Tumor Cell Membrane-Encapsulated MLA Solid Lipid Nanoparticles for Targeted Diagnosis and Radiosensitization Therapy of Cutaneous Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) is a common nonmelanoma skin cancer. Radiotherapy plays an integral role in treating SCC due to its characteristics, such as diminished intercellular adhesion, heightened cell migration and invasion capabilities, and immune evasion. These problems lead to inaccurate tumor boundary positioning and radiotherapy tolerance in SCC treatment. Thus, accurate localization and enhanced radiotherapy sensitivity are imperative for effective SCC treatment. To address the existing limitations in SCC therapy, we developed monoglyceride solid lipid nanoparticles (MG SLNs) and enveloped them with the A431 cell membrane (A431 CM) to create A431@MG. The characterization results showed that A431@MG was spherical. Furthermore, A431@MG had specific targeting for A431 cells. In A431 tumor-bearing mice, A431@MG demonstrated prolonged accumulation within tumors, ensuring precise boundary localization of SCC. We further advanced the approach by preparing MG SLNs encapsulating 5-aminolevulinic acid methyl ester (MLA) and desferrioxamine (DFO) with an A431 CM coating to yield A431@MG-MLA/DFO. Several studies have revealed that DFO effectively reduced iron content, impeding protoporphyrin IX (PpIX) biotransformation and promoting PpIX accumulation. Simultaneously, MLA was metabolized into PpIX upon cellular entry. During radiotherapy, the heightened PpIX levels enhanced reactive oxygen species (ROS) generation, inducing DNA and mitochondrial damage and leading to cell apoptosis. In A431 tumor-bearing mice, the A431@MG-MLA/DFO group exhibited notable radiotherapy sensitization, displaying superior tumor growth inhibition. Combining A431@MG-MLA/DFO with radiotherapy significantly improved anticancer efficacy, highlighting its potential to serve as an integrated diagnostic and therapeutic strategy for SCC.

Advances in Composite Biofilm Biomimetic Nanodrug Delivery Systems for Cancer Treatment.

Single biofilm biomimetic nanodrug delivery systems based on single cell membranes, such as erythrocytes and cancer cells, have immune evasion ability, good biocompatibility, prolonged blood circulation, and high tumor targeting. Because of the different characteristics and functions of each single cell membrane, more researchers are using various hybrid cell membranes according to their specific needs. This review focuses on several different types of biomimetic nanodrug-delivery systems based on composite biofilms and looks forward to the challenges and possible development directions of biomimetic nanodrug-delivery systems based on composite biofilms to provide reference and ideas for future research.

Nanofabrications of Erythrocyte Membrane-Coated Telmisartan Delivery System Effective for Radiosensitivity of Tumor Cells in Mice Model.

Background: Radiation stimulates the secretion of tumor stroma and induces resistance, recurrence, and metastasis of stromal-vascular tumors during radiotherapy. The proliferation and activation of tumor-associated fibroblasts (TAFs) are important reasons for the production of tumor stroma. Telmisartan (Tel) can inhibit the proliferation and activation of TAFs (resting TAFs), which may promote radiosensitization. However, Tel has a poor water solubility. Methods: In this study, self-assembled telmisartan nanoparticles (Tel NPs) were prepared by aqueous solvent diffusion method to solve the insoluble problem of Tel and achieve high drug loading of Tel. Then, erythrocyte membrane (ECM) obtained by hypotonic lysis was coated on the surface of Tel NPs (ECM/Tel) for the achievement of in vivo long circulation and tumor targeting. Immunofluorescence staining, western blot and other biological techniques were used to investigate the effect of ECM/Tel on TAFs activation inhibition (resting effect) and mechanisms involved. The multicellular spheroids (MCSs) model and mouse breast cancer cells (4T1) were constructed to investigate the effect of ECM/Tel on reducing stroma secretion, alleviating hypoxia, and the corresponding promoting radiosensitization effect in vitro. A mouse orthotopic 4T1 breast cancer model was constructed to investigate the radiosensitizing effect of ECM/Tel on inhibiting breast cancer growth and lung metastasis of breast cancer. Results: ECM/Tel showed good physiological stability and tumor-targeting ability. ECM/Tel could rest TAFs and reduce stroma secretion, alleviate hypoxia, and enhance penetration in tumor microenvironment. In addition, ECM/Tel arrested the cell cycle of 4T1 cells to the radiosensitive G2/M phase. In mouse orthotopic 4T1 breast cancer model, ECM/Tel played a superior role in radiosensitization and significantly inhibited lung metastasis of breast cancer. Conclusion: ECM/Tel showed synergistical radiosensitization effect on both the tumor microenvironment and tumor cells, which is a promising radiosensitizer in the radiotherapy of stroma-vascular tumors.

