Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs
Cell Mol Life Sci. 2021 Nov 16:1-29. doi: 10.1007/s00018-021-03983-8. Online ahead of print.ABSTRACTArticular cartilage damage caused by sports injury or osteoarthritis (OA) has gained increased attention as a worldwide health burden. Pharmaceutical treatments are considered cost-effective means of promoting cartilage regeneration, but are limited by their inability to generate sufficient functional chondrocytes and modify disease progression. Small molecular chemical compounds are an abundant source of new pharmaceutical therapeutics for cartilage regeneration, as they have advantages in design, fabrication, and applicati...
Source: Cellular and Molecular Life Sciences : CMLS - November 16, 2021 Category: Cytology Authors: Yishan Chen Heng Sun Xudong Yao Yeke Yu Tian Tian Weiyang Xu Yujie Zhou Hongwei Ouyang Source Type: research

Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs
Cell Mol Life Sci. 2021 Nov 16:1-29. doi: 10.1007/s00018-021-03983-8. Online ahead of print.ABSTRACTArticular cartilage damage caused by sports injury or osteoarthritis (OA) has gained increased attention as a worldwide health burden. Pharmaceutical treatments are considered cost-effective means of promoting cartilage regeneration, but are limited by their inability to generate sufficient functional chondrocytes and modify disease progression. Small molecular chemical compounds are an abundant source of new pharmaceutical therapeutics for cartilage regeneration, as they have advantages in design, fabrication, and applicati...
Source: Cellular and Molecular Life Sciences : CMLS - November 16, 2021 Category: Cytology Authors: Yishan Chen Heng Sun Xudong Yao Yeke Yu Tian Tian Weiyang Xu Yujie Zhou Hongwei Ouyang Source Type: research

Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs
Cell Mol Life Sci. 2021 Nov 16:1-29. doi: 10.1007/s00018-021-03983-8. Online ahead of print.ABSTRACTArticular cartilage damage caused by sports injury or osteoarthritis (OA) has gained increased attention as a worldwide health burden. Pharmaceutical treatments are considered cost-effective means of promoting cartilage regeneration, but are limited by their inability to generate sufficient functional chondrocytes and modify disease progression. Small molecular chemical compounds are an abundant source of new pharmaceutical therapeutics for cartilage regeneration, as they have advantages in design, fabrication, and applicati...
Source: Cellular and Molecular Life Sciences : CMLS - November 16, 2021 Category: Cytology Authors: Yishan Chen Heng Sun Xudong Yao Yeke Yu Tian Tian Weiyang Xu Yujie Zhou Hongwei Ouyang Source Type: research

Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs
Cell Mol Life Sci. 2021 Nov 16:1-29. doi: 10.1007/s00018-021-03983-8. Online ahead of print.ABSTRACTArticular cartilage damage caused by sports injury or osteoarthritis (OA) has gained increased attention as a worldwide health burden. Pharmaceutical treatments are considered cost-effective means of promoting cartilage regeneration, but are limited by their inability to generate sufficient functional chondrocytes and modify disease progression. Small molecular chemical compounds are an abundant source of new pharmaceutical therapeutics for cartilage regeneration, as they have advantages in design, fabrication, and applicati...
Source: Cellular and Molecular Life Sciences : CMLS - November 16, 2021 Category: Cytology Authors: Yishan Chen Heng Sun Xudong Yao Yeke Yu Tian Tian Weiyang Xu Yujie Zhou Hongwei Ouyang Source Type: research

Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs
Cell Mol Life Sci. 2021 Nov 16:1-29. doi: 10.1007/s00018-021-03983-8. Online ahead of print.ABSTRACTArticular cartilage damage caused by sports injury or osteoarthritis (OA) has gained increased attention as a worldwide health burden. Pharmaceutical treatments are considered cost-effective means of promoting cartilage regeneration, but are limited by their inability to generate sufficient functional chondrocytes and modify disease progression. Small molecular chemical compounds are an abundant source of new pharmaceutical therapeutics for cartilage regeneration, as they have advantages in design, fabrication, and applicati...
Source: Cellular and Molecular Life Sciences : CMLS - November 16, 2021 Category: Cytology Authors: Yishan Chen Heng Sun Xudong Yao Yeke Yu Tian Tian Weiyang Xu Yujie Zhou Hongwei Ouyang Source Type: research

Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs
Cell Mol Life Sci. 2021 Nov 16:1-29. doi: 10.1007/s00018-021-03983-8. Online ahead of print.ABSTRACTArticular cartilage damage caused by sports injury or osteoarthritis (OA) has gained increased attention as a worldwide health burden. Pharmaceutical treatments are considered cost-effective means of promoting cartilage regeneration, but are limited by their inability to generate sufficient functional chondrocytes and modify disease progression. Small molecular chemical compounds are an abundant source of new pharmaceutical therapeutics for cartilage regeneration, as they have advantages in design, fabrication, and applicati...
Source: Cellular and Molecular Life Sciences : CMLS - November 16, 2021 Category: Cytology Authors: Yishan Chen Heng Sun Xudong Yao Yeke Yu Tian Tian Weiyang Xu Yujie Zhou Hongwei Ouyang Source Type: research

Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs
Cell Mol Life Sci. 2021 Nov 16:1-29. doi: 10.1007/s00018-021-03983-8. Online ahead of print.ABSTRACTArticular cartilage damage caused by sports injury or osteoarthritis (OA) has gained increased attention as a worldwide health burden. Pharmaceutical treatments are considered cost-effective means of promoting cartilage regeneration, but are limited by their inability to generate sufficient functional chondrocytes and modify disease progression. Small molecular chemical compounds are an abundant source of new pharmaceutical therapeutics for cartilage regeneration, as they have advantages in design, fabrication, and applicati...
Source: Cellular and Molecular Life Sciences : CMLS - November 16, 2021 Category: Cytology Authors: Yishan Chen Heng Sun Xudong Yao Yeke Yu Tian Tian Weiyang Xu Yujie Zhou Hongwei Ouyang Source Type: research

Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases
Cell Mol Life Sci. 2021 Nov 15. doi: 10.1007/s00018-021-04011-5. Online ahead of print.ABSTRACTThe incidence of gastrointestinal (GI) mucosal diseases, including various types of gastritis, ulcers, inflammatory bowel disease and GI cancer, is increasing. Therefore, it is necessary to identify new therapeutic targets. Ion channels/transporters are located on cell membranes, and tight junctions (TJs) affect acid-base balance, the mucus layer, permeability, the microbiota and mucosal blood flow, which are essential for maintaining GI mucosal integrity. As ion channel/transporter dysfunction results in various GI mucosal disea...
Source: Cellular and Molecular Life Sciences : CMLS - November 15, 2021 Category: Cytology Authors: Zilin Deng Yingying Zhao Zhiyuan Ma Minglin Zhang Hu Wang Zhiqiang Yi Biguang Tuo Taolang Li Xuemei Liu Source Type: research

Noncanonical ER-Golgi trafficking and autophagy of endogenous procollagen in osteoblasts
Cell Mol Life Sci. 2021 Nov 15. doi: 10.1007/s00018-021-04017-z. Online ahead of print.ABSTRACTSecretion and quality control of large extracellular matrix proteins remain poorly understood and debated, particularly transport intermediates delivering folded proteins from the ER to Golgi and misfolded ones to lysosomes. Discrepancies between different studies are related to utilization of exogenous cargo, off-target effects of experimental conditions and cell manipulation, and identification of transport intermediates without tracing their origin and destination. To address these issues, here we imaged secretory and degradat...
Source: Cellular and Molecular Life Sciences : CMLS - November 15, 2021 Category: Cytology Authors: Laura Gorrell Shakib Omari Elena Makareeva Sergey Leikin Source Type: research

Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases
Cell Mol Life Sci. 2021 Nov 15. doi: 10.1007/s00018-021-04011-5. Online ahead of print.ABSTRACTThe incidence of gastrointestinal (GI) mucosal diseases, including various types of gastritis, ulcers, inflammatory bowel disease and GI cancer, is increasing. Therefore, it is necessary to identify new therapeutic targets. Ion channels/transporters are located on cell membranes, and tight junctions (TJs) affect acid-base balance, the mucus layer, permeability, the microbiota and mucosal blood flow, which are essential for maintaining GI mucosal integrity. As ion channel/transporter dysfunction results in various GI mucosal disea...
Source: Cellular and Molecular Life Sciences : CMLS - November 15, 2021 Category: Cytology Authors: Zilin Deng Yingying Zhao Zhiyuan Ma Minglin Zhang Hu Wang Zhiqiang Yi Biguang Tuo Taolang Li Xuemei Liu Source Type: research

Noncanonical ER-Golgi trafficking and autophagy of endogenous procollagen in osteoblasts
Cell Mol Life Sci. 2021 Nov 15. doi: 10.1007/s00018-021-04017-z. Online ahead of print.ABSTRACTSecretion and quality control of large extracellular matrix proteins remain poorly understood and debated, particularly transport intermediates delivering folded proteins from the ER to Golgi and misfolded ones to lysosomes. Discrepancies between different studies are related to utilization of exogenous cargo, off-target effects of experimental conditions and cell manipulation, and identification of transport intermediates without tracing their origin and destination. To address these issues, here we imaged secretory and degradat...
Source: Cellular and Molecular Life Sciences : CMLS - November 15, 2021 Category: Cytology Authors: Laura Gorrell Shakib Omari Elena Makareeva Sergey Leikin Source Type: research

Regulation of energy metabolism in human pluripotent stem cells
Cell Mol Life Sci. 2021 Nov 13. doi: 10.1007/s00018-021-04016-0. Online ahead of print.ABSTRACTAll living organisms need energy to carry out their essential functions. The importance of energy metabolism is increasingly recognized in human pluripotent stem cells. Energy production is not only essential for cell survival and proliferation, but also critical for pluripotency and cell fate determination. Thus, energy metabolism is an important target in cellular regulation and stem cell applications. In this review, we will discuss key factors that influence energy metabolism and their association with stem cell functions.PMI...
Source: Cellular and Molecular Life Sciences : CMLS - November 13, 2021 Category: Cytology Authors: Weiwei Liu Guokai Chen Source Type: research

