Association of novel lipid indices with the white matter hyperintensities in cerebral small vessel disease: a cross-sectional study.

BACKGROUND: Lipids are associated with atherosclerosis, and novel lipid indices have been recently identified to be closely linked to cardiovascular diseases. This study explored the association between four novel lipid indices and the white matter hyperintensities (WMHs) in patients diagnosed with cerebral small vessel disease (CSVD). METHODS: Between January 2023 and February 2024, 219 patients were recruited, including 165 patients with CSVD WMHs and 54 healthy controls. Based on WMHs severity, patients with CSVD were categorised into mild and moderate-to-severe cohorts using the Fazekas rating scale. The plasma levels of four novel lipid indices (low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio [LDL-C/HDL-C], triglyceride/high-density lipoprotein cholesterol ratio [TG/HDL-C], total cholesterol/high-density lipoprotein cholesterol ratio [TC/HDL-C], and non-high-density lipoprotein cholesterol [Non-HDL-C]), were rigorously monitored in the enrolled patients. RESULTS: A total of 165 patients with CSVD WMHs were enrolled, including 94 with mild WMHs and 71 with moderate-to-severe WMHs. Multivariable logistic regression analysis revealed that LDL-C/HDL-C, TG/HDL-C, TC/HDL-C, and Non-HDL-C levels were significantly associated with WMHs (all P ≤ 0.001). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of plasma lipid levels for WMHs in patients with CSVD. The novel lipid indicators outperformed traditional lipid indicators in assessing the diagnostic capability of WMHs. The combined index of the four blood lipid indices had an optimal cutoff point (OCP) of 0.489, with 88.3% sensitivity and 60.6% specificity. The area under the curve (AUC) is 0.800 (95% confidence interval [CI], 0.731-0.869; P < 0.001). Compared with males (OR = 1.126, 95% CI = 0.779-1.628), females (OR = 2.484, 95% CI = 1.398-4.414; P for interaction = 0.023) had a higher risk of developing WMHs. CONCLUSION: This study demonstrates a significant association between four novel lipid indices and the cerebral WMHs in CSVD, highlighting the potential of these markers as novel plasma biomarkers and predictive indicators for assessing CSVD progression and guiding clinical management.

Cytotoxic and Antiangiogenetic Xanthones Inhibiting Tumor Proliferation and Metastasis from Garcinia xipshuanbannaensis.

Eight prenylated xanthones including four new analogues were extracted and purified from the leaves of Garcinia xipshuanbannaensis. Multiple techniques including UV, 1D and 2D NMR, and HRESIMS were used to determine the structures of the isolated xanthones. These xanthones were evaluated for their cytotoxicity toward human cancer cells, and compound 4 exhibited activity against HeLa cells. A cytotoxic mechanism examination revealed the active compound induced cell apoptosis by arresting the cell cycle, increasing the levels of ROS, and inhibiting the expression of p-STAT3 in HeLa cells. In in vivo zebrafish experiments, compound 4 was found to block tumor proliferation and migration and have antiangiogenetic activity, and thus seems worthy of further laboratory evaluation.

Antimicrobial Furancarboxylic Acids from a Penicillium sp.

Ten novel (1, 2, 3a, 3b, 4a, 4b, 5a, 5b, 6a, and 6b) furancarboxylic acids including four pairs of epimers (3a, 3b; 4a, 4b; 5a, 5b; 6a, 6b), together with seven known analogues (7a, 7b, 8a, 8b, 9a, 9b, and 10), were isolated from the fermentation of the soil-derived fungus Penicillium sp. sb62. Their structures were established on the basis of spectroscopic data analysis, and the absolute configurations were determined by time-dependent density functional theory electronic circular dichroism calculations, comparison of the specific optical rotation values, and modified Mosher's method. Compounds 1-4 represent the first class of natural furancarboxylic acids featuring a thiophene moiety. Compounds 1-7 showed antimicrobial inhibitory activities against Escherichia coli, Staphylococcus aureus, and Candida albicans with MIC values ranging from 0.9 to 7.0 µg/mL, from 1.7 to 3.5 µg/mL, and from 3.3 to 7.0 µg/mL, respectively.

Anti-inflammatory neo-Clerodane Diterpenoids from Ajuga pantantha.

