High levels circulating saturated fatty acids are associated with diabetes, obesity and hyperlipidemia. In heart, the accumulation of saturated fatty acids has been determined to play a role in the ...development of heart failure and diabetic cardiomyopathy. High-density lipoprotein (HDL) has been reported to possess key atheroprotective biological properties, including cellular cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities. However, the underlying mechanisms are still largely unknown. Therefore, the aim of the present study is to test whether HDL could protect palmitic acid (PA)-induced cardiomyocyte injury and explore the possible mechanisms.
H9c2 cells were pretreated with HDL (50-100 μg/ml) for 2 h followed by PA (0.5 mM) for indicated time period. Our results showed that HDL inhibited PA-induced cell death in a dose-dependent manner. Moreover, HDL rescued PA-induced ROS generation and the phosphorylation of JNK which in turn activated NF-κB-mediated inflammatory proteins expressions. We also found that PA impaired the balance of BCL
family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase 3. These detrimental effects were ameliorated by HDL treatment.
PA-induced ROS accumulation and results in cardiomyocyte apoptosis and inflammation. However, HDL attenuated PA-induced lipotoxicity and oxidative dysfunction via ROS suppression. These results may provide insight into a possible molecular mechanism underlying HDL suppression of the free fatty acid-induced cardiomyocyte apoptosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Cisplatin resistance is a major clinical problem in the clinical management of oral squamous cell carcinoma (OSCC) patients. Resveratrol is a natural phytoestrogen with antitumor activities. Whether ...resveratrol can overcome cisplatin resistance and prevent metastasis in OSCC cells is not known. In this study, we first examined the anti‐metastatic capacity of resveratrol and then explored the underlying mechanisms using a cisplatin‐resistant human OSCC cell line (CAR). The results demonstrated that at a non‐toxic dose range (25 to 75 µM), 24‐hr treatment of resveratrol was able to suppress the migration and invasion capacities of CAR cells dose dependently. Interestingly, 50 µM resveratrol treatment could significantly down‐regulate the expression of the phosphorylated forms of ERK and p‐38, in addition to those of MMP‐2 and MMP‐9. At the same time, the expression levels of phosphorylated ERK together with those unphosphorylated forms of ERK, p38, and JNK were all insignificantly altered. In conclusion, the signaling cascade for resveratrol's suppression of cisplatin‐resistant human oral cancer CAR cells was revealed and summarized. Also the rapid effectiveness in suppressing metastatic behaviors of drug‐resistant oral cancer cells of non‐toxic resveratrol might extend its application to the drug‐resistant oral cancer treatment in the near future.
Practical applications
Based on the evidence we provided in the study, we have proposed a model recording the possible pathway for resveratrol inhibiting the metastasis of cisplatin‐resistant oral cancer cells. We suppose this signaling pathway may work in other cancer cell lines, and can be helpful in full understanding of the drug‐resistance
The current study provides the drug reposition evidence for resveratrol can inhibit the metastasis behaviors of cisplatin‐resistant oral cancer cells. This novel application is beneficial in not only clinical therapy for the oral cancer patients but also in translational medical science achievements.
Liquefaction-induced lateral spreading is a main cause of pile failure during earthquakes because it places considerable soil pressure on piles. The lateral spreading pressure originates not only ...from liquefied soil but also from nonliquefied soil when it overlays a liquefied soil layer. In this study, we develop a practical lateral spreading pressure model for pseudostatic analysis to analyze pile response in inclined liquefied ground. The model comprises two parts. First, using a laminar flow model, the lateral spreading pressure of liquefied soil is modeled as the equivalent fluid flowing pressure. The coefficient of viscosity of the liquefied soil is constructed on the basis of shaking table tests in the literature. The normalized lateral spreading pressure depends on the liquefied soil thickness-to-pile diameter ratio. Second, for nonliquefied soil, individual p–y curves for uphill and downhill soils are used to simulate their distinctive soil reaction mechanisms. The uphill soil is subjected to lateral spreading soil displacement, whereas the downhill soil is subjected to pile displacement. This approach can elucidate the net soil reactions of the downhill and uphill soils that vary depending on pile stiffness. The proposed model is validated through simulations involving 1-g shaking table tests, centrifuge tests, and case histories reported in the literature.
•Lateral spreading pressure of liquefied soil is modeled as equivalent fluid flowing pressure based on a laminar flow model.•The normalized lateral spreading pressure depends on the liquefied soil thickness-to-pile diameter ratio.•P–y curves of uphill and downhill nonliquefied soils are used to simulate their distinctive soil reaction mechanisms.•The stiff pile sustains larger lateral spreading pressure because of larger soil reactions from the uphill soil.
