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1.
Int Wound J ; 21(4): e14884, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38654483

ABSTRACT

Mechanical bowel preparation (MBP), a routine nursing procedure before paediatric bowel surgery, is widely should in clinical practice, but its necessity remains controversial. In a systematic review and meta-analysis, we evaluated the effect of preoperative MBP in paediatric bowel surgery on postoperative wound-related complications in order to analyse the clinical application value of MBP in paediatric bowel surgery. As of November 2023, we searched four online databases: the Cochrane Library, Embase, PubMed, and Web of Science. Two investigators screened the collected studies against inclusion and exclusion criteria, and ROBINS-I was used to evaluate the quality of studies. Using RevMan5.3, a meta-analysis of the collected data was performed, and a fixed-effect model or a random-effect model was used to analyse OR, 95% CI, SMD, and MD. A total of 11 studies with 2556 patients were included. Most of studies had moderate-to-severe quality bias. The results of meta-analysis showed no statistically significant difference in the incidence of complications related to postoperative infections in children with MBP before bowel surgery versus those with No MBP, wound infection (OR 1.11, 95% CI:0.76 ~ 1.61, p = 0.59, I2 = 5%), intra-abdominal infection (OR 1.26, 95% CI:0.58 ~ 2.77, p = 0.56, I2 = 9%). There was no significant difference in the risk of postoperative bowel anastomotic leak (OR 1.07, 95% CI:0.68 ~ 1.68, p = 0.78, I2 = 12%), and anastomotic dehiscence (OR 1.67, 95% CI:0.13 ~ 22.20, p = 0.70, I2 = 73%). Patients' intestinal obstruction did not show an advantage of undergoing MBP preoperatively, with an incidence of intestinal obstruction (OR 1.95, 95% CI:0.55 ~ 6.93, p = 0.30, I2 = 0%). Based on existing evidence that preoperative MBP in paediatric bowel surgery did not reduce the risk of postoperative wound complications, we cautiously assume that MBP before surgery is unnecessary for children undergoing elective bowel surgery. However, due to the limited number of study participants selected for this study and the overall low quality of evidence, the results need to be interpreted with caution. It is suggested that more high quality, large-sample, multicenter clinical trials are required to validate our findings.


Subject(s)
Preoperative Care , Surgical Wound Infection , Humans , Preoperative Care/methods , Child , Surgical Wound Infection/prevention & control , Surgical Wound Infection/epidemiology , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Child, Preschool , Adolescent , Male , Female , Infant , Digestive System Surgical Procedures/adverse effects , Digestive System Surgical Procedures/methods , Cathartics/therapeutic use
2.
Biogerontology ; 24(1): 99-110, 2023 02.
Article in English | MEDLINE | ID: mdl-36463389

ABSTRACT

Endothelial aging is a sign of vascular aging that predisposes patients to vascular disease. We explored the effects of IL-17A on endothelial cell aging and determined the potential underlying mechanisms. In human umbilical vein endothelial cells, IL-17A promoted senescence, evidenced as increased positive staining of senescence-associated ß-galactosidase, increased proportion of cells arrested at G0/G1 stage, and upregulated p21 and p16 expression. IL-17A increased the expression of the m6A methylase FTO. We then investigated the relationship between FTO and endothelial cell aging. After interfering with FTO expression by siRNA, we observed that FTO induced endothelial cell aging. An increase in the expression of p-Jun N-terminal kinases (JNK) increased after IL-17A treatment indicated, that the JNK signaling pathway affected FTO expression. Moreover, the addition of the JNK signaling pathway inhibitor SP600125 blocked the effect of IL-17A on FTO expression. In conclusion, our findings revealed that IL-17A can promote endothelial cell aging by activating the JNK signaling pathway and upregulating FTO expression. This discovery can help in the identification of new therapeutic targets against endothelial cell aging and related vascular complications.


Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Interleukin-17 , MAP Kinase Signaling System , Humans , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Cellular Senescence , Human Umbilical Vein Endothelial Cells , Interleukin-17/metabolism , Interleukin-17/pharmacology
3.
Mar Drugs ; 21(6)2023 May 26.
Article in English | MEDLINE | ID: mdl-37367652

ABSTRACT

To discover bioactive natural products from mangrove sediment-derived microbes, a chemical investigation of the two Beibu Gulf-derived fungi strains, Talaromyces sp. SCSIO 41050 and Penicillium sp. SCSIO 41411, led to the isolation of 23 natural products. Five of them were identified as new ones, including two polyketide derivatives with unusual acid anhydride moieties named cordyanhydride A ethyl ester (1) and maleicanhydridane (4), and three hydroxyphenylacetic acid derivatives named stachylines H-J (10-12). Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses, while the absolute configurations were established by theoretical electronic circular dichroism (ECD) calculation. A variety of bioactive screens revealed three polyketide derivatives (1-3) with obvious antifungal activities, and 4 displayed moderate cytotoxicity against cell lines A549 and WPMY-1. Compounds 1 and 6 at 10 µM exhibited obvious inhibition against phosphodiesterase 4 (PDE4) with inhibitory ratios of 49.7% and 39.6%, respectively, while 5, 10, and 11 showed the potential of inhibiting acetylcholinesterase (AChE) by an enzyme activity test, as well as in silico docking analysis.


Subject(s)
Polyketides , Polyketides/chemistry , Benzene Derivatives , Acetylcholinesterase/metabolism , Circular Dichroism , Fungi/metabolism , Molecular Structure
4.
Int J Mol Sci ; 24(17)2023 Aug 22.
Article in English | MEDLINE | ID: mdl-37685881

ABSTRACT

Highly virulent Streptococcus suis (S. suis) infections can cause Streptococcal toxic shock-like syndrome (STSLS) in pigs and humans, in which an excessive inflammatory response causes severe damage. Hemolysin (SLY) is a major virulence factor of S. suis serotype 2 that produces pores in the target cell membrane, leading to cytoplasmic K+ efflux and activation of the NLRP3 inflammasome, ultimately causing STSLS. The critical aspect of hemolysin in the pathogenesis of S. suis type 2 makes it an attractive target for the development of innovative anti-virulence drugs. Here, we use the S. suis toxin protein (SLY) as a target for virtual screening. A compound called canagliflozin, a hypoglycemic agent, was identified through screening. Canagliflozin significantly inhibits the hemolytic activity of hemolysin. The results combined with molecular dynamics simulation, surface plasmon resonance, and nano differential scanning fluorimetry show that canagliflozin inhibits the hemolytic activity of SLY by binding to SLY. In addition, canagliflozin markedly reduced the release of SC19-induced inflammatory factors at the cellular level and in mice. Importantly, the combination of canagliflozin and ampicillin had a 90% success rate in mice, significantly greater than the therapeutic effect of ampicillin. The findings suggest that canagliflozin may be a promising new drug candidate for S. suis infections.


Subject(s)
Streptococcal Infections , Streptococcus suis , Humans , Animals , Mice , Swine , Hemolysin Proteins , Canagliflozin , Ampicillin , Biological Transport , Streptococcal Infections/drug therapy
5.
Molecules ; 28(2)2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36677936

ABSTRACT

Pseudorabies virus (PRV) is a pathogen that causes Aujeszky's disease (AD) in animals, leading to huge economic losses to swine farms. In order to discover anti-PRV compounds, we studied the extracts of the strain Streptomyces jiujiangensis NBERC-24992, which showed significant anti-PRV activity. Eight benzoheterocyclic secondary metabolites, including three new compounds (1-3, virantmycins D-G) and five known compounds (4-8, virantmycin, A-503451 D, A-503451 D acetylate, A-503451 A, and A-503451 B), were isolated from the broth of NBERC-24992. The structures of the new compounds were identified by using extensive spectroscopic data, including mass spectrometry (MS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD). Compound 1 was found to be a novel heterocyclic compound with a tricyclic skeleton from natural product. All compounds were tested for antiviral activity, and 4 (virantmycin) showed an excellent effect against PRV and was better than ribavirin and acyclovir. Our study revealed that chlorine atom and tetrahydroquinoline skeleton were important active moiety for antiviral activity. Virantmycin could be a suitable leading compound for an antiviral drug against PRV.


