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Sarglanoids A-F, six new sesquiterpenoids belonging to eudesmane (1-5) and eremophilane (6) types, were isolated from the leaves of Sarcandra glabra, a famous traditional Chinese medicine (TCM). Their structures including absolute configurations were elucidated through extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Compounds 1-2 were rare N-containing eudesmane-type sesquiterpenoids. Compound 3 exhibited inhibitory activity against nitric oxide (NO) production in lipopolysaccharides (LPS)-induced RAW 264.7 cells with IC50 values at 20.00 ± 1.30 μmol·L-1. These findings provide scientific evidence for sesquiterpenoids as the material foundation of S. glabra.
Subject(s)
Molecular Structure , Plant Leaves , Polycyclic Sesquiterpenes , Seeds , Sesquiterpenes/pharmacologyABSTRACT
Buxrugulosides A-E, four lignan glycosides (1-4) and a protocatechuate derivative (5) featuring a rare (N, N-diethyl)methyl amino group at aromatic rings, were obtained from the aerial parts of Buxus rugulosa, which is famous for treating coronary heart disease. Their structures including absolute configurations were elucidated by HRMS, 1D and 2D NMR, and by comparing their CD data with previous reports. Compound 1 was a rare sesquilignan, and all of these compounds were the first example of lignans with (N, N-diethyl)methyl amino group.
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Objective:This study aims to characterize the bacterial profile presenting in peripheral blood of severe acute pancreatitis (SAP) patients and investigate the potential role of circulating microorganisms in the development of systemic infection.Methods:A total of 30 patients with SAP were recruited in this study and divided into three groups:infected,sepsis and Septic shock (n =10 for each group).The peripheral blood was collected sterilely for extraction of DNA,which was subsequently amplified using the universe primers targeted the V6-V8 region of 16S ribosomal RNA genes.The amplicons were separated by denaturing gradient gel electrophoresis (DGGE),and then the gels were stained and photographed.The bands were cut out and sequenced to determine the closest bacterial relatives.Results:As shown in DGGE profile,multiple DNA bands (3 to 8 bands) were detected in peripheral blood from all (100％) of SAP patients complicated with septic shock.The microorganisms most frequently presenting in the blood of these cases included Escherichia coli,Bacillus coagulans,Pseudomonas putida,Pseudomonas aeruginosa,and Klebsiella pneumonia,with an incidence of 40 ％ or higher.In patients with sepsis,bacterial DNA consisting of 2 to 4 bands was observed in 90％ of the blood samples.The most common bacterial species was Pseudomonas putida (60％),followed by Shigella flexneri (40％),Staphylococcus aureus (30％) and Enterococcusfaecium (20％).By contrast,the positive rate of blood bacterial DNA was relatively lower in infected patients (70 ％).Of them,single bacterial species was commonly found in the blood samples.Conclusions:Our data showed that the bacterial profiles presenting in peripheral blood are distinct among SAP patients with different manifestations.Polymicrobial translocation could contribute to the development of systemic infection,offering novel insights into the pathogenesis of sepsis in SAE The findings are helpful for the prevention and treatment for bacterial infection and complications of SAP.
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<p><b>BACKGROUND</b>Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia). However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.</p><p><b>METHODS</b>Twelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection) while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment) for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05). Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.</p><p><b>CONCLUSIONS</b>Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after alemtuzumab treatment.</p>
Subject(s)
Animals , Male , Alemtuzumab , Antibodies, Monoclonal, Humanized , Therapeutic Uses , Apoptosis , Flow Cytometry , Intestines , Cell Biology , Lymphocytes , Macaca fascicularis , Microscopy, Electron, TransmissionABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of nuclear factor kappa B (NF-kappaB) on insulin signaling in skeletal muscle cells of rat with sepsis.</p><p><b>METHODS</b>SD rats were randomly divided into two groups: control group and sepsis group.Sepsis model was reproduced by cecal ligation and puncture in sepsis group. At 8, 16, 24, 48 and 72 h after operation, the gastrocnemius was harvested. Conventional HE staining was used to observe the morphology of skeletal muscle cells. IRS-1 protein and tyrosine phosphorylation of IRS-1 and Ser(307) phosphorylation of IRS-1 were detected by Western Blotting and immuno-precipitation. Activities of NF-kappaB in skeletal muscle cells were detected by electrophoretic mobility shift assay.</p><p><b>RESULTS</b>Tyrosine phosphorylation of IRS-1 in sepsis group was significantly lower than in control group (P < 0.01), while Ser(307) phosphorylation of IRS-1 in sepsis group was significantly higher than in control group (P < 0.01). In sepsis group, NF-kappaB activity in skeletal muscle cells was significantly higher than in control group (P < 0.01). There was significant negative correlation between activity of NF-kappaB and tyrosine phosphorylation of IRS-1 (r = 0.972, P < 0.01). There was significant positive correlation between activities of NF-kappaB and Ser(307) phosphorylation of IRS-1 (r = 0.969, P < 0.01).</p><p><b>CONCLUSIONS</b>There is no inflammatory cell infiltrate in skeletal muscle cells with sepsis. But the activity of NF-kappaB in skeletal muscle cells is obviously enhanced, and it is closely related with disorder of insulin signaling in skeletal muscle cells of rat with sepsis.</p>