ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

To explore the chemical constituents of Ecballium elaterium and their cytotoxicity, this study employed multiple chromatographic techniques including normal-phase silica gel, MCI, octadecylsilyl(ODS), Sephadex LH-20 gel, and semi-preparative liquid chromatography for compound isolation from its active fraction. A total of 12 compounds were obtained, and they were identified according to the analysis of a variety of spectral data and literature comparison as 24Z-20,27-dihydroxy-16α,23α-epoxy-cucurbita-2-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside(1), cucurbitacin R(2), cucurbitacin B(3), cucurbitacin D(4), cucurbitacin I(5), cucurbitacin L(6), dehydrodiconiferyl alcohol(7), 3-hydroxy-4-methoxycinnamic acid(8), ferulaic acid(9), p-coumaric acid(10), rutin(11), and lariciresinol-4'-O-β-D-glucoside(12), among which compound 1 was a new compound. Compounds 2-6 had strong cytotoxicity against human lung carcinoma A549 cells with the IC_(50) values of(0.48±0.09),(0.03±0.002),(0.13±0.03),(0.87±0.14),(0.15±0.03) μmol·L~(-1), respectively, which were stronger than the positive control doxorubicin \[IC_(50)=(3.92±1.60) μmol·L~(-1)\].
Humans ; Drugs, Chinese Herbal/toxicity* ; Cell Line, Tumor ; Cucurbitaceae/chemistry* ; Cell Survival/drug effects*

Three taraxerane nortriterpenoids were isolated from mastic by using various modern chromatographic separation techniques. They were identified as(5R,8R,9R,10S,11S,12R,13S,17R,18R)-28-norlupa-11,12-epoxy-14-taraxerene-3,16-dione(1),(5R,8R,9R,10S,11S,12R,13S,17S,18S)-17-hydroxy-28-norlupa-11,12-epoxy-14-taraxerene-3-one(2), and(5R,8R,9R,10R,11S,12R,13R,14S,17S,18S)-14,17-epoxy-28-norlupa-11,12-oxidotaraxerone(3) through the high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), infrared(IR), ultraviolet(UV), nuclear magnetic resonance(NMR), and single-crystal X-ray diffraction techniques as well as comparison with literature data. Compounds 1-3 were C-28 nortriterpenoids and isolated from mastic for the first time, and compounds 1-2 were new ones. In the model for RAW264.7 cell anti-inflammation induced by lipopolysaccharide(LPS), compound 1 demonstrates an inhibitory effect on nitric oxide(NO) [IC_(50)=(13.38±0.68) μmol·L~(-1)], comparable to the activity of the positive control dexamethasone [IC_(50)=(14.59±1.49) μmol·L~(-1)]. Compounds 2 and 3 exhibit weaker inhibitory effects, with IC_(50) values of(24.17±2.56) and(22.25±2.84) μmol·L~(-1), respectively.
Animals ; Mice ; Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Mastic Resin/chemistry* ; Nitric Oxide ; Molecular Structure ; Macrophages/immunology* ; RAW 264.7 Cells

Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Ten compounds were separated by various modern chromatographic methods from mastic. They were identified by HR-ESI-MS, IR, UV, NMR, quantum chemical calculation of NMR(qcc-NMR) and comparison with reported data in literature as 17β-hydroxy-28-norolean-18-en-3-one(1), 28-norolean-12,17-dien-3,11-dione(2), 28-norolean-16,18-dien-3-one(3),(24Z)-26-hydroxy-7,24-dientirucalla-3-one(4), masticadienonic acid(5)、masticadienolic acid(6)、erythrodiol(7), 3β,28-dihydroxyoleana-11,13(18)-diene(8), 3-oxo-olean-9(11),12-dien-28-oic acid(9), and 12-oleane-3,11-dione(10). Among them, compound 1 was a novel compound and compound 2 was a novel natural product. Compounds 1-2, 4, and 7-9 were isolated from mastic for the first time. Compound 1 significantly inhibited lipopolysaccharide-induced production of nitric oxide in mouse monocyte macrophage RAW264.7 cells with the IC_(50) of(7.44±0.49) μmol·L~(-1), which was more potent than the positive control, dexamethasone \[IC_(50)=(9.93±1.17) μmol·L~(-1)\]. Compounds 2-3, 5, and 9-10 also showed inhibitory effects, with the IC_(50) ranging from 14.82 to 28.82 μmol·L~(-1). Compounds 4-5, and 7 markedly inhibited the growth of human colon adenocarcinoma cells SW480, with the IC_(50) of(16.13±1.69),(27.40±1.81), and(10.01±0.10) μmol·L~(-1), respectively.
Mice ; Animals ; Mastic Resin/chemistry* ; Humans ; Macrophages/metabolism* ; Triterpenes/isolation & purification* ; Nitric Oxide ; Molecular Structure ; RAW 264.7 Cells ; Drugs, Chinese Herbal/isolation & purification*

