Redox-Regulated Iron Metabolism and Ferroptosis in Ovarian Cancer: Molecular Insights and Therapeutic Opportunities.

Ovarian cancer (OC), known for its lethality and resistance to chemotherapy, is closely associated with iron metabolism and ferroptosis-an iron-dependent cell death process, distinct from both autophagy and apoptosis. Emerging evidence suggests that dysregulation of iron metabolism could play a crucial role in OC by inducing an imbalance in the redox system, which leads to ferroptosis, offering a novel therapeutic approach. This review examines how disruptions in iron metabolism, which affect redox balance, impact OC progression, focusing on its essential cellular functions and potential as a therapeutic target. It highlights the molecular interplay, including the role of non-coding RNAs (ncRNAs), between iron metabolism and ferroptosis, and explores their interactions with key immune cells such as macrophages and T cells, as well as inflammation within the tumor microenvironment. The review also discusses how glycolysis-related iron metabolism influences ferroptosis via reactive oxygen species. Targeting these pathways, especially through agents that modulate iron metabolism and ferroptosis, presents promising therapeutic prospects. The review emphasizes the need for deeper insights into iron metabolism and ferroptosis within the redox-regulated system to enhance OC therapy and advocates for continued research into these mechanisms as potential strategies to combat OC.

The roles of long non-coding RNAs in ovarian cancer: from functions to therapeutic implications.

Long non-coding RNAs (lncRNAs) are multifunctional and participate in a variety of biological processes and gene regulatory networks. The deregulation of lncRNAs has been extensively implicated in diverse human diseases, especially in cancers. Overwhelming evidence demonstrates that lncRNAs are essential to the pathophysiological processes of ovarian cancer (OC), acting as regulators involved in metastasis, cell death, chemoresistance, and tumor immunity. In this review, we illustrate the expanded functions of lncRNAs in the initiation and progression of OC and elaborate on the signaling pathways in which they pitch. Additionally, the potential clinical applications of lncRNAs as biomarkers in the diagnosis and treatment of OC were emphasized, cementing the bridge of communication between clinical practice and basic research.

A combined amplicon approach to nematode polyparasitism occurring in captive wild animals in southern China.

BACKGROUND: Gastrointestinal tract (GIT) nematodes prefer to live in the intestines of wild animals, causing damage and even death, and posing a zoonotic risk. The polyparasitism of GIT nematodes results in the complex dynamics of the nematode communities that occur naturally in wild animals. However, the nematode community in captive wild animals is poorly understood. METHODS: We combined  microscopic examination and amplicon sequencing for community diversity. RESULTS: We characterized GIT nematode assemblages to one order, one family, four genera, and ten species, in 512 fecal samples of 121 species from captive wild animals in southern China. The positive rate of GIT nematodes was 20.7% (106/512), including 42.3% (11/26) in reptiles, 26.5% (39/147) in herbivores, 25.0% (25/100) in non-human primates, 20.0% (5/25) in omnivores, 12.2% (9/74) in carnivores, and 12.1% (17/140) in avians. The dominant nematodes were Haemonchus contortus in herbivores and Trichuris species in primates. The nematode communities of arboreal primates differed from their terrestrial counterparts, reflecting both host phylogeny and ecological constraints. Soil-transmitted Strongyloides species were widespread throughout the herbivore, primate, avian, and carnivore communities, and tended to infect omnivorous primates and terrestrial herbivores. In addition, new Trichuris and Heterakis species were found in the nematode communities of captive porcupines and peafowls. CONCLUSION: This study highlights the variation in the composition of the GIT nematode community and strengthens the attention to the harms induced by zoonotic nematodes and co-infective nematodes with low species richness.

Molecular characterization of a novel Spiruromorpha species in wild Chinese pangolin by mitogenome sequence analysis.

Pangolins are susceptible to a variety of gastrointestinal nematodes due to their burrowing lifestyle and feeding habits, and few parasitic nematodes have been reported. Here, a Chinese pangolin with old wounds on its leg and tail was rescued from the Heyuan City, Guangdong Province. The cox1 and SSU rRNA of the worms from the intestine of the Chinese pangolin had the highest sequence identity of 89.58% and 97.95% to the species in the infraorder Spiruromorpha. The complete mitogenome of the worm was further assembled by next-generation sequencing, with a size of 13,708 bp and a GC content of 25.6%. The worm mitogenome had the highest sequence identity of 78.56% to that of Spirocerca lupi, sharing the same gene arrangement with S. lupi and some species in other families under Spiruromorpha. However, the mitogenome between the worm and S. lupi showed differences in codon usage of PCGs, sequences of NCR, and tRNA secondary structures. Phylogenetic analysis showed that the worm mitogenome was clustered with S. lupi in the family Thelaziidae to form a separate branch. However, it is still difficult to identify the worm in the family Thelaziidae because the species in the family Thelaziidae are confused, specifically S. lupi and Thelazia callipaeda in the family Thelaziidae were separated and grouped with species from other families. Thus, the parasitic nematode from the Chinese pangolin may be a novel species in Spiruromorpha and closely related to S. lupi. This study enriches the data on gastrointestinal nematodes in the Chinese pangolin.