Eight new neo-clerodane diterpenoids (1-8) were acquired from the aerial parts of Ajuga pantantha. Spectroscopic data analysis permitted the definition of their structures, and experimental and calculated electronic circular dichroism data were used to define their absolute configurations. Compounds 2 and 4-8 were found to have NO inhibitory effects with IC50 values of 20.2, 45.5, 34.0, 27.0, 45.0, and 25.8 µM, respectively. The more potent compounds 2, 6, and 8 were analyzed to establish their anti-inflammatory mechanism, including regulation of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins as well as their binding interactions with the two proteins.

Tsaokopyranols A-M, 2,6-epoxydiarylheptanoids from Amomum tsao-ko and their α-glucosidase inhibitory activity.

The dried fruits of Amomum tsao-ko are well-known dietary spices and traditional Chinese medicines. The random screen revealed that 50% ethanol-water extract of A. tsao-ko demonstrated significant α-glucosidase inhibitory activity with an IC50 value of 38.6 µg/mL. Bioactivity-guided isolation on the active fraction afforded 13 new 2,6-epoxy diarylheptanoids, tsaokopyranols A-M (1-13), and four known ones (14-17). Their structures featuring a 2,6-epoxy pyran ring were established by extensively spectroscopic analyses (HRESIMS, IR, UV, 1D and 2D NMR) and ECD calculations. Seven new (4-6, 8-11) and one known (16) compounds showed obvious α-glucosidase inhibitory activity with IC50 values ranging from 59.4 to 116.5 µM, higher than acarbose (IC50: 219.0 µM). An enzyme kinetic analysis indicated that compounds 12 and 13 were noncompetitive-type inhibitors of α-glucosidase with Ki values of 539.6 and 385.2 µM. This result provided new insights for the usage of A. tsao-ko, and 2,6-epoxydiarylheptanoids as new anti-diabetic candidates.

Diterpenoids from the leaves of Casearia kurzii showing cytotoxic activities.

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new and two known clerodane diterpenoids from the leaves of Casearia kurzii. Their structures were elucidated using NMR techniques and electronic circular dichroism (ECD) calculations. The subsequent biological cytotoxicity evaluation of these isolates toward human lung cancer A549, human cervical cancer HeLa, human chronic myeloid leukemia K562, and human hepatocellular carcinoma HepG2 was carried out. The most active compound 4 with an IC50 value of 9.7 µM against HepG2 cells was selected to examine the cytotoxic mechanism, which induced the apoptosis and arrested the HepG2 cell cycle at S stage. The in vivo zebrafish experiments revealed that compound 4 had the property of inhibiting tumor proliferation and migration.

Bioactive Diterpenoids from the Stems of Euphorbia antiquorum.

A total of 18 diterpenoids, including 10 new analogues (1-10), were isolated from Euphorbia antiquorum. The structures were characterized by spectroscopic techniques, and circular dichroism data analysis was adopted to confirm the absolute configurations of 1-10. Compounds 1-9 were classified as ent-atisane diterpenoids, and 10 was assigned as an ent-kaurane diterpenoid. The biological evaluation of nitric oxide (NO) production inhibition was conducted, and all of these isolates showed the property of inhibiting NO generation in lipopolysaccharide-induced BV-2 cells. Further research on molecular docking disclosed the affinities between the diterpenoids obtained and inducible nitric oxide synthase.

Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii.

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new clerodane diterpenoids, designated as kurzipenes A-F (1-6), from the leaves of Casearia kurzii. Their structures were elucidated on the basis of NMR spectroscopic data analysis and the absolute configurations were confirmed by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The cytotoxic activities of compounds 1-6 were evaluated against human lung cancer A549 cell line, human cervical cancer Hela cell line, and human hepatocellular carcinoma HepG2 cell line. Most diterpenoids showed potent cytotoxicities against the three selected cancer cell lines. The preliminary mechanism studies revealed that the most active compound 2, with an IC50 value of 5.3 µM against Hela cells, induced apoptosis and arrested the Hela cell cycle at the G0/G1 stage to exert cytotoxic effects.

Withanolides from Physalis peruviana showing nitric oxide inhibitory effects and affinities with iNOS.

A phytochemical study to obtain new nitric oxide (NO) inhibitors resulted in the isolation of five new withanolides from the whole plants of Physalis peruviana. The structures were determined on the basis of extensive NMR spectroscopic data analysis as well as the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The NO inhibitory effects were examined by inhibiting NO release in lipopolysaccharide-stimulated murine microglial BV-2 cells. Molecular docking studies showed the strong interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein, revealing the potential mechanism of NO inhibition of bioactive compounds.

