Bethune Second Hospital

Vulnerable areas of atherosclerotic plaques often contain lipid-laden macrophages and display matrix metalloproteinase activity. We hypothesized that reactive oxygen species released by macrophage-derived foam cells could trigger activation of latent proforms of metalloproteinases in the vascular interstitium. We showed that in vivo generated macrophage foam cells produce superoxide, nitric oxide, and hydrogen peroxide after isolation from hypercholesterolemic rabbits. Effects of these reactive oxygens and that of peroxynitrite, likely to result from simultaneous production of nitric oxide and superoxide, were tested in vitro using metalloproteinases secreted by cultured human vascular smooth muscle cells. Enzymes in culture media or affinity-purified (pro-MMP-2 and MMP-9) were examined by SDS-PAGE zymography, Western blotting, and enzymatic assays. Under the conditions used, incubation with xanthine/xanthine oxidase increased the amount of active gelatinases, while nitric oxide donors had no noticeable effect. Incubation with peroxynitrite resulted in nitration of MMP-2 and endowed it with collagenolytic activity. Hydrogen peroxide treatment showed a catalase-reversible biphasic effect (gelatinase activation at concentrations of 4 microM, inhibition at > or = 10-50 microM). Thus, reactive oxygen species can modulate matrix degradation in areas of high oxidant stress and could therefore contribute to instability of atherosclerotic plaques.

As the burgeoning field of Artificial Intelligence (AI) continues to permeate the fabric of healthcare, particularly in the realms of patient surveillance and telemedicine, a transformative era beckons. This manuscript endeavors to unravel the intricacies of recent AI advancements and their profound implications for reconceptualizing the delivery of medical care. Through the introduction of innovative instruments such as virtual assistant chatbots, wearable monitoring devices, predictive analytic models, personalized treatment regimens, and automated appointment systems, AI is not only amplifying the quality of care but also empowering patients and fostering a more interactive dynamic between the patient and the healthcare provider. Yet, this progressive infiltration of AI into the healthcare sphere grapples with a plethora of challenges hitherto unseen. The exigent issues of data security and privacy, the specter of algorithmic bias, the requisite adaptability of regulatory frameworks, and the matter of patient acceptance and trust in AI solutions demand immediate and thoughtful resolution .The importance of establishing stringent and far-reaching policies, ensuring technological impartiality, and cultivating patient confidence is paramount to ensure that AI-driven enhancements in healthcare service provision remain both ethically sound and efficient. In conclusion, we advocate for an expansion of research efforts aimed at navigating the ethical complexities inherent to a technology-evolving landscape, catalyzing policy innovation, and devising AI applications that are not only clinically effective but also earn the trust of the patient populace. By melding expertise across disciplines, we stand at the threshold of an era wherein AI's role in healthcare is both ethically unimpeachable and conducive to elevating the global health quotient.

Glioblastoma multiforme (GBM) is the most malignant and aggressive primary brain tumor in adults. Despite concerted efforts to improve current therapies, the prognosis of glioblastoma remains very poor. Alantolactone, a sesquiterpene lactone compound, has been reported to exhibit antifungal, antibacteria, antihelminthic, and anticancer properties. In this study, we found that alantolactone effectively inhibits growth and triggers apoptosis in glioblastoma cells in a time- and dose-dependent manner. The alantolactone-induced apoptosis was found to be associated with glutathione (GSH) depletion, reactive oxygen species (ROS) generation, mitochondrial transmembrane potential dissipation, cardiolipin oxidation, upregulation of p53 and Bax, downregulation of Bcl-2, cytochrome c release, activation of caspases (caspase 9 and 3), and cleavage of poly (ADP-ribose) polymerase. This alantolactone-induced apoptosis and GSH depletion were effectively inhibited or abrogated by a thiol antioxidant, N-acetyl-L-cysteine, whereas other antioxidant (polyethylene glycol (PEG)-catalase and PEG-superoxide-dismutase) did not prevent apoptosis and GSH depletion. Alantolactone treatment inhibited the translocation of NF-κB into nucleus; however, NF-κB inhibitor, SN50 failed to potentiate alantolactone-induced apoptosis indicating that alantolactone induces NF-κB-independent apoptosis in glioma cells. These findings suggest that the sensitivity of tumor cells to alantolactone appears to results from GSH depletion and ROS production. Furthermore, our in vivo toxicity study demonstrated that alantolactone did not induce significant hepatotoxicity and nephrotoxicity in mice. Therefore, alantolactone may become a potential lead compound for future development of antiglioma therapy.