Hypertension in non-obese children and BMI in adulthood: the Bogalusa heart study.

OBJECTIVE: This study explored the association between hypertension(HTN) in non-obese children body mass index (BMI) in adulthood. METHODS: A retrospective analysis of 1111 participants from the Bogalusa Heart Study was conducted, in which data on hypertension history during childhood in non-obese children, anthropometric and cardiovascular risk factors and other indicators from cross-sectional examinations in adulthood were collected. BMI was used as both a continuous and a categorical variable, and multivariate linear regression modelling and logistic regression modelling were used. RESULTS: Of the 1111 participants finally enrolled, 40 (3.60%) had HTN during childhood. After adjusting for demographic characteristics, lipid, glucose and insulin levels in childhood, and smoking status, alcohol intake, and disease history as adults, HTN among non-obese children was positively associated with BMI in adulthood (ß = 2.64 kg/m2, 95% CI: 0.88-4.40, P = 0.0033), and the odds of being overweight or obese was 3.71 times higher in the group with a history of hypertension in childhood than those without a history of HTN(95% CI: 1.11-12.46, P = 0.0337). CONCLUSION: Among non-obese children, hypertension is at risk for higher levels of BMI in adulthood. Identifying and controlling blood pressure and childhood may aid in the prevention of adult obesity.

The novel effectiveness of Tai Chi on cardiopulmonary fitness among stroke patients in the recovery phase: a study protocol for a randomized controlled trial.

BACKGROUND: Stroke is the leading cause of death worldwide. China faces a similar risk of stroke as developed countries because of considerable changes in lifestyle, such as overeating and smoking. Tai Chi is a traditional form of mind-body exercise that has been widely practiced in China for thousands of years. However, there are few studies on the effect of Tai Chi on the cardiopulmonary function of stroke patients in the recovery phase. Therefore, it is necessary to observe the effect of Tai Chi on the cardiorespiratory fitness of patients after stroke. METHODS: This is a parallel-design, two-arm, analyst assessor-blinded, randomized controlled trial. A total of 226 stroke patients in the recovery phase will be recruited and assigned randomly to a control group or Tai Chi group at a 1:1 ratio. The patients in the Tai Chi group will perform the Tai Chi exercise. The patients in the control group will perform walking exercises. Patients in both groups will receive conventional treatments and healthy education. The primary outcomes will be VO2peak and scores on the MOS item short form health survey (SF-36) scale. Secondary outcomes will include vital capacity (VC), ejection fractions (EF), and cardiac output (CO). The assessments of the tests will be performed at three time points (before exercise, at the end of exercise, and 6 weeks after exercise). Adverse events will be recorded faithfully during the study. DISCUSSION: If the results are positive, this study will contribute to the establishment of further guided Tai Chi rehabilitation programs. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000034719 . Registered on 16 July 2020.

Superhydrophobic and Flexible Silver Nanowire-Coated Cellulose Filter Papers with Sputter-Deposited Nickel Nanoparticles for Ultrahigh Electromagnetic Interference Shielding.

Superhydrophobic, flexible, and ultrahigh-performance electromagnetic interference (EMI) shielding papers are of paramount importance to safety and long-term service under external mechanical deformations or other harsh service environments because they fulfill the growing demand for multipurpose materials. Herein, we fabricated multifunctional papers by incorporating sputter-deposited nickel nanoparticles (NiNPs) and a fluorine-containing coating onto cellulose filter papers coated with silver nanowires (AgNWs). AgNW networks with sputter-deposited NiNPs provide outstanding magnetic properties, electrical conductivity, and EMI shielding performance. At an AgNW content of 0.109 vol % and a NiNP content of 0.013 mg/cm2, the resultant papers exhibit a superior EMI shielding effectiveness (SE) of 88.4 dB. Additionally, the fluorine-containing coating endows the resultant papers with a high contact angle of 149.7°. Remarkably, the obtained papers still maintain a high EMI SE even after 1500 bending cycles or immersion in water, salt, or strong alkaline solutions for 2 h, indicating their outstanding mechanical robustness and chemical durability. This work opens a new window for designing and implementing ultrahigh-performance EMI shielding materials.