Subject(s)
Herpesvirus 1, Suid , Pseudorabies , Streptomyces , Swine , Animals , Antiviral Agents/therapeutic use , Pseudorabies/drug therapy , Streptomyces/metabolism
6.
Molecules ; 28(2)2023 Jan 08.
Article in English | MEDLINE | ID: mdl-36677698

ABSTRACT

Two new napyradiomycins derivatives, napyradiomycin A4 (1) and A80915 H (2), along with five known ones, were isolated from the ethyl acetate extract of fermentation culture of Streptomyces kebangsaanensis WS-68302. Their structures were elucidated by extensive spectroscopic analysis, including HR-MS, 1D and 2D NMR, CD spectrum, as well as comparison with literature data. Compound 1 exhibited significant antiviral activity against PRV (Pseudorabies virus) with an IC50 value of 2.056 µM and therapeutic ratio at 14.98, suggesting that it might have potential for development of an antiviral agent. Moreover, compound 1 displayed the strongest inhibition against PRV protein among the tested napyradiomycins in the indirect immunofuorescence assay. Compounds 3 and 4 showed higher activities against swine pathogenic Streptococcus suis than the positive control penicillin G sodium salt, with MIC values of 3.125 and 6.25 µg/mL, respectively. Compounds 1 and 3-6 exhibited moderate antibacterial activity against the swine pathogenic Erysipelothrix rhusiopathiae, with MIC values ranging from 25 to 50 µg/mL.


Subject(s)
Anti-Bacterial Agents , Streptomyces , Animals , Swine , Anti-Bacterial Agents/chemistry , Streptomyces/chemistry , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests
7.
Molecules ; 28(6)2023 Mar 16.
Article in English | MEDLINE | ID: mdl-36985662

ABSTRACT

Two series of novel steroidal[17,16-d]pyrimidines derived from natural epiandrosterone and androsterone were designed and synthesized, and these compounds were screened for their potential anticancer activities. The preliminary bioassay indicated that some of these prepared compounds exhibited significantly good cytotoxic activities against human gastric cancer (SGC-7901), lung cancer (A549), and hepatocellular liver carcinoma (HepG2) cell lines compared with 5-fluorouracil (5-FU), epiandrosterone, and androsterone. Especially the respective pairs from epiandrosterone and androsterone showed significantly different inhibitory activities, and the possible configuration-activity relationships have also been summarized and discussed based on kinase assay and molecular docking, which indicated that the inhibition activities of these steroidal[17,16-d]pyrimidines might obviously be affected by the configuration of the hydroxyl group in the part of the steroidal scaffold.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Androsterone/pharmacology , Pyrimidines/pharmacology , Molecular Docking Simulation , Cell Proliferation , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Steroids/pharmacology , Fluorouracil/pharmacology , Drug Screening Assays, Antitumor , Structure-Activity Relationship
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(4): 788-791, 2023 Jul.
Article in Zh | MEDLINE | ID: mdl-37545075

ABSTRACT

Objective: To explore the effect of pulsating vacuum cleaning sterilizer on the cleaning quality of dental handpieces. Methods: A total of 390 newly-purchased high-speed dental handpieces were covered in the study. By the random number table method, the handpieces were divided into three groups that were cleaned by different methods-Group A ( n=130), pulsating vacuum cleaning sterilizer, group B ( n=130), automatic thermal cleaning and disinfection machine, and group C ( n=130), manual cleaning. The cleaning quality, internal cavity drying and the length of cleaning time of the three groups were compared. Results: The cleaning quality of group A (100%) was better than those of groups B (89.2%) and C (83.8%) and the length of cleaning time of group A (1.13 h) was shorter than those of group B (1.80 h) and C (2.60 h), all showing significant differences ( P<0.05). In addition, the cleaning quality of group B was better than that of group C and the length of cleaning time of group B was shorter than that of group C, all showing significant differences ( P<0.05). However, there was no significant difference in the internal cavity drying effects between the three groups ( P>0.05). Conclusions: The pulsating vacuum cleaning sterilizer can effectively improve the cleaning quality of dental handpieces and shorten the cleaning time. Hence, it should be extensively applied and promoted in clinic service.