DHX9 contributes to the malignant phenotypes of colorectal cancer via activating NF- κB signaling pathway
In this study, DHX9 was filtered out as the prominent proliferation promoters of CRC by siRNA screening. Moreover, DHX9 was overexpressed in CRC cell lines, clinical CRC tissues and colitis-associated colorectal cancer (CAC) mouse model. The upregulation of DHX9 was positively correlated with poor prognosis in patients with CRC. Through gain- and loss-of function experiments, we found that DHX9 promoted CRC cell proliferation, colony formation, apoptosis resistance, migration and invasion in vitro. Furthermore, a xenograft mouse model and a hepatic metastasis mouse model were utilized to confirm that forced overexpression ...
Source: Cellular and Molecular Life Sciences : CMLS - November 13, 2021 Category: Cytology Authors: Shenglan Liu Liangmei He Junhong Wu Xinqiang Wu Lu Xie Wei Dai Lingxia Chen Fuhua Xie Zhiping Liu Source Type: research

Regulation of energy metabolism in human pluripotent stem cells
Cell Mol Life Sci. 2021 Nov 13. doi: 10.1007/s00018-021-04016-0. Online ahead of print.ABSTRACTAll living organisms need energy to carry out their essential functions. The importance of energy metabolism is increasingly recognized in human pluripotent stem cells. Energy production is not only essential for cell survival and proliferation, but also critical for pluripotency and cell fate determination. Thus, energy metabolism is an important target in cellular regulation and stem cell applications. In this review, we will discuss key factors that influence energy metabolism and their association with stem cell functions.PMI...
Source: Cellular and Molecular Life Sciences : CMLS - November 13, 2021 Category: Cytology Authors: Weiwei Liu Guokai Chen Source Type: research

DHX9 contributes to the malignant phenotypes of colorectal cancer via activating NF- κB signaling pathway
In this study, DHX9 was filtered out as the prominent proliferation promoters of CRC by siRNA screening. Moreover, DHX9 was overexpressed in CRC cell lines, clinical CRC tissues and colitis-associated colorectal cancer (CAC) mouse model. The upregulation of DHX9 was positively correlated with poor prognosis in patients with CRC. Through gain- and loss-of function experiments, we found that DHX9 promoted CRC cell proliferation, colony formation, apoptosis resistance, migration and invasion in vitro. Furthermore, a xenograft mouse model and a hepatic metastasis mouse model were utilized to confirm that forced overexpression ...
Source: Cellular and Molecular Life Sciences : CMLS - November 13, 2021 Category: Cytology Authors: Shenglan Liu Liangmei He Junhong Wu Xinqiang Wu Lu Xie Wei Dai Lingxia Chen Fuhua Xie Zhiping Liu Source Type: research

The marriage of chemokines and galectins as functional heterodimers
Cell Mol Life Sci. 2021 Nov 12. doi: 10.1007/s00018-021-04010-6. Online ahead of print.ABSTRACTTrafficking of leukocytes and their local activity profile are of pivotal importance for many (patho)physiological processes. Fittingly, microenvironments are complex by nature, with multiple mediators originating from diverse cell types and playing roles in an intimately regulated manner. To dissect aspects of this complexity, effectors are initially identified and structurally characterized, thus prompting familial classification and establishing foci of research activity. In this regard, chemokines present themselves as role m...
Source: Cellular and Molecular Life Sciences : CMLS - November 12, 2021 Category: Cytology Authors: Philipp von Hundelshausen Kanin Wichapong Hans-Joachim Gabius Kevin H Mayo Source Type: research

The marriage of chemokines and galectins as functional heterodimers
Cell Mol Life Sci. 2021 Nov 12. doi: 10.1007/s00018-021-04010-6. Online ahead of print.ABSTRACTTrafficking of leukocytes and their local activity profile are of pivotal importance for many (patho)physiological processes. Fittingly, microenvironments are complex by nature, with multiple mediators originating from diverse cell types and playing roles in an intimately regulated manner. To dissect aspects of this complexity, effectors are initially identified and structurally characterized, thus prompting familial classification and establishing foci of research activity. In this regard, chemokines present themselves as role m...
Source: Cellular and Molecular Life Sciences : CMLS - November 12, 2021 Category: Cytology Authors: Philipp von Hundelshausen Kanin Wichapong Hans-Joachim Gabius Kevin H Mayo Source Type: research

Lipin-1-derived diacylglycerol activates intracellular TRPC3 which is critical for inflammatory signaling
Cell Mol Life Sci. 2021 Nov 10. doi: 10.1007/s00018-021-03999-0. Online ahead of print.ABSTRACTExposure to Gram-negative bacterial LPS exacerbates host immune responses and may lead to sepsis, a life-threatening condition. Despite its high mortality and morbidity, no drugs specifically directed to treating sepsis are currently available. Using human cell genetic depletion, pharmacological inhibition, live-cell microscopy and organelle-targeted molecular sensors we present evidence that the channel TRPC3 is activated intracellularly during macrophage exposure to LPS and is essential for Ca2+ release from internal stores. In...
Source: Cellular and Molecular Life Sciences : CMLS - November 10, 2021 Category: Cytology Authors: Javier Casas Clara Meana Jos é Ramón López-López Jes ús Balsinde Mar ía A Balboa Source Type: research