Metastasis leads to poor prognosis in colorectal cancer patients, and there is a growing need for new therapeutic targets. TMEM16A (ANO1, DOG1 or TAOS2) has recently been identified as a calcium-activated chloride channel (CaCC) and is reported to be overexpressed in several malignancies; however, its expression and function in colorectal cancer (CRC) remains unclear. In this study, we found expression of TMEM16A mRNA and protein in high-metastatic-potential SW620, HCT116 and LS174T cells, but not in primary HCT8 and SW480 cells, using RT-PCR, western blotting and immunofluorescence labeling. Patch-clamp recordings detected CaCC currents regulated by intracellular Ca(2+) and voltage in SW620 cells. Knockdown of TMEM16A by short hairpin RNAs (shRNA) resulted in the suppression of growth, migration and invasion of SW620 cells as detected by MTT, wound-healing and transwell assays. Mechanistically, TMEM16A depletion was accompanied by the dysregulation of phospho-MEK, phospho-ERK1/2 and cyclin D1 expression. Flow cytometry analysis showed that SW620 cells were inhibited from the G1 to S phase of the cell cycle in the TMEM16A shRNA group compared with the control group. In conclusion, our results indicate that TMEM16A CaCC is involved in growth, migration and invasion of metastatic CRC cells and provide evidence for TMEM16A as a potential drug target for treating metastatic colorectal carcinoma.

Evodiamine, an alkaloid isolated from Evodia rutaecarpa, possesses potent anticancer activity. Although many reports have elucidated the cytotoxic effects of evodiamine in a variety of cancer cells, little is known about the mechanism of evodiamine-induced cytotoxic activity in gastric cancer cells. To date, no report has addressed the synchronized role of autophagy and apoptosis in evodiamine-induced cytotoxic activity. This study was conducted to investigate the synchronized role of autophagy and apoptosis in evodiamine-induced cytotoxic activity on SGC-7901 human gastric adenocarcinoma cells and further to elucidate the underlying molecular mechanisms. The MTT assay was used to examine the cytotoxicity of evodiamine against SGC-7901 gastric adenocarcinoma cells. The effects of evodiamine on the cell cycle and apoptosis were measured by flow cyto-metry and cellular morphology was observed under a phase contrast microscope. Acridine orange (AO) staining was used to detect autophagy. The expression levels of Bcl-2 and Bax were detected by Western blotting. The expression level of Beclin‑1 in SGC-7901 cells was monitored by reverse transcription-polymerase chain reaction (RT-PCR). Here, we found that evodiamine significantly inhibited the proliferation of SGC-7901 cells and induced G2/M phase cell cycle arrest. Furthermore, both autophagy and apoptosis were activated during the evodiamine-induced death of SGC-7901 cells. Evodiamine-induced autophagy is partially involved in the death of SGC-7901 cells which was confirmed by using the autophagy inhibitor 3-methyladenine (3-MA). Additionally, Beclin-1 is involved in evodiamine-induced autophagy and the pro-apoptotic mechanisms of evodiamine may be associated with down-regulation of Bcl-2 and up-regulation of Bax expression. The inhibitory effects on SGC-7901 cells were associated with apoptosis, autophagy and cell cycle arrest at the G2/M phase in a dose-dependent manner. These results suggest that evodiamine is an effective natural compound for the treatment of gastric cancer and may represent a candidate for in vivo studies of monotherapies or combined antitumor therapies.

