：铸塑 + Veh vs. 铸塑 + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg，P < 0.01）：Cast + Veh vs. Cast + Bet = 222 ± 4.8 vs. 245 ± 3.6 g，P < 0.05）。此外，白桦脂酸还能部分抑制骨骼肌横截面积的减少。结论白桦脂酸可缓解石膏模型肌肉萎缩，具有治疗固定失用性骨骼肌萎缩的潜力。

{"title":"Betulinic acid ameliorates cast-immobilized skeletal muscle atrophy but not denervation-induced skeletal muscle atrophy","authors":"Yuki Enoki, Yuki Kanezaki, Isamu Takahata, Kazuaki Taguchi, Kazuaki Matsumoto","doi":"10.1002/rco2.89","DOIUrl":"https://doi.org/10.1002/rco2.89","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Terpenoids have gained attention as therapeutic agents for skeletal muscle atrophy owing to their various physiological activities. In this study, we screened four terpenoids for their therapeutic potential against muscle atrophy in cultured cells and evaluated the effectiveness of betulinic acid in two disuse muscle atrophy models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>C2C12 cells were used as the skeletal muscle model in cell culture experiments. Betulinic acid (100 mg/kg, twice daily) was administered to two different mouse models of muscle atrophy (established using the sciatic denervation and casting methods) for 7 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In myotube experiments, the mRNA expression of atrogin-1 and myostatin was significantly suppressed by betulinic and ursolic acids (<i>P</i> < 0.05). In the differentiation phase of C2C12 myotubes, the mRNA expression levels of myoD and myogenin were significantly increased by betulinic acid (<i>P</i> < 0.05). In addition, apelin and irisin were also significantly increased by betulinic acid (<i>P</i> < 0.05 and 0.01, respectively). Consequently, betulinic acid was administered to the aforementioned muscle atrophy models. Betulinic acid did not inhibit the decrease in skeletal muscle weight observed in the denervation model. However, it significantly inhibited the decrease in tibialis anterior (TA) and extensor digitorum longus (EDL) weights and grip strength observed in the cast-immobilized skeletal muscle atrophy model (TA: Cast + Veh vs. Cast + Bet = 42.6 ± 1.0 vs. 46.0 ± 0.8 mg, <i>P</i> < 0.01; EDL: Cast + Veh vs. Cast + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg, <i>P</i> < 0.01; grip strength: Cast + Veh vs. Cast + Bet = 222 ± 4.8 vs. 245 ± 3.6 g, <i>P</i> < 0.05). In addition, betulinic acid administration partially inhibited the decrease in skeletal muscle cross-sectional area.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Betulinic acid alleviated muscle atrophy in the cast model of muscle atrophy and has therapeutic potential for the treatment of immobilized disuse skeletal muscle atrophy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 1","pages":"30-39"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.89","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Publication trends and hot spots in the Journal of Cachexia, Sarcopenia and Muscle: A bibliometric analysis (2010–2022) 痛症、肌肉疏松症与肌肉杂志》的出版趋势与热点：文献计量分析（2010-2022 年）

JCSM rapid communications

Pub Date : 2024-02-29 DOI: 10.1002/rco2.88

Dong-liang Yuan, Wen-qing Xie, Miao He, Deng-jie Yu, Heng-zhen Li, Hong-fu Jin, Guang Yang, Bing-zhou Ji, Wen-feng Xiao, Yu-sheng Li

Background

The Journal of Cachexia, Sarcopenia and Muscle is a quarterly peer-reviewed medical journal published by WILEY since 2010 and has been dedicated to advancing research on chronic diseases, especially cachexia and sarcopenia. Over the past 12 years, sarcopenia research worldwide has significantly changed. This study aimed to investigate different aspects of studies published in this journal.

Methods

Using the term ‘Journal of Cachexia, Sarcopenia and Muscle’, we retrieved related publications from the Web of Science and PubMed databases. Studies published in this journal were classified and analysed from different perspectives, such as the number of studies, total citations, times cited per item, H-index, research area, article types, institutions, country and funding agency. The VOS viewer software was used for co-occurrence, bibliographic coupling, co-citation and co-authorship analyses.

Results

From 2010 to 2022, 1194 studies were published in the Journal of Cachexia, Sarcopenia and Muscle. The United States was the highest contributor, with the most publications and citations and the highest H-index. Italy ranked first for the times cited per item. The main research area was geriatrics and gerontology. von Haehling S was the author with the highest impact. The National Institutes of Health, USA, and the United States Department of Health Human Services funded the maximum number of studies. The top 5 most frequently used keywords in all publications over 12 years were sarcopenia, cachexia, skeletal muscle, body composition and muscle mass. The Journal of Cachexia, Sarcopenia and Muscle was cited the most by Nutrients, and PLOS ONE was cited the most by the Journal of Cachexia, Sarcopenia and Muscle.

Conclusions

Publications in the Journal of Cachexia, Sarcopenia and Muscle have significantly increased from 2010 to 2022, especially in recent years. The United States is still the leader in sarcopenia research. Future submissions to this journal will continue to focus on sarcopenia, cachexia, skeletal muscle, body-composition and muscle mass. The aetiology, molecular mechanisms and outcomes of sarcopenia and cachexia are current research hotspots.