Lipin-1-derived diacylglycerol activates intracellular TRPC3 which is critical for inflammatory signaling
Cell Mol Life Sci. 2021 Nov 10. doi: 10.1007/s00018-021-03999-0. Online ahead of print.ABSTRACTExposure to Gram-negative bacterial LPS exacerbates host immune responses and may lead to sepsis, a life-threatening condition. Despite its high mortality and morbidity, no drugs specifically directed to treating sepsis are currently available. Using human cell genetic depletion, pharmacological inhibition, live-cell microscopy and organelle-targeted molecular sensors we present evidence that the channel TRPC3 is activated intracellularly during macrophage exposure to LPS and is essential for Ca2+ release from internal stores. In...
Source: Cellular and Molecular Life Sciences : CMLS - November 10, 2021 Category: Cytology Authors: Javier Casas Clara Meana Jos é Ramón López-López Jes ús Balsinde Mar ía A Balboa Source Type: research

Post-transcriptional regulation in spermatogenesis: all RNA pathways lead to healthy sperm
Cell Mol Life Sci. 2021 Nov 8. doi: 10.1007/s00018-021-04012-4. Online ahead of print.ABSTRACTMultiple RNA pathways are required to produce functional sperm. Here, we review RNA post-transcriptional regulation during spermatogenesis with particular emphasis on the role of 3' end modifications. From early studies in the 1970s, it became clear that spermiogenesis transcripts could be stored for days only to be translated at advanced stages of spermatid differentiation. The transition between the translationally repressed and active states was observed to correlate with the shortening of the transcripts' poly(A) tail, establi...
Source: Cellular and Molecular Life Sciences : CMLS - November 8, 2021 Category: Cytology Authors: Marcos Morgan Lokesh Kumar Yin Li Marine Baptissart Source Type: research

Post-transcriptional regulation in spermatogenesis: all RNA pathways lead to healthy sperm
Cell Mol Life Sci. 2021 Nov 8. doi: 10.1007/s00018-021-04012-4. Online ahead of print.ABSTRACTMultiple RNA pathways are required to produce functional sperm. Here, we review RNA post-transcriptional regulation during spermatogenesis with particular emphasis on the role of 3' end modifications. From early studies in the 1970s, it became clear that spermiogenesis transcripts could be stored for days only to be translated at advanced stages of spermatid differentiation. The transition between the translationally repressed and active states was observed to correlate with the shortening of the transcripts' poly(A) tail, establi...
Source: Cellular and Molecular Life Sciences : CMLS - November 8, 2021 Category: Cytology Authors: Marcos Morgan Lokesh Kumar Yin Li Marine Baptissart Source Type: research

Post-transcriptional regulation in spermatogenesis: all RNA pathways lead to healthy sperm
Cell Mol Life Sci. 2021 Nov 8. doi: 10.1007/s00018-021-04012-4. Online ahead of print.ABSTRACTMultiple RNA pathways are required to produce functional sperm. Here, we review RNA post-transcriptional regulation during spermatogenesis with particular emphasis on the role of 3' end modifications. From early studies in the 1970s, it became clear that spermiogenesis transcripts could be stored for days only to be translated at advanced stages of spermatid differentiation. The transition between the translationally repressed and active states was observed to correlate with the shortening of the transcripts' poly(A) tail, establi...
Source: Cellular and Molecular Life Sciences : CMLS - November 8, 2021 Category: Cytology Authors: Marcos Morgan Lokesh Kumar Yin Li Marine Baptissart Source Type: research

Role for animal models in understanding essential fatty acid deficiency in cystic fibrosis
Cell Mol Life Sci. 2021 Nov 5. doi: 10.1007/s00018-021-04014-2. Online ahead of print.ABSTRACTEssential fatty acid deficiency has been observed in most patients with Cystic Fibrosis (CF); however, pancreatic supplementation does not restore the deficiency, suggesting a different pathology independent of the pancreas. At this time, the underlying pathological mechanisms are largely unknown. Essential fatty acids are obtained from the diet and processed by organs including the liver and intestine, two organs significantly impacted by mutations in the cystic fibrosis transmembrane conductance regulator gene (Cftr). There are ...
Source: Cellular and Molecular Life Sciences : CMLS - November 6, 2021 Category: Cytology Authors: Deanne H Hryciw Courtney A Jackson Nirajan Shrestha David Parsons Martin Donnelley Andrew J McAinch Source Type: research

Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells
In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK-ATF4-CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2...
Source: Cellular and Molecular Life Sciences : CMLS - November 6, 2021 Category: Cytology Authors: Li-Xue Wang Chao Ren Ren-Qi Yao Yi-Nan Luo Yue Yin Yao Wu Ning Dong Xiao-Mei Zhu Yong-Ming Yao Source Type: research

Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors
Cell Mol Life Sci. 2021 Nov 6. doi: 10.1007/s00018-021-04005-3. Online ahead of print.ABSTRACTMitogen-activated protein kinase (MAPK) signalling pathways are crucial for developmental processes, oncogenesis, and inflammation, including the production of proinflammatory cytokines caused by reactive oxygen species and upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are no drugs that can effectively prevent excessive inflammatory responses in endothelial cells in the lungs, heart, brain, and kidneys, which are considered the main causes of severe coronavirus disease 2019 (COVID-19). In this ...
Source: Cellular and Molecular Life Sciences : CMLS - November 6, 2021 Category: Cytology Authors: Hanna Galganska Wieslawa Jarmuszkiewicz Lukasz Galganski Source Type: research