Signal transducer and activator of transcription 3 (STAT3) constitutively expresses in human liver cancer cells and has been implicated in apoptosis resistance and tumorigenesis. Alantolactone, a sesquiterpene lactone, has been shown to possess anticancer activities in various cancer cell lines. In our previous report, we showed that alantolactone induced apoptosis in U87 glioblastoma cells via GSH depletion and ROS generation. However, the molecular mechanism of GSH depletion remained unexplored. The present study was conducted to envisage the molecular mechanism of alantolactone-induced apoptosis in HepG2 cells by focusing on the molecular mechanism of GSH depletion and its effect on STAT3 activation. We found that alantolactone induced apoptosis in HepG2 cells in a dose-dependent manner. This alantolactone-induced apoptosis was found to be associated with GSH depletion, inhibition of STAT3 activation, ROS generation, mitochondrial transmembrane potential dissipation, and increased Bax/Bcl-2 ratio and caspase-3 activation. This alantolactone-induced apoptosis and GSH depletion were effectively inhibited or abrogated by a thiol antioxidant, N-acetyl-L-cysteine (NAC). The data demonstrate clearly that intracellular GSH plays a central role in alantolactone-induced apoptosis in HepG2 cells. Thus, alantolactone may become a lead chemotherapeutic candidate for the treatment of liver cancer.

Introduction: The natural disasters and climate anomalies caused by increasing global carbon emissions have seriously threatened public health. To solve increasingly serious environmental pollution problems, the Chinese government has committed itself to achieving the goals of peak carbon emissions and carbon neutrality. The low-carbon patent application is an important means to achieve these goals and promote public health. Methods: This study analyzes the basic situation, spatial network, and influencing factors of low-carbon patent applications in China since 2001 at the provincial and urban agglomeration levels using social network analysis based on data from the Incopat global patent database. Results: The following findings are established. (1) From the number of low-carbon patent applications, the total number of low-carbon patent applications in China increased year by year, while the number of applications in the eastern region was larger than those in the central and western regions, but such regional differences had been decreasing. (2) At the interprovincial level, low-carbon patent applications showed a complex and multithreaded network structure. In particular, the eastern coastal provinces occupied the core position in the network. The weighted degree distribution of China's interprovincial low-carbon patent cooperation network is affected by various factors, including economic development, financial support, local scientific research level, and low-carbon awareness. (3) At the urban agglomeration level, the eastern coastal urban agglomerations showed a radial structure with the central city as the core. Urban innovation capability, economic development, low-carbon development awareness, level of technology import from overseas, and informatization level are highly correlated with the weighted degree of low-carbon cooperation networks of urban agglomerations. Discussion: This study provides ideas for the construction and governance of low-carbon technology innovation system and perspectives for theoretical research on public health and high-quality development in China.

Isoalantolactone, a sesquiterpene lactone compound possesses antifungal, antibacteria, antihelminthic and antiproliferative activities. In the present study, we found that isoalantolactone inhibits growth and induces apoptosis in pancreatic cancer cells. Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of reactive oxygen species, cardiolipin oxidation, reduced mitochondrial membrane potential, release of cytochrome c and cell cycle arrest at S phase. N-Acetyl Cysteine (NAC), a specific ROS inhibitor restored cell viability and completely blocked isoalantolactone-mediated apoptosis in PANC-1 cells indicating that ROS are involved in isoalantolactone-mediated apoptosis. Western blot study showed that isoalantolactone increased the expression of phosphorylated p38 MAPK, Bax, and cleaved caspase-3 and decreased the expression of Bcl-2 in a dose-dependent manner. No change in expression of phosphorylated p38 MAPK and Bax was found when cells were treated with isoalantolactone in the presence of NAC, indicating that activation of these proteins is directly dependent on ROS generation. The present study provides evidence for the first time that isoalantolactone induces ROS-dependent apoptosis through intrinsic pathway. Furthermore, our in vivo toxicity study demonstrated that isoalantolactone did not induce any acute or chronic toxicity in liver and kidneys of CD1 mice at dose of 100 mg/kg body weight. Therefore, isoalantolactone may be a safe chemotherapeutic candidate for the treatment of human pancreatic carcinoma.

