OBJECTIVE To investigate the intervention effect of kushenol F （KSC-F） on ulcerative colitis （UC） mice. METHODS Totally 30 male C57BL/6J mice were randomly divided into the normal group， model group， positive drug group （sulfasalazine， 703 mg/kg）， KSC-F 50 mg/kg group （KSC-F50 group）， and KSC-F 100 mg/kg group （KSC-F100 group）， with 6 mice in each group. Except for the normal group， the mice in the remaining groups were given 3% dextran sulfate sodium solution continuously for 7 days to induce UC model. Concurrently， administration groups received corresponding drug solution intragastrically， once a day， for 10 consecutive days. During the experiment， the changes in body weight and bowel movements of the mice were observed. Disease activity index scoring was performed after the last administration. The histopathological morphology of colonic tissue was examined. The levels of inflammatory factors in the serum and colon tissue were measured. Additionally， the mRNA expression of inflammatory factors， and the protein expressions of inflammation-related proteins [interleukin-1β （IL-1β）， forkhead box O1（FOXO1）， phosphoinositide 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， p38 mitogen-activated protein kinase（p38 MAPK）， phosphorylated p38 MAPK（p-p38 MPAK） and phosphorylated protein kinase B（p- Akt）] were determined in colonic tissue. RESULTS KSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC- F reduced the levels of IL-1β， IL-6， IL-8 and tumor necrosis factor-α （TNF-α） in serum， as well as IL-1β， IL-6， IL-17 and TNF- α in colonic tissue to varying degrees and increased the levels of IL-10 in both serum and colonic tissue （P＜0.05 or P＜0.01）. Moreover， KSC-F decreased the expression levels of IL-1β， IL-17 and TNF-α mRNA， as well as p-PI3K， p-p38 MAPK， and p- Akt proteins in colonic tissue to varying degrees， and increased the expression levels of IL-10 mRNA and FOXO1 protein in colonic tissue （P＜0.05 or P＜0.01）. CONCLUSIONS KSC-F effectively alleviates UC symptoms in mice by inhibiting PI3K， Akt and p38 MAPK activation， mitigating the release of pro-inflammatory factors such as IL-1β， IL-6， TNF- α，promoting the anti-inflammatory factor IL-10 secretion， and reducing inflammation-induced colonic tissue damage.

Objective:To investigate the etiological characteristics of hand, foot and mouth disease (HFMD) and the VP1 gene evolution of coxsackievirus A6 (CVA6) in Qingdao from 2020 to 2022.Methods:Total enterovirus (EV), enterovirus 71 (EV71), coxsackievirus A16 (CVA16), CVA6 and coxsackievirus A10 (CVA10) were detected by fluorescent RT-PCR in throat swab samples from HFMD patients in Qingdao from 2020 to 2022. The full-length sequence amplification of VP1 gene and gene sequence determination of CVA6 isolates were performed, and the phylogenetic and molecular characteristics were analyzed by MEGA-X software.Results:The overall positive rate of enteroviruses in 1 645 samples collected during 2020-2021 was 80.73%(1 328/1 645). The proportions of EV71, CVA16, CVA6, CVA10 and other enteroviruses were 0.08%(1/1 328), 19.65%(261/1 328), 68.15%(905/1 328), 0.98%(13/1 328) and 11.14%(148/1 328), respectively. Children under 5 years old accounted for 75.68% (1 245/1 645) of all cases and 100% (2/2) of severe cases. A phylogenetic tree was constructed based on the VP1 region sequences of 45 CVA6 strains showing all strains belonging to the D3a subtype. There were 10 non-synonymous mutations of amino acids in the VP1 protein by gene evolution analysis.Conclusions:CVA6 D3a subtype is the main epidemic strain causing HFMD in Qingdao from 2020 to 2022, especially in children under 5 years old.

Triterpenoid saponins are widely used in medicine, health cares, cosmetics, food additives and agriculture because of their unique chemical properties and rich pharmacological activities. UDP-dependent glycosyltransferases (UGTs) are the key enzymes involved in triterpenoid saponin biosynthesis, and play important roles in the diversity of triterpenoid saponin structures and pharmacological activities. This review summarized the UGTs involved in plant triterpenoid saponin biosynthesis based on the sources of UGTs and the types of receptors. Moreover, the application of UGTs in heterologous biosynthesis of triterpenoid saponins based on synthetic biology was also discussed.
Glycosyltransferases/genetics* ; Plants ; Saponins/chemistry* ; Triterpenes

Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from Panax ginseng, enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-O-Glc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titers of F2 and 3β,20S-Di-O-Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-Glc-DM was even better. Furthermore, the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM, and achieving their de novo biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass, which lays a foundation for drug research and development.

Objective:To investigate the changes of serum catecholamines (CST) and oxidative stress index in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) with hypertension and the correlation with blood pressure.Methods:Total of 100 OSAHS patients admitted to Jingmen No.1 People′s Hospital from February 2018 to August 2020 were selected. According to whether patients combined with hypertension, they were divided into OSAHS group (54 cases) and OSAHS combined with hypertension group (46 cases). The changes of serum CST and oxidative stress index in the two groups were compared and analyzed the correlation of blood pressure and CST and oxidative stress index.Results:The level of myeloperoxidase(MPO) in the OSAHS combined with hypertension group was higher than that in the OSAHS group: (41.67 ± 3.02) U/L vs. (39.11 ± 2.65) U/L; the levels of catalase (CAT) and CST in the OSAHS combined with hypertension group were higher than those in the OSAHS group: (11.47 ± 2.54) kU/L vs. (15.88 ± 2.31) kU/L, (23.63 ± 4.38) ng/L vs. (28.61 ± 5.42) ng/L, there were statistically differences ( P<0.05). The levels of respiratory disturbance index, lowest oxygen saturation, triacylglycerol, total cholesterol, low density lipoprotein cholesterin, high density lipoproteincholesterol, epinephrine, noradrenaline in the two groups had no significant differences ( P>0.05). Spearman correlation analysis showed that the systolic pressure and diastolic pressure had positive correlation with MPO ( P<0.05), and had negative correlation with CAT and CST ( P<0.05). Conclusions:The serum CST and CAT are down-regulated in patients with OSAHS with hypertension, and serum MPO is up-regulated. Oxidative stress may be related to OSAHS with hypertension.