背景《恶病质、肌肉疏松症与肌肉杂志》是由 WILEY 于 2010 年出版的同行评审医学季刊，一直致力于推动慢性疾病，尤其是恶病质和肌肉疏松症的研究。在过去的 12 年中，全球范围内的肌肉疏松症研究发生了重大变化。本研究旨在调查在该期刊上发表的研究的各个方面。方法我们以 "Journal of Cachexia, Sarcopenia and Muscle "为关键词，从 Web of Science 和 PubMed 数据库中检索了相关出版物。我们从研究数量、总引用次数、每项被引次数、H 指数、研究领域、文章类型、机构、国家和资助机构等不同角度对发表在该期刊上的研究进行了分类和分析。使用 VOS 浏览器软件进行共现、书目耦合、共引和合著分析。结果从 2010 年到 2022 年，《痛症、肉质疏松症和肌肉杂志》共发表了 1194 篇研究论文。美国是贡献最多的国家，发表的论文最多，被引用的次数最多，H 指数也最高。意大利的单篇引用次数排名第一。von Haehling S 是影响最大的作者。美国国立卫生研究院和美国卫生人类服务部资助的研究数量最多。12 年来，所有出版物中使用频率最高的 5 个关键词是肌肉疏松症、恶病质、骨骼肌、身体成分和肌肉质量。营养素》对《恶病质、肌肉减少症与肌肉杂志》的引用率最高，而《PLOS ONE》对《恶病质、肌肉减少症与肌肉杂志》的引用率最高。结论从2010年到2022年，《痛症、肌肉疏松症与肌肉杂志》上的论文数量显著增加，尤其是近年来。美国在肌肉疏松症研究方面仍处于领先地位。本期刊今后的投稿将继续关注肌肉疏松症、恶病质、骨骼肌、身体结构和肌肉质量。肌肉疏松症和恶病质的病因、分子机制和结果是当前的研究热点。

{"title":"Publication trends and hot spots in the Journal of Cachexia, Sarcopenia and Muscle: A bibliometric analysis (2010–2022)","authors":"Dong-liang Yuan, Wen-qing Xie, Miao He, Deng-jie Yu, Heng-zhen Li, Hong-fu Jin, Guang Yang, Bing-zhou Ji, Wen-feng Xiao, Yu-sheng Li","doi":"10.1002/rco2.88","DOIUrl":"https://doi.org/10.1002/rco2.88","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The <i>Journal of Cachexia, Sarcopenia and Muscle</i> is a quarterly peer-reviewed medical journal published by WILEY since 2010 and has been dedicated to advancing research on chronic diseases, especially cachexia and sarcopenia. Over the past 12 years, sarcopenia research worldwide has significantly changed. This study aimed to investigate different aspects of studies published in this journal.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the term ‘Journal of Cachexia, Sarcopenia and Muscle’, we retrieved related publications from the Web of Science and PubMed databases. Studies published in this journal were classified and analysed from different perspectives, such as the number of studies, total citations, times cited per item, H-index, research area, article types, institutions, country and funding agency. The VOS viewer software was used for co-occurrence, bibliographic coupling, co-citation and co-authorship analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 2010 to 2022, 1194 studies were published in the <i>Journal of Cachexia, Sarcopenia and Muscle</i>. The United States was the highest contributor, with the most publications and citations and the highest H-index. Italy ranked first for the times cited per item. The main research area was geriatrics and gerontology. von Haehling S was the author with the highest impact. The National Institutes of Health, USA, and the United States Department of Health Human Services funded the maximum number of studies. The top 5 most frequently used keywords in all publications over 12 years were sarcopenia, cachexia, skeletal muscle, body composition and muscle mass. The <i>Journal of Cachexia, Sarcopenia and Muscle</i> was cited the most by <i>Nutrients</i>, and PLOS ONE was cited the most by the <i>Journal of Cachexia, Sarcopenia and Muscle</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Publications in the <i>Journal of Cachexia, Sarcopenia and Muscle</i> have significantly increased from 2010 to 2022, especially in recent years. The United States is still the leader in sarcopenia research. Future submissions to this journal will continue to focus on sarcopenia, cachexia, skeletal muscle, body-composition and muscle mass. The aetiology, molecular mechanisms and outcomes of sarcopenia and cachexia are current research hotspots.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 1","pages":"17-29"},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.88","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia-inducible factor prolyl hydroxylase domain inhibitors may mitigate loss of skeletal muscle mass in haemodialysis patients 缺氧诱导因子脯氨酰羟化酶结构域抑制剂可减轻血液透析患者骨骼肌质量的损失

JCSM rapid communications

Pub Date : 2024-01-04 DOI: 10.1002/rco2.87

Hiroko Hashimoto, Shintaro Mandai, Satomi Shikuma, Mai Kimura, Hayato Toma, Yuki Sakaguchi, Moe Kimura, Jun Ota, Yoshihiko Chiba, Keigo Sakai, Susumu Horiuchi, Susumu Adachi, Shinichi Uchida

Background

Chronic kidney disease patients particularly with renal anaemia hyporesponsive to erythropoiesis-stimulating agents (ESAs) are at a greater risk of having skeletal muscle mass (SMM) loss. Hypoxia-inducible factor prolyl hydroxylase domain inhibitor (HIF-PHI), a novel therapeutic agent for renal anaemia, potentially promotes angiogenesis, muscle repair, and homeostasis. However, effects of HIF-PHIs on SMM remain unknown.