Gastric cancer is the fourth most commonly diagnosed cancer with the second highest mortality rate worldwide. Surgery, chemotherapy and radiation therapy are generally used for the treatment of stomach cancer but only limited clinical response is shown by these therapies and still no effectual therapy for advanced gastric adenocarcinoma patients is available. Therefore, there is a need to identify other therapeutic agents against this life-threatening disease. Plants are considered as one of the most important sources for the development of anticancer drugs. Magnolol, a natural compound possesses anticancer properties. However, effects of Magnolol on human gastric cancer remain unexplored. The effects of Magnolol on the viability of SGC-7901 cells were determined by the MTT assay. Apoptosis, mitochondrial membrane potential and cell cycle were evaluated by flow cytometry. Protein expression of Bcl-2, Bax, caspase-3 and PI3K/Akt was analysed by Western blotting. Magnolol induced morphological changes in SGC-7901 cells and its cytotoxic effects were linked with DNA damage, apoptosis and S-phase arrest in a dose-dependent manner. Magnolol triggered the mitochondrial-mediated apoptosis pathway as shown by an increased ratio of Bax/Bcl-2, dissipation of mitochondrial membrane potential (ΔΨm), and sequential activation of caspase-3 and inhibition of PI3K/Akt. Additionally, Magnolol induced autophagy in SGC-7901 cells at high concentration but was not involved in cell death. Magnolol-induced apoptosis of SGC-7901 cells involves mitochondria and PI3K/Akt-dependent pathways. These findings provide evidence that Magnolol is a promising natural compound for the treatment of gastric cancer and may represent a candidate for in vivo studies of monotherapies or combination antitumor therapies.

The retinal pigment epithelium (RPE) is a highly specialized and polarized epithelial cell layer that plays an important role in sustaining the structural and functional integrity of photoreceptors. However, the death of RPE is a common pathological feature in various retinal diseases, especially in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitophagy, as a programmed self-degradation of dysfunctional mitochondria, is crucial for maintaining cellular homeostasis and cell survival under stress. RPE contains a high density of mitochondria necessary for it to meet energy demands, so severe stimuli can cause mitochondrial dysfunction and the excess generation of intracellular reactive oxygen species (ROS), which can further trigger oxidative stress-involved mitophagy. In this review, we summarize the classical pathways of oxidative stress-involved mitophagy in RPE and investigate its role in the progression of retinal diseases, aiming to provide a new therapeutic strategy for treating retinal degenerative diseases. The role of mitophagy in AMD and DR. In AMD, excessive ROS production promotes mitophagy in the RPE by activating the Nrf2/p62 pathway, while in DR, ROS may suppress mitophagy by the FOXO3-PINK1/parkin signaling pathway or the TXNIP-mitochondria-lysosome-mediated mitophagy.

The shikonin mixture was used for 19 cases of later-stage lung cancer who were not the candidates for operation, radiotherapy and chemotherapy. The clinical observation showed that shikonin mixture could inhibit the growth of lung cancer and improve the immune function of the body. The tumors were reduced over 25% in diameter. The effective rate was 63.3%, remission rate 36.9%, survival rate of one year 47.3%. The intermedium survival period was about 10 months, including adenocarcinoma 10 months, squamous carcinoma 12 months. After treatment the life quality of patients were greatly improved. The patients got better appetite and their body weights were increased. They could manage themselves in daily life. The Karnofsky scores were enhanced by 20. The authors also observed that shikonin mixture could relieve such symptoms as cough, bloody sputum and chest pain caused by lung cancer. The levels of cells and interleukin-2 were increased (P less than 0.001). It had no harmful effects on peripheral blood picture, heart, kidney and liver. Shikonin mixture is safe and effective for later-stage cancer.