Bioactive terpenoids from Euonymus verrucosus var. pauciflorus showing NO inhibitory activities.

In our continuous search for new nitric oxide (NO) inhibitory compounds as potential anti-inflammatory agents or lead compounds for inflammatory diseases, the chemical constituents of Euonymus verrucosus var. pauciflorus were investigated, leading to the isolation of eleven terpenoids including six new diterpenoids, designated as euonymupenes A-F. The structures were elucidated on the basis of NMR and ECD data analysis. Euonymupenes A, C, and F feature rare labdane-type norditerpenoid skeletons. The NO inhibitory effects were evaluated and all of the isolates were found to inhibit lipopolysaccharide (LPS)-induced NO production in murine microglial BV-2 cells. Western blotting analysis indicated that the most active compound (5) can regulate iNOS (inducible nitric oxide synthase) expression. The further molecular docking studies exhibited the affinities of bioactive compounds with iNOS.

Cytotoxic diterpenoids as potential anticancer agents from the twigs of Casearia kurzii.

A search for bioactive natural products as anticancer lead compounds has led to the isolation of five new clerodane diterpenoids (1-5) from the twigs of Casearia kurzii. Their structures were elucidated by extensive analysis of their NMR, IR, and HRESIMS data, and the absolute configurations were determined by experimental and calculated electronic circular dichroism (ECD) data analysis. The isolates were biologically evaluated and showed cytotoxic activities toward human lung cancer cells (A549), human cervical cancer cells (HeLa), and human hepatocellular carcinoma cells (HepG2). The most active compound (5) with an IC50 value of 5.3 µM against HeLa cells, was found to induce apoptosis and arrest the HeLa cell cycle at G0/G1 stage to exert cytotoxic effects.

Eimeria maxima: efficacy of recombinant Mycobacterium bovis BCG expressing apical membrane antigen1 against homologous infection.

Coccidiosis is one of the most important protozoan diseases and inflicts severe economic losses on the poultry industry. The aim of this study was to evaluate the capacity of Bacillus Calmette-Guerin (BCG) to deliver apical membrane antigen1 (AMA1) of Eimeria maxima to stimulate specific cellular and humoral immune responses in chickens. Day-old birds were immunized twice with rBCG/pMV261-AMA1, rBCG/pMV361-AMA1, or BCG via oral, intranasal, and subcutaneous routes and then orally challenged with homologous E. maxima sporulated oocysts. Gain of body weight, fecal oocyst output, lesion scores, serum antibody responses, numbers of splenocyte CD4(+) and CD8(+) T cells, and gut cytokine transcript levels were assessed as measures of protective immunity. Challenge experiments demonstrated that rBCG vaccination via intranasal or subcutaneous routes could increase weight gain, decrease intestinal lesions, and reduce fecal oocyst shedding, and the subcutaneous and intranasal routes were superior to the oral route based on the immune effects. Furthermore, intranasal rBCG immunization could also lead to a significant increase in serum antibody, the percentage of CD4+ and CD8+ T lymphocyte cells, and the levels of IL-1ß, IFN-γ, IL-15, and IL-10 mRNAs compared with the control group. These results suggested that intranasal rBCG immunization could induce a strong humoral and cellular response directed against homologous E. maxima infection. This study provides data for the use of rBCG to develop a prophylactic vaccine against coccidiosis.

A natural xanthone suppresses lung cancer growth and metastasis by targeting STAT3 and FAK signaling pathways.