Methods

This retrospective observational cohort study enrolled 292 Japanese adults receiving maintenance haemodialysis at our dialysis centre. The dataset included 11 patients who received daprodustat for 6 months or longer during 1 December 2020 through 30 June 2022. From the previously published pooled cohort, we enrolled 281 participants from 1 August 2018 to 31 July 2019 prior to the approval of HIF-PHIs for renal anaemia. SMM was assessed using modified creatinine index (mg/kg/day) calculated by age, sex, serum creatinine, and single-pool Kt/V. Annual changes of SMM [ΔSMM (%)] were analysed with the least squares regression model and mixed-effects model during 6- to 12-month follow-up period.

Results

The median age of the participants was 63 years [interquartile range (IQR), 54–71 years], and 33% were female. The median ΔSMM levels (IQR) in the least squares regression model were 4.0% (−1.7% to 9.3%) in the HIF-PHI group, 0.20% (−2.1% to 2.1%) in the no ESA group, and −0.94% (−3.0% to 1.3%) in the high ESA group using darbepoetin equivalent to 20 μg or more per week. Those in the mixed-effects model were −1.7% (−1.2% to 3.8%), 0.09% (−1.4% to 1.3%), and −0.74% (−2.0% to 0.8%), respectively. The multivariable linear regression models revealed that HIF-PHI use was associated with greater ΔSMM compared with the high ESA group [coefficient, 3.737; 95% confidence interval (CI), 1.216–6.258 in the least squares regression model or coefficient, 1.635; 95% CI, 0.068–3.201 in the mixed-effects model, respectively].

Conclusions

HIF-PHI use led to greater ΔSMM in maintenance haemodialysis patients. HIF-PHIs may minimize loss of SMM in patients with end-stage kidney disease and renal anaemia.

慢性肾病患者，尤其是对促红细胞生成药（ESAs）反应迟钝的肾性贫血患者，骨骼肌质量（SMM）下降的风险更大。缺氧诱导因子脯氨酰羟化酶结构域抑制剂（HIF-PHI）是一种治疗肾性贫血的新型药物，可促进血管生成、肌肉修复和平衡。然而，HIF-PHIs 对 SMM 的影响仍然未知。这项回顾性观察队列研究纳入了 292 名在我们的透析中心接受维持性血液透析的日本成年人。数据集包括在 2020 年 12 月 1 日至 2022 年 6 月 30 日期间接受达泊司他（daprodustat）治疗 6 个月或更长时间的 11 名患者。从之前发表的汇集队列中，我们在肾性贫血 HIF-PHIs 批准之前的 2018 年 8 月 1 日至 2019 年 7 月 31 日期间招募了 281 名参与者。SMM采用按年龄、性别、血清肌酐和单池Kt/V计算的改良肌酐指数（毫克/千克/天）进行评估。在 6 至 12 个月的随访期间，采用最小二乘法回归模型和混合效应模型分析了 SMM 的年度变化[ΔSMM (%)]。在最小二乘法回归模型中，HIF-PHI组的中位ΔSMM水平（IQR）为4.0%（-1.7%至9.3%），无ESA组为0.20%（-2.1%至2.1%），每周使用相当于20微克或更多达贝泊汀的高ESA组为-0.94%（-3.0%至1.3%）。在混合效应模型中，这一比例分别为-1.7%（-1.2%至3.8%）、0.09%（-1.4%至1.3%）和-0.74%（-2.0%至0.8%）。多变量线性回归模型显示，与高ESA组相比，使用HIF-PHI与更大的ΔSMM相关[最小二乘回归模型中的系数为3.737；95%置信区间（CI）为1.216-6.258，混合效应模型中的系数为1.635；95%置信区间（CI）为0.068-3.201]。HIF-PHI可最大限度地减少终末期肾病和肾性贫血患者的SMM损失。

{"title":"Hypoxia-inducible factor prolyl hydroxylase domain inhibitors may mitigate loss of skeletal muscle mass in haemodialysis patients","authors":"Hiroko Hashimoto, Shintaro Mandai, Satomi Shikuma, Mai Kimura, Hayato Toma, Yuki Sakaguchi, Moe Kimura, Jun Ota, Yoshihiko Chiba, Keigo Sakai, Susumu Horiuchi, Susumu Adachi, Shinichi Uchida","doi":"10.1002/rco2.87","DOIUrl":"10.1002/rco2.87","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic kidney disease patients particularly with renal anaemia hyporesponsive to erythropoiesis-stimulating agents (ESAs) are at a greater risk of having skeletal muscle mass (SMM) loss. Hypoxia-inducible factor prolyl hydroxylase domain inhibitor (HIF-PHI), a novel therapeutic agent for renal anaemia, potentially promotes angiogenesis, muscle repair, and homeostasis. However, effects of HIF-PHIs on SMM remain unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective observational cohort study enrolled 292 Japanese adults receiving maintenance haemodialysis at our dialysis centre. The dataset included 11 patients who received daprodustat for 6 months or longer during 1 December 2020 through 30 June 2022. From the previously published pooled cohort, we enrolled 281 participants from 1 August 2018 to 31 July 2019 prior to the approval of HIF-PHIs for renal anaemia. SMM was assessed using modified creatinine index (mg/kg/day) calculated by age, sex, serum creatinine, and single-pool <i>Kt</i>/<i>V</i>. Annual changes of SMM [ΔSMM (%)] were analysed with the least squares regression model and mixed-effects model during 6- to 12-month follow-up period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median age of the participants was 63 years [interquartile range (IQR), 54–71 years], and 33% were female. The median ΔSMM levels (IQR) in the least squares regression model were 4.0% (−1.7% to 9.3%) in the HIF-PHI group, 0.20% (−2.1% to 2.1%) in the no ESA group, and −0.94% (−3.0% to 1.3%) in the high ESA group using darbepoetin equivalent to 20 μg or more per week. Those in the mixed-effects model were −1.7% (−1.2% to 3.8%), 0.09% (−1.4% to 1.3%), and −0.74% (−2.0% to 0.8%), respectively. The multivariable linear regression models revealed that HIF-PHI use was associated with greater ΔSMM compared with the high ESA group [coefficient, 3.737; 95% confidence interval (CI), 1.216–6.258 in the least squares regression model or coefficient, 1.635; 95% CI, 0.068–3.201 in the mixed-effects model, respectively].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HIF-PHI use led to greater ΔSMM in maintenance haemodialysis patients. HIF-PHIs may minimize loss of SMM in patients with end-stage kidney disease and renal anaemia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 1","pages":"6-16"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.87","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of microRNAs in critical illness—do miRs truly ‘miRror’ muscle wasting? microRNA 在危重病中的作用--miRs 真的能 "miRror "肌肉萎缩吗？