Changing trends in disease burden of lung cancer in China from 1990-2019 and following 15-year prediction.

BACKGROUND: As lung cancer becomes a primary source of death in China, investigation on incidence rate, death rate, and disability-adjusted life years (DALYs) is of great significance to optimize prevention measures and allocation of healthcare resources. METHODS: We utilized data from the Global Burden of Disease (GBD) database to evaluate the incidence rate, death rate, and DALYs of lung cancer in China from 1990 to 2019. Analysis of lung cancer risk factor-related death rate and DALYs was performed. Age-standardized rates (ASR) and estimated annual percentage change (EAPC) were calculated. The incidence trend of lung cancer from 2020 to 2034 was predicted by the Nordpred age-period-cohort (APC) model. RESULTS: Age-standardized incidence rate (ASIR) increased from 30.2/100000 (95 % UI 26.2-34.3) in 1990 to 41.7/100000 (95 % UI 35.2-48.8) in 2019, and EAPC was 1.33 (95 % CI 1.16-1.49). From 1990 to 2019, men were noted for the highest incidence rate, death rate, and DALYs rate across three age groups (15-49 years, 50-69 years, and over 70). During this period, the ASIR of lung cancer in females was always lower than that in males. The predominant risk factors of lung cancer were smoking, air pollution, and diet, among which smoking was the most significant one. The analysis results showed that new cases and deaths may increase in the following 15 years since 2020 in the context of lung cancer. CONCLUSION: Faced with the heavy burden of lung cancer, China must issue corresponding policies and roll out prevention avenues against smoking and air pollution.

An Overview of Heavy Chain Ferritin in Cancer.

As a spherical protein that acts as a repository for intracellular iron, Ferritin is the most important iron storage form and is known to influence tumor immunity. Unbound ferritin is composed of 24 subunits, made up of ferritin light chain (FTL) and ferritin heavy chain (FTH). Ferritin can be automatically put together to form hollow nanocages that measure 12 nm around the outside and 8 nm around the inside. Cancer causes the second-most deaths worldwide, effective elimination of tumor cells while protecting normal cells is the foundation of modern tumor therapy. To this end, the innate tumor-targeting activity of human FTH1, first identified ten years ago, is highly appealing. Unmodified human FTH1 binds to its receptor, transferrin receptor 1 (TfR1), which is frequently overexpressed in cancer cells. FTH1-TfR1 binding permits improved drug efficacy by promoting ferritin-mediated targeted delivery. In addition, FTH is also associated with the prognosis of multiple typies of cancer. The level of FTH1 is significantly and positively correlated with the infiltration of tumor-associated macrophages. FTH1 also plays an important role in regulating the tumor immunity of solid cancer. As such, FTH1 has been extensively applied in the targeted delivery of anticancer drugs, diagnostic molecules (e.g., radioisotopes and fluorophones), and inorganic nanoparticles (NPs) to tumors.This article reviews the role of FTH in cancer and its potential as a therapeutic target.

Identification of EMP1 as a critical gene for cisplatin resistance in ovarian cancer by using integrated bioinformatics analysis.

