Trace Amine-Associated Receptor 1 as a Target for the Development of New Antipsychotics: Current Status of Research and Future Directions

AbstractHuman papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to 38%–80% of head and neck squamous cell carcinoma (HNSCC) in oropharyngeal location (OPSCC) and nearly all cervical cancers contain the HPV genome which is implicated in causing cancer through its oncoproteins E6 and E7. Given by the biologically distinct HPV-related OPSCC and a more favorable prognosis compared to HPV-negative tumors, clinical trials on de-escalation treatment strategies for these patients have been studied. It is therefore raised the questions for the patient stratification if treatment de-escalation is feasible. Moreover, understanding the crosstalk of HPV-mediated malignancy and immunity with clinical insights from the proportional response rate to immune checkpoint blockade treatments in patients with HNSCC is of importance to substantially improve the treatment efficacy. This review discusses the biology of HPV-related HNSCC as well as successful clinically findings with promising candidates in the pipeline for future directions. With the advent of various sequencing technologies, further biomolecules associated with HPV-related HNSCC progression are currently being identified to be used as potential biomarkers or targets for clinical decisions throughout the continuum of cancer care.

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Understanding and assessing flood risk in Vietnam: Current status, persisting gaps, and future directions

Journal of Flood Risk Management ◽

10.1111/jfr3.12689 ◽

2021 ◽

Author(s):

Minh Tu Nguyen ◽

Zita Sebesvari ◽

Maxime Souvignet ◽

Felix Bachofer ◽

Andreas Braun ◽

...

Keyword(s):

Flood Risk ◽

Current Status ◽

Future Directions

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Biased ligands at opioid receptors: Current status and future directions

Science Signaling ◽

10.1126/scisignal.aav0320 ◽

2021 ◽

Vol 14 (677) ◽

pp. eaav0320

Author(s):

Tao Che ◽

Hemlata Dwivedi-Agnihotri ◽

Arun K. Shukla ◽

Bryan L. Roth

Keyword(s):

Opioid Receptors ◽

Current Status ◽

Functional Responses ◽

Future Directions ◽

Health Crisis ◽

Biased Agonism ◽

Opioid Ligands ◽

Therapeutic Benefits ◽

Ligand Discovery ◽

Opioid Medications

The opioid crisis represents a major worldwide public health crisis that has accelerated the search for safer and more effective opioids. Over the past few years, the identification of biased opioid ligands capable of eliciting selective functional responses has provided an alternative avenue to develop novel therapeutics without the side effects of current opioid medications. However, whether biased agonism or other pharmacological properties, such as partial agonism (or low efficacy), account for the therapeutic benefits remains questionable. Here, we provide a summary of the current status of biased opioid ligands that target the μ- and κ-opioid receptors and highlight advances in preclinical and clinical trials of some of these ligands. We also discuss an example of structure-based biased ligand discovery at the μ-opioid receptor, an approach that could revolutionize drug discovery at opioid and other receptors. Last, we briefly discuss caveats and future directions for this important area of research.

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Necrotizing enterocolitis and the microbiome: Current status and future directions

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa604 ◽

2020 ◽

Author(s):

Robert Thänert ◽

Eric C Keen ◽

Gautam Dantas ◽

Barbara B Warner ◽

Phillip I Tarr

Keyword(s):

Risk Factors ◽

Preterm Infant ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Clinical Characteristics ◽

Gastrointestinal Disorder ◽

Current Status ◽

Future Directions ◽

Barrier Integrity ◽

Microbial Dysbiosis

Abstract Decades of research have failed to define the pathophysiology of necrotizing enterocolitis (NEC), a devastating pediatric gastrointestinal disorder of preterm infants. However, recent evidence suggests that host-microbiota interactions, in which microbial dysbiosis is followed by loss of barrier integrity, inflammation, and necrosis, are central to NEC development. Thus, greater knowledge of the preterm infant microbiome could accelerate attempts to diagnose, treat, and prevent NEC. Here, we summarize clinical characteristics of and risk factors for NEC, the structure of the pre-event NEC microbiome, how this community interfaces with host immunology, and microbiome-based approaches that might prevent or lessen the severity of NEC in this very vulnerable population.

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