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Article ; Online: A hydrolyzed casein diet promotes Ngn3 controlling enteroendocrine cell differentiation to increase gastrointestinal motility in mice.

Liu, Siqiang / Zhu, Haining / Ren, Yuting / Fan, Wenlu / Wu, Haiqin / Wu, Huipeng / Huang, Zan / Zhu, Weiyun

2024 Volume 15, Issue 3, Page(s) 1237–1249

Abstract: Gut hormones are produced by enteroendocrine cells (EECs) found along the intestinal epithelium, and these cells play a crucial role in regulating intestinal function, nutrient absorption and food intake. A hydrolyzed casein diet has been reported to ... ...

Abstract	Gut hormones are produced by enteroendocrine cells (EECs) found along the intestinal epithelium, and these cells play a crucial role in regulating intestinal function, nutrient absorption and food intake. A hydrolyzed casein diet has been reported to promote the secretion of gut hormones through the regulation of EEC development, but the underlying mechanism remains unclear. Therefore, this study was conducted to investigate whether the hydrolyzed casein diet can regulate EEC differentiation by employing mouse and organoid models. Mice were fed diets containing either casein (casein group) or hydrolyzed casein (hydrolyzed casein group) as the sole protein source. The hydrolyzed casein diet upregulated the expression of transcription factors, induced EEC differentiation, increased fasting serum ghrelin concentrations and promoted gastrointestinal (GI) motility in the duodenum compared to the casein diet. Interestingly, these differences could be abolished when there is addition of antibiotics to the drinking water, suggesting a significant role of gut microbiota in the hydrolyzed casein-mediated EEC function. Further investigation showed that the hydrolyzed casein diet led to reduced microbial diversity, especially the abundance of
MeSH term(s)	Mice ; Animals ; Caseins/metabolism ; Cell Differentiation ; Enteroendocrine Cells ; Diet ; Transcription Factors/metabolism ; Gastrointestinal Hormones/metabolism ; Gastrointestinal Motility
Chemical Substances	Caseins ; Transcription Factors ; Gastrointestinal Hormones
Language	English
Publishing date	2024-02-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d3fo04152b
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Article: Postbiotics from

Wang, Mengting / Ren, Yuting / Guo, Xin / Ye, Yanxin / Zhu, Haining / Zhang, Jiaqi / Huang, Zan / Yu, Kaifan

Foods (Basel, Switzerland)

2024 Volume 13, Issue 6

Abstract: Previous studies have demonstrated ... ...

Abstract	Previous studies have demonstrated that
Language	English
Publishing date	2024-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704223-6
ISSN	2304-8158
ISSN	2304-8158
DOI	10.3390/foods13060874
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Article ; Online: Long noncoding RNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote lung carcinogenesis.

Wang, Po-Shun / Liu, Zulong / Sweef, Osama / Xie, Jie / Chen, Jing / Zhu, Haining / Zeidler-Erdely, Patti C / Yang, Chengfeng / Wang, Zhishan

Environment international

2024 Volume 185, Page(s) 108494

Abstract: Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer in humans, however, the mechanism of Cr(VI) carcinogenesis has not been well understood. Lung cancer is the leading cause of cancer-related ...