The role of carbon nanoparticles in guiding central neck dissection and protecting the parathyroid in transoral vestibular endoscopic thyroidectomy for thyroid cancer.

INTRODUCTION: Transoral vestibular endoscopic thyroidectomy (TOET) is sometimes used in young and middle-aged patients with papillary thyroid microcarcinoma (PTMC), but it is still difficult to identify lymph nodes (LNs) and parathyroid glands (PGs). Carbon nanoparticle (CN) is a novel lymph node tracer and has been widely used in open thyroid surgery. AIM: To evaluate the efficacy of CN in identifying LNs and preserving PGs in TOET with central neck dissection (CND). MATERIAL AND METHODS: A total of 72 PTMC patients undergoing TOET with CND were retrospectively enrolled from January 2017 to January 2019. Patients were divided into a CN group (n = 38) and a control group (n = 34). The parameters including pathological characteristics, surgery related indicators, serum Ca2+ and parathyroid hormone (PTH) levels were compared. RESULTS: No significant differences were found in patient characteristics, operative complications and superior PGs preserved in situ (all p > 0.05). Total LNs and number of LNs less than 5 mm were significantly higher in the CN group than in the control group (p = 0.021, p < 0.01). The number of superior PGs preserved in situ discovered in the CN group was greater than the control group (p = 0.038). Serum PTH and Ca2+ levels dropped markedly in each group after surgery and gradually recovered in time. The CN group recovered faster than the control group. CONCLUSIONS: CN may be a good choice for TOET for PTMC because of better protection and faster recovery of parathyroid function, and more LNs removed.

Corosolic acid attenuates cardiac fibrosis following myocardial infarction in mice.

Corosolic acid (CRA) is a pentacyclic triterpenoid isolated from Lagerstroemia speciosa. The aim of the present study was to determine whether CRA reduces cardiac remodelling following myocardial infarction (MI) and to elucidate the underlying mechanisms. C57BL/6J mice were randomly divided into control (PBS­treated) or CRA­treated groups. After 14 days of pre­treatment, the mice were subjected to either sham surgery or permanent ligation of the left anterior descending artery. Following surgery, all animals were treated with PBS or CRA (10 or 20 mg/kg/day) for 4 weeks. After 4 weeks, echocardiographic, haemodynamic, gravimetric, histological and biochemical analyses were conducted. The results revealed that, upon MI, mice with CRA treatment exhibited decreased mortality rates, improved ventricular function and attenuated cardiac fibrosis compared with those in control mice. Furthermore, CRA treatment resulted in reduced oxidative stress, inflammation and apoptosis, as well as inhibited the transforming growth factor ß1/Smad signalling pathway activation in cardiac tissue. In vitro studies further indicated that inhibition of AMP­activated protein kinase α (AMPKα) reversed the protective effect of CRA. In conclusion, the study revealed that CRA attenuated MI­induced cardiac fibrosis and dysfunction through modulation of inflammation and oxidative stress associated with AMPKα.

Metabolite-mediated TOR signaling regulates the circadian clock in Arabidopsis.

Circadian clocks usually run with a period close to 24 h, but are also plastic and can be entrained by external environmental conditions and internal physiological cues. Two key nutrient metabolites, glucose and vitamin B3 (nicotinamide), can influence the circadian period in both mammals and plants; however, the underlying molecular mechanism is still largely unclear. We reveal that the target of rapamycin (TOR) kinase, a conserved central growth regulator, is essential for glucose- and nicotinamide-mediated control of the circadian period in Arabidopsis Nicotinamide affects the cytosolic adenosine triphosphate concentration, and blocks the effect of glucose-TOR energy signaling on period length adjustment, meristem activation, and root growth. Together, our results uncover a missing link between cellular metabolites, energy status, and circadian period adjustment, and identify TOR kinase as an essential energy sensor to coordinate circadian clock and plant growth.