Subject(s)
Sterilization , Sterilization/methods , Vacuum
9.
Ecotoxicol Environ Saf ; 240: 113689, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35636240

ABSTRACT

Airborne E. coli, fecal coliform, and Enterococcus are all related to sewage worker's syndrome and therefore used as target enteric bioaerosols about researches in wastewater treatment plants (WWTPs). However, most of the studies are often inadequately carried out because they lack systematic studies reports bioaerosols emission characteristics and health risk assessments for these three enteric bacteria during seasonal variation. Therefore, quantitative microbial risk assessment based on Monte Carlo simulation was utilized in this research to assess the seasonal variations of health risks of the three enteric bioaerosols among exposure populations (academic visitors, field engineers, and office staffs) in a WWTP equipped with rotating-disc and microporous aeration modes. The results show that the concentrations of the three airborne bacteria from the rotating-disc aeration mode were 2-7 times higher than the microporous aeration mode. Field engineers had health risks 1.5 times higher than academic visitors due to higher exposure frequency. Health risks of airborne Enterococcus in summer were up to 3 times higher than those in spring and winter. Similarly, health risks associated to E. coli aerosol exposure were 0.3 times higher in summer compared to spring. In contrast, health risks associated with fecal coliform aerosol were between 2 and 19 times lower in summer compared to spring and winter seasons. Data further suggest that wearing of N95 mask could minimize health risks by 1-2 orders of magnitude. This research shed light on seasonal variation of health risks associated with bioaerosol emission from wastewater utilities.


Subject(s)
Gastrointestinal Microbiome , Water Purification , Aerosols , Air Microbiology , Escherichia coli , Gram-Negative Bacteria , Humans , Risk Assessment , Seasons , Wastewater/microbiology
10.
Molecules ; 27(5)2022 Feb 22.
Article in English | MEDLINE | ID: mdl-35268580

ABSTRACT

Primary arylsulfonamide functional groups feature prominently in diverse pharmaceuticals. However, natural arylsulfonamides are relatively infrequent. In this work, two novel arylsulfonamide natural products were first synthesized, and then a series of novel molecules derived from natural arylsulfonamides were designed and synthesized, and their in vitro cytotoxic activities against A875, HepG2, and MARC145 cell lines were systematically evaluated. The results indicate that some of these arylsulfonamide derivatives exhibit significantly good cytotoxic activity against the tested cell lines compared with the control 5-fluorouracil (5-FU), such as compounds 10l, 10p, 10q, and 10r. In particular, the potential molecule 10q, containing a carbazole moiety, exhibited the highest inhibitory activity against all tested cell lines, with IC50 values of 4.19 ± 0.78, 3.55 ± 0.63, and 2.95 ± 0.78 µg/mL, respectively. This will offer the potential to discover novel drug-like compounds from the sparsely populated area of natural products that can lead to effective anticancer agents.


Subject(s)
Antineoplastic Agents
11.
Res Sports Med ; 30(1): 92-100, 2022.
Article in English | MEDLINE | ID: mdl-33620005

ABSTRACT

To study the relationship between daily activity level and cognitive function in community-dwelling elderly. We collected demographic features, cognitive function, activity level and self-rating depression scale scores in 53 community-dwelling olderly aged 60 years or above. The activity level and moderate-to-vigorous physical activity (MVPA) time were assessed by using the accelerometer for 7 consecutive days. We compared activity level, MVPA time and depression scores between cognitive impaired and normal groups. Cognitive functions were compared in groups with different MVPA level, and the correlation between cognitive function and MVPA time was analysed. Of the 53 subjects, 27 had varying degrees of cognitive impairment. Individuals with cognitive impairment shown significantly shorter MVPA time and higher depression score compared to the cognitive normal group (P < 0.05). After controlling for confounding factors (age, BMI), MVPA time was associated with cognitive function (r = 0.358, P = 0.009). The memory factor score correlated with MVPA time (r = 0.357, P = 0.012) and mean activity level (r = 0.287, P = 0.046). Moderate-to-vigorous physical activity in the elderly was positively related to their cognitive function. Strengthening daily activities may beneficial for the elderly to maintain better cognitive function.