BACKGROUND: Cisplatin resistance is among the main reasons for the poor prognosis of ovarian cancer (OC) patients. Until now, effective biomarkers for predicting cisplatin resistance in OC and specific drugs for reversing this resistance are lacking. This study identified the critical gene associated with cisplatin resistance in OC and provided a potential target for overcoming this resistance. METHODS: Differentially expressed genes between cisplatin-resistant and -sensitive OCs were identified by screening public datasets. Survival analysis was conducted to screen prognosis-related DEGs. CIBERSORT, ESTIMATE, and immune checkpoint genes were used to assess the association between EMP1 expression and tumor microenvironment features. CTRP and GDSC databases were employed to analyze the correlation between EMP1 expression and cisplatin resistance. Furthermore, immunohistochemistry, qPCR, Western blotting, siRNA interference, and the CCK8 assay were performed to verify the role of EMP1 in cisplatin resistance in vitro. Finally, xenograft mouse models were generated to further confirm the role of EMP1 in cisplatin resistance in vivo. RESULTS: EMP1 was identified as a critical gene associated with cisplatin resistance in OC. According to bioinformatics analyses, increased EMP1 expression was linked to higher stromal/ESTIMATE scores as well as greater ICG expression levels. The in vitro experiments showed that EMP1 was highly expressed in cisplatin-resistant OC tissues and cells, and silencing this EMP1 expression enhanced OC cell sensitivity to cisplatin. Finally, in vivo experiments confirmed that EMP1 promotes tumor growth and cisplatin resistance. CONCLUSIONS: EMP1 can act as a predictive biomarker for cisplatin resistance in OC and as a potential therapeutic target.

Application of Mimics Medical 21.0 Software in thoracoscopic anatomical sublobectomy.

BACKGROUND: The anatomical structure of pulmonary segments is complex, and there are many anatomical variations, making the operation more difficult, so we used Mimics Medical 21.0 software for three-dimensional computed tomography bronchography and angiography (3D-CTBA), carefully formulated the surgical plan and on this basis completed the video-assisted thoracoscopic anatomical sublobectomy. METHODS: A total of 38 patients with pulmonary nodules were selected and received video-assisted thoracoscopic anatomical sublobectomy after using Mimics Medica 21.0 software for 3D-CTBA. RESULTS: The mean operative duration was 158.42±20.21 minutes, and the operative hemorrhage was 97.66±22.37 mL. In pathological diagnoses, there were 5 benign cases (13.2%), 9 cases with atypical adenomatous hyperplasia (23.7%), 12 cases with adenocarcinoma in situ (31.6%), 11 cases with minimally invasive adenocarcinoma (28.9%) and 1 case with invasive adenocarcinoma (2.6%); 8.29±0.98 lymph nodes sampled had no metastasis. The chest tube drainage duration and postoperative hospital stay were 2.47±0.73 days and 5.47±0.73 days, respectively. CONCLUSIONS: Using Mimics Medical 21.0 software can quickly and accurately complete 3D-CTBA, which is beneficial to formulate a personalized anatomical sublobectomy surgical plan.

Direct Synthesis of Nanosheet-Stacked Hierarchical "Honey Stick-like" MFI Zeolites by an Aromatic Heterocyclic Dual-Functional Organic Structure-Directing Agent.

Soft template designing is the most promising strategy for the synthesis of zeolite nanosheets. MFI nanosheets directed by soft templates (containing long-chain alkyl groups or aromatic groups as hydrophobic component) can be found frequently; however, so far, MFI nanosheets synthesized by soft templates with aromatic heterocycle groups (e. g., s-triazine groups) are rare. Herein, a nanosheet-stacked hierarchical MFI zeolite (NSHM) has been synthesized by using a triply branched s-triazine-based surfactant as a bifunctional organic structure-directing agent. On the basis of a geometrical match relationship, a formation model has been proposed. Synthesized NSHM had abundant mesopores stacked by nanosheets and exhibited a high surface area (430 m2 ⋅ g-1 ). The 1 wt% Pd/NSHM attained a significant increase in yield of cyclohexanol/cyclohexanone mixture (from 66 to 85 %) in the oxidation of cyclohexane compared with Silicalite-1 and SBA-15 as supports.

COVID-19 data visualization public welfare activity.

The coronavirus disease 2019 (COVID-19) pandemic started in early 2020. At the beginning of February, a public welfare activity in epidemic data visualization, jointly launched by China Computer Federation (CCF) (CCF) CAD & CG Technical Committee, Alibaba Cloud Tianchi (Alibaba Cloud Tianch), JiqiZhixin (JiqiZhixin), Alibaba Cloud DataV (Alibaba Cloud DataV), and DataWhale (DataWhale), was launched with the theme "Fighting the Epidemic with One Mind and Talents like Tianchi." Developers in general are expected to focus on several demand scenarios, such as epidemic situation display, epidemic popular science, trend prediction, material-supply situation, and rework and return situation of employees from all sectors and areas, to discover the relationship between complex heterogeneous multi-source data, develop various upbeat works and present useful information to the public in a coherent manner. The entry works take the form of data visualization and are divided into two categories: popular science publicity and application scenarios. The popular science publicity category includes works for the public, focused on epidemic situation display, epidemic popular science publicity, epidemic prevention and control, and others. The application scenario category consists of the works of frontline officers, which can provide anti-epidemic workers with effective data tools for efficient and intuitive epidemic analysis; offer reliable, understandable, and easily transmitted information for disease prevention; and assist governments, enterprises, and institutions in the fight against COVID-19.