Myricetin Alleviates Pathological Cardiac Hypertrophy via TRAF6/TAK1/MAPK and Nrf2 Signaling Pathway.

Myricetin (Myr) is a common plant-derived polyphenol and is well recognized for its multiple activities including antioxidant, anti-inflammation, anticancer, and antidiabetes. Our previous studies indicated that Myr protected mouse heart from lipopolysaccharide and streptozocin-induced injuries. However, it remained to be unclear whether Myr could prevent mouse heart from pressure overload-induced pathological hypertrophy. Wild type (WT) and cardiac Nrf2 knockdown (Nrf2-KD) mice were subjected to aortic banding (AB) surgery and then administered with Myr (200 mg/kg/d) for 6 weeks. Myr significantly alleviated AB-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction in both WT and Nrf2-KD mice. Myr also inhibited phenylephrine- (PE-) induced neonatal rat cardiomyocyte (NRCM) hypertrophy and hypertrophic markers' expression in vitro. Mechanically, Myr markedly increased Nrf2 activity, decreased NF-κB activity, and inhibited TAK1/p38/JNK1/2 MAPK signaling in WT mouse hearts. We further demonstrated that Myr could inhibit TAK1/p38/JNK1/2 signaling via inhibiting Traf6 ubiquitination and its interaction with TAK1 after Nrf2 knockdown in NRCM. These results strongly suggested that Myr could attenuate pressure overload-induced pathological hypertrophy in vivo and PE-induced NRCM hypertrophy via enhancing Nrf2 activity and inhibiting TAK1/P38/JNK1/2 phosphorylation by regulating Traf6 ubiquitination. Thus, Myr might be a potential strategy for therapy or adjuvant therapy for malignant cardiac hypertrophy.

Corosolic acid ameliorates cardiac hypertrophy via regulating autophagy.

AIM: In this work, we explored the role of corosolic acid (CRA) during pressure overload-induced cardiac hypertrophy. METHODS AND RESULTS: Cardiac hypertrophy was induced in mice by aortic banding. Four weeks post-surgery, CRA-treated mice developed blunted cardiac hypertrophy, fibrosis, and dysfunction, and showed increased LC3 II and p-AMPK expression. In line with the in vivo studies, CRA also inhibited the hypertrophic response induced by PE stimulation accompanying with increased LC3 II and p-AMPK expression. It was also found that CRA blunted cardiomyocyte hypertrophy and promoted autophagy in Angiotensin II (Ang II)-treated H9c2 cells. Moreover, to further verify whether CRA inhibits cardiac hypertrophy by the activation of autophagy, blockade of autophagy was achieved by CQ (an inhibitor of the fusion between autophagosomes and lysosomes) or 3-MA (an inhibitor of autophagosome formation). It was found that autophagy inhibition counteracts the protective effect of CRA on cardiac hypertrophy. Interestingly, AMPK knockdown with AMPKα2 siRNA-counteracted LC3 II expression increase and the hypertrophic response inhibition caused by CRA in PE-treated H9c2 cells. CONCLUSION: These results suggest that CRA may protect against cardiac hypertrophy through regulating AMPK-dependent autophagy.

Comparative analysis of proteomic and metabolomic profiles of different species of Paris.

An extract prepared from species of Paris is the most widely consumed herbal product in China. The genus Paris includes a variety of genotypes with different medicinal component contents but only two are defined as official sources. Closely related species have different medicinal properties because of differential expression of proteins and metabolites. To better understand the molecular basis of these differences, we examined proteomic and metabolomic changes in rhizomes of P. polyphylla var. chinensis, P. polyphylla var. yunnanensis, and P. fargesii var. fargesii using a technique known as sequential window acquisition of all theoretical mass spectra as well as gas chromatography-time-of-flight mass spectrometry. In total, 419 proteins showed significant abundance changes, and 33 metabolites could be used to discriminate Paris species. A complex analysis of proteomic and metabolomic data revealed a higher efficiency of sucrose utilization and an elevated protein abundance in the sugar metabolic pathway of P. polyphylla var. chinensis. The pyruvate content and efficiency of acetyl-CoA-utilization in saponin biosynthesis were also higher in P. polyphylla var. chinensis than in the other two species. The results expand our understanding of the proteome and metabolome of Paris and offer new insights into the species-specific traits of these herbaceous plants. SIGNIFICANCE: The traditional Chinese medicine Paris is the most widely consumed herbal product for the treatment of joint pain, rheumatoid arthritis and antineoplastic. All Paris species have roughly the same morphological characteristics; however, different members have different medicinal compound contents. Efficient exploitation of genetic diversity is a key factor in the development of rare medicinal plants with improved agronomic traits and malleability to challenging environmental conditions. Nevertheless, only a partial understanding of physiological and molecular mechanisms of different plants of Paris can be achieved without proteomics. To better understand the molecular basis of these differences and facilitate the use of other Paris species, we examine proteomic metabolomic changes in rhizomes of Paris using the technique known as SWATH-MS and GC/TOF-MS. Our research has provided information that can be used in other studies to compare metabolic traits in different Paris species. Our findings can also serve as a theoretical basis for the selection and cultivation of other Paris species with a higher medicinal value.