Abstract	Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer in humans, however, the mechanism of Cr(VI) carcinogenesis has not been well understood. Lung cancer is the leading cause of cancer-related death, although the mechanisms of how lung cancer develops and progresses have been poorly understood. While long non-coding RNAs (lncRNAs) are found abnormally expressed in cancer, how dysregulated lncRNAs contribute to carcinogenesis remains largely unknown. The goal of this study is to investigate the mechanism of Cr(VI)-induced lung carcinogenesis focusing on the role of the lncRNA ABHD11 antisense RNA 1 (tail to tail) (ABHD11-AS1). It was found that the lncRNA ABHD11-AS1 expression levels are up-regulated in chronic Cr(VI) exposure-transformed human bronchial epithelial cells, chronically Cr(VI)-exposed mouse lung tissues, and human lung cancer cells as well. Bioinformatics analysis revealed that ABHD11-AS1 levels are up-regulated in lung adenocarcinomas (LUADs) tissues and associated with worse overall survival of LUAD patients but not in lung squamous cell carcinomas. It was further determined that up-regulation of ABHD11-AS1 expression plays an important role in chronic Cr(VI) exposure-induced cell malignant transformation and tumorigenesis, and the stemness of human lung cancer cells. Mechanistically, it was found that ABHD11-AS1 directly binds SART3 (spliceosome associated factor 3, U4/U6 recycling protein). The interaction of ABHD11-AS1 with SART3 promotes USP15 (ubiquitin specific peptidase 15) nuclear localization. Nuclear localized USP15 interacts with pre-mRNA processing factor 19 (PRPF19) to increase CD44 RNA alternative splicing activating β-catenin and enhancing cancer stemness. Together, these findings indicate that lncRNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote cell malignant transformation and lung carcinogenesis.
MeSH term(s)	Humans ; Animals ; Mice ; RNA, Antisense/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Alternative Splicing ; Carcinogenesis/genetics ; Cell Transformation, Neoplastic ; Lung ; Lung Neoplasms/genetics ; Cell Proliferation/genetics ; Cell Line, Tumor ; Antigens, Neoplasm/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; RNA Splicing Factors/genetics ; RNA Splicing Factors/metabolism ; Nuclear Proteins ; Serine Proteases ; DNA Repair Enzymes ; Hyaluronan Receptors ; Ubiquitin-Specific Proteases ; Chromium
Chemical Substances	RNA, Antisense ; RNA, Long Noncoding ; chromium hexavalent ion (18540-29-9) ; SART3 protein, human ; Antigens, Neoplasm ; RNA-Binding Proteins ; PRPF19 protein, human (EC 6.5.1.-) ; RNA Splicing Factors ; CD44 protein, human ; ABHD11 protein, human (EC 3.4.-) ; USP15 protein, human (EC 3.4.19.12) ; Nuclear Proteins ; Serine Proteases (EC 3.4.-) ; DNA Repair Enzymes (EC 6.5.1.-) ; Hyaluronan Receptors ; Ubiquitin-Specific Proteases (EC 3.4.19.12) ; Chromium (0R0008Q3JB)
Language	English
Publishing date	2024-02-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2024.108494
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Article ; Online: The first detection of mpox virus DNA from wastewater in China.

Xu, Jin / Liu, Chao / Zhang, Qun / Zhu, Haining / Cui, Feng / Zhao, Zhiqiang / Song, Mingfang / Zhou, Bo / Zhang, Yunxiao / Hu, Peilong / Li, Lei / Wang, Qin / Wang, Peng

The Science of the total environment

2024 , Page(s) 172742

Abstract: Wastewater monitoring may be a valuable early surveillance tool for studying mpox virus (MPXV) circulation in China, a country with high population density and very few mpox patients. To evaluate the effectiveness of wastewater monitoring for MPXV in ... ...

Abstract	Wastewater monitoring may be a valuable early surveillance tool for studying mpox virus (MPXV) circulation in China, a country with high population density and very few mpox patients. To evaluate the effectiveness of wastewater monitoring for MPXV in detecting local hidden transmission of the epidemic in the early period, the Chinese Center for Disease Control and Prevention initiated a wastewater monitoring program for MPXV in China in July 2023. To enhance the monitoring sensitivity of the program, an MPXV monitoring point was established in a gathering place of high-risk mpox population. Three different concentration methods, PEG precipitation, ultrafiltration, and magnetic beads method were evaluated and compared. Due to its high recovery efficiency, low limit of detection, and high degree of automation, the magnetic beads method was selected for the daily surveillance of MPXV in wastewater. On September 5, 2023, MPXV DNA was detected at the MPXV monitoring point in Zibo City, marking the first instance of MPXV detection of MPXV in wastewater in China. Next-generation sequencing was conducted on the MPXV genome obtained from the positive wastewater, positive environmental samples, and the single case of mpox in Zibo in September. The results showed that the genotypes of these three genomes were different but all belong to the IIb branch of the C.1 lineage, indicating a probably hidden transmission of mpox. Wastewater monitoring is potentially an effective early surveillance tool for tracking the spread of MPXV in areas with high population density and very few mpox patients.
Language	English
Publishing date	2024-04-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2024.172742
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Article ; Online: FUS regulates autophagy by mediating the transcription of genes critical to the autophagosome formation.