Subject(s)
Exercise , Independent Living , Aged , China/epidemiology , Cognition , Humans
12.
Lab Invest ; 101(11): 1418-1426, 2021 11.
Article in English | MEDLINE | ID: mdl-34172831

ABSTRACT

Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. Interleukin-17A (IL-17A) is an inflammatory cytokine produced by Th17 cells (a subgroup of helper T cells), which is a key factor in the development of atherosclerosis. However, the effect of IL-17A on the senescence of vascular endothelial cells is still unclear. In this study, we aimed to explore the role of IL-17A on endothelial cell senescence and its signaling pathways associated with senescence. The proportion of Th17 cells in the spleen and the expression levels of IL-17A, IL-6, and vascular cell adhesion molecule-1 (VCAM-1) in mice of different ages were increased with aging. In vitro experiments showed that proliferation was inhibited, senescent ß-galactosidase and senescence-associated proteins (p16, p19, p21, and p53) of mouse aortic endothelial cells (MAECs) were increased with IL-17A treatment. Blocking the NF-κB pathway with ammonium pyrrolidinedithiocarbamate (PDTC) successfully inhibited IL-17A-induced expression of senescence-associated proteins. In conclusion, our data reveal a previously unsuspected link between IL-17A and endothelial cell senescence, which was mediated by the NF-κB /p53/Rb pathway.


Subject(s)
Cellular Senescence , Endothelial Cells/metabolism , Interleukin-17/metabolism , Th17 Cells/metabolism , Animals , Arteries/physiology , Interleukin-6/metabolism , Male , Mice, Inbred C57BL , NF-kappa B/metabolism , Retinoblastoma Protein/metabolism , Signal Transduction , Tumor Suppressor Protein p53/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
13.
Appl Environ Microbiol ; 87(10)2021 04 27.
Article in English | MEDLINE | ID: mdl-33674433

ABSTRACT

Streptococcal toxic shock-like syndrome (STSLS) caused by the epidemic strain of Streptococcus suis leads to severe inflammation and high mortality. The life and health of humans and animals are also threatened by the increasingly severe antimicrobial resistance in Streptococcus suis There is an urgent need to discover novel strategies for the treatment of S. suis infection. Suilysin (SLY) is considered to be an important virulence factor in the pathogenesis of S. suis In this study, ellipticine hydrochloride (EH) was reported as a compound that antagonizes the hemolytic activity of SLY. In vitro, EH was found to effectively inhibit SLY-mediated hemolytic activity. Furthermore, EH had a strong affinity for SLY, thereby directly binding to SLY to interfere with the hemolytic activity. Meanwhile, it was worth noting that EH was also found to have a significant antibacterial activity. In vivo, compared with traditional ampicillin, EH not only significantly improved the survival rate of mice infected with S. suis 2 strain Sc19 but also relieved lung pathological damage. Furthermore, EH effectively decreased the levels of inflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α]) and blood biochemistry enzymes (alanine transaminase [ALT], aspartate transaminase [AST], creatine kinase [CK]) in Sc19-infected mice. Additionally, EH markedly reduced the bacterial load of tissues in Sc19-infected mice. In conclusion, our findings suggest that EH can be a potential compound for treating S. suis infection in view of its antibacterial and antihemolysin activity.IMPORTANCE In recent years, the inappropriate use of antibiotics has unnecessarily caused the continuous emergence of resistant bacteria. The antimicrobial resistance of Streptococcus suis has also become an increasingly serious problem. Targeting virulence can reduce the selective pressure of bacteria on antibiotics, thereby alleviating the development of bacterial resistance to a certain extent. Meanwhile, the excessive inflammatory response caused by S. suis infection is considered the primary cause of acute death. Here, we found that ellipticine hydrochloride (EH) exhibited effective antibacterial and antihemolysin activities against S. suisin vitroIn vivo, compared with ampicillin, EH had a significant protective effect on S. suis serotype 2 strain Sc19-infected mice. Our results indicated that EH, with dual antibacterial and antivirulence effects, will contribute to treating S. suis infections and alleviating the antimicrobial resistance of S. suis to a certain extent. More importantly, EH may develop into a promising drug for the prevention of acute death caused by excessive inflammation.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/metabolism , Ellipticines/therapeutic use , Hemolysin Proteins/metabolism , Streptococcal Infections/drug therapy , Streptococcus suis , Virulence Factors/metabolism , Animals , Anti-Bacterial Agents/pharmacology , Cytokines/blood , Disease Models, Animal , Ellipticines/pharmacology , Female , Hemolysis/drug effects , Mice, Inbred BALB C , Streptococcal Infections/blood , Streptococcus suis/drug effects , Streptococcus suis/growth & development , Streptococcus suis/metabolism
14.
Graefes Arch Clin Exp Ophthalmol ; 259(1): 197-204, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32808064

