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Article ; Online: Structure and Function of Ligand CX3CL1 and its Receptor CX3CR1 in Cancer.

Lu, Xinjie

2022 Volume 29, Issue 41, Page(s) 6228–6246

Abstract: The C-X3-C motif chemokine ligand (CX3CL)1 (also known as Fractalkine) and its receptor CX3CR1 (also known as G-protein coupled receptor 13) are expressed on the membranes of many different cells such as epithelial cells, dendritic cells, smooth muscle ... ...

Abstract	The C-X3-C motif chemokine ligand (CX3CL)1 (also known as Fractalkine) and its receptor CX3CR1 (also known as G-protein coupled receptor 13) are expressed on the membranes of many different cells such as epithelial cells, dendritic cells, smooth muscle cells, and neurons. CX3CR1 is primarily expressed on monocytes, macrophages, dendritic cells, T cells, and natural killer cells. The binding of CX3CL1 to CX3CR1 induces the activation of heterotrimeric G proteins associated with this receptor. In addition, it triggers the signal pathways of MAPK and AKT, which play essential roles in tumour biology. Mechanistically, the CX3CL1-CX3CR1 axis has an antitumour role by recruiting antitumoural immune cells such as NK cells and T cells into the tumour microenvironment to control tumour growth. On the other hand, accumulated evidence indicates that the CX3CL1-CX3CR1 axis also activates a pro-tumoral response. This review will focus on the unique structural biology features of CX3CL1 and CX3CR1, their interactions in tumour inflammatory response, and antitumour effects, which highlights possible potential therapeutic targets.
MeSH term(s)	Humans ; Chemokine CX3CL1/genetics ; Chemokine CX3CL1/metabolism ; CX3C Chemokine Receptor 1/genetics ; CX3C Chemokine Receptor 1/metabolism ; Ligands ; Neoplasms/genetics ; Neoplasms/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Tumor Microenvironment/genetics ; Tumor Microenvironment/physiology
Chemical Substances	Chemokine CX3CL1 ; CX3C Chemokine Receptor 1 ; CX3CL1 protein, human ; CX3CR1 protein, human ; Ligands ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2022-06-30
Publishing country	United Arab Emirates
Document type	Review ; Journal Article
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0929867329666220629140540
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Article ; Online: Structure and Functions of T-cell Immunoglobulin-domain and Mucin- domain Protein 3 in Cancer.

Lu, Xinjie

Current medicinal chemistry

2021 Volume 29, Issue 11, Page(s) 1851–1865

Abstract: Background: T-cell immunoglobulin (Ig)-domain and mucin-domain (TIM) proteins represent a family of receptors expressed on T-cells that play essential cellular immunity roles. The TIM proteins span across the membrane belonging to type I transmembrane ... ...

Abstract	Background: T-cell immunoglobulin (Ig)-domain and mucin-domain (TIM) proteins represent a family of receptors expressed on T-cells that play essential cellular immunity roles. The TIM proteins span across the membrane belonging to type I transmembrane proteins. The N terminus contains an Ig-like V-type domain and a Ser/Thr-rich mucin stalk as a co-inhibitory receptor. The C-terminal tail oriented toward the cytosol predominantly mediates intracellular signaling. Methods: This review discusses the structural features and functions of TIM-3, specifically on its role in mediating immune responses in different cell types and the rationale for TIM-3-targeted cancer immunotherapy. Results: TIM-3 has gained significant importance to be a potential biomarker in cancer immunotherapy. It has been shown that blockade with checkpoint inhibitors promotes anti-tumor immunity and inhibits tumor growth in several preclinical tumor models. Conclusion: TIM-3 is an immune regulating molecule expressed on several cell types, including IFNγ-producing T-cells, FoxP3+ Treg cells, and innate immune cells. The roles of TIM-3 in immunosuppression support its merit as a target for cancer immunotherapy.
MeSH term(s)	Hepatitis A Virus Cellular Receptor 2/metabolism ; Humans ; Immunoglobulins ; Immunotherapy ; Mucin-3 ; Neoplasms/therapy
Chemical Substances	Hepatitis A Virus Cellular Receptor 2 ; Immunoglobulins ; Mucin-3
Language	English
Publishing date	2021-08-07
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0929867328666210806120904
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Article ; Online: OX40 and OX40L Interaction in Cancer.

Lu, Xinjie

Current medicinal chemistry

2020 Volume 28, Issue 28, Page(s) 5659–5673

Abstract: Background: OX40 (CD134) and its binding partner, OX40L (CD252), are expressed on activated CD4, CD8 T-cells, and several other lymphoid and non-lymphoid cells. OX40L belongs to a TNF family member, a 34 kDa type II transmembrane protein. The ... ...