JCSM rapid communications

Pub Date : 2023-12-26 DOI: 10.1002/rco2.86

Ryosuke Sato, Stephan von Haehling

引用次数: 0

Molecular changes in skeletal muscle in chronic kidney disease: A systematic review 慢性肾脏病骨骼肌的分子变化：系统综述

JCSM rapid communications

Pub Date : 2023-12-26 DOI: 10.1002/rco2.82

Limy Wong, Rachel Kenny, Jennifer Howard, Lawrence P. McMahon

Background

Loss of skeletal muscle mass is prevalent among patients affected by chronic kidney disease (CKD). It is associated with significant morbidity and mortality. The underlying molecular pathogenesis has yet to be fully understood. The aim of this systematic review is to summarize the current evidence on molecular changes in the skeletal muscle of humans and rodents with CKD and to assess the strength of such evidence.

Methods

The PubMed and EMBASE databases were searched using three main themes: messenger ribonucleic acid/protein/microRNA expression, skeletal muscle and CKD. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards.

Results

A total of 98 studies were included in the systematic review, comprising 26 prospective human clinical studies, four human and rodent studies, and 68 rodent-only studies (32 mouse and 36 rat models respectively). The sample sizes of human studies were largely small (40% of studies had ≤20 participants). Qualitative polymerase chain reaction (qPCR) was the most commonly used method for gene expression and none of the studies fulfilled the Minimum Information for Publication of qPCR Experiments criteria for quality assessment. Majority of the studies investigated only a few genes or a specific signalling pathway. FBXO32, TRIM63, MSTN, IL6, TNF and IGF1 were the most investigated genes. The identified differentially expressed genes and proteins belonged to eight major pathways, including apoptosis, autophagy, inflammation, insulin/insulin-like growth factor 1 signalling, lipid metabolism, mitochondrial function, muscle cell growth and differentiation, and protein degradation, similar to other chronic disease states.

Conclusions

The current evidence regarding molecular alterations in the skeletal muscle in CKD is largely derived from small and heterogenous studies. Markedly similar modifications in the major biological pathways between CKD and other chronic diseases supports shared deleterious molecular mechanisms producing muscle atrophy, irrespective of the underlying specific disease.

背景慢性肾脏病（CKD）患者普遍存在骨骼肌质量下降的问题。它与严重的发病率和死亡率有关。其潜在的分子发病机制尚未完全明了。本系统综述旨在总结目前有关 CKD 患者和啮齿类动物骨骼肌分子变化的证据，并评估这些证据的强度。方法使用三个主题对 PubMed 和 EMBASE 数据库进行检索：信使核糖核酸/蛋白质/microRNA 表达、骨骼肌和 CKD。本研究按照系统综述和荟萃分析首选报告项目（PRISMA）标准进行。结果总共有 98 项研究被纳入系统综述，其中包括 26 项前瞻性人类临床研究、4 项人类和啮齿动物研究以及 68 项纯啮齿动物研究（分别为 32 个小鼠模型和 36 个大鼠模型）。人类研究的样本量大多较小（40% 的研究参与者少于 20 人）。定性聚合酶链反应（qPCR）是最常用的基因表达方法，但没有一项研究符合《qPCR 实验发表最低信息量》的质量评估标准。大多数研究只调查了几个基因或特定的信号通路。FBXO32、TRIM63、MSTN、IL6、TNF 和 IGF1 是调查最多的基因。已确定的差异表达基因和蛋白质属于八种主要通路，包括细胞凋亡、自噬、炎症、胰岛素/胰岛素样生长因子 1 信号传导、脂质代谢、线粒体功能、肌肉细胞生长和分化以及蛋白质降解，这与其他慢性疾病状态类似。结论目前有关慢性肾脏病患者骨骼肌分子改变的证据主要来自小型和异质性研究。CKD 和其他慢性疾病的主要生物通路发生了明显的相似变化，这支持了产生肌肉萎缩的共同有害分子机制，而与潜在的特定疾病无关。