ABSTRACT

PURPOSE: To analyze the etiology, microbiological isolates, and antibiotic susceptibilities of endophthalmitis in pediatric patients. METHODS: Patients aged < 18 years with culture-positive endophthalmitis in Zhongshan Ophthalmic Center between January 2010 and December 2018 were included retrospectively. RESULTS: A total of 127 patients (127 eyes) were included, and 108 (85%) had posttraumatic endophthalmitis. Streptococcus (21.4%), coagulase-negative Staphylococcus (14.5%), Aspergillus (6.9%), and Bacillus cereus (5.3%) were the common organisms. The proportion of Streptococcus decreased with age (40.0% in 0-3 years, 16.3% in 4-12 years, and 6.3% in 13-17 years), while coagulase-negative Staphylococcus increased from 5.7% to 18.8%. Overall, fluoroquinolones achieved the highest antibiotic susceptibility rate (> 95%), while the susceptibility of isolated bacteria to tobramycin and cefazolin was only 60.2% and 59.4%, respectively. The susceptibility rates of Gram-positive cocci to cephalosporins were nearly 90%. For Gram-negative bacilli, susceptibility to neomycin was 91.3%. CONCLUSION: Trauma was the main etiology for pediatric endophthalmitis. Although Streptococcus was the most prevalent organism in general, the dominant pathogen varied with age, which merits clinical attention. Fluoroquinolones showed the highest antibiotic efficacy; however, commonly used antibiotics tobramycin and cefazolin showed relatively low antibiotic susceptibility. Thus, antibiotic resistance in pediatric populations merits clinical attention.


Subject(s)
Endophthalmitis , Eye Infections, Bacterial , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Child , Endophthalmitis/diagnosis , Endophthalmitis/drug therapy , Endophthalmitis/epidemiology , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/drug therapy , Eye Infections, Bacterial/epidemiology , Humans , Infant, Newborn , Microbial Sensitivity Tests , Retrospective Studies
15.
Int J Mol Sci ; 22(11)2021 May 29.
Article in English | MEDLINE | ID: mdl-34072443

ABSTRACT

As an important zoonotic pathogen, Streptococcus suis (S. suis) infection has been reported to be a causative agent for variety of diseases in humans and animals, especially Streptococcal toxic shock-like syndrome (STSLS), which is commonly seen in cases of severe S. suis infection. STSLS is often accompanied by excessive production of inflammatory cytokines, which is the main cause of death. This calls for development of new strategies to avert the damage caused by STSLS. In this study, we found for the first time that Baicalein, combined with ampicillin, effectively improved severe S. suis infection. Further experiments demonstrated that baicalein significantly inhibited the hemolytic activity of SLY by directly binding to SLY and destroying its secondary structure. Cell-based assays revealed that Baicalein did not exert toxic effects and conferred protection in S. suis-infected cells. Interestingly, compared with ampicillin alone, Baicalein combined with ampicillin resulted in a higher survival rate in mice severely infected with S. suis. At the same time, we found that baicalein can be combined with meropenem against MRSA. In conclusion, these results indicate that baicalein has a good application prospect.


Subject(s)
Anti-Bacterial Agents/pharmacology , Flavanones/pharmacology , Streptococcal Infections/microbiology , Streptococcus suis/drug effects , Animals , Anti-Bacterial Agents/chemistry , Cytokines/biosynthesis , Disease Models, Animal , Drug Resistance, Bacterial/drug effects , Drug Therapy, Combination , Flavanones/chemistry , Hemolysis/drug effects , Host-Pathogen Interactions , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Microbial Sensitivity Tests , Models, Molecular , Molecular Conformation , Streptococcal Infections/drug therapy , Streptococcal Infections/metabolism , Streptococcal Infections/pathology , Structure-Activity Relationship
16.
Molecules ; 26(7)2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33915741