This study aims to identify the chemical constituents from Callicarpa kwangtungensis and determine their activities. MCI, ODS, and Sephadex LH-20 chromatography and semi-preparative HPLC were employed to separate the chemical constituents. A total of 15 compounds were separated, and their structures were identified on the basis of spectroscopic analysis and comparison with the data in relevant literature. Specifically, the 15 compounds were 3-O-α-L-rhamnopyranosyl-6-O-β-D-apiofuranosyl-4-O-E-caffeoyl-D-glucopyranoside(1), 3,6-O-α-L-dirhamnopyranosyl-4-O-E-caffeoyl-D-glucopyranoside(2), β-OH-forsythoside B(3), β-OH-poliumoside(4),(+)-lyoniresinol-3α-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside(5),(+)-lyoniresinol-3α-O-β-D-glucopyranoside(6),(-)-lyoniresinol-3α-O-β-D-glucopyranoside(7), kelampayoside A(8), descaffeoylpoliumoside(9), acteoside(10), alyssonoside(11), poliumoside(12), isacteoside(13), acetyl forsythoside B(14), and forsythoside B(15). Compounds 1 and 2 were novel, and the NMR data of compounds 3 and 4 were reported here for the first time. Furthermore, the hemostatic activities of the extract and abundant ingredients(compounds 12 and 15) of C. kwangtungensis were determined with Yunnan Baiyao as the positive control and normal saline as the negative control. The extract and compounds 12 and 15 significantly shortened the tail tip bleeding time in mice.
Animals ; Mice ; Callicarpa ; Hemostatics ; China ; Glycosides/chemistry*

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.

Objective To evaluate the value of third-generation dual-source CT scanner in application of high-pitch aorta CT angiography(CTA). Methods Totally 59 patients clinically indicated for whole aorta angiography were divided into 2 groups using a simple random method:in group 1 there were 28 patients who underwent the examination on a third-generation dual-source CT device,with a collimation of 2×192×0.6 mm and a rotation time of 0.25 s;in group 2 there were 31 patients who underwent the examination on a second generation dual-source CT device,with a collimation of 2×128×0.6 mm and a rotation time of 0.28 s. Both groups were given the examination operated in dual-source high-pitch ECG-gating mode with a pitch of 3.0,a tube voltage of 100 kV,and automated tube current modulation using a reference tube current of 288 mA. A contrast material bolus of 45 ml with a flow of 4.5 ml/s followed by a 50 ml saline chaser in 5.0 ml/s was used. CTA scan was automatically started using a bolus tracking technique at the level of the original part of aorta after a trigger threshold of 100 HU was reached. The start delay was set to 6 s in both groups. Effective dose(ED),signal to noise ratio (SNR),contrast to noise ratio (CNR),and subjective diagnostic quality of both groups were evaluated. Results The mean ED were 19.44% lower (t=-3.989,P=0.000) in group 1 [(3.15±0.86)mSv] than in group 2 [(3.91±0.60)mSv]. These two groups showed no significant differences in SNR or CNR (all P >0.05). The subjective diagnostic quality values also showed no significant difference between two groups [(1.39±0.50)scores vs. (1.45±0.51)scores;W=814.5,P=0.651].Conclusion Compared with the second-generation dual-source CT scanner,the third-generation dual-source CT scanner in whole aorta CTA can remarkably reduce the radiation dose without affecting image quality.
Aorta ; diagnostic imaging ; Computed Tomography Angiography ; methods ; Humans ; Radiation Dosage ; Retrospective Studies ; Signal-To-Noise Ratio