{"title":"Molecular changes in skeletal muscle in chronic kidney disease: A systematic review","authors":"Limy Wong, Rachel Kenny, Jennifer Howard, Lawrence P. McMahon","doi":"10.1002/rco2.82","DOIUrl":"https://doi.org/10.1002/rco2.82","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Loss of skeletal muscle mass is prevalent among patients affected by chronic kidney disease (CKD). It is associated with significant morbidity and mortality. The underlying molecular pathogenesis has yet to be fully understood. The aim of this systematic review is to summarize the current evidence on molecular changes in the skeletal muscle of humans and rodents with CKD and to assess the strength of such evidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The PubMed and EMBASE databases were searched using three main themes: messenger ribonucleic acid/protein/microRNA expression, skeletal muscle and CKD. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 98 studies were included in the systematic review, comprising 26 prospective human clinical studies, four human and rodent studies, and 68 rodent-only studies (32 mouse and 36 rat models respectively). The sample sizes of human studies were largely small (40% of studies had ≤20 participants). Qualitative polymerase chain reaction (qPCR) was the most commonly used method for gene expression and none of the studies fulfilled the Minimum Information for Publication of qPCR Experiments criteria for quality assessment. Majority of the studies investigated only a few genes or a specific signalling pathway. <i>FBXO32</i>, <i>TRIM63</i>, <i>MSTN</i>, <i>IL6</i>, <i>TNF</i> and <i>IGF1</i> were the most investigated genes. The identified differentially expressed genes and proteins belonged to eight major pathways, including apoptosis, autophagy, inflammation, insulin/insulin-like growth factor 1 signalling, lipid metabolism, mitochondrial function, muscle cell growth and differentiation, and protein degradation, similar to other chronic disease states.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The current evidence regarding molecular alterations in the skeletal muscle in CKD is largely derived from small and heterogenous studies. Markedly similar modifications in the major biological pathways between CKD and other chronic diseases supports shared deleterious molecular mechanisms producing muscle atrophy, irrespective of the underlying specific disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 2","pages":"93-110"},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.82","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139047487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacological inhibition of IRAK4 kinase activity does not prevent cachexia in mice with pancreatic cancer 药物抑制 IRAK4 激酶的活性并不能防止胰腺癌小鼠出现恶病质

JCSM rapid communications

Pub Date : 2023-12-26 DOI: 10.1002/rco2.85

Shuxi Qiao, Brianna LaViolette, Brianna LaCarubba Paulhus, Xiangping Li, John Litchfield, Zhenhong Li, John C. Stansfield, Richard L. Gieseck III, Bei B. Zhang, Danna M. Breen

Background

Inflammation is a hallmark of cachexia; however, effective anti-inflammatory treatments have not yet been identified. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a key signalling node linking interleukin-1 receptor (IL-1R) and toll-like receptor (TLR) activation to the production of multiple proinflammatory cytokines that are elevated in cancer cachexia. The purpose of this work is to evaluate whether pharmacological inhibition of IRAK4 kinase activity with PF-06426779 could prevent cachexia using a model of pancreatic cancer. The effect of appetite stimulation via the ghrelin receptor agonist anamorelin was also examined as a benchmark of clinically validated mechanisms.

Methods

Female C57Bl/6J mice were given an intraperitoneal injection of Kras^G12D; p53^R172H; Pdx1-Cre (KPC) pancreatic tumour cells. PF-06426779 or anamorelin treatment was initiated at the onset of anorexia. Body weight and food intake were measured throughout the study. Body composition, muscle function (force), and physical activity (treadmill running endurance) were assessed at the end of the study.

Results

Chronic treatment with PF-06426779, at doses covering in vitro IC50 and IC90 at C_min, did not increase body weight, food intake, and muscle function in the KPC tumour model. In contrast, anamorelin (vs. vehicle) increased food intake (P < 0.01), hindlimb skeletal muscle mass (P < 0.01), and muscle strength (P < 0.05); however, treadmill running endurance was not increased.

Conclusions

These data suggest that inhibition of IRAK4 kinase activity is not sufficient to treat cachexia, at least in pancreatic cancer, and exploration of alternative anti-inflammatory strategies that increase appetite is required.

背景炎症是恶病质的一个特征；然而，有效的抗炎治疗方法尚未确定。白细胞介素-1受体相关激酶4（IRAK4）是连接白细胞介素-1受体（IL-1R）和收费样受体（TLR）活化与多种促炎细胞因子产生的关键信号节点，而癌症恶病质中这些细胞因子会升高。这项研究的目的是利用胰腺癌模型评估 PF-06426779 对 IRAK4 激酶活性的药理抑制能否预防恶病质。作为临床验证机制的基准，还研究了通过胃泌素受体激动剂阿那莫瑞林刺激食欲的效果。方法给雌性 C57Bl/6J 小鼠腹腔注射 KrasG12D; p53R172H; Pdx1-Cre (KPC) 胰腺肿瘤细胞。厌食症发生时开始使用 PF-06426779 或阿那莫林治疗。在整个研究过程中测量体重和食物摄入量。研究结束时对身体成分、肌肉功能（力量）和体力活动（跑步机跑步耐力）进行评估。结果在 KPC 肿瘤模型中，PF-06426779 的体外 IC50 和 Cmin IC90 剂量的慢性治疗不会增加体重、食物摄入量和肌肉功能。相反，阿那莫瑞林（与车辆相比）增加了食物摄入量（P < 0.01）、后肢骨骼肌质量（P < 0.01）和肌肉力量（P < 0.05）；但是，跑步机跑步耐力没有增加。结论这些数据表明，抑制 IRAK4 激酶活性不足以治疗恶病质，至少在胰腺癌患者中是如此，因此需要探索能增加食欲的其他抗炎策略。