Abstract	Background: OX40 (CD134) and its binding partner, OX40L (CD252), are expressed on activated CD4, CD8 T-cells, and several other lymphoid and non-lymphoid cells. OX40L belongs to a TNF family member, a 34 kDa type II transmembrane protein. The crystallized complex of human OX40 and OX40L is a trimeric contableuration of one OX40L (trimer) and three OX40 monomers. OX40 and OX40L regulate cytokine production from T-cells, antigen-presenting cells, and natural killer (NK) cells, and modulate cytokine receptor signaling. Methods: In this review, an updated overview of the structural features of OX40/OX40L and their interactions with cancer are provided. Results: Recent studies have shown that stimulation of OX40 is useful for therapeutic immunization strategies for cancer. OX40 serves as a secondary costimulatory immune checkpoint molecule; the binding of OX40 to its ligand enhances the augmentation, survival, memory formation, effector function, and recall responses of both CD4+ and CD8+ T-cells. Conclusion: This review highlights that OX40-OX40L interactions play crucial roles in both CD4+ and CD8+ T-cells. Signals through OX40 can abolish the suppressive activity of Tregs, prevent the induction of Tregs from effector T-cells, reduce Foxp3 expression, and induce the proliferation of memory and effector T lymphocytes. Additionally, when transferred into tumor-bearing recipients, they generate proliferation capability and successfully eliminate the established tumor.
MeSH term(s)	CD8-Positive T-Lymphocytes ; Humans ; Killer Cells, Natural ; Neoplasms ; OX40 Ligand ; Receptors, OX40 ; Signal Transduction
Chemical Substances	OX40 Ligand ; Receptors, OX40
Language	English
Publishing date	2020-12-28
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0929867328666201229123151
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Article ; Online: Structure and Function of Angiopoietin-like Protein 3 (ANGPTL3) in Atherosclerosis.

Lu, Xinjie

Current medicinal chemistry

2019 Volume 27, Issue 31, Page(s) 5159–5174

Abstract: Background: Angiopoietin-Like Proteins (ANGPTLs) are structurally related to the angiopoietins. A total of eight ANGPTLs (from ANGPTL1 to ANGPTL8) have been identified so far. Most ANGPTLs possess multibiological functions on lipid metabolism, ... ...

Abstract	Background: Angiopoietin-Like Proteins (ANGPTLs) are structurally related to the angiopoietins. A total of eight ANGPTLs (from ANGPTL1 to ANGPTL8) have been identified so far. Most ANGPTLs possess multibiological functions on lipid metabolism, atherosclerosis, and cancer. Among them, ANGPTL3 has been shown to regulate the levels of Very Low-Density Lipoprotein (VLDL) made by the liver and play a crucial role in human lipoprotein metabolism. Method: A systematic appraisal of ANGPTLs was conducted, focusing on the main features of ANGPTL3 that has a significant role in atherosclerosis. Results: Angiopoietins including ANGPTL3 are vascular growth factors that are highly specific for endothelial cells, perform a variety of other regulatory activities to influence inflammation, and have been shown to possess both pro-atherosclerotic and atheroprotective effects. Conclusion: ANGPTL3 has been demonstrated as a promising target in the pharmacological management of atherosclerosis. However, many questions remain about its biological functions.
MeSH term(s)	Angiopoietin-like Proteins/genetics ; Angiopoietins ; Atherosclerosis/genetics ; Endothelial Cells ; Humans ; Lipid Metabolism ; Peptide Hormones
Chemical Substances	ANGPTL3 protein, human ; ANGPTL8 protein, human ; Angiopoietin-like Proteins ; Angiopoietins ; Peptide Hormones
Language	English
Publishing date	2019-06-20
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0929867326666190621120523
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Article ; Online: The Role of Large Neutral Amino Acid Transporter (LAT1) in Cancer.

Lu, Xinjie

Current cancer drug targets

2019 Volume 19, Issue 11, Page(s) 863–876

Abstract: Background: The solute carrier family 7 (SLC7) can be categorically divided into two subfamilies, the L-type amino acid transporters (LATs) including SLC7A5-13, and SLC7A15, and the cationic amino acid transporters (CATs) including SLC7A1-4 and SLC7A14. ...