Arenas, Alexandra / Kuang, Lisha / Zhang, Jiayu / Kingren, Meagan S / Zhu, Haining

Journal of neurochemistry

2021 Volume 157, Issue 3, Page(s) 752–763

Abstract: Fused in sarcoma (FUS) is a ubiquitously expressed RNA/DNA-binding protein that plays different roles in the cell. FUS pathology has been reported in neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ... ...

Abstract	Fused in sarcoma (FUS) is a ubiquitously expressed RNA/DNA-binding protein that plays different roles in the cell. FUS pathology has been reported in neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in FUS have also been linked to a subset of familial ALS. FUS is mainly localized in the nucleus although it shuttles between the nucleus and the cytoplasm. ALS-linked mutations cause the accumulation of the FUS protein in cytoplasm where it forms stress granule-like inclusions. The protein- and RNA-containing inclusions are reported to be positive of autophagosome markers and degraded by the autophagy pathway. However, the role of FUS in the autophagy pathway remains to be better understood. Using immunoblot and confocal imaging techniques in this study, we found that FUS knockout (KO) cells showed a decreased basal autophagy level. Rapamycin and bafilomycin A1 treatment showed that FUS KO cells were not able to initiate autophagy as efficiently as wild-type cells, suggesting that the autophagosome formation is affected in the absence of FUS. Moreover, using immunoblot and quantitative PCR techniques, we found that the mRNA and protein levels of the genes critical in the initial steps of the autophagy pathway (FIP200, ATG16L1 and ATG12) were significantly lower in FUS KO cells. Re-expressing FUS in the KO cells restored the expression of FIP200 and ATG16L1. Our findings demonstrate a novel role of FUS in the autophagy pathway, that is, regulating the transcription of genes involved in early stages of autophagy such as the initiation and elongation of autophagosomes.
MeSH term(s)	Animals ; Autophagosomes/drug effects ; Autophagosomes/genetics ; Autophagosomes/physiology ; Autophagy/drug effects ; Autophagy/genetics ; Autophagy/physiology ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/physiology ; Cell Line ; Gene Expression Regulation ; Gene Knockout Techniques ; Macrolides/pharmacology ; Mice ; Proteasome Endopeptidase Complex ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; RNA-Binding Protein FUS/genetics ; RNA-Binding Protein FUS/physiology ; Signal Transduction/genetics ; Sirolimus/pharmacology
Chemical Substances	Atg16l1 protein, mouse ; Autophagy-Related Proteins ; FUS protein, mouse ; Macrolides ; RNA, Messenger ; RNA-Binding Protein FUS ; Rb1cc1 protein, mouse ; bafilomycin A1 (88899-55-2) ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2021-01-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.15281
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Article ; Online: Yin and yang regulation of stress granules by Caprin-1.

Song, Dan / Kuang, Lisha / Yang, Lin / Wang, Lei / Li, Hao / Li, Xiu / Zhu, Zhimin / Shi, Chaowei / Zhu, Haining / Gong, Weimin

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 44, Page(s) e2207975119

Abstract: Stress granules (SGs) are cytoplasmic biomolecular condensates containing proteins and RNAs in response to stress. Ras-GTPase-activating protein binding protein 1 (G3BP1) is a core SG protein. Caprin-1 and ubiquitin specific peptidase 10 (USP10) interact ...

