Antagonizing leptin: current status and future directions

Abstract The adipocyte-derived hormone/cytokine leptin acts as a metabolic switch, connecting the body’s nutritional status to high energy consuming processes such as reproduction and immune responses. Inappropriate leptin responses can promote autoimmune diseases and tumorigenesis. In this review we discuss the current strategies to modulate leptin signaling and the possibilities for their use in research and therapy.

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Parton Distributions in Nucleons and Nuclei

Annual Review of Nuclear and Particle Science ◽

10.1146/annurev-nucl-011720-042725 ◽

2020 ◽

Vol 70 (1) ◽

pp. 43-76 ◽

Cited By ~ 7

Author(s):

Jacob J. Ethier ◽

Emanuele R. Nocera

Keyword(s):

Parton Distribution Function ◽

High Energy ◽

Experimental Information ◽

Current Status ◽

Future Directions ◽

Perturbative Quantum Chromodynamics ◽

Polarized Protons ◽

Accuracy And Precision ◽

Perturbative Quantum ◽

Methodological Aspects

We review the current status of parton distribution function (PDF) determinations for unpolarized and longitudinally polarized protons and for unpolarized nuclei, which are probed by high-energy hadronic scattering in perturbative quantum chromodynamics (QCD). We present the established theoretical framework, the experimental information, and the methodological aspects inherent to any modern PDF extraction. Furthermore, we summarize the present knowledge of PDFs and discuss their limitations in both accuracy and precision relevant to advancing our understanding of QCD proton substructure and pursuing our quest for precision in the Standard Model and beyond. In this respect, we highlight various achievements, discuss contemporary issues in PDF analyses, and outline future directions of progress.

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Halomonas as a chassis

Essays in Biochemistry ◽

10.1042/ebc20200159 ◽

2021 ◽

Author(s):

Jian-Wen Ye ◽

Guo-Qiang Chen

Keyword(s):

Synthetic Biology ◽

Rapid Development ◽

High Energy ◽

Strain Engineering ◽

Current Status ◽

Industrial Biotechnology ◽

Cell Factories ◽

Energy Consuming ◽

Significant Cost Reduction ◽

Process Complexity

Abstract With the rapid development of systems and synthetic biology, the non-model bacteria, Halomonas spp., have been developed recently to become a cost-competitive platform for producing a variety of products including polyesters, chemicals and proteins owing to their contamination resistance and ability of high cell density growth at alkaline pH and high salt concentration. These salt-loving microbes can partially solve the challenges of current industrial biotechnology (CIB) which requires high energy-consuming sterilization to prevent contamination as CIB is based on traditional chassis, typically, Escherichia coli, Bacillus subtilis, Pseudomonas putida and Corynebacterium glutamicum. The advantages and current status of Halomonas spp. including their molecular biology and metabolic engineering approaches as well as their applications are reviewed here. Moreover, a systematic strain engineering streamline, including product-based host development, genetic parts mining, static and dynamic optimization of modularized pathways and bioprocess-inspired cell engineering are summarized. All of these developments result in the term called next-generation industrial biotechnology (NGIB). Increasing efforts are made to develop their versatile cell factories powered by synthetic biology to demonstrate a new biomanufacturing strategy under open and continuous processes with significant cost-reduction on process complexity, energy, substrates and fresh water consumption.

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Selection of non-competitive leptin antagonists using a random nanobody-based approach

Biochemical Journal ◽

10.1042/bj20110438 ◽

2011 ◽

Vol 441 (1) ◽

pp. 425-434 ◽

Cited By ~ 27

Author(s):

Lennart Zabeau ◽

Annick Verhee ◽

Dominiek Catteeuw ◽

Liesbeth Faes ◽

Sylvie Seeuws ◽

...

Keyword(s):

Leptin Receptor ◽

Serum Insulin ◽

High Energy ◽

Single Chain ◽

Liver Size ◽

Metabolic Switch ◽

Body Fat Content ◽

Fibronectin Type Iii ◽

Energy Consuming ◽

Study Support

The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. Accumulating evidence suggests that leptin plays a role in human pathologies, such as autoimmune diseases and cancer, thus providing a rationale for the development of leptin antagonists. In the present study, we generated and evaluated a panel of neutralizing nanobodies targeting the LR (leptin receptor). A nanobody comprises the variable domain of the naturally occurring single-chain antibodies found in members of the Camelidae family. We identified three classes of neutralizing nanobodies targeting different LR subdomains: i.e. the CRH2 (cytokine receptor homology 2), Ig-like and FNIII (fibronectin type III) domains. Only nanobodies directed against the CRH2 domain inhibited leptin binding. We could show that a nanobody that targets the Ig-like domain potently interfered with leptin-dependent regulation of hypothalamic NPY (neuropeptide Y) expression. As a consequence, daily intraperitoneal injection increased body weight, body fat content, food intake, liver size and serum insulin levels. All of these characteristics resemble the phenotype of leptin and LR-deficient animals. The results of the present study support proposed models of the activated LR complex, and demonstrate that it is possible to block LR signalling without affecting ligand binding. These nanobodies form new tools to study the mechanisms of BBB (blood–brain barrier) leptin transport and the effect of LR inhibition in disease models.

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Nutritional status of older people in long term care settings: current status and future directions

International Journal of Nursing Studies ◽

10.1016/s0020-7489(03)00131-7 ◽

2004 ◽

Vol 41 (3) ◽

pp. 225-237 ◽

Cited By ~ 64

Author(s):

David T. Cowan ◽

Julia D. Roberts ◽

Joanne M. Fitzpatrick ◽

Alison E. While ◽

Julie Baldwin

Keyword(s):

Nutritional Status ◽

Older People ◽

Long Term Care ◽

Current Status ◽

Term Care ◽

Future Directions

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Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China

Frontiers in Oncology ◽

10.3389/fonc.2021.757993 ◽

2021 ◽

Vol 11 ◽

Author(s):

Anwen Xiong ◽

Jiali Wang ◽

Caicun Zhou

Keyword(s):

Lung Cancer ◽

Immune Responses ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Chinese Patients ◽

Current Status ◽

Line Treatment ◽

First Line ◽

Future Directions ◽

First Line Treatment

Lung cancer causes significant morbidity and mortality in China and worldwide. In China, lung cancer accounts for nearly one-fourth of all cancer deaths. Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, accounting for approximately 80%–85% of all lung cancer cases. Immunotherapy with immune checkpoint inhibitors (ICIs) is revolutionizing the treatment of NSCLC. Immune checkpoint molecules, including PD-1/PD-L1 and CTLA-4, can suppress immune responses by delivering negative signals to T cells. By interfering with these immunosuppressive axes, ICIs unleash antitumor immune responses, ultimately eliminating cancer cells. ICIs have demonstrated promising antitumor efficacy in NSCLC, and mounting evidence supports the use of ICIs in treatment-naïve patients with advanced NSCLC. A comprehensive overview of current and emerging ICIs for the first-line treatment of NSCLC in China will facilitate a better understanding of NSCLC immunotherapy using ICIs and optimize the clinical use of ICIs in previously untreated Chinese patients with NSCLC. Herein, we review the efficacy and safety of currently approved and investigational ICIs as the first-line treatment of NSCLC in China. We also discuss the challenges limiting more widespread use of ICIs and future directions in the first-line treatment of NSCLC using ICIs.

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