Autophagy and apoptosis cascade: which is more prominent in neuronal death?
Cell Mol Life Sci. 2021 Nov 6. doi: 10.1007/s00018-021-04004-4. Online ahead of print.ABSTRACTAutophagy and apoptosis are two crucial self-destructive processes that maintain cellular homeostasis, which are characterized by their morphology and regulated through signal transduction mechanisms. These pathways determine the fate of cellular organelle and protein involved in human health and disease such as neurodegeneration, cancer, and cardiovascular disease. Cell death pathways share common molecular mechanisms, such as mitochondrial dysfunction, oxidative stress, calcium ion concentration, reactive oxygen species, and end...
Source: Cellular and Molecular Life Sciences : CMLS - November 6, 2021 Category: Cytology Authors: Rohan Gupta Rashmi K Ambasta None Pravir Kumar Source Type: research

Role for animal models in understanding essential fatty acid deficiency in cystic fibrosis
Cell Mol Life Sci. 2021 Nov 5. doi: 10.1007/s00018-021-04014-2. Online ahead of print.ABSTRACTEssential fatty acid deficiency has been observed in most patients with Cystic Fibrosis (CF); however, pancreatic supplementation does not restore the deficiency, suggesting a different pathology independent of the pancreas. At this time, the underlying pathological mechanisms are largely unknown. Essential fatty acids are obtained from the diet and processed by organs including the liver and intestine, two organs significantly impacted by mutations in the cystic fibrosis transmembrane conductance regulator gene (Cftr). There are ...
Source: Cellular and Molecular Life Sciences : CMLS - November 6, 2021 Category: Cytology Authors: Deanne H Hryciw Courtney A Jackson Nirajan Shrestha David Parsons Martin Donnelley Andrew J McAinch Source Type: research

Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells
In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK-ATF4-CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2...
Source: Cellular and Molecular Life Sciences : CMLS - November 6, 2021 Category: Cytology Authors: Li-Xue Wang Chao Ren Ren-Qi Yao Yi-Nan Luo Yue Yin Yao Wu Ning Dong Xiao-Mei Zhu Yong-Ming Yao Source Type: research

Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors
Cell Mol Life Sci. 2021 Nov 6. doi: 10.1007/s00018-021-04005-3. Online ahead of print.ABSTRACTMitogen-activated protein kinase (MAPK) signalling pathways are crucial for developmental processes, oncogenesis, and inflammation, including the production of proinflammatory cytokines caused by reactive oxygen species and upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are no drugs that can effectively prevent excessive inflammatory responses in endothelial cells in the lungs, heart, brain, and kidneys, which are considered the main causes of severe coronavirus disease 2019 (COVID-19). In this ...
Source: Cellular and Molecular Life Sciences : CMLS - November 6, 2021 Category: Cytology Authors: Hanna Galganska Wieslawa Jarmuszkiewicz Lukasz Galganski Source Type: research

A survey of substrate specificity among Auxiliary Activity Family 5 copper radical oxidases 
This study furthers our understanding of CROs by doubling the number of characterized AA5_2 members, which may find future applications as biocatalysts in diverse processes.PMID:34738149 | DOI:10.1007/s00018-021-03981-w (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 5, 2021 Category: Cytology Authors: Maria E Cleveland Yann Mathieu David Ribeaucourt Mireille Haon Paul Mulyk Jason E Hein Mickael Lafond Jean-Guy Berrin Harry Brumer Source Type: research

A survey of substrate specificity among Auxiliary Activity Family 5 copper radical oxidases 
This study furthers our understanding of CROs by doubling the number of characterized AA5_2 members, which may find future applications as biocatalysts in diverse processes.PMID:34738149 | DOI:10.1007/s00018-021-03981-w (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 5, 2021 Category: Cytology Authors: Maria E Cleveland Yann Mathieu David Ribeaucourt Mireille Haon Paul Mulyk Jason E Hein Mickael Lafond Jean-Guy Berrin Harry Brumer Source Type: research

The base excision repair process: comparison between higher and lower eukaryotes
Cell Mol Life Sci. 2021 Nov 3. doi: 10.1007/s00018-021-03990-9. Online ahead of print.ABSTRACTThe base excision repair (BER) pathway is essential for maintaining the stability of DNA in all organisms and defects in this process are associated with life-threatening diseases. It is involved in removing specific types of DNA lesions that are induced by both exogenous and endogenous genotoxic substances. BER is a multi-step mechanism that is often initiated by the removal of a damaged base leading to a genotoxic intermediate that is further processed before the reinsertion of the correct nucleotide and the restoration of the g...
Source: Cellular and Molecular Life Sciences : CMLS - November 4, 2021 Category: Cytology Authors: Nagham Nafiz Hindi Noha Elsakrmy Dindial Ramotar Source Type: research