The coronavirus disease 2019 (COVID‑19) outbreak, which has caused >46 millions confirmed infections and >1.2 million coronavirus related deaths, is one of the most devastating worldwide crises in ...recent years. Infection with COVID‑19 results in a fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and a sore throat, similar to those of acute respiratory distress syndrome. The causative agent of COVID‑19, SARS‑CoV‑2, is a novel coronavirus strain. To date, remdesivir has been granted emergency use authorization for use in the management of infection. Additionally, several efficient diagnostic tools are being actively developed, and novel drugs and vaccines are being evaluated for their efficacy as therapeutic agents against COVID‑19, or in the prevention of infection. The present review highlights the prevalent clinical manifestations of COVID‑19, characterizes the SARS‑CoV‑2 viral genome sequence and life cycle, highlights the optimal methods for preventing viral transmission, and discusses possible molecular pharmacological mechanisms and approaches in the development of anti‑SARS‑CoV‑2 therapeutic agents. In addition, the use of traditional Chinese medicines for management of COVID‑19 is discussed. It is expected that novel anti‑viral agents, vaccines or an effective combination therapy for treatment/management of SARS‑CoV‑2 infection and spread therapy will be developed and implemented in 2021, and we would like to extend our best regards to the frontline health workers across the world in their fight against COVID‑19.
Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers, and gastric cancer. The flavonoid compounds baicalin and baicalein found in many medicinal plants exhibit an ...anti‐inflammatory effect. The administration of Lactobacillus strains reducing the risk of H. pylori infection is well accepted. In this study, the therapeutic effects against H. pylori infection of baicalin, baicalein, and L. rhamnosus JB3 (LR‐JB3), isolated from a dairy product, were investigated. Compared to baicalin, baicalein exhibited stronger anti‐H. pylori activity and cytotoxicity on human gastric cancer epithelial AGS cells. Baicalin and baicalein both suppressed the vacA gene expression of H. pylori and interfered with the adhesion and invasion ability of H. pylori to AGS cells, as well as decreased H. pylori‐induced interleukin (IL)‐8 expression. In the mice infection model, high dosages of baicalin and baicalein inhibited H. pylori growth in the mice stomachs. Serum IL‐1β levels and H. pylori‐specific serum IgM and IgA levels in mice treated with baicalin and baicalein were decreased. Moreover, a synergistic therapeutic effect of baicalein and LR‐JB3 on eradicating H. pylori infections was observed. Thus, administrating baicalin, baicalein, or LR‐JB3 for an H. pylori infection could offer similar therapeutic effects to administering antibiotics while not disturbing the balance of gut microbiota. This study revealed the effects of baicalin, baicalein, and LR‐JB3 on attenuating the virulence of H. pylori. The synergistic effect with baicalein and LR‐JB3 provides the experimental rationale for testing the reliability, safety, and efficacy of this approach in higher animals and perhaps ultimately in humans to eradicate H. pylori infections.
Practical Application
Baicalin and baicalein exert health promotion and avoidance of H. pylori infections by interfering with H. pylori growth and virulence. Lactobacillus rhamnosus JB3 was used to reduce the gastric inflammation caused by H. pylori infection.
Resveratrol is known to be an effective chemo-preventive phytochemical against multiple tumor cells. However, the increasing drug resistance avoids the cancer treatment in oral cavity cancer. In this ...study, we investigated the oral antitumor activity of resveratrol and its mechanism in cisplatin-resistant human oral cancer CAR cells. Our results demonstrated that resveratrol had an extremely low toxicity in normal oral cells and provoked autophagic cell death to form acidic vesicular organelles (AVOs) and autophagic vacuoles in CAR cells by acridine orange (AO) and monodansylcadaverine (MDC) staining. Either DNA fragmentation or DNA condensation occurred in resveratrol-triggered CAR cell apoptosis. These inhibitors of PI3K class III (3-MA) and AMP-activated protein kinase (AMPK) (compound c) suppressed the autophagic vesicle formation, LC3-II protein levels and autophagy induced by resveratrol. The pan-caspase inhibitor Z-VAD-FMK attenuated resveratrol-triggered cleaved caspase-9, cleaved caspase-3 and cell apoptosis. Resveratrol also enhanced phosphorylation of AMPK and regulated autophagy- and pro-apoptosis-related signals in resveratrol-treated CAR cells. Importantly, resveratrol also stimulated the autophagic mRNA gene expression, including Atg5, Atg12, Beclin-1 and LC3-II in CAR cells. Overall, our findings indicate that resveratrol is likely to induce autophagic and apoptotic death in drug-resistant oral cancer cells and might become a new approach for oral cancer treatment in the near future.