Macrophages play an essential role in innate immunity. We found that mouse resident peritoneal macrophages (mRPMs) express the aquaglyceroporin aquaporin-3 (AQP3) in a plasma membrane pattern. AQP3-deficient (AQP3(-/-)) mice showed significantly greater mortality than wild-type (AQP3(+/+)) mice in a model of bacterial peritonitis. To establish the cellular mechanism of the peritonitis phenotype, measurements were made of mRPM phagocytosis, migration, and water/glycerol permeability. We found significantly impaired engulfment of Escherichia coli and chicken erythrocytes in AQP3(-/-) vs. AQP3(+/+) mRPMs, as well as impaired migration of AQP3(-/-) mRPMs in response to a chemotactic stimulus. In AQP3(+/+) mRPMs, AQP3 was polarized to pseudopodia at the leading edge during migration and around the phagocytic cup during engulfment. Water and glycerol permeabilities in mRPMs from AQP3(-/-) mice were reduced compared to mRPMs from AQP3(+/+) mice. Cellular glycerol and ATP content were remarkably lower in AQP3(-/-) vs. AQP3(+/+) mRPMs, and glycerol supplementation partially rescued the reduced ATP content and impaired function of AQP3(-/-) mRPMs. These data implicate AQP3 as a novel determinant in macrophage immune function by a cellular mechanism involving facilitated water and glycerol transport, and consequent phagocytic and migration activity. This is the first study demonstrating involvement of an aquaporin in innate immunity. Our results suggest AQP3 as a novel therapeutic target in modulating the immune response in various infectious and inflammatory conditions.

We have recently shown that insulin-like growth factor I (IGF I) is a mediator of angiotensin II-induced mitogenesis in vascular smooth muscle cells (Delafontaine, P., and Lou H.(1993) J. Biol. Chem. 268, 16866-16870). To study the role of the IGF I receptor in vascular smooth muscle cell growth, phosphorothioate oligonucleotides were used to modulate IGF I receptors. An antisense oligonucleotide targeting the ATG site inhibited basal and serum-induced DNA synthesis in vascular smooth muscle cells. Mismatch oligonucleotide had no effect, while surprisingly sense oligonucleotide increased IGF I receptor number and basal and serum-induced DNA synthesis. A 51% reduction in IGF I receptor number following exposure to 5 μM antisense oligonucleotide markedly inhibited angiotensin II-induced mitogenesis. A 70% increase in IGF I receptor number following exposure to 5 μM sense oligonucleotide resulted in a 4-fold increase in basal [3H]thymidine incorporation, and angiotensin II (1-1000 nM) had no additive stimulatory effect. An antisense oligonucleotide targeting a sequence starting at +109 base pairs (relative to ATG) also reduced IGF I receptor number, however, the corresponding sense oligonucleotide was without effect. These findings demonstrate that alterations in vascular smooth muscle cell IGF I receptor density play a critical role in the proliferative response of vascular smooth muscle cells to serum and to angiotensin II. In addition, the surprising observation that an ATG-directed sense oligonucleotide up-regulates IGF I receptors identifies a novel effect of oligonucleotides on gene expression. We have recently shown that insulin-like growth factor I (IGF I) is a mediator of angiotensin II-induced mitogenesis in vascular smooth muscle cells (Delafontaine, P., and Lou H.(1993) J. Biol. Chem. 268, 16866-16870). To study the role of the IGF I receptor in vascular smooth muscle cell growth, phosphorothioate oligonucleotides were used to modulate IGF I receptors. An antisense oligonucleotide targeting the ATG site inhibited basal and serum-induced DNA synthesis in vascular smooth muscle cells. Mismatch oligonucleotide had no effect, while surprisingly sense oligonucleotide increased IGF I receptor number and basal and serum-induced DNA synthesis. A 51% reduction in IGF I receptor number following exposure to 5 μM antisense oligonucleotide markedly inhibited angiotensin II-induced mitogenesis. A 70% increase in IGF I receptor number following exposure to 5 μM sense oligonucleotide resulted in a 4-fold increase in basal [3H]thymidine incorporation, and angiotensin II (1-1000 nM) had no additive stimulatory effect. An antisense oligonucleotide targeting a sequence starting at +109 base pairs (relative to ATG) also reduced IGF I receptor number, however, the corresponding sense oligonucleotide was without effect. These findings demonstrate that alterations in vascular smooth muscle cell IGF I receptor density play a critical role in the proliferative response of vascular smooth muscle cells to serum and to angiotensin II. In addition, the surprising observation that an ATG-directed sense oligonucleotide up-regulates IGF I receptors identifies a novel effect of oligonucleotides on gene expression.