{"title":"Pharmacological inhibition of IRAK4 kinase activity does not prevent cachexia in mice with pancreatic cancer","authors":"Shuxi Qiao, Brianna LaViolette, Brianna LaCarubba Paulhus, Xiangping Li, John Litchfield, Zhenhong Li, John C. Stansfield, Richard L. Gieseck III, Bei B. Zhang, Danna M. Breen","doi":"10.1002/rco2.85","DOIUrl":"https://doi.org/10.1002/rco2.85","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammation is a hallmark of cachexia; however, effective anti-inflammatory treatments have not yet been identified. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a key signalling node linking interleukin-1 receptor (IL-1R) and toll-like receptor (TLR) activation to the production of multiple proinflammatory cytokines that are elevated in cancer cachexia. The purpose of this work is to evaluate whether pharmacological inhibition of IRAK4 kinase activity with PF-06426779 could prevent cachexia using a model of pancreatic cancer. The effect of appetite stimulation via the ghrelin receptor agonist anamorelin was also examined as a benchmark of clinically validated mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Female C57Bl/6J mice were given an intraperitoneal injection of Kras<sup>G12D</sup>; p53<sup>R172H</sup>; Pdx1-Cre (KPC) pancreatic tumour cells. PF-06426779 or anamorelin treatment was initiated at the onset of anorexia. Body weight and food intake were measured throughout the study. Body composition, muscle function (force), and physical activity (treadmill running endurance) were assessed at the end of the study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chronic treatment with PF-06426779, at doses covering in vitro IC50 and IC90 at C<sub>min</sub>, did not increase body weight, food intake, and muscle function in the KPC tumour model. In contrast, anamorelin (vs. vehicle) increased food intake (<i>P</i> < 0.01), hindlimb skeletal muscle mass (<i>P</i> < 0.01), and muscle strength (<i>P</i> < 0.05); however, treadmill running endurance was not increased.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data suggest that inhibition of IRAK4 kinase activity is not sufficient to treat cachexia, at least in pancreatic cancer, and exploration of alternative anti-inflammatory strategies that increase appetite is required.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 2","pages":"122-133"},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.85","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139047610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Programmed myofibre necrosis in critical illness acquired muscle wasting 危重病获得性肌肉萎缩中的程序性肌纤维坏死

JCSM rapid communications

Pub Date : 2023-12-03 DOI: 10.1002/rco2.83

Sunil Patel, Thomas Francis, Raghini Rajaram, Rhodri Handslip, Sharon Mumby, Danielle E. Bear, Rahul Padhke, Nicholas Hart, Hugh Montgomery, Masao Takata, Stephen D.R. Harridge, Brijesh V. Patel, Zudin Puthucheary

Background

Acute skeletal muscle wasting during critical illness is common and causes significant morbidity and functional limitation. Myofibre necrosis is a major histological finding but is often considered an unprogrammed by-product of muscle inflammation. This study sought to evaluate if a form of programmed necrosis, necroptosis, is activated in skeletal muscle during critical illness.

Methods

A cohort of 28 patients from the MUSCLE-UK study (ClinicalTrials.gov: NCT01106300) with serum and skeletal muscle biopsy samples were identified. Samples were available from ICU admission (T1) and between day 7–10 post admission (T2). Skeletal muscle was stratified by a histopathologist in the original study as necrotic (NEC, N = 14) or non-necrotic (NONEC, N = 14) using haematoxylin and eosin staining. We used phosphorylated mixed-lineage kinase domain-like (pMLKL) protein (a key terminal effector protein) and receptor-interacting protein kinase 3 (RIPK3) as markers of necroptosis activation using Western blotting and immunohistochemistry.

Results

We show that pMLKL expression is significantly higher in the NEC group [NEC: T2:T1 expression; 9.1 (IQR 3.9–22.3) vs. NONEC: T2:T1 expression; 0.9 (IQR 0.6–1.1), P = 0.003]. We then confirm this upregulation and describe co-localization with receptor interacting protein kinase 3 (RIPK3) in skeletal muscle using immunohistochemistry. We show that both RIPK3 and pMLKL are present within intact myofibres at the intermediate timepoint day 3 without cellular infiltrate. At T2, pMLKL is also present in the interstitial space where there is infiltrate of CD68 positive immune cells. The observed necroptosis may originate from both internal and infiltrating sources. These findings were absent in samples from patients who did not exhibit histopathological features of necrosis.

Conclusions

We show that necroptosis machinery, RIPK3 and pMLKL, are associated with conventional histopathological features of myonecrosis in a critically ill cohort.

急性骨骼肌萎缩在危重疾病期间是常见的，并引起显著的发病率和功能限制。肌纤维坏死是一种主要的组织学发现，但通常被认为是肌肉炎症的非程序性副产品。本研究旨在评估是否一种形式的程序性坏死，坏死性上睑下垂，骨骼肌在危重疾病期间被激活。来自MUSCLE‐UK研究(ClinicalTrials.gov: NCT01106300)的28例患者的血清和骨骼肌活检样本被确定。样本可从ICU入院(T1)和入院后7-10天(T2)获得。在最初的研究中，组织病理学家使用血红素和伊红染色将骨骼肌分层为坏死(NEC, N = 14)或非坏死(NONEC, N = 14)。我们使用磷酸化的混合谱系激酶结构域样蛋白(pMLKL)(一种关键的末端效应蛋白)和受体相互作用蛋白激酶3 (RIPK3)作为necroptosis激活的标记物，使用Western blotting和免疫组织化学。我们发现pMLKL的表达在NEC组中显著升高[NEC: T2:T1表达;9.1 (IQR 3.9-22.3) vs. NONEC: T2:T1表达;0.9 (iqr 0.6 ~ 1.1)， p = 0.003]。然后，我们用免疫组织化学方法证实了这种上调，并描述了骨骼肌中受体相互作用蛋白激酶3 (RIPK3)的共定位。我们发现RIPK3和pMLKL在没有细胞浸润的情况下，在第3天的中间时间点存在于完整的肌纤维中。T2时，pMLKL也存在于CD68阳性免疫细胞浸润的间质间隙。观察到的坏死性下垂可能来源于内部和浸润性来源。这些发现在没有表现出坏死组织病理特征的患者样本中是不存在的。我们发现坏死坏死机制RIPK3和pMLKL与危重患者群体中肌坏死的常规组织病理学特征相关。