A comparison of transoral vestibular and bilateral areolar endoscopic thyroidectomy approaches for unilateral papillary thyroid microcarcinomas.

INTRODUCTION: A transoral (TO) vestibular approach is a new remote access approach to avoid cutaneous scars in an endoscopic thyroidectomy (ET). And transoral endoscopic thyroidectomy (TOET) has been widely used in papillary thyroid microcarcinomas (PTMCs). AIM: To evaluate and compare endoscopic thyroidectomies with central neck dissection using a bilateral areolar (BA) approach and TO approach in patients with unilateral PTMCs. MATERIAL AND METHODS: In total, 92 papillary thyroid cancer (PTC) patients undergoing an endoscopic unilateral thyroidectomy with central neck dissection via a TO (n = 48) or BA (n = 44) approach were retrospectively enrolled from August 2017 to December 2018. Differences in various factors, such as clinical characteristics, surgery-related parameters, including operative complications, and hospital durations and costs, were compared. RESULTS: No significant between-group differences in the age and sex of the patients or the side, body mass index, total operative time, operative bleeding, superior parathyroid preservation in situ, operative complications, and postoperative day of discharge were found (all p > 0.05). The mean central neck dissection time, amount of postoperative drainage, extubation time, and inferior parathyroid preservation in situ were lower in the TO group as compared with these parameters in the BA group (all p < 0.05). The number of central lymph nodes resected and hospitalization costs were higher in the TO group as compared with those in the BA group (all p < 0.05). CONCLUSIONS: An ET via the TO approach may be a good choice for unilateral PTMCs because of the shorter central neck dissection time, reduced postoperative drainage, better cosmetic satisfaction, and higher number of lymph nodes removed.

Sanguinarine Attenuates Lipopolysaccharide-induced Inflammation and Apoptosis by Inhibiting the TLR4/NF-κB Pathway in H9c2 Cardiomyocytes.

The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine (SAN) has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, antitumor, and immune-enhancing properties. However, few studies have investigated the effects of SAN on lipopolysaccharide (LPS)-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes. Therefore, in this study, H9c2 cells were co-treated with SAN and LPS, and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation. The underlying mechanism was further investigated by detecting the activation of Toll-like receptor (TLR)4/nuclear factor-κB (NF-κB) signaling pathways. As a result, increased mRNA expression of interleukin (IL)-1ß, IL-6, and TNFα induced by LPS was attenuated after SAN treatment; LPS-induced apoptosis of H9c2 cardiomyocytes and cleaved-caspase 8, 9, 3 were all significantly reduced by SAN. Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway. It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes, which may be mediated by inhibition of the TLR4/NF-κB signaling pathway. Thus, SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.

Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress.

Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling. Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.

The protease inhibitor E64d improves ox-LDL-induced endothelial dysfunction in human aortic endothelial cells.