Diabetic patients are highly vulnerable to hypoxic injury, which is associated with hypoxia induced BNIP3 expression that subsequently activate apoptosis. Our previous research show that ...Tetramethylpyrazine (TMP), a food flavoring agent, represses the hypoxia induced BNIP3 expression attenuate myocardial apoptosis. In this study, we evaluate the effect of TMP to provide protection against hypoxia aggravated high-glucose associated cellular apoptosis.
The cytoprotective effect of TMP against high glucose induced cellular damages was determined on embryo derived H9c2 cardiomyoblast cells that were subjected to 5% hypoxia for 24 h and subjected to different duration of 33 mM high glucose challenge. Further, the involvement of HIF-1α and BNIP3 in cellular damage and the mechanism of protection of TMP were determined by overexpression and silencing HIF-1α and BNIP3 protein expression.
The results show that hypoxic effects on cell viability aggravates with high glucose challenge and this augmentative effect is mediated through BNIP3 in H9c2 cardiomyoblast cells. However, TMP administration effectively reversed the augmented HIF-1α levels and BNIP3 elevation. TMP improved the survival of H9c2 cells and effectively suppressed apoptosis in H9c2 cells. Further comparison on the effects of TMP on H9c2 cells challenged with high glucose and those challenged with hypoxia show that TMP precisely regulated the hypoxic intensified apoptotic effects in high-glucose condition.
The results clearly show that flavoring agent-TMP attenuates cytotoxicity amplified by hypoxia challenge in high glucose condition by destabilizing HIF-1α.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Osteoarthritis (OA) commonly affects the synovial joint and is characterized by degradation of articular cartilage, which is largely mobilized by increased matrix metalloproteinase (MMP) activity. ...Soya-cerebroside, an extract of Cordyceps militaris, inhibits inflammatory cytokine production and monocyte migration in human synovial fibroblasts, although its effects are uncertain on MMP expression in chondrocytes and cartilage degradation. In this study, soya-cerebroside antagonized interleukin 1 beta (IL-1β)-induced MMP-1 production in chondrocytes, without cytotoxic effects. Functional genomic data confirm high levels of MMP-1 expression in OA tissue compared with normal tissue. Soya-cerebroside reduced MMP-1 expression via the focal adhesion kinase (FAK), mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK) and AP-1 signalling pathways. In addition, soya-cerebroside suppressed IL-1β-promoted MMP-1 expression and cartilage degradation in animal models. Our report is the first to reveal that soya-cerebroside reduces MMP-1 production in chondrocytes and protects cartilage degradation through the FAK, MEK, ERK, and AP-1 signalling cascade.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Eradication of Helicobacter pylori infection is the most direct and effective way for preventing gastric cancer. Lactic acid bacteria are considered as alternative therapeutic agents ...against H. pylori infection.
Methods
Effects of Lactobacillus rhamnosus JB3 (LR‐JB3) on the virulence gene expression of H. pylori and infection‐induced cellular responses of AGS cells were investigated by co‐cultivating infected AGS cells with different multiplicity of infections (MOIs) of LR‐JB3.
Results
LR‐JB3, specifically at a MOI of 25, suppressed the association ability of H. pylori and its induced IL‐8 levels, as well as the mRNA levels of vacA, sabA, and fucT of H. pylori, infection‐induced Lewis (Le)x antigen and Toll‐like receptor 4 (TLR4) expressions in AGS cells. However, the apoptosis mediated by infection was inhibited by LR‐JB3 in a dose‐dependent manner. In addition, autoinducer (AI)‐2 was observed to have increased the association ability and fucT expression of H. pylori, and Lex antigen and TLR4 expression of AGS cells. Interestingly, an unknown bioactive cue was hypothesized to have been secreted from LR‐JB3 at a MOI of 25 to act as an antagonist of AI‐2.
Conclusions
LR‐JB3 possesses various means to interfere with H. pylori pathogenesis and infection‐induced cellular responses of AGS cells to fight against infection.
The recruitment of bone marrow-derived endothelial progenitor cells (EPCs) facilitates physiological and pathological processes involved in new blood vessel synthesis. Glucocerebroside, an extract of ...Cordyceps militaris, inhibits inflammatory cytokine production and monocyte migration, although its anti-angiogenic properties in human EPCs has remained largely unknown up until now. We describe how glucocerebroside reduces migration as well as tube formation induced by vascular endothelial growth factor (VEGF) stimulation in human EPCs, without affecting cell viability. This inhibitory effect was achieved through the focal adhesion kinase (FAK)/c-Src pathways. We also found that glucocerebroside reduced VEGF-promoted upregulation of the transcription factor Runx2 in the EPCs. The in vivo chick embryo chorioallantoic membrane model demonstrated that glucocerebroside reduces new vessel formation. Our investigation is the first to show that glucocerebroside reduces angiogenesis in human EPCs and to describe the underlying mechanisms. Further investigations are needed to examine the effects of glucocerebroside in other angiogenesis-related disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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