{"title":"Programmed myofibre necrosis in critical illness acquired muscle wasting","authors":"Sunil Patel, Thomas Francis, Raghini Rajaram, Rhodri Handslip, Sharon Mumby, Danielle E. Bear, Rahul Padhke, Nicholas Hart, Hugh Montgomery, Masao Takata, Stephen D.R. Harridge, Brijesh V. Patel, Zudin Puthucheary","doi":"10.1002/rco2.83","DOIUrl":"10.1002/rco2.83","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute skeletal muscle wasting during critical illness is common and causes significant morbidity and functional limitation. Myofibre necrosis is a major histological finding but is often considered an unprogrammed by-product of muscle inflammation. This study sought to evaluate if a form of programmed necrosis, necroptosis, is activated in skeletal muscle during critical illness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort of 28 patients from the MUSCLE-UK study (ClinicalTrials.gov: NCT01106300) with serum and skeletal muscle biopsy samples were identified. Samples were available from ICU admission (T1) and between day 7–10 post admission (T2). Skeletal muscle was stratified by a histopathologist in the original study as necrotic (NEC, <i>N</i> = 14) or non-necrotic (NONEC, <i>N</i> = 14) using haematoxylin and eosin staining. We used phosphorylated mixed-lineage kinase domain-like (pMLKL) protein (a key terminal effector protein) and receptor-interacting protein kinase 3 (RIPK3) as markers of necroptosis activation using Western blotting and immunohistochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We show that pMLKL expression is significantly higher in the NEC group [NEC: T2:T1 expression; 9.1 (IQR 3.9–22.3) vs. NONEC: T2:T1 expression; 0.9 (IQR 0.6–1.1), <i>P</i> = 0.003]. We then confirm this upregulation and describe co-localization with receptor interacting protein kinase 3 (RIPK3) in skeletal muscle using immunohistochemistry. We show that both RIPK3 and pMLKL are present within intact myofibres at the intermediate timepoint day 3 without cellular infiltrate. At T2, pMLKL is also present in the interstitial space where there is infiltrate of CD68 positive immune cells. The observed necroptosis may originate from both internal and infiltrating sources. These findings were absent in samples from patients who did not exhibit histopathological features of necrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We show that necroptosis machinery, RIPK3 and pMLKL, are associated with conventional histopathological features of myonecrosis in a critically ill cohort.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 2","pages":"111-121"},"PeriodicalIF":0.0,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.83","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138605382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Relationship between sacral-abdominal wall distance and grip strength in postmenopausal osteoporotic patients 绝经后骨质疏松症患者骶腹壁距离与握力之间的关系

JCSM rapid communications

Pub Date : 2023-09-11 DOI: 10.1002/rco2.81

Takashi Nagai, Makoto Miyagami, Shota Nakamura, Yayoi Amemiya, Ichiro Okano, Keizo Sakamoto, Kasai Fumihito, Yoshifumi Kudo, Katsunori Inagaki, Nobuyuki Kawate

Background

An increase in waist circumference (WC) is a factor in lifestyle-related diseases. The rectus abdominis muscle is a skeletal muscle that attaches to the pelvis from the xiphoid process and is thought to be affected by kyphosis deformity and posterior pelvic tilt. The purpose of this study is to examine differences between sacral-abdominal wall distance (SAD) and WC and to determine whether they are associated with fall risk, frailty, markers of sarcopenia (grip strength and lean body mass), and spinal alignment. A secondary objective is to examine these differences by stratification by grip strength.

Methods

This retrospective study included 239 women aged 65 years or older (mean age 76.5 ± 6.7 years) attending an outpatient osteoporosis clinic. Bone mineral density and skeletal body composition (muscle mass index and trunk lean mass) were measured using dual-energy X-ray absorptiometry. SAD, pelvic tilt, and sagittal longitudinal axis were measured from simple X-ray images of the spine sides. WC, grip strength, frailty, and fall risk score were investigated. Statistics were performed using Stat Flex, with two-sided P < 0.05 being significantly different.

Results

WC was correlated with SAD (R = 0.68, P < 0.001). The SAD cut-off value for a WC of 90 cm was 167 mm. The relationship between grip strength, SAD, and WC, weaker grip strength was associated with greater SAD; however, no significant difference was noted in WC. WC was not correlated with pelvic alignment but was correlated with body mass index (P < 0.01). Meanwhile, SAD was correlated with body mass index, pelvic tilt, sagittal longitudinal axis (P < 0.01), spinal alignment, and WC. Logistic regression analysis was performed with a grip strength of less than 18 kg as the objective variable. We found that the conditions for a grip strength of less than 18 kg were older age (P < 0.001), increased SAD (P = 0.02), and decreased trunk lean body mass. There was a decrease in grip strength (P < 0.05) and an increase in frailty (P < 0.05) and falls (P < 0.01) score in patients with SAD of 167 mm or greater.