Abstract	Background: The solute carrier family 7 (SLC7) can be categorically divided into two subfamilies, the L-type amino acid transporters (LATs) including SLC7A5-13, and SLC7A15, and the cationic amino acid transporters (CATs) including SLC7A1-4 and SLC7A14. Members of the CAT family transport predominantly cationic amino acids by facilitating diffusion with intracellular substrates. LAT1 (also known as SLC7A5), is defined as a heteromeric amino acid transporter (HAT) interacting with the glycoprotein CD98 (SLC3A2) through a conserved disulfide to uptake not only large neutral amino acids, but also several pharmaceutical drugs to cells. Methods: In this review, we provide an overview of the interaction of the structure-function of LAT1 and its essential role in cancer, specifically, its role at the blood-brain barrier (BBB) to facilitate the transport of thyroid hormones, pharmaceuticals (e.g., I-DOPA, gabapentin), and metabolites into the brain. Results: LAT1 expression increases as cancers progress, leading to higher expression levels in highgrade tumors and metastases. In addition, LAT1 plays a crucial role in cancer-associated reprogrammed metabolic networks by supplying tumor cells with essential amino acids. Conclusion: The increasing understanding of the role of LAT1 in cancer has led to an increase in interest surrounding its potential as a drug target for cancer treatment.
MeSH term(s)	Amino Acids, Essential/metabolism ; Blood-Brain Barrier/metabolism ; Humans ; Large Neutral Amino Acid-Transporter 1/chemistry ; Large Neutral Amino Acid-Transporter 1/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology
Chemical Substances	Amino Acids, Essential ; Large Neutral Amino Acid-Transporter 1 ; SLC7A5 protein, human
Language	English
Publishing date	2019-08-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2064824-8
ISSN	1873-5576 ; 1568-0096
ISSN (online)	1873-5576
ISSN	1568-0096
DOI	10.2174/1568009619666190802135714
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Article ; Online: Structure and Function of Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in Hyperlipidemia and Atherosclerosis.

Lu, Xinjie

Current drug targets

2019 Volume 20, Issue 10, Page(s) 1029–1040

Abstract: Background: One of the important factors in Low-Density Lipoprotein (LDL) metabolism is the LDL receptor (LDLR) by its capacity to bind and subsequently clear cholesterol derived from LDL (LDL-C) in the circulation. Proprotein Convertase Subtilisin-like ...

Abstract	Background: One of the important factors in Low-Density Lipoprotein (LDL) metabolism is the LDL receptor (LDLR) by its capacity to bind and subsequently clear cholesterol derived from LDL (LDL-C) in the circulation. Proprotein Convertase Subtilisin-like Kexin type 9 (PCSK9) is a newly discovered serine protease that destroys LDLR in the liver and thereby controls the levels of LDL in plasma. Inhibition of PCSK9-mediated degradation of LDLR has, therefore, become a novel target for lipid-lowering therapy. Methods: We review the current understanding of the structure and function of PCSK9 as well as its implications for the treatment of hyperlipidemia and atherosclerosis. Results: New treatments such as monoclonal antibodies against PCSK9 may be useful agents to lower plasma levels of LDL and hence prevent atherosclerosis. Conclusion: PCSK9's mechanism of action is not yet fully clarified. However, treatments that target PCSK9 have shown striking early efficacy and promise to improve the lives of countless patients with hyperlipidemia and atherosclerosis.
MeSH term(s)	Atherosclerosis/metabolism ; Catalytic Domain ; Cholesterol, LDL/blood ; Humans ; Hyperlipidemias/metabolism ; Proprotein Convertase 9/chemistry ; Proprotein Convertase 9/metabolism ; Protein Binding ; Protein Conformation ; Protein Domains
Chemical Substances	Cholesterol, LDL ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-)
Language	English
Publishing date	2019-02-15
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2064859-5
ISSN	1873-5592 ; 1389-4501
ISSN (online)	1873-5592
ISSN	1389-4501
DOI	10.2174/1389450120666190214141626
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Article: Immunity and Growth Plasticity of Asian Short-Toed Lark Nestlings in Response to Changes in Food Conditions: Can It Buffer the Challenge of Climate Change-Induced Trophic Mismatch?

Lu, Guang / Zhang, Xinjie / Li, Xinyu / Zhang, Shuping

Animals : an open access journal from MDPI

2023 Volume 13, Issue 5

Abstract: Passerine nestlings frequently suffer from sub-optimal food conditions due to climate change-induced trophic mismatch between the nestlings and their optimal food resources. The ability of nestlings to buffer this challenge is less well understood. We ... ...

Abstract	Passerine nestlings frequently suffer from sub-optimal food conditions due to climate change-induced trophic mismatch between the nestlings and their optimal food resources. The ability of nestlings to buffer this challenge is less well understood. We hypothesized that poor food conditions might induce a higher immune response and lower growth rate of nestlings, and such physiological plasticity is conducive to nestling survival. To test this, we examined how food (grasshopper nymphs) abundance affects the expression of interferon-γ (
Language	English
Publishing date	2023-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani13050860
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Article: Design and Control of a Trapezoidal Piezoelectric Bimorph Actuator for Optical Fiber Alignment.