Abstract	Stress granules (SGs) are cytoplasmic biomolecular condensates containing proteins and RNAs in response to stress. Ras-GTPase-activating protein binding protein 1 (G3BP1) is a core SG protein. Caprin-1 and ubiquitin specific peptidase 10 (USP10) interact with G3BP1, facilitating and suppressing SG formation, respectively. The crystal structures of the nuclear transport factor 2-like (NTF2L) domain of G3BP1 in complex with the G3BP1-interacting motif (GIM) of Caprin-1 and USP10 show that both GIMs bind to the same hydrophobic pocket of G3BP1. Moreover, both GIMs suppressed the liquid-liquid phase separation (LLPS) of G3BP1, suggesting that Caprin-1 likely facilitates SG formation via other mechanisms. Thus, we dissected various domains of Caprin-1 and investigated their role in LLPS in vitro and SG formation in cells. The C-terminal domain of Caprin-1 underwent spontaneous LLPS, whereas the N-terminal domain and GIM of Caprin-1 suppressed LLPS of G3BP1. The opposing effect of the N- and C-terminal domains of Caprin-1 on SG formation were demonstrated in cells with or without the endogenous Caprin-1. We propose that the N- and C-terminal domains of Caprin-1 regulate SG formation in a "yin and yang" fashion, mediating the dynamic and reversible assembly of SGs.
MeSH term(s)	RNA Recognition Motif Proteins/metabolism ; Poly-ADP-Ribose Binding Proteins/metabolism ; RNA Helicases/metabolism ; DNA Helicases/metabolism ; Cytoplasmic Granules/metabolism ; Stress Granules ; GTPase-Activating Proteins/metabolism ; Ubiquitin-Specific Proteases/metabolism
Chemical Substances	RNA Recognition Motif Proteins ; Poly-ADP-Ribose Binding Proteins ; RNA Helicases (EC 3.6.4.13) ; DNA Helicases (EC 3.6.4.-) ; GTPase-Activating Proteins ; Ubiquitin-Specific Proteases (EC 3.4.19.12)
Language	English
Publishing date	2022-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2207975119
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Article: NEK1 Phosphorylation of YAP Promotes Its Stabilization and Transcriptional Output.

Khalil, Md Imtiaz / Ghosh, Ishita / Singh, Vibha / Chen, Jing / Zhu, Haining / De Benedetti, Arrigo

Cancers

2020 Volume 12, Issue 12

Abstract: Most prostate cancer (PCa) deaths result from progressive failure in standard androgen deprivation therapy (ADT), leading to metastatic castration-resistant PCa (mCRPC); however, the mechanism and key players leading to this are not fully understood. ... ...

Abstract	Most prostate cancer (PCa) deaths result from progressive failure in standard androgen deprivation therapy (ADT), leading to metastatic castration-resistant PCa (mCRPC); however, the mechanism and key players leading to this are not fully understood. While studying the role of tousled-like kinase 1 (TLK1) and never in mitosis gene A (NIMA)-related kinase 1 (NEK1) in a DNA damage response (DDR)-mediated cell cycle arrest in LNCaP cells treated with bicalutamide, we uncovered that overexpression of wt-NEK1 resulted in a rapid conversion to androgen-independent (AI) growth, analogous to what has been observed when YAP1 is overexpressed. We now report that overexpression of wt-NEK1 results in accumulation of YAP1, suggesting the existence of a TLK1>NEK1>YAP1 axis that leads to adaptation to AI growth. Further, YAP1 is co-immunoprecipitated with NEK1. Importantly, NEK1 was able to phosphorylate YAP1 on six residues in vitro, which we believe are important for stabilization of the protein, possibly by increasing its interaction with transcriptional partners. In fact, knockout (KO) of NEK1 in NT1 PCa cells resulted in a parallel decrease of YAP1 level and reduced expression of typical YAP-regulated target genes. In terms of cancer potential implications, the expression of NEK1 and YAP1 proteins was found to be increased and correlated in several cancers. These include PCa stages according to Gleason score, head and neck squamous cell carcinoma, and glioblastoma, suggesting that this co-regulation is imparted by increased YAP1 stability when NEK1 is overexpressed or activated by TLK1, and not through transcriptional co-expression. We propose that the TLK1>NEK1>YAP1 axis is a key determinant for cancer progression, particularly during the process of androgen-sensitive to -independent conversion during progression to mCRPC.
Language	English
Publishing date	2020-12-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12123666
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Article: ABL1/2 and DDR1 Drive MEKi Resistance in NRAS-Mutant Melanomas by Stabilizing RAF/MYC/ETS1 and Promoting RAF Homodimerization.

Lyon, Anastasia / Tripathi, Rakshamani / Meeks, Christina / He, Daheng / Wu, Yuanyuan / Liu, Jinpeng / Wang, Chi / Chen, Jing / Zhu, Haining / Mukherjee, Sujata / Ganguly, Saptadwipa / Plattner, Rina

Cancers

2023 Volume 15, Issue 3

Abstract: Melanomas ... ...

Abstract	Melanomas harboring
Language	English
Publishing date	2023-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15030954
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Article ; Online: Early concentrate starter introduction induces rumen epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation.