The base excision repair process: comparison between higher and lower eukaryotes
Cell Mol Life Sci. 2021 Nov 3. doi: 10.1007/s00018-021-03990-9. Online ahead of print.ABSTRACTThe base excision repair (BER) pathway is essential for maintaining the stability of DNA in all organisms and defects in this process are associated with life-threatening diseases. It is involved in removing specific types of DNA lesions that are induced by both exogenous and endogenous genotoxic substances. BER is a multi-step mechanism that is often initiated by the removal of a damaged base leading to a genotoxic intermediate that is further processed before the reinsertion of the correct nucleotide and the restoration of the g...
Source: Cellular and Molecular Life Sciences : CMLS - November 4, 2021 Category: Cytology Authors: Nagham Nafiz Hindi Noha Elsakrmy Dindial Ramotar Source Type: research

Gremlin: a complex molecule regulating wound healing and fibrosis
Cell Mol Life Sci. 2021 Nov 3. doi: 10.1007/s00018-021-03964-x. Online ahead of print.ABSTRACTGremlin-1 is part of the TGF-β superfamily and is a BMP antagonist that blocks BMP signalling to precisely control BMP gradients. Gremlin-1 is primarily involved in organogenesis and limb patterning however, has recently been described as being involved in fibrotic diseases. Initially described as a key factor involved in diabetic kidney fibrosis due to being induced by high glucose, it has now been described as being associated with lung, liver, eye, and skin fibrosis. This suggests that it is a key conserved molecule mediat...
Source: Cellular and Molecular Life Sciences : CMLS - November 3, 2021 Category: Cytology Authors: Steven O'Reilly Source Type: research

Bacterial lectin BambL acts as a B cell superantigen
Cell Mol Life Sci. 2021 Nov 3. doi: 10.1007/s00018-021-04009-z. Online ahead of print.ABSTRACTB cell superantigens crosslink conserved domains of B cell receptors (BCRs) and cause dysregulated, polyclonal B cell activation irrespective of normal BCR-antigen complementarity. The cells typically succumb to activation-induced cell death, which can impede the adaptive immune response and favor infection. In the present study, we demonstrate that the fucose-binding lectin of Burkholderia ambifaria, BambL, bears functional resemblance to B cell superantigens. By engaging surface glycans, the bacterial lectin activated human peri...
Source: Cellular and Molecular Life Sciences : CMLS - November 3, 2021 Category: Cytology Authors: Marco Frensch Christina J äger Peter F M üller Annamaria Tadi ć Isabel Wilhelm Sarah Wehrum Britta Diedrich Beate Fischer Ana Valeria Mel éndez Joern Dengjel Hermann Eibel Winfried R ömer Source Type: research

Revisiting definition and assessment of intestinal trans-epithelial passage
This study aims to remind that Intestinal Passage (IP) measurement is a complex task that cannot be achieved by a unique measure of an orally given exogenous marker in blood or urine. This will be illustrated in the case of NOD mice. Indeed, various methods have been proposed to measure IP. Among them ex vivo measurement in Ussing chambers of luminal to serosal fluxes of exogenous markers and in vivo measurement of exogenous markers in blood or urine after oral gavage are the more commonly used. Even though they are commonly used indifferently, they do not give the same information and can provide contradictory results. Pu...
Source: Cellular and Molecular Life Sciences : CMLS - November 3, 2021 Category: Cytology Authors: Hanna Ilchmann-Diounou Marie Buleon Val érie Bacquie Vassilia Theodorou Colette Denis Sandrine Menard Source Type: research

Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants
Cell Mol Life Sci. 2021 Nov 3. doi: 10.1007/s00018-021-04008-0. Online ahead of print.ABSTRACTSince the emergence of the first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), the viral genome has constantly undergone rapid mutations for better adaptation in the host system. These newer mutations have given rise to several lineages/ variants of the virus that have resulted in high transmission and virulence rates compared to the previously circulating variants. Owing to this, the overall caseload and related mortality have tremendously increased globally to&...
Source: Cellular and Molecular Life Sciences : CMLS - November 3, 2021 Category: Cytology Authors: Deepali Gupta Priyanka Sharma Mandeep Singh Mukesh Kumar A S Ethayathulla Punit Kaur Source Type: research

Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes
Cell Mol Life Sci. 2021 Nov 3. doi: 10.1007/s00018-021-03984-7. Online ahead of print.ABSTRACTGlobal genome nucleotide excision repair (GG-NER) eliminates a broad spectrum of DNA lesions from genomic DNA. Genomic DNA is tightly wrapped around histones creating a barrier for DNA repair proteins to access DNA lesions buried in nucleosomal DNA. The DNA-damage sensors XPC and DDB2 recognize DNA lesions in nucleosomal DNA and initiate repair. The emerging view is that a tight interplay between XPC and DDB2 is regulated by post-translational modifications on the damage sensors themselves as well as on chromatin containing DNA le...
Source: Cellular and Molecular Life Sciences : CMLS - November 3, 2021 Category: Cytology Authors: Katja Apelt Hannes Lans Orlando D Sch ärer Martijn S Luijsterburg Source Type: research

