1.Novel benzothiazole derivatives target the Gac/Rsm two-component system as antibacterial synergists against Pseudomonas aeruginosa infections.
Jun LIU ; Wenfu WU ; Jiayi HU ; Siyu ZHAO ; Yiqun CHANG ; Qiuxian CHEN ; Yujie LI ; Jie TANG ; Zhenmeng ZHANG ; Xiao WU ; Shumeng JIAO ; Haichuan XIAO ; Qiang ZHANG ; Jiarui DU ; Jianfu ZHAO ; Kaihe YE ; Meiyan HUANG ; Jun XU ; Haibo ZHOU ; Junxia ZHENG ; Pinghua SUN
Acta Pharmaceutica Sinica B 2024;14(11):4934-4961
The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC50 = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.
2.Early weight-bearing walking with inflatable boots after repair of acute Achilles tendon rupture based on the concept of rapid rehabilitation
Wenfu YANG ; Xuejun WU ; Jingui LIN ; Yongliang YOU ; Shibei LIN
Chinese Journal of Orthopaedic Trauma 2023;25(7):589-594
Objective:To evaluate early weight-bearing walking with inflatable boots after repair of acute Achilles tendon rupture based on the concept of rapid rehabilitation.Methods:A retrospective study was conducted to analyze the data of 69 patients with acute Achilles tendon rupture who had been treated at Department of Orthopaedics, The Second Fuzhou Hospital Affiliated to Xiamen University from April 2020 to July 2021. There were 56 males and 13 females with a mean age of 37.0(31.0, 47.0) years and a body mass index of (23.7±2.6) kg/m 2. There were 55 cases of closed injury and 14 cases of open injury; 62 cases had simple Achilles tendon injury and 7 cases were complicated with neurovascular tendon injury. The patients were divided into 2 groups according to their rehabilitation methods. The treatment group of 23 cases was subjected to weight-bearing walking with inflatable boots early after repair while the control group of 46 cases to traditional plaster bracket fixation for 4 weeks before weight-bearing walking with inflatable boots. The 2 groups were compared in terms of hospitalization time, wound infection rate, return to sports time, single heel lifting time, Achilles tendon re-rupture rate, Victorian Institute of Sports Assessment (VISA-A), Achilles tendon total rupture score (ATRS), and American Orthopaedic Foot & Ankle Society ankle-hindfoot score (AOFAS-AH). Results:There was no statistically significant difference in the comparison of preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for 11 (10, 11) months after surgery. In the treatment group, the hospitalization time [4 (3, 5) days] and single heel lifting time [(12.5±1.4) weeks] were significantly shorter than those in the control group [6 (5, 9) days and (17.0±1.5) weeks], the return to sports time [21 (20, 22) months] was significantly earlier than that in the control group [23 (22, 24) months], and the VISA-A score [(89.4±1.3) points] was significantly higher than that in the control group [(78.5±1.7) points] ( P<0.05). There was no statistically significant difference in the wound infection rate between the 2 groups ( P>0.05). At 3 and 6 months after surgery, respectively, the treatment group had significantly higher ATRS scores [(85.5±1.4) and (89.0±1.6) points] and AOFAS ankle-hindfoot scores [(89.0±1.7) and (92.0±1.5) points] than the control group [(79.3±1.8) and (87.0±1.3) points; (80.2±1.9) and (88.4±1.9) points] (all P<0.05). In all patients, the AOFAS ankle-hindfoot score at 6 months postoperatively was significantly higher than that at 3 months postoperatively ( P<0.05). Achilles tendon re-rupture occurred in none of the patients. Conclusion:After repair of acute Achilles tendon rupture, compared with traditional plaster bracket fixation, early weight-bearing walking with inflatable boots can lead to better short-term clinical outcomes to enhance recovery after surgery without increasing the rate of open wound infection or re-rupture.
3.Emodin attenuates severe acute pancreatitis-associated acute lung injury by suppressing pancreatic exosome-mediated alveolar macrophage activation.
Qian HU ; Jiaqi YAO ; Xiajia WU ; Juan LI ; Guixiang LI ; Wenfu TANG ; Jingping LIU ; Meihua WAN
Acta Pharmaceutica Sinica B 2022;12(10):3986-4003
Severe acute pancreatitis-associated acute lung injury (SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI; however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely, emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury, and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.