Zhang, Kai / Zhang, Yali / Qin, Jing / Zhu, Haining / Liu, Ning / Sun, Daming / Yin, Yuyang / Mao, Shengyong / Zhu, Weiyun / Huang, Zan / Liu, Junhua

Journal of advanced research

2023

Abstract: Introduction: Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively impacts ruminant health and performance. However, we still lack a ... ...

Abstract	Introduction: Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively impacts ruminant health and performance. However, we still lack a comprehensive perception of the underlying mechanisms and the predisposing factors for this disorder. Objectives: Here, we investigated rumen epithelial cell heterogeneity, differentiation trajectories, and cornification to clarify the rumen epithelial keratinization process and discern the key ruminal metabolites contributing to rumen epithelial parakeratosis. Methods: Twenty-four 14-day-old lambs were divided into three groups, including only milk feeding, milk plus alfalfa hay feeding, and milk plus corn-soybean concentrate starter feeding. At 42 days of age, the lambs were slaughtered, and rumen tissues were collected for single-cell RNA-sequencing (scRNA-seq), immunofluorescence, and quantitative real-time PCR (qRT-PCR) analyses. Ruminal fluid samples were collected for metabolomic analyses. Rumen epithelial organoid was used to verify the key ruminal metabolites contributing to parakeratosis. Results: As expected, we observed that concentrate starter introduction resulted in rumen epithelial parakeratosis. Moreover, scRNA-seq analysis revealed a developmental impediment in the transition from differentiated keratinocytes to terminally differentiated keratinocytes (TDK) in lambs with concentrate starter introduction. Immunofluorescence and qRT-PCR analyses further verified the location and expression of marker genes of TDK. Metabolomic analysis showed a robust positive correlation between ruminal butyrate levels and rumen epithelial keratinization. More importantly, we successfully established a rumen organoid model capable of facilitating the study of the keratinization process in the rumen epithelia and further confirmed that high dose butyrate indeed contributed to rumen epithelial parakeratosis. Conclusion: Collectively, concentrate starter introduction induces ruminal epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation in a neonatal lamb model. These findings enhance our understanding of rumen epithelial keratinization and provide valuable insights for addressing rumen epithelial parakeratosis using early nutritional intervention strategies.
Language	English
Publishing date	2023-12-19
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2541849-X
ISSN	2090-1224 ; 2090-1224
ISSN (online)	2090-1224
ISSN	2090-1224
DOI	10.1016/j.jare.2023.12.016
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Article ; Online: An immortal porcine preadipocyte cell strain for efficient production of cell-cultured fat.

Cheng, Yun-Mou / Hong, Peng-Cheng / Song, Ming-Mei / Zhu, Hai-Ning / Qin, Jing / Zhang, Zeng-Di / Chen, Hao / Ma, Xing-Zhou / Tian, Meng-Yuan / Zhu, Wei-Yun / Huang, Zan

Communications biology

2023 Volume 6, Issue 1, Page(s) 1202

Abstract: Adding adipose cells to cell-cultured meat can provide a distinctive aroma and juicy texture similar to real meat. However, a significant challenge still exists in obtaining seed cells that can be propagated for long periods, maintain their adipogenic ... ...

Abstract	Adding adipose cells to cell-cultured meat can provide a distinctive aroma and juicy texture similar to real meat. However, a significant challenge still exists in obtaining seed cells that can be propagated for long periods, maintain their adipogenic potential, and reduce production costs. In this study, we present a cell strain derived from immortalized porcine preadipocytes that can be subculture for over 40 passages without losing differentiation capacity. This cell strain can be differentiated within 3D bioscaffolds to generate cell-cultured fat using fewer chemicals and less serum. Additionally, it can be expanded and differentiated on microcarriers with upscaled culture to reduce costs and labor. Moreover, it can co-differentiate with muscle precursor cells, producing a pattern similar to real meat. Therefore, our cell strain provides an exceptional model for studying and producing cell-cultured fat.
MeSH term(s)	Swine ; Animals ; Cells, Cultured ; Adipocytes ; Adipogenesis ; Cell Differentiation
Language	English
Publishing date	2023-11-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-05583-7
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