Inhibition of the hERG potassium channel by phenanthrene: a polycyclic aromatic hydrocarbon pollutant
This study was undertaken to investigate the ability of phenanthrene to interact with hERG (human Ether-à-go-go-Related Gene) encoded Kv11.1 K+ channels, which play a central role in human ventricular repolarization. Pharmacological inhibition of hERG can be proarrhythmic. Whole-cell patch clamp recordings of hERG current (IhERG) were made from HEK293 cells expressing wild-type (WT) and mutant hERG channels. WT IhERG1a was inhibited by phenanthrene with an IC50 of 17.6 ± 1.7 µM, whilst IhERG1a/1b exhibited an IC50 of 1.8 ± 0.3 µM. WT IhERG block showed marked voltage and time dependence, in...
Source: Cellular and Molecular Life Sciences : CMLS - November 2, 2021 Category: Cytology Authors: Ehab Al-Moubarak Holly A Shiels Yihong Zhang Chunyun Du Oliver Hanington Stephen C Harmer Christopher E Dempsey Jules C Hancox Source Type: research

Correction to: TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development
Cell Mol Life Sci. 2021 Nov 2. doi: 10.1007/s00018-021-03982-9. Online ahead of print.NO ABSTRACTPMID:34727195 | DOI:10.1007/s00018-021-03982-9 (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 2, 2021 Category: Cytology Authors: Mei Yi Yixin Tan Li Wang Jing Cai Xiaoling Li Zhaoyang Zeng Wei Xiong Guiyuan Li Xiayu Li Pingqing Tan Bo Xiang Source Type: research

Inhibition of the hERG potassium channel by phenanthrene: a polycyclic aromatic hydrocarbon pollutant
This study was undertaken to investigate the ability of phenanthrene to interact with hERG (human Ether-à-go-go-Related Gene) encoded Kv11.1 K+ channels, which play a central role in human ventricular repolarization. Pharmacological inhibition of hERG can be proarrhythmic. Whole-cell patch clamp recordings of hERG current (IhERG) were made from HEK293 cells expressing wild-type (WT) and mutant hERG channels. WT IhERG1a was inhibited by phenanthrene with an IC50 of 17.6 ± 1.7 µM, whilst IhERG1a/1b exhibited an IC50 of 1.8 ± 0.3 µM. WT IhERG block showed marked voltage and time dependence, in...
Source: Cellular and Molecular Life Sciences : CMLS - November 2, 2021 Category: Cytology Authors: Ehab Al-Moubarak Holly A Shiels Yihong Zhang Chunyun Du Oliver Hanington Stephen C Harmer Christopher E Dempsey Jules C Hancox Source Type: research

Correction to: TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development
Cell Mol Life Sci. 2021 Nov 2. doi: 10.1007/s00018-021-03982-9. Online ahead of print.NO ABSTRACTPMID:34727195 | DOI:10.1007/s00018-021-03982-9 (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 2, 2021 Category: Cytology Authors: Mei Yi Yixin Tan Li Wang Jing Cai Xiaoling Li Zhaoyang Zeng Wei Xiong Guiyuan Li Xiayu Li Pingqing Tan Bo Xiang Source Type: research

Vascular adhesion protein-1 defines a unique subpopulation of human hematopoietic stem cells and regulates their proliferation
In conclusion, VAP-1 expression allows the characterization and prospective isolation of a new subset of human HSC. Since VAP-1 serves as a check point-like inhibitor in HSC differentiation, the use of VAP-1 inhibitors enables the expansion of HSC.PMID:34719737 | DOI:10.1007/s00018-021-03977-6 (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 1, 2021 Category: Cytology Authors: Imtiaz Iftakhar-E-Khuda Alberto Pessia Shuyu Zheng Matti Kankainen Mika Kontro Marika Karikoski Juha Laurila Heidi Gerke Sina Tadayon Maija Hollm én Jing Tang Beat A Imhof Marko Salmi Sirpa Jalkanen Source Type: research

Role of Akt isoforms in neuronal insulin signaling and resistance
Cell Mol Life Sci. 2021 Nov 1. doi: 10.1007/s00018-021-03993-6. Online ahead of print.ABSTRACTThe aim of the present study was to determine the role of Akt isoforms in insulin signaling and resistance in neuronal cells. By silencing Akt isoforms individually and in pairs, in Neuro-2a and HT22 cells we observed that, in insulin-sensitive condition, Akt isoforms differentially reduced activation of AS160 and glucose uptake with Akt2 playing the major role. Under insulin-resistant condition, phosphorylation of all isoforms and glucose uptake were severely affected. Over-expression of individual isoforms in insulin-sensitive a...
Source: Cellular and Molecular Life Sciences : CMLS - November 1, 2021 Category: Cytology Authors: Medha Sharma Chinmoy Sankar Dey Source Type: research

α-Klotho released from HK-2 cells inhibits osteogenic differentiation of renal interstitial fibroblasts by inactivating the Wnt-β-catenin pathway
This study found that both soluble KL (s-KL) and transmembrane KL (m-KL) were downregulated, and that s-KL but not m-KL was inversely correlated with upregulation of osteogenic markers in RP tissues. Additionally, s-KL expression was markedly suppressed in human renal interstitial fibroblasts (hRIFs) and slightly suppressed in HK-2 cells after osteogenic induction, intriguingly, which was echoed to the greater osteogenic capability of hRIFs than HK-2 cells. Further investigations showed the inhibitory effect of s-KL on hRIF osteogenic differentiation in vitro and in vivo. Moreover, coculture with recombinant human KL (r-KL...
Source: Cellular and Molecular Life Sciences : CMLS - November 1, 2021 Category: Cytology Authors: Zewu Zhu Shuhao Ruan Yingcheng Jiang Fang Huang Weiping Xia Jinbo Chen Yu Cui Cheng He Feng Zeng Yang Li Zhiyong Chen Hequn Chen Source Type: research

