The growing demand for new therapeutic strategies in the medical and pharmaceutic fields has resulted in a pressing need for novel druggable targets. Paradoxically, however, the targets of certain drugs that are already widely used in clinical practice have largely not been annotated. Because the pharmacologic effects of a drug can only be appreciated when its interactions with cellular components are clearly delineated, an integrated deconvolution of drug-target interactions for each drug is necessary. The emerging field of chemical proteomics represents a powerful mass spectrometry (MS)-based affinity chromatography approach for identifying proteome-wide small molecule-protein interactions and mapping these interactions to signaling and metabolic pathways. This technique could comprehensively characterize drug targets, profile the toxicity of known drugs, and identify possible off-target activities. With the use of this technique, candidate drug molecules could be optimized, and predictable side effects might consequently be avoided. Herein, we provide a holistic overview of the major chemical proteomic approaches and highlight recent advances in this area as well as its potential applications in drug discovery.
Chromatography, Affinity ; Drug Delivery Systems ; methods ; Drug Design ; Drug Discovery ; methods ; Humans ; Mass Spectrometry ; Proteome ; chemistry ; Proteomics ; methods ; Small Molecule Libraries ; chemistry

Objective:To explore the protective effect and underlying mechanism of hyperbaric oxygen (HBO) on delayed encephalopathy after carbon monoxide poisoning (DEACMP) in mice.Methods:Totally 225 adult male Kunming mice were selected to establish CO poisoning model via intraperitoneal injection carbon monoxide (CO), and were randomly divided into the air control group, CO poisoning group, and HBO group. Each group was further divided into five time points group, that was 1, 3, 7, 14 and 21 d. The mice in the air control group were injected intraperitoneally with the same amount of air, and the HBO group received HBO treatment at the same time every day. DEACMP mice model was screened by behaviors using the open field test, new object recognition test and nesting test, and the content of myelin basic protein (MBP) were assayed. The mouse brain tissue and mitochondrial were prepared and malonialdehyde (MDA) and adenosine triphosphate (ATP) content were measured with ultraviolet spectrophotometer. MBP content in brain tissue and cytochrome C (CytC) content in the mitochondrial were measured by ELISA. The mitochondria membrane potential (MMP) was measured by flow cytometry.Results:Compared with the air control group, the content of carboxyhemoglobin (COHB) in blood increased significantly and the content of MBP in brain tissue decreased significantly in CO poisoning mice. CO poisoning mice showed motor ability and cognitive dysfunction. Compared with the air control group, the contents of MMP, CytC and ATP were significantly decreased ( P<0.01) in the CO poisoning group; while the MDA content was significantly increased ( P<0.01). Compared with the CO poisoning group, mice behaviors were improved significantly ( P<0.05), the content of MBP, MMP, CytC and ATP were increased ( P<0.05), while the MDA content decreased significantly ( P<0.01) in the HBO group. Conclusions:The abnormal mitochondrial function might be closely related to the occurrence and development of DEACMP, and HBO therapy plays an effective role in preventing and treating the DEACMP mice model via the mitochondrial pathway.

Objective To investigate the prognostic value of serum bispecific phosphatase 1(DUSP1)ex-pression level in patients with acute pulmonary thromboembolism(APTE).Methods A total of 112 patients with APTE admitted to the hospital from March 2020 to July 2022 were enrolled as the observation group,and 50 healthy individuals who underwent physical examinations in the hospital during the same period were en-rolled as the control group.The APTE patients were followed up for 6 months after treatment,and were grouped into a good prognosis group(90 cases)and a poor prognosis group(22 cases)based on their progno-sis.The serum DUSP1 relative expression level and pulmonary embolism severity index(PESI)score were compared among the groups before admission.Spearman correlation was applied to analyze the relationship between serum DUSP1 relative expression level and PESI score.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum DUSP1 relative expression level and PESI score on the prognosis of APTE patients.Results Compared with the control group,the serum DUSP1 relative expres-sion level in the observation group was increased(P<0.05).There were statistically significant differences in serum DUSP1 relative expression level and PESI score among patients with different risk levels(P<0.05),the serum DUSP1 relative expression level and PESI score in high-risk APTE patients were higher than those in medium-risk patients(P<0.05),and those in medium-risk patients were higher than those in low-risk pa-tients(P<0.05).Spearman correlation analysis showed that serum DUSP1 relative expression level was posi-tively correlated with PESI score(r=0.561,P<0.05).ROC curve results showed that the area under the curve(AUC)of DUSP1 and PESI score alone for predicting the poor prognosis in APTE patients was 0.789 and 0.867,with sensitivity of 65.8%and 86.8%,specificity of 44.2%and 67.2%,respectively.The AUC of the combination of the two for predicting the poor prognosis in APTE patients was 0.952,with sensitivity and specificity of 92.1%and 75.6%,respectively.Conclusion The serum DUSP1 relative expression level in APTE patients is elevated,and with the aggravation of the disease,the serum DUSP1 relative expression level gradually increases.DUSP1 is an effective indicator for predicting poor prognosis in APTE patients.