There are direct and indirect interactions between gut microbiota and host immune response, which can have a multifaceted impact on host health. Dysbiosis caused by disturbances in the gut microbiota is associated with susceptibility to many diseases, especially immune-related diseases. Based on the research results in recent years, this paper introduced the mechanism of the interaction between gut microbiota and host immunity, and expounded the role of gut microbiota in the occurrence and development of immune-related diseases, including intestinal system diseases such as inflammatory bowel disease and other systemic diseases such as rheumatoid arthritis, and summarized disease treatment strategies targeting gut microbiota. A better understanding of the research progress of gut microbiota and immune-related diseases will help us in the prevention and management of such diseases, and broaden our path to discover disease intervention targets.
Gastrointestinal Microbiome/physiology* ; Humans ; Inflammatory Bowel Diseases ; Intestines

Objective:To investigate the whole genome characteristics of coxsackievirus A4 (CVA4) circulating in Qingdao city.Methods:Four CVA4 isolates circulating in Qingdao city during 2013 to 2015 were selected. Whole genome sequences of these strains were amplified by one-step reverse transcription-polymerase chain reaction (RT-PCR). Sequence alignment and phylogenetic analysis were performed using MEGA7.0 software package. Genetic recombination analysis was performed using similarity plots 3.5.1 software package.Results:Phylogenetic analysis showed that based on the sequences of the whole genome and P1, P2 and P3 regions, HS312/QD/CHN/2013 and HS605/QD/CHN/2014 strains together with the early domestic isolates belonged to the same clade, while FY218/QD/CHN/2015 strain and CV-A4/P1033/2013/China strain collected in Wenzhou in 2013 formed another clade in each phylogenetic tree. HS144/QD/CHN/2014 strain belonged to the same clade as HS312/QD/CHN/2014, HS605/QD/CHN/2014 and the early domestic CVA4 isolates in the phylogenetic tree based on the P1 region, but formed a separate clade in the phylogenetic trees based on the whole genome, P2 region and P3 region. Genetic recombination analysis revealed that there was genetic recombination between HS144/QD/CHN/2014 strain and the CVA2 strain of CV-A2/P373/2013/China isolated in mainland China in 2013 in the region of 2C-3D (5 081-7 301); FY218/QD/CHN/2015 and CV-A4/P1033/2013/China strains were highly homologous and recombination signal sequences were detected in the region of 2A-2B (3 821-4 161) between the two strains and the CVA2 strain of CV-A2/P373/2013/China.Conclusions:The CVA4 isolates circulating in Qingdao city presented obvious genetic diversity at the genome-wide level.

Objective To investigate the effect of sarcopenia on the efficacy of percutaneous kyphoplasty(PKP)in the treatment of osteoporotic spinal compression fracture(OSCF)in elderly patients. Methods From February 2017 to June 2018,a total of 77 elderly patients who met the inclusion and exclusion criteria were included in this study.Grip strength of dominant hand was measured by an electronic grip dynamometer with cut-off values of 27 kg for males and 16 kg for females.The cross-sectional area of the pedicle level muscle of the 12th thoracic vertebra(T12)was measured by chest CT.The skeletal muscle index(SMI)was calculated by dividing the T12 pedicle level muscle cross-sectional area by the square of body height.The SMI cut-off value used to diagnose sarcopenia was 42.6 cm
Aged ; Female ; Fractures, Compression/surgery* ; Humans ; Kyphoplasty ; Male ; Osteoporotic Fractures/surgery* ; Retrospective Studies ; Sarcopenia/complications* ; Spinal Fractures ; Treatment Outcome

Medicinal natural products derived from plants are usually of low content and difficult to extract and isolate. Moreover, these compounds are structurally complex, making it difficult to obtain them by environmental unfriendly chemical synthesis. Biosynthesis of medicinal natural products through synthetic biology is a novel, environment-friendly and sustainable approach. Taking terpenoids (ginsenosides, paclitaxel, artemisinin, tanshinones), alkaloids (vincristine and morphine), and flavonoids (breviscapine) as examples, this review summarizes the advances of the biosynthetic pathways and synthetic biology strategies of plant-derived medicinal natural products. Moreover, we introduce the key technologies and methods of synthetic biology used in the research of medicinal natural products, and provide future prospects in this area.
Biological Products ; Biosynthetic Pathways ; Plants ; Synthetic Biology ; Terpenes

Cadinanes are a class of bicyclic sesquiterpenes with complex stereochemistry and broad pharmacological activities, such as antibacterial, anti-inflammatory, and hypoglycemic activities. To date, structurally diverse and bioactive cadinane sesquiterpenes have been isolated and identified from a variety of plants and microorganisms. Moreover, deeper understandings on cadinane sesquiterpene synthases have been made. This article categorized the 124 new cadinanes which were published in the literatures in the past four years (2017-2020) into five structural types, and presented their pharmacological activities. We also illustrated the elucidation of the biosynthetic pathways for typical cadinanes, summarized the research progress on cadinane sesquiterpene synthases. Finally, current challenges and future prospects were proposed and discussed.
Anti-Inflammatory Agents ; Polycyclic Sesquiterpenes ; Sesquiterpenes