Vascular adhesion protein-1 defines a unique subpopulation of human hematopoietic stem cells and regulates their proliferation
In conclusion, VAP-1 expression allows the characterization and prospective isolation of a new subset of human HSC. Since VAP-1 serves as a check point-like inhibitor in HSC differentiation, the use of VAP-1 inhibitors enables the expansion of HSC.PMID:34719737 | DOI:10.1007/s00018-021-03977-6 (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - November 1, 2021 Category: Cytology Authors: Imtiaz Iftakhar-E-Khuda Alberto Pessia Shuyu Zheng Matti Kankainen Mika Kontro Marika Karikoski Juha Laurila Heidi Gerke Sina Tadayon Maija Hollm én Jing Tang Beat A Imhof Marko Salmi Sirpa Jalkanen Source Type: research

Role of Akt isoforms in neuronal insulin signaling and resistance
Cell Mol Life Sci. 2021 Nov 1. doi: 10.1007/s00018-021-03993-6. Online ahead of print.ABSTRACTThe aim of the present study was to determine the role of Akt isoforms in insulin signaling and resistance in neuronal cells. By silencing Akt isoforms individually and in pairs, in Neuro-2a and HT22 cells we observed that, in insulin-sensitive condition, Akt isoforms differentially reduced activation of AS160 and glucose uptake with Akt2 playing the major role. Under insulin-resistant condition, phosphorylation of all isoforms and glucose uptake were severely affected. Over-expression of individual isoforms in insulin-sensitive a...
Source: Cellular and Molecular Life Sciences : CMLS - November 1, 2021 Category: Cytology Authors: Medha Sharma Chinmoy Sankar Dey Source Type: research

α-Klotho released from HK-2 cells inhibits osteogenic differentiation of renal interstitial fibroblasts by inactivating the Wnt-β-catenin pathway
This study found that both soluble KL (s-KL) and transmembrane KL (m-KL) were downregulated, and that s-KL but not m-KL was inversely correlated with upregulation of osteogenic markers in RP tissues. Additionally, s-KL expression was markedly suppressed in human renal interstitial fibroblasts (hRIFs) and slightly suppressed in HK-2 cells after osteogenic induction, intriguingly, which was echoed to the greater osteogenic capability of hRIFs than HK-2 cells. Further investigations showed the inhibitory effect of s-KL on hRIF osteogenic differentiation in vitro and in vivo. Moreover, coculture with recombinant human KL (r-KL...
Source: Cellular and Molecular Life Sciences : CMLS - November 1, 2021 Category: Cytology Authors: Zewu Zhu Shuhao Ruan Yingcheng Jiang Fang Huang Weiping Xia Jinbo Chen Yu Cui Cheng He Feng Zeng Yang Li Zhiyong Chen Hequn Chen Source Type: research

Mitigating the pro-oxidant state and melanogenesis of Retinitis pigmentosa: by counteracting mitochondrial dysfunction
Cell Mol Life Sci. 2021 Oct 31. doi: 10.1007/s00018-021-04007-1. Online ahead of print.ABSTRACTRetinitis pigmentosa (RP) is a group of mitochondrial diseases characterized by progressive degeneration of rods and cones leading to retinal loss of light sensitivity and, consequently, to blindness. To date, no cure is available according to the clinical literature. As a disease associated with pigmentation-related, pro-oxidant state, and mitochondrial dysfunction, RP may be viewed at the crossroads of different pathogenetic pathways involved in adverse health outcomes, where mitochondria play a preeminent role. RP has been inv...
Source: Cellular and Molecular Life Sciences : CMLS - October 31, 2021 Category: Cytology Authors: Giovanni Pagano Federico V Pallard ó Alex Lyakhovich Luca Tiano Marco Trifuoggi Source Type: research

Dihydrolipoamide dehydrogenase, pyruvate oxidation, and acetylation-dependent mechanisms intersecting drug iatrogenesis
Cell Mol Life Sci. 2021 Oct 31. doi: 10.1007/s00018-021-03996-3. Online ahead of print.ABSTRACTIn human metabolism, pyruvate dehydrogenase complex (PDC) is one of the most intricate and large multimeric protein systems representing a central hub for cellular homeostasis. The worldwide used antiepileptic drug valproic acid (VPA) may potentially induce teratogenicity or a mild to severe hepatic toxicity, where the underlying mechanisms are not completely understood. This work aims to clarify the mechanisms that intersect VPA-related iatrogenic effects to PDC-associated dihydrolipoamide dehydrogenase (DLD; E3) activity. DLD i...
Source: Cellular and Molecular Life Sciences : CMLS - October 31, 2021 Category: Cytology Authors: I F Duarte J Caio M F Moedas L A Rodrigues A P Leandro I A Rivera M F B Silva Source Type: research