Conclusions

SAD and WC were found to be correlated; SAD was associated with body weight, posterior pelvic tilt, and anterior spinal tilt deformity, while WC was related to body weight. Increased SAD was found to be linked with decreased grip strength a

背景腰围（WC）的增加是导致生活方式相关疾病的一个因素。腹直肌是从剑突附着于骨盆的骨骼肌，被认为会受到脊柱后凸畸形和骨盆后倾的影响。本研究的目的是检查骶腹壁距离（SAD）和腹围之间的差异，并确定它们是否与跌倒风险、虚弱程度、肌肉疏松症指标（握力和瘦体重）以及脊柱排列有关。次要目的是通过握力分层来研究这些差异。方法这项回顾性研究包括 239 名 65 岁或以上（平均年龄 76.5 ± 6.7 岁）的女性骨质疏松症门诊患者。使用双能 X 射线吸收测量法测量了骨质密度和骨骼身体成分（肌肉质量指数和躯干瘦体重）。通过脊柱两侧的简单 X 光图像测量了 SAD、骨盆倾斜度和矢状纵轴。对体重、握力、虚弱程度和跌倒风险评分进行了调查。使用 Stat Flex 进行统计，双侧 P < 0.05 为显著差异。结果 WC 与 SAD 相关（R = 0.68，P < 0.001）。WC 为 90 厘米的 SAD 临界值为 167 毫米。从握力、SAD 和 WC 之间的关系来看，握力越弱，SAD 越大；但 WC 没有显著差异。腹围与骨盆排列无关，但与体重指数相关（P < 0.01）。同时，SAD 与体重指数、骨盆倾斜、矢状纵轴（P < 0.01）、脊柱排列和腹围相关。以握力小于 18 公斤为客观变量进行了逻辑回归分析。我们发现，握力小于 18 公斤的条件是年龄较大（P < 0.001）、SAD 增加（P = 0.02）和躯干瘦体重减少。在 SAD 达到或超过 167 毫米的患者中，握力下降（P < 0.05），虚弱（P < 0.05）和跌倒（P < 0.01）评分增加。结论 SAD 和 WC 存在相关性；SAD 与体重、骨盆后倾和脊柱前倾畸形相关，而 WC 与体重相关。研究发现，SAD 的增加与握力下降和跌倒风险增加有关。这项研究首次检验了一种新的测量方法--SAD，以评估其在握力、脊柱排列、虚弱和跌倒风险方面的实用性。

{"title":"Relationship between sacral-abdominal wall distance and grip strength in postmenopausal osteoporotic patients","authors":"Takashi Nagai, Makoto Miyagami, Shota Nakamura, Yayoi Amemiya, Ichiro Okano, Keizo Sakamoto, Kasai Fumihito, Yoshifumi Kudo, Katsunori Inagaki, Nobuyuki Kawate","doi":"10.1002/rco2.81","DOIUrl":"10.1002/rco2.81","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>An increase in waist circumference (WC) is a factor in lifestyle-related diseases. The rectus abdominis muscle is a skeletal muscle that attaches to the pelvis from the xiphoid process and is thought to be affected by kyphosis deformity and posterior pelvic tilt. The purpose of this study is to examine differences between sacral-abdominal wall distance (SAD) and WC and to determine whether they are associated with fall risk, frailty, markers of sarcopenia (grip strength and lean body mass), and spinal alignment. A secondary objective is to examine these differences by stratification by grip strength.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 239 women aged 65 years or older (mean age 76.5 ± 6.7 years) attending an outpatient osteoporosis clinic. Bone mineral density and skeletal body composition (muscle mass index and trunk lean mass) were measured using dual-energy X-ray absorptiometry. SAD, pelvic tilt, and sagittal longitudinal axis were measured from simple X-ray images of the spine sides. WC, grip strength, frailty, and fall risk score were investigated. Statistics were performed using Stat Flex, with two-sided <i>P</i> < 0.05 being significantly different.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>WC was correlated with SAD (<i>R</i> = 0.68, <i>P</i> < 0.001). The SAD cut-off value for a WC of 90 cm was 167 mm. The relationship between grip strength, SAD, and WC, weaker grip strength was associated with greater SAD; however, no significant difference was noted in WC. WC was not correlated with pelvic alignment but was correlated with body mass index (<i>P</i> < 0.01). Meanwhile, SAD was correlated with body mass index, pelvic tilt, sagittal longitudinal axis (<i>P</i> < 0.01), spinal alignment, and WC. Logistic regression analysis was performed with a grip strength of less than 18 kg as the objective variable. We found that the conditions for a grip strength of less than 18 kg were older age (<i>P</i> < 0.001), increased SAD (<i>P</i> = 0.02), and decreased trunk lean body mass. There was a decrease in grip strength (<i>P</i> < 0.05) and an increase in frailty (<i>P</i> < 0.05) and falls (<i>P</i> < 0.01) score in patients with SAD of 167 mm or greater.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SAD and WC were found to be correlated; SAD was associated with body weight, posterior pelvic tilt, and anterior spinal tilt deformity, while WC was related to body weight. Increased SAD was found to be linked with decreased grip strength a","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"6 2","pages":"81-92"},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.81","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135980406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

JCSM rapid communications

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀

微信

客服QQ

扫码关注我们

反馈

Book学术文献互助群
群号：604180095

文献互助智能选刊最新文献互助须知联系我们：info@booksci.cn

Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。