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis. E64d, a cysteine protease inhibitor, blocks the elastolytic activity of cathepsin essential for vascular matrix remodeling and reduces neurovascular endothelial apoptosis. The objective of this study was to investigate the effects and the underling mechanisms of E64d on ox-LDL-induced endothelial dysfunction in human aortic endothelial cells (HAECs). HAECs were treated with various concentrations of ox-LDL (0-200 mg/L) for 24 h with or without E64d. The results showed that E64d attenuated ox-LDL-induced increase in soluble intercellular adhesion molecule-1 (sICAM-1) concentration and reduction in endothelial nitric oxide synthase (eNOS) expression, prevented ox-LDL-induced reduction in cell viability and migration ability of HAECs. E64d decreased the protein expression of cathepsin B (CTSB), Beclin 1, and microtubule-associated protein light chain 3 (LC3)-II, but not p62. LC3 puncta and autophagosome formation were also reduced by E64d in HAECs. Moreover, E64d decreased the production of MDA and increased the activity of SOD. The results showed that E64d ameliorated ox-LDL-induced endothelial dysfunction in HAECs.

Recuperating Lung Decoction Attenuates the Oxidative Stress State of Chronic Obstructive Pulmonary Disease by Inhibiting the MAPK/AP-1 Signal Pathway and Regulating γ-GCS.

Purpose/Objective. To evaluate the effects of Recuperating Lung Decoction (RLD) on the indices of oxidative stress in a rat model of COPD and detect the indices of the MAPK/AP-1/γ-GCS signal pathway for a further survey of the possible targeting site of RLD. Methods/Materials. The rats of COPD were treated with RLD. The protein levels of glutathione (GSH), oxidized glutathione (GSSG), 8-hydroxy-2-deoxyguanosine (8-OHdG), and 4-hydroxynonenal (4-HNE) were measured. In addition, the levels of key signaling molecules (extracellular signal-regulated kinases [ERK], the c-jun N-terminal kinase [JNKs signal pathway], and p38 MAP kinase [p38MAPK], AP-1 proteins [C-fos, C-jun], and γ-glutamyl-cysteine synthetase [γ-GCS-h]) of the MAPK/AP-1/γ-GCS-h signal pathway were assessed. Results. After treatment, the protein level of GSH and the ratio of GSH/GSSG were increased and the amounts of 8-OHdG and 4-HNE were decreased significantly in lung tissues when compared with the nontreated COPD group. Further results showed that the RLD could effectively inhibit the MAPK pathway by inactivation of p38MAPK and ERK and could also downregulate the AP-1 and the γ-GCS-h genes expressions in both protein and mRNA levels. Conclusion. RLD might improve the state of oxidative stress by downregulation of the expression of γ-GCS-h gene by inhibition of the MAPK/AP-1 pathway, thereafter enhancing the ability of antioxidation in COPD.

The protective effect of geniposide on human neuroblastoma cells in the presence of formaldehyde.

BACKGROUND: Formaldehyde can induce misfolding and aggregation of Tau protein and ß amyloid protein, which are characteristic pathological features of Alzheimer's disease (AD). An increase in endogenous formaldehyde concentration in the brain is closely related to dementia in aging people. Therefore, the discovery of effective drugs to counteract the adverse impact of formaldehyde on neuronal cells is beneficial for the development of appropriate treatments for age-associated cognitive decline. METHODS: In this study, we assessed the neuroprotective properties of TongLuoJiuNao (TLJN), a traditional Chinese medicine preparation, against formaldehyde stress in human neuroblastoma cells (SH-SY5Y cell line). The effect of TLJN and its main ingredients (geniposide and ginsenoside Rg1) on cell viability, apoptosis, intracellular antioxidant activity and the expression of apoptotic-related genes in the presence of formaldehyde were monitored. RESULTS: Cell counting studies showed that in the presence of TLJN, the viability of formaldehyde-treated SH-SY5Y cells significantly recovered. Laser scanning confocal microscopy revealed that the morphology of formaldehyde-injured cells was rescued by TLJN and geniposide, an effective ingredient of TLJN. Moreover, the inhibitory effect of geniposide on formaldehyde-induced apoptosis was dose-dependent. The activity of intracellular antioxidants (superoxide dismutase and glutathione peroxidase) increased, as did mRNA and protein levels of the antiapoptotic gene Bcl-2 after the addition of geniposide. In contrast, the expression of the apoptotic-related gene - P53, apoptotic executer - caspase 3 and apoptotic initiator - caspase 9 were downregulated after geniposide treatment. CONCLUSIONS: Our results indicate that geniposide can protect SH-SY5Y cells against formaldehyde stress through modulating the expression of Bcl-2, P53, caspase 3 and caspase 9, and by increasing the activity of intracellular superoxide dismutase and glutathione peroxidase.