A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8+ T cells.

CD8+ memory T (Tm) cells are fundamental for protective immunity against infections and cancers 1-5 . Metabolic activities are crucial in controlling memory T-cell homeostasis, but mechanisms linking metabolic signals to memory formation and survival remain elusive. Here we show that CD8+ Tm cells markedly upregulate cytosolic phosphoenolpyruvate carboxykinase (Pck1), the hub molecule regulating glycolysis, tricarboxylic acid cycle and gluconeogenesis, to increase glycogenesis via gluconeogenesis. The resultant glycogen is then channelled to glycogenolysis to generate glucose-6-phosphate and the subsequent pentose phosphate pathway (PPP) that generates abundant NADPH, ensuring high levels of reduced glutathione in Tm cells. Abrogation of Pck1-glycogen-PPP decreases GSH/GSSG ratios and increases levels of reactive oxygen species (ROS), leading to impairment of CD8+ Tm formation and maintenance. Importantly, this metabolic regulatory mechanism could be readily translated into more efficient T-cell immunotherapy in mouse tumour models.

Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-γ-induced immunologic dormancy of tumor-repopulating cells.

Interactions with the immune system may lead tumorigenic cells into dormancy. However, the underlying molecular mechanism is poorly understood. Using a 3D fibrin gel model, we show that IFN-γ induces tumour-repopulating cells (TRCs) to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, IFN-γ signalling triggers differentiated tumour cell apoptosis via STAT1; however, when IDO1 and AhR are highly expressed as in TRCs, IFN-γ results in IDO1/AhR-dependent p27 induction that prevents STAT1 signalling, thus suppressing the process of cell death and activating the dormancy program. Blocking the IDO/AhR metabolic circuitry not only abrogates IFN-γ-induced dormancy but also results in enhanced repression of tumour growth by IFN-γ-induced apoptosis of TRCs both in vitro and in vivo. These data present a previously unrecognized mechanism of inducing TRC dormancy by IFN-γ, suggesting a potential effective cancer immunotherapeutic modality through the combination of IFN-γ and IDO/AhR inhibitors.

Pre-instillation of tumor microparticles enhances intravesical chemotherapy of nonmuscle-invasive bladder cancer through a lysosomal pathway.

Nonmuscle-invasive bladder cancer (NMIBC) is treated with transurethral resection followed by intravesical chemotherapy. However, drug-resistant tumorigenic cells cannot be eliminated, leading to half of the treated cancers recur with increased stage and grade. Innovative approaches to enhance drug sensitivity and eradicate tumorigenic cells in NMIBC treatment are urgently needed. Here, we show that pre-instillation of tumor cell-derived microparticles (T-MP) as natural biomaterials markedly enhance the inhibitory effects of intravesical chemotherapy on growth and hematuria occurrence of orthotropic bladder cancer in mice. We provide evidence that T-MPs enter and increase the pH value of lysosomes from 4.6 to 5.6, leading to the migration of drug-loaded lysosomes along microtubule tracks toward the nucleus and discharging the drugs whereby for the entry of the nucleus. We propose that T-MPs may function as a potent sensitizer for augmenting NMIBC chemotherapy with unprecedented clinical benefits.

Abnormal Expression of TRAIL Receptors in Decidual Tissue of Chlamydia trachomatis-Infected Rats During Early Pregnancy Loss.

Chlamydia trachomatis is the scientific name of pathogenic bacteria causing infection that has been linked to spontaneous abortion. In this study, the expression pattern of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL; a cytokine related to cell apoptosis) and its receptors was monitored in the decidua of C trachomatis-infected pregnant rats during early gestation to investigate the potential role of this molecular system in C trachomatis-induced spontaneous abortion. The data showed that C trachomatis infection significantly altered the messenger RNA (mRNA) expression of the receptors; death receptor (DR) 4 and DR5 increased, but decoy receptor (DcR) 1 and DcR2 decreased. Consistent with mRNA data, immunohistochemical staining of TRAIL and its receptors indicated that both DR4 and DR5 protein levels were elevated in infected tissues, primarily, decidual cells, decidual vessel wall, and uterine glands, whereas