ABSTRACT

As an important zoonotic pathogen, Streptococcus suis (S. suis) can cause a variety of diseases both in human and animals, especially Streptococcal toxic shock-like syndrome (STSLS), which commonly appears in severe S. suis infection. STSLS is often accompanied by excessive production of inflammatory cytokines, which is the main cause of host death. Therefore, it is urgent to find a new strategy to relieve the damage caused by STSLS. In this study, we found, for the first time, that apigenin, as a flavonoid compound, could combine with ampicillin to treat severe S. suis infection. Studies found that apigenin did not affect the growth of S. suis and the secretion of suilysin (SLY), but it could significantly inhibit the hemolytic activity of SLY by directly binding to SLY and destroying its secondary structure. In cell assays, apigenin was found to have no significant toxic effects on effective concentrations, and have a good protective effect on S. suis-infected cells. More importantly, compared with the survival rate of S. suis-infected mice treated with only ampicillin, the survival rate of apigenin combined with an ampicillin-treated group significantly increased to 80%. In conclusion, all results indicate that apigenin in combination with conventional antibiotics can be a potential strategy for treating severe S. suis infection.


Subject(s)
Ampicillin/pharmacology , Anti-Bacterial Agents/pharmacology , Apigenin/pharmacology , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Streptococcus suis/drug effects , Ampicillin/chemistry , Ampicillin/therapeutic use , Animals , Anti-Bacterial Agents/chemistry , Apigenin/chemistry , Apigenin/therapeutic use , Binding Sites , Cell Line , Cell Survival/drug effects , Cytokines/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Therapy, Combination , Erythrocytes/drug effects , Hemolysin Proteins/antagonists & inhibitors , Hemolysin Proteins/chemistry , Host-Pathogen Interactions , Humans , Inflammation Mediators/metabolism , Mice , Microbial Sensitivity Tests , Models, Molecular , Molecular Conformation , Molecular Structure , Protein Binding , Streptococcal Infections/diagnosis , Streptococcal Infections/metabolism , Structure-Activity Relationship , Treatment Outcome
17.
Org Biomol Chem ; 17(14): 3635-3639, 2019 04 03.
Article in English | MEDLINE | ID: mdl-30916700

ABSTRACT

Oxazoles are an important class of biologically active metabolites from nature, and exhibit broad biological activities as the lead for drug discovery. Hinduchelins are a class of unusual natural products with an oxazole unit, isolated from Streptoalloteichus hindustanus, and with a potential iron-chelating ability. These compounds are the first identified naturally occurring unusual oxazole derivatives to possess a catechol unit. However, some of these compounds are not abundant in nature, and thus, the efficient syntheses of these compounds are advantageous in exploring their potential applications. This paper reports the efficient synthesis and bio-evaluation of hinduchelins A-D and their derivatives with convenient procedures and high yields.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Antineoplastic Agents/pharmacology , Biological Products/pharmacology , Insecticides/pharmacology , Oxazoles/pharmacology , Actinomycetales/chemistry , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Aphids/drug effects , Biological Products/chemical synthesis , Biological Products/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Fungi/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Insecticides/chemical synthesis , Insecticides/chemistry , Microbial Sensitivity Tests , Moths , Oxazoles/chemical synthesis , Oxazoles/chemistry
18.
J Enzyme Inhib Med Chem ; 34(1): 1607-1614, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31474167

ABSTRACT

Steroids are classes of natural products widely distributed in nature, which have been demonstrated to exhibit broad biological functions, and have also attracted increasing interest from bioorganic and pharmaceutical researches. In order to develop novel chemical entities as potential cytotoxic agents, a series of steroidal isatin conjugations derived from epiandrosterone and androsterone were efficiently prepared and characterized, and all these obtained compounds were screened for their potential cytotoxic activities. The preliminary bioassay indicated that most of the newly synthesized compounds exhibited good cytotoxic activities against human gastric cancer (SGC-7901), melanoma (A875), and hepatocellular liver carcinoma (HepG2) cell lines compared with 5-fluorouracil (5-FU), which might be considered as promising scaffold for further development of potential anticancer agents.