4.The diagnosis applying effects of ocular vestibular evoked myogenic potentials in BBPV disease.
Baocai LU ; Wenfu YU ; Zhiyan WU ; Rong LIAN ; Zhenmin LU ; Jianbin YANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2015;29(14):1256-1259
OBJECTIVE:
To investigate the diagnosis applying effects of ocular vestibular evoked myogenic potentials(oVEMP) in peripheral BPPV disease.
METHOD:
During September 2012 to January 2015, we selected 80 healthy people in our hospital medical center as the control group, choose the same period of primary benign paroxysmal positional vertigo as the observation group of 80 patients. Two groups were carried out fully functional auditory evoked potential analysis, determination of oVEMP and cervical vestibular evoked myogenic potentials (cVEMP) anomaly amplitude threshold, P1 latencies, N1 incubation period.
RESULT:
The cVEMP abnormal rate in the observation group was 28.8%, the oVEMP abnormal rate was 38.8%, while cVEMP and oVEMP abnormal rates in the control group was 1.3% and 2.5% respectively that compared to significant differences between the two groups (P < 0.05). The oVEMP test amplitude in the observation group was (5.98 ± 2.15) µv, the N1 incubation period was (10.03 ± 0.76)ms, while the control group were (4.09 ± 2.11)µv and (11.67 ± 0.78) ms that compared difference were statistically significant (P < 0.05). The cVEMP test amplitude in the observation group was (154.8 ± 43.9)2 µv, while the control group was (180.49 ± 45.34)µv, compared the difference was statistically significant (P < 0.05).
CONCLUSION
Paroxysmal positional vertigo patients ocular vestibular evoked myogenic potentials abnormal rate is relatively high, the utricle dysfunction for more severe than the balloon can be the subject of an objective function of the ear stone judgment, judgment in favor of the disease.
Benign Paroxysmal Positional Vertigo
;
diagnosis
;
Case-Control Studies
;
Humans
;
Saccule and Utricle
;
physiopathology
;
Vestibular Evoked Myogenic Potentials
5.Lung cancer risk associated with genetic polymorphism in myeloperoxidase (-463 G/A) in a Chinese population.
Wenfu LU ; Jun QI ; Deyin XING ; Wen TAN ; Xiaoping MIAO ; Wei SU ; Min WU ; Dongxin LIN
Chinese Journal of Oncology 2002;24(3):250-253
OBJECTIVETo examine the relationship between susceptibility to lung cancer among Chinese and genetic polymorphism at nucleotide -463 (G/A) in myeloperoxidase (MPO), an enzyme found in lysosomes of phagocytes and involved in the formation of hydroxyl radicals and activation of various smoking-related carcinogens.
METHODSThe association of this polymorphism with lung cancer in a hospital-based case-control study of 314 patients and 320 age- and sex-matched controls was tested. The MPO genotypes were determined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP).
RESULTSThe allele frequency for MPO-463A was found to be 11.0% for controls, compared with 15.0% for patients. Multivariate analysis showed an increased risk for overall lung cancer in subjects having GG genotype (OR, 1.7; 95% CI, 1.2 - 2.5), however, the elevated risk was limited to squamous cell carcinoma (OR, 2.4; 95% CI, 1.4 - 3.9; n = 177) but not to adenocarcinoma (OR, 1.3; 95% CI, 0.8 - 2.1; n = 137). In addition, the risky effect of the GG genotype on squamous cell carcinoma of the lung was evident only in the smokers and those who smoked >/= 26 pack-years (OR, 20.5; 95% CI, 5.6 - 75.3) as compared with GA and AA genotypes (OR, 6.2; 95% CI, 1.7 - 22.5) but not in the nonsmokers or those who smoked < 26 pack-years.
CONCLUSIONOur data support the hypothesis that -463A polymorphism in the MPO gene may reduce the susceptibility to lung cancer in the Chinese.
Asian Continental Ancestry Group ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms ; genetics ; Male ; Middle Aged ; Peroxidase ; genetics ; Point Mutation ; Polymorphism, Genetic ; Risk Factors

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