Biology subjects

Cao, Y.-Q.

Publications and source records attributed to Cao, Y.-Q..

3 recordsLinked to original sources

bioRxiv2026

Low-Dose Interleukin-2 Resolves Stress-Induced Chronic Sensitization Independent of Opioid Receptor Signaling

Stress is a common trigger of headache and widespread somatic pain. Repeated exposure to stress establishes latent sensitization that is tonically suppressed by endogenous inhibitory systems. Using brain-penetrating and peripherally restricted receptor antagonists in a mouse model of repetitive restraint stress, we systematically identified these protective pathways. Peripheral kappa opioid receptors as well as GABA type A and type B (GABAA and GABAB) receptors, alongside central opioid and cannabinoid signaling, actively suppress headache-related facial mechanical hypersensitivity in stressed mice. Blocking any pathway quickly reinstated cephalic allodynia. Peripheral opioid and GABAA receptor signaling also inhibited stress-induced latent sensitization on hindpaw. In contrast, depletion of anti-inflammatory regulatory T (Treg) cells prolonged facial but not hindpaw sensitization, suggesting that Tregs preferentially limit stress-induced chronic headache. Next, we administered low-dose interleukin-2 (LD-IL-2) to stressed mice to preferentially expand and activate Treg cells. Following LD-IL-2 treatment, neither subthreshold pain triggers nor blockade of endogenous inhibitory pathways reinstated cephalic or hindpaw allodynia in either sex, indicating elimination of stress-induced sensitization. Mechanistically, LD-IL-2 acted through Treg cells to recruit multiple peripheral cytokine pathways without engaging endogenous opioid, GABA, or cannabinoid receptor signaling. Notably, LD-IL-2 was more effective than anti-CGRP (calcitonin gene-related peptide) therapy in preventing headache-related chronic sensitization in stressed mice. Collectively, these findings reveal multiple central and peripheral pathways that act concertedly to mask stress-induced latent sensitization and strongly support further evaluation of LD-IL-2 as a novel treatment for stress-induced headache and widespread pain with a distinct mechanism of action.

neuroscience↗

bioRxiv2025

Exploring PBP2a resistance in MRSA by comparison between molecular covalent docking and non-covalent docking

Background and objectivesThe presence of penicillin-binding protein 2a (PBP2a) is the cause of Methicillin-resistant Staphylococcus aureus (MRSA), which is important nosocomial pathogens worldwide and now are also of growing importance in community-acquired infection. The PBP2a resistance depends upon a supplementary peptidoglycan transpeptidase, which continues to function when normal PBPs have been inactivated by beta-lactam antibiotics. Analysis and quantitative study of the molecular interactions of PBP2a against {beta}-lactam antibiotics are required, as they support explaining and enhance understanding of the structure-activity relationship of antibiotic resistance. MethodsBioinformatics and computational methods have been highly effective tools for {beta}-lactams targeting PBPs to tackle the urgent threat of antimicrobial resistance. Regarding {beta}-lactam antibiotics targeting PBP2a and PBPs, we applied different docking programs to illustrate inhibition mode, MM/GBSA to estimate the binding free energies, and molecular dynamic simulation to validate and analyze the molecular interactions. ResultsBased on {beta}-lactam antibiotics targeting PBPs as covalent inhibitors, covalent docking was employed to provide explicit models of PBP2a against susceptible {beta}-lactam antibiotics. The simultaneous use of non-covalent docking enhances our comprehensive comprehension of the resistance of PBP 2a, which resulted from the lack of covalent linked to {beta}-lactam antibiotics. The selected antibiotics strongly interact with PBP2a, revealing the essential amino acid residues and binding affinity for inhibition. MD simulations were performed for the ligand-bound state of PBP-2a to explain their interaction and conformational changes. These findings are also strongly supported by root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF) and Hydrogen bond analysis of the protein-ligand complex. ConclusionsOur research offers extensive knowledge of the PBP2a-lactam interactions for the ability of known antibiotics to combat MRSA. The simulation results indicating stability and accuracy provide valuable insights for the advancement of pharmaceutical interventions against infectious diseases O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/639213v1_ufig1.gif" ALT="Figure 1"> View larger version (88K): org.highwire.dtl.DTLVardef@1dc180forg.highwire.dtl.DTLVardef@afb81borg.highwire.dtl.DTLVardef@6014c4org.highwire.dtl.DTLVardef@1f35113_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure abstract:C_FLOATNO The interaction of Methicillin with PBP2a of MRSA. The protein is shown as a cartoon model, and the covalent binding of the ligand and serine active site is shown as a stick model. C_FIG

bioinformatics↗

bioRxiv2019

TRESK K+ Channel Activity Regulates Trigeminal Nociception and Headache

Although dominant-negative mutations of TRESK background K+ channel have been reported in migraine patients, whether TRESK activity controls the generation of trigeminal pain, especially headache, is not established. We found that loss of TRESK in all trigeminal ganglia (TG) neurons preferentially increased the intrinsic excitability of small-diameter TG nociceptors that express neuropeptide CGRP or TRPM8 channels. Surprisingly, loss of TRESK increased the number of TG neurons expressing TRPV1 channels. In dorsal root ganglia neurons, neither the persistent outward current nor the intrinsic excitability was affected by the loss of TRESK. Compared with wild-type controls, TRESK knockout mice exhibited more robust trigeminal pain, especially headache-like behaviors; but displayed normal body and visceral pain responses. Our findings indicate that endogenous TRESK activity is required for trigeminal pain regulation. A substantial reduction of TRESK activity may selectively affect the functions of TG nociceptors, thereby increasing the susceptibility to migraine headache in humans.

neuroscience↗