Background: Henoch-Schönlein purpura, more recently renamed immunoglobulin A vasculitis (IgAV), is a systemic vasculitis characterized by IgA deposits. The current markers used to assess IgAV inaccurately evaluate the risk of nephritis occurrence and its long-term outcomes. The current study assessed biomarkers of nephritis outcomes. Methods: This French multicentre prospective study enrolled 85 adult patients at the time of disease onset. Patients were assessed for clinical and biological parameters and re-examined after 1 year. Immunoglobulins, cytokines, IgA glycosylation, IgA complexes and neutrophil gelatinase-associated lipocalin (NGAL) concentrations were assessed in blood and urine. Results: We identified 60 patients with IgAV-related nephritis (IgAV-N) and 25 patients without nephritis (IgAV-woN). At the time of inclusion (Day 1), the serum levels of galactose-deficient IgA1 (Gd-IgA1) and urinary concentrations of IgA, IgG, IgM, NGAL, interleukin (IL)-1β, IL-6, IL-8, IL-10, IgA-IgG and IgA-sCD89 complexes were higher in the IgAV-N patients than in the IgAV-woN patients (P < 0.005 for all comparisons). After follow-up (1 year), 22 patients showed a poor outcome. Among the tested markers, urine IgA at disease onset adequately reclassified the risk of poor outcome over conventional clinical factors, including estimated glomerular filtration rate, proteinuria and age (continuous net reclassification improvement = 0.72, P = 0.001; integrated discrimination improvement = 0.13, P = 0.009) in IgAV patients. Conclusions: Taken together, these results showed that serum Gd-IgA1 and urinary IgA, IgG, IgM, NGAL, IL-1β, IL-6, IL-8, IL-10, IgA-IgG and IgA-sCD89 complexes were associated with nephritis in IgAV patients. Urinary IgA level may improve patient risk stratification for poor outcome.

Calycosin, an isoflavonoid phytoestrogen, isolated from Radix Astragali, was reported to possess anti-tumor, anti-inflammation, and osteogenic properties, but its impact on osteoclast differentiation remains unclear. In this study, we examined the effects of calycosin on osteoclastogenesis induced by RANKL. The results showed that calycosin significantly inhibited RANKL-induced osteoclast formation from primary bone marrow macrophages (BMMs). Calycosin also dose-dependently suppressed the formation of bone resorption pits by mature osteoclasts. In addition, the expression of osteoclatogenesis-related genes, including cathepsin K (CtsK), tartrate-resistant acid phosphatase (TRAP), and MMP-9, was significantly inhibited by calycosin. Furthermore, the results indicated that calycosin down-regulated the expression levels of NFATc1 and c-Fos through suppressing the activation of NF-κB and MAPKs. Our results indicate that calycosin has an inhibitory role in the bone loss by preventing osteoclast formation, as well as its bone resorptive activity. Therefore, calycosin may be useful as a therapeutic reagent for bone loss-associated diseases.

Saikosaponin‑d (SSd), a triterpene saponin compound derived from Bupleurum radix, has been shown to have a cytotoxic effect on various cancer cell lines. However, its effect on prostate cancer cells has remained unexplored. The present study reports the apoptosis‑inducing effect of SSd on the DU145 human prostate carcinoma cell line. Treatment with SSd inhibited DU145 cell proliferation in a concentration‑dependent manner. Flow cytometric analysis showed that SSd inhibited the proliferation of DU145 cells by induction of apoptosis and cell cycle arrest at G0/G1 phase. Further mechanistic experiments demonstrated that SSd arrested the cell cycle at G0/G1 phase via upregulation of p53 and p21 and induced apoptosis by modulating B‑cell lymphoma 2 family proteins, dissipation of the mitochondrial membrane potential, release of cytochrome c into the cytosol and activation of caspase‑3. In conclusion the present study indicated that SSd induced apoptosis in DU145 cells by the intrinsic apoptotic pathway. Therefore, SSd may become a leading candidate drug for the therapy of prostate carcinoma.

Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30-150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.

The study was designed as one of a series to find novel anticancer compounds from Chinese herbs. For this purpose, we screened an ethanol extract of 300 herbs against SGC-7901 cells. Sophora flavescen was included in those showing potential cytotoxic activity. Target compounds were therefore isolated and analyzed on analytical HPLC. Chromatography showed only one peak with a purity of 97%. The ESI-MS spectrum showed two molecular ions: m/z 424(M+) and 438(M+). Furthermore, combining the data of 1HNMR and 13CNMR, it was deduced that this product was a mixture of two compounds; kuraridin (1) and nor-kurarinone (2). The concentration was [1]:[2]=9:10, the chemical structural formulae are C25H28O6 and C26H30O6. In this study, mechanisms involved by the mixture of compounds 1 and 2-induced growth inhibition including apoptosis and G2/M phase arrest in human gastric adenocarcinoma SGC-7901 cells were examined for the first time. Triggering of the mitochondrial apoptotic pathway was demonstrated by loss of mitochondrial membrane potential, reduction in the Bcl-2/Bax ratio, and significant activation and cleavage of caspase-3. Additionally, the production of reactive oxygen species (ROS) was also increased. Taken together, our results indicated that the cytotoxic efficacy of the mixture of compounds 1 and 2 is mainly due to induction of cell cycle arrest and apoptosis.

Currently an ample interest is found among oncologists to explore anticancer compounds from herbs. Sesquiterpene lactones have accredited significant attention in pharmacological research. Costunolide is a well-known sesquiterpene lactone present in plants used as popular herbal remedy. Several plant-derived compounds are currently successfully employed in cancer treatment. Growing evidences demonstrated that costunolide possesses anticancer activities by inhibiting cell proliferation, tumor invasion, angiogenesis, metastasis and inducing apoptosis of a variety of tumor cell lines. This review is aimed to summarize the recent researches about costunolide focusing on anti-tumor activity and to lay emphasis on its molecular targets and its mechanisms, which may help the further design and conduct of preclinical and clinical trials.

BACKGROUND/AIMS: Salvia miltiorrhiza (SM) contains four major aqueous active ingredients, which have been isolated, purified and identified as danshensu (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic aldehyde (PAL), totally abbreviated as SABP. Although SM is often used to treat various cardiovascular diseases in traditional Chinese medicine, the efficacy and function of optimal compatibility ratio of SM's active ingredients (SABP) in the prevention and treatment of cardiovascular diseases remain uncertain. This study investigated antihypertensive effect and underlying mechanisms of SABP vs. SM lyophilized powder (SMLP) in spontaneously hypertensive rats (SHR) and to establish the ratio of the optimal compatibility of DSS, Sal-A, Sal-B and PAL in improving cardiovascular functions. METHODS: The SHRs were treated with either SABP or SMLP and their systolic blood pressures (SBP) were monitored. The isolated thoracic aorta of SHRs was segregated for immunohistochemistry, Hematoxylin-Eosin stain and mRNA and protein expression of NOX4, TGF-β1, Col-I, ET-1, α-SMA and Smad7. Moreover, the adventitial fibroblasts (AFs) were isolated and cultured from SD rats' aorta and the reactive oxygen species (ROS) production was determined after SABP or SMLP treatment. RESULTS: SABP, but not SMLP, significantly reduced SBP, which were accompanied by the inhibited morphological changes in the thoracic aorta and the reduced mRNA and protein expression of NOX4, TGF-β1, Col-I, ET-1 and α-SMA, but the increased Smad 7 expression in SHRs. Moreover, SABP also resulted in a decreased ROS production in AFs of SD rats. CONCLUSIONS: These results indicate that SABP, but not SMLP, treatment potently inhibits hypertension through improvements of vascular remodeling and oxidative stress. The present study provides new evidence that the efficacy and function from optimal compatibility ratio of SM active ingredients is much better than its lyophilized powder, which represents a strategy to develop SM's new beneficial effect in improving cardiovascular functions.