Wang, Xinjie / Li, Jianhui / Lu, Xingfan

Materials (Basel, Switzerland)

2023 Volume 16, Issue 17

Abstract: To align a pair of optical fibers, it is required that the micro actuators used be small and have the characteristics of high accuracy and fast response time. A trapezoidal piezoelectric bimorph actuator was proposed for pushing and pulling an optical ... ...

Abstract	To align a pair of optical fibers, it is required that the micro actuators used be small and have the characteristics of high accuracy and fast response time. A trapezoidal piezoelectric bimorph actuator was proposed for pushing and pulling an optical fiber. Based on a mathematical model and finite element model established in this paper, we analyzed the output displacement and output force of the proposed trapezoidal piezoelectric actuator under the influence of structural parameters. Since the piezoelectric bimorph actuator had a hysteresis effect, we applied particle swarm optimization to establish a Prandtl-Ishlinskii (PI) model for actuator and parameter identification. Then, two control methods, namely feedforward control considering hysteresis effects and fuzzy proportional-integral-derivative (PID) control employing feedback, were proposed. Finally, a composite control model combining the two control methods with fewer tracking errors was designed. The results show that the output displacement of this actuator is larger than that of a rectangular one. Additionally, the fuzzy PID control has a lower response time (15 ms) and an overshoot (5%).
Language	English
Publishing date	2023-08-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma16175811
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Article ; Online: The dsRNA isolated from Escherichia coli infected with the MS2 bacteriophage induces the production of interferons.

Han, Lu / Guo, Xinjie / Xu, Cunshuan / Shen, Wenlong / Zhao, Zhihu

Biochemical and biophysical research communications

2024 Volume 712-713, Page(s) 149915

Abstract: Viral infections pose a significant threat to public health, and the production of interferons represents one of the most critical antiviral innate immune responses of the host. Consequently, the screening and identification of compounds or reagents that ...

Abstract	Viral infections pose a significant threat to public health, and the production of interferons represents one of the most critical antiviral innate immune responses of the host. Consequently, the screening and identification of compounds or reagents that induce interferon production are of paramount importance. This study commenced with the cultivation of host bacterium 15,597, followed by the infection of Escherichia coli with the MS2 bacteriophage. Utilizing the J2 capture technique, a class of dsRNA mixtures (MS2+15,597) was isolated from the E. coli infected with the MS2 bacteriophage. Subsequent investigations were conducted on the immunostimulatory activity of the MS2+15,597 mixture. The results indicated that the dsRNA mixtures (MS2+15,597) extracted from E. coli infected with the MS2 bacteriophage possess the capability to activate innate immunity, thereby inducing the production of interferon-β. These dsRNA mixtures can activate the RIG-I and TLR3 pattern recognition receptors, stimulating the expression of interferon stimulatory factors 3/7, which in turn triggers the NF-κB signaling pathway, culminating in the cellular production of interferon-β to achieve antiviral effects. This study offers novel insights and strategies for the development of broad-spectrum antiviral drugs, potentially providing new modalities for future antiviral therapies.
Language	English
Publishing date	2024-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2024.149915
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Article ; Online: Immunity and Growth Plasticity of Asian Short-Toed Lark Nestlings in Response to Changes in Food Conditions

Guang Lu / Xinjie Zhang / Xinyu Li / Shuping Zhang

Animals, Vol 13, Iss 860, p

Can It Buffer the Challenge of Climate Change-Induced Trophic Mismatch?

2023 Volume 860

Abstract	Passerine nestlings frequently suffer from sub-optimal food conditions due to climate change-induced trophic mismatch between the nestlings and their optimal food resources. The ability of nestlings to buffer this challenge is less well understood. We hypothesized that poor food conditions might induce a higher immune response and lower growth rate of nestlings, and such physiological plasticity is conducive to nestling survival. To test this, we examined how food (grasshopper nymphs) abundance affects the expression of interferon-γ ( IFN-γ ), tumor necrosis factor-α ( TNF-α ), interleukin-1 β ( IL-1β ) genes, plasma IGF-1 levels, body mass, and fledging rates in wild Asian short-toed lark ( Alaudala cheleensis ) nestlings. Linear mixed models revealed that nymph biomass significantly influenced the expression of IFN-γ , TNF-α , and IL-1β genes, and the level of plasma IGF-1. The expressions of IFN-γ , TNF-α , and IL-1β genes were negatively correlated with nymph biomass and plasma IGF-1 level. Plasma IGF-1 level, nestling body mass growth rate, was positively correlated with nymph biomass. Despite a positive correlation between the nestling fledge rate and nymph biomass, more than 60% of nestlings fledged when nymph biomass was at the lowest level. These results suggest that immunity and growth plasticity of nestlings may be an adaptation for birds to buffer the negative effects of trophic mismatch.
Keywords	nestling ; immunity ; growth ; trophic mismatch ; physiological plasticity ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
Subject code	590
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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