Objective To evaluate the application of automated tube potential selection technique in high-pitch dual-source CT aortic angiography on a third-generation dual-source CT scanner. Methods Whole aorta angiography were indiated in 59 patients,who were divided into 2 groups using a simple random method:in group 1 there were 31 patients who underwent the examination with automated tube potential selection using a vascular setting with a preferred image quality of 288 mA/100 kV;in group 2 there were 28 patients who underwent the examination with a tube voltage of 100 kV and automated tube current modulation using a reference tube current of 288 mA. Both groups were scanned on a third generation dual-source CT device operated in dual-source high-pitch ECG-gating mode with a pitch of 3.0,collimation of 2×192×0.6 mm,and a rotation time of 0.25 s. Iterative reconstruction algorithm was used. For group 1,the volume and flow of contrast medium and chasing saline were adapted to the tube voltage. For group 2,a contrast material bolus of 45 ml with a flow of 4.5 ml/s followed by a 50 ml saline chaser at 5 ml/s was used. CTA scan was automatically started using a bolus tracking technique at the level of the original part of aorta after a trigger threshold of 100 HU was reached. The start delay was set to 6 s in both groups. Effective dose (ED),signal to noise ratio (SNR),contrast to noise ratio (CNR),and subjective diagnostic quality of both groups were evaluated. Results The mean ED were 21.3% lower (t=-3.099,P=0.000) in group 1 [(2.48±0.80) mSv] than in group 2 [(3.15±0.86) mSv]. Two groups showed no significant difference in attenuation,SD,SNR,or CNR at all evaluational parts of aorta (ascending aorta,aortic arch,diaphragmatic aorta,or iliac bifurcation)(all P>0.05). There was no significant difference in subjective diagnostic quality values of two groups [(1.41±0.50) scores vs. (1.39±0.50) scores;W=828.5,P=0.837]. Conclusion Compared with automated tube current modulation,the automated tube potential selection technique in aorta CT angiography on a third-generation dual-source CT can dramatically reduce radiation dose without affecting image quality.
Algorithms ; Aorta ; diagnostic imaging ; Computed Tomography Angiography ; methods ; Humans ; Radiation Dosage ; Radiographic Image Interpretation, Computer-Assisted ; Signal-To-Noise Ratio

BACKGROUND:Abnormal activation of lymphocytes and nuclear factorκB-dependent non-specific inflammation are two major manifestations of joint damage in rheumatoid arthritis. Co-stimulatory signal CD40/CD40L is the dominant co-stimulatory factor in the recognition and activation of T cel s. IκBαeffectively inhibits nuclear factorκB pathway, prevent the inflammation in the central link, and suppress the damage caused by inflammatory factor in the synovial tissue.
OBJECTIVE:To investigate the therapeutic effect of double gene co-expressing adenovirus vector on arthritis based on an arthritis model rat transfected by CD40LIg-IRES2-IκBαco-expressing adenovirus vector.
METHODS:The pAdCD40LIg-IRES2-IκBαco-expressing adenovirus vector was established. Arthritic model was established through multi-subcutaneous injections of complete Freund's adjuvant of type col agen II (1 g/L) into Wistar rats. Then 20 arthritic rats were divided into two groups:untreated group and transfection group, receiving an injection of saline and pAdCD40LIg-IRES2-IκBαadenovirus vector to distal joint cavity of limbs, respectively.
RESULTS AND CONCLUSION:At 14 days post-transfection, compared with the untreated group, the mean arthritis index score, the CD40L expression of lymphocytes in synovial fluid, the nuclear factor-κB p65 expression in synovial tissue, and levels of interleukin-2, interleukin-6, tumor necrosis factor-α, matrix metal oproteinase-3 and matrix metal oproteinase-9 in synovial fluid of rats in transfection group were significantly lower than those in untreated group. Focal transfection of the CD40LIg-IκBαco-expression adenovirus vector can effectively inhibit arthritic symptoms, and reduce the expressions of inflammatory cytokine in synovial fluid and inflammatory molecule in synovial tissue of arthritic rats, which shows good therapeutic effect.