Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

Objective To investigate the mechanism of apoptosis induced by acetyl-11-keto-3-boswellic acid(AKBA)in oral squamous cell carcinoma(OSCC)cells.Methods CAL27 were randomly divided into control group(conventional culture),low-dose group(40.00 μmol·L-1 AKBA),middle-dose group(80.00 μmol·L-1 AKBA),high-dose group(120.00 μmol·L-1 AKBA),3-methyladenine(3-MA)group(120.00 μmol·L-1 AKBA+2 mmol·L-1 autophagy inhibitor 3-MA).5-ethynyl-2'-deoxyuridine(Edu)assay was used to detect cell proliferation;Western blot assay was used to detect protein expression;flow cytometry was used to detect apoptosis.Mice were randomly divided into model group(construct OSCC mouse model),AKBA-L group(10.00 mg·kg-1 AKBA after modeling),AKBA-H group(20.00 mg·kg-1 AKBA after modeling),10 animals per group.After 28 days of continuous administration,weight were detected;and the expression of related proteins were detected by Western blot assay.Results The Edu positive cell rates in control group,high-dose group were(40.18±2.53)％,(12.08±0.93)％,respectively;the protein levels of autophagy associated microtubule associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ in control group,high-dose group and 3-MA group were 0.33±0.05,2.93±0.39,0.56±0.07,respectively;phosphorylated adenylate activated protein kinase catalytic subunit alpha subunit 1(p-PRKAA1)protein levels were 0.34±0.04,1.03±0.07,0.99±0.09,respectively;the apoptosis rates were(4.65±0.39)％,(25.75±2.29)％,(14.92±1.49)％,respectively.The above indexes in hige-dose group were significantly different from those in the control group(all P＜0.05).The above indexes in 3-MA group were significantly different from those in high-dose group(all P＜0.05).The tumor weight of model group,AKBA-L group and AKBA-H group were(0.96±0.08),(0.55±0.06),(0.43±0.05)g,respectively;the protein levels of LC3 Ⅱ/LC3 Ⅰ were 0.47±0.09,0.94±0.21 and 1.69±0.34,respectively.The above indexes in AKBA-L group and AKBA-H group were significantly different from those in model group(all P＜0.05).Conclusion AKBA can induce cytotoxic autophagy related apoptosis and inhibit CAL27 cell proliferation,which may be related to activation of AMPK signal.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

A quartz crystal microbalance(QCM)-systematic evolution of ligands by the exponential en-richment(SELEX)technique was developed to screen out aptamers with high affinity for arsenic(Ⅲ).A random single strand DNA library was designed and fixed on the mercaptoethylamine-modified crystal plate with arsenic(Ⅲ)as the target,and the free aptamer was captured in the solution,and the QCM-SELEX screening method was constructed.After 6 rounds of screening,the secondary library was se-quenced with high throughput method,and the 6S1 dissociation coefficient Kd value was 0.36 μmol/L based on QCM resonance frequency.Using 6S1 as a probe,the QCM biosensor was constructed for the detection of arsenic(Ⅲ).The sensor has a good linear relationship in the range of 0.01 μmol/L～0.2μmol/L,and the detection limit of arsenic(Ⅲ)is 5.2 nmol/L(3σ),indicatinggood selectivity.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

An open reading frame (ORF) of isopentenyl-diphosphate delta isomerase gene (FuIPI) was cloned from Fritillaria unibracteata Hsiao et K. C. Hsia. (F. unibracteata). Furthermore, the bioinformatics and functional analyses of FuIPI were performed in this study. The result showed that, the ORF of FuIPI gene was 825 bp, encoding a polypeptide of 274 amino acids in length, with a relative molecular mass of about 31 kD and a theoretical isoelectric point of 5.61. Sequence analysis showed that FuIPI contained conserved structural domains and key residues involved in the catalyzing process. The phylogenetic analysis exhibited that FuIPI was closely related to IPIs of Dendrobium officinale and Musa acuminate. Real-time PCR analysis showed that FuIPI was distributed in different tissues of F. unibracteata, but had the highest transcriptional level in leaves, followed by stems, bulbs, and flowers. Furthermore, the FuIPI protein was successfully expressed in Escherichia coli BL21(DE3). The purified FuIPI protein successfully catalyzed the conversion from isopentenyl diphosphate (IPP) to dimethylallyl pyrophosphate (DMAPP). The above results provided a theoretical basis for further investigation of the molecular role of FuIPI in the biosynthesis of alkaloids.

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.
Humans ; Male ; Adult ; Female ; Xanthomatosis, Cerebrotendinous/pathology* ; Pedigree ; Cholestanetriol 26-Monooxygenase/genetics* ; Mutation ; Ataxia

With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.
Humans ; Glucose ; Lipid Metabolism ; Molecular Docking Simulation ; Drugs, Chinese Herbal/pharmacology* ; Ginsenosides ; Proteins ; Saponins ; RNA, Messenger

Aim To investigate the effect of Sijunzi Decoction on mRNA and protein expression related to growth and cell cycle in polyamine/HuR signaling pathway during small intestinal epithelial cell (IEC-6) proliferation, and to explore its mechanism on intestinal mucosal injury repair. Methods Sijunzi Decoction-containing serum (SJZD) was prepared from SD rats, the expression of HuR protein in cytoplasm and nucleus was analyzed by immunofluorescence and Western blot, the mRNA level of activating transcription factor-2 (A T F - 2), JunD and cyclin dependent kinase 4 (CDK4) were determined by real-time fluorescent quantitative PCR (RT-PCR), Western blot was used to detect protein level of HuR, ATF-2, JunD and CDK4, and flow cytometry was applied to analyse cell cycle distribution. Results Compared with the control group, the mRNA and protein expression of ATF-2 and JunD decreased, while the expression of Cdk4 mRNA and protein increased in SZJD group, and the proportion of G