BACKGROUND: Nonsmall-cell lung cancer (NSCLC) is one of the most common malignant tumors, and the current drugs have not achieved ideal therapeutic effects. The abnormal activation of STAT3 and FAK signal transduction in tumor cells is highly correlated with their proliferation and migration ability. Therefore, bioactive compounds that can inhibit STAT3 and FAK activation have the potential to become agents to treat NSCLC. PURPOSE: This study aims to discover new antitumor compounds from Garcinia xipshuanbannaensis and investigate the molecular mechanism by which they inhibit lung cancer proliferation and metastasis in vivo and in vitro, all of which may lead to obtainment of a potential antitumor agent. METHODS: Xipsxanthone H was obtained by various chromatography methods (including silica gel, medium pressure liquid chromatography (MPLC), and preparative high-performance liquid chromatography (HPLC)). 1D and 2D nuclear magnetic resonance (NMR) spectra were used to analyze the structure. Cell viability and wound healing assays were employed to detect changes in the proliferation and migration of cancer cells. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression of STAT3 and FAK signaling pathways affected by xipsxanthone H was determined by Western blotting. The zebrafish model was used to evaluate the in vivo effects of xipshantone H on tumor proliferation and metastasis. Molecular docking was utilized to explore the interaction between xipsxanthone H and STAT3. Cellular thermal shift assays (CETSAs) were employed to explore the possible target of xipsxanthone H. RESULTS: The novel compound xipsxanthone H was purified and characterized from G. xipshuanbannaensis. Xipsxanthone H exhibited strong anti-proliferation activity in a variety of tumor cell lines. In addition to inducing reactive oxygen species (ROS) production and arresting the cell cycle, mechanistic studies demonstrated that xipsxanthone H suppressed STAT3 and FAK phosphorylation and regulated the downstream protein expression of the STAT3 and FAK signaling pathways. The in vivo studies using the zebrafish model revealed that xipsxanthone H inhibited tumor proliferation, metastasis, and angiogenesis. CONCLUSIONS: A new xanthone was obtained from G. xipshuanbannaensis, and this compound had the property of inhibiting tumor proliferation and metastasis by targeting STAT3 and FAK signaling pathways in NSCLC. These findings suggested that xipsxanthone H might be a potential candidate agent for NSCLC treatment.

Nineteen New Flavanol-Fatty Alcohol Hybrids with α-Glucosidase and PTP1B Dual Inhibition: One Unusual Type of Antidiabetic Constituent from Amomum tsao-ko.

The dried fruits of Amomum tsao-ko were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S (1-19), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which 1, 2, 6, 11, and 18 exhibited obvious activity against α-glucosidase with IC50 values of 5.2-9.0 µM, 20-35 times stronger than that of acarbose (IC50, 180.0 µM); meanwhile, 6, 10-12, and 19 were PTP1B/TCPTP-selective inhibitors with IC50 values of 56.4-80.4 µM, 2-4 times stronger than that of suramin sodium (IC50, 200.5 µM). Enzyme kinetics study indicated that compounds 1, 2, 6, and 11 were α-glucosidase and PTP1B mixed-type inhibitors with Ki values of 13.0, 11.7, 2.9, and 5.3 µM and 142.3, 88.9, 39.2, and 40.8 µM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.

Lactobacillus plantarum vaccine vector expressing hemagglutinin provides protection against H9N2 challenge infection.

Hemagglutinin (HA) has been demonstrated as an effective candidate vaccine antigen against AIVs. Dendritic cell-targeting peptide (DCpep) can enhance the robustness of immune responses. The purpose of this study was to evaluate whether DCpep could enhance the immune response against H9N2 AIV when utilizing Lactobacillus plantarum NC8 (NC8) to present HA-DCpep in mouse and chicken models. To accomplish this, a mucosal vaccine of a recombinant NC8 strain expressing HA and DCpep that was constructed in a previous study was employed. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. These results revealed that recombinant L. plantarum NC8-pSIP409-HA-DCpep is an effective vaccine candidate against H9N2 AIVs.

Emergence of virulent pseudorabies virus infection in northern China.

Our investigation was conducted in order to verify a recent severe epidemic at several swine farms in northern China that indicated a newly emerging disease. Evidence confirmed that the epidemic was caused by a virulent Pseudorabies virus infection in swine herds.

Characterization of influenza A virus with nine segments: effect gene segment on virus property.

The influenza A virus genome consists of eight segments of negative-strand RNA. In previous study, we generated a recombinant influenza virus with nine segments by reverse genetics. In present study, we evaluated characteristics of the recombinant influenza virus. The recombinant virus exhibited similar property to wild-type virus on virion morphology, virion composition, plaque phenotype and other aspects. Whereas, the recombinant virus propagated to lower titers than did wild-type virus in cells and mice, and there was decreased protein level and vRNA incorporation in the recombinant virions compared to wild-type H9N2 virions. Our results indicated that influenza A virus with eight segments exhibits more advantages than the virus with nine segments.