Subject(s)
Androsterone/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Biological Products/pharmacology , Isatin/pharmacology , Steroids/pharmacology , Androsterone/analogs & derivatives , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Isatin/chemical synthesis , Isatin/chemistry , Molecular Structure , Steroids/chemical synthesis , Steroids/chemistry , Structure-Activity Relationship
19.
Molecules ; 25(1)2019 Dec 20.
Article in English | MEDLINE | ID: mdl-31861925

ABSTRACT

Background: Tuberculosis remains a global disease that poses a serious threat to human health, but there is lack of new and available anti-tuberculosis agents to prevent the emergence of drug-resistant strains. To address this problem natural products are still potential sources for the development of novel drugs. Methods: A whole-cell screening approach was utilized to obtain a natural compound enniatin A1 from a natural products library. The target compound's antibacterial activity against Mycobacterium tuberculosis (M. tuberculosis) was evaluated by using the resazurin reduction micro-plate assay (REMA) method. The cytotoxicity of the compound against Vero cells was measured to calculate the selectivity index. The intracellular inhibition activity of enniatin A1 was determined. We performed its time-kill kinetic assay against M. tuberculosis. We first tested its synergistic effect in combination with the first and second-line anti-tuberculosis drugs. Finally, we measured the membrane potential and intracellular ATP levels of M. tuberculosis after exposure to enniatin A1. Results: We identified enniatinA1 as a potential antibacterial agent against M. tuberculosis, against which it showed strong selectivity. Enniatin A1 exhibited a time-concentration-dependent bactericidal effect against M. tuberculosis, and it displayed synergy with rifamycin, amikacin, and ethambutol. After exposure to enniatinA1, the membrane potential and intracellular ATP levels of M. tuberculosis was significantly decreased. Conclusions: Enniatin A1 exhibits the positive potential anti-tuberculosis agent characteristics.


Subject(s)
Adenosine Triphosphate/metabolism , Antitubercular Agents/pharmacology , Depsipeptides/pharmacology , Membrane Potentials/drug effects , Mycobacterium tuberculosis/metabolism , Tuberculosis/drug therapy , Animals , Antitubercular Agents/agonists , Chlorocebus aethiops , Depsipeptides/agonists , Drug Evaluation , Drug Synergism , Humans , THP-1 Cells , Vero Cells
20.
Graefes Arch Clin Exp Ophthalmol ; 256(1): 199-207, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28963702

ABSTRACT

PURPOSE: To evaluate the microstructural modifications and safety of small incision lenticule extraction combined with accelerated cross-linking (SMILE Xtra) in high myopia and thin corneas by means of in vivo confocal microscopy (IVCM) and 3D-OCT after a 6-month follow-up. METHODS: Forty-three eyes with high myopia and thin corneas were enrolled. All eyes underwent SMILE procedure. After the lenticule was extracted, 0.25% riboflavin was injected into the interface and allowed to diffuse for 60 s. The eye was irradiated with UVA radiation of 30 mW/cm2 for 90 s through the cap. The total energy delivered was 2.7 J/cm2. Morphologic modifications of corneal architecture were evaluated prior to SMILE Xtra and 7 days, 1, 3, and 6 months after SMILE by in vivo confocal microscopy (IVCM) and 3D-OCT. RESULTS: The corneal epithelial cells showed slight damage until 3 months postoperatively. The subepithelial nerve plexus decreased but no absence within the treatment zone at the first week after treatment, recolonized at 3 months postoperatively, and had mostly recovered at the 6 months postoperative but remained less than its normal baseline state. Keratocytes were absent in the surgical interface area, and the presence of strong reflective particles and cicatricial reaction in the anterior stroma were observed during the entire 6-month examination period. Increased hyperreflectivity was observed from the cap side at a depth of 60 µm to stroma bed at a depth of 388 µm through 6 months. The depth of the demarcation line in 40 eyes (93.0%) was at a mean depth of 296.12 ± 47.86 µm (range, 211-388 µm). No particular change between preoperative and postoperative corneal endothelium was observed. CONCLUSIONS: Confocal microscopy showed increased hyperreflectivity in the SMILE Xtra eyes, and no changes in corneal endothelium. We confirmed the safety of the SMILE Xtra but recognize that larger and longer-term studies of SMILE Xtra are necessary.


Subject(s)
Collagen/pharmacology , Cornea/pathology , Cross-Linking Reagents/pharmacology , Lasers, Excimer/therapeutic use , Myopia/diagnosis , Refractive Surgical Procedures/methods , Tomography, Optical Coherence/methods , Adolescent , Adult , Cornea/surgery , Female , Follow-Up Studies , Humans , Imaging, Three-Dimensional , Male , Microscopy, Confocal , Myopia/physiopathology , Myopia/therapy , Prospective Studies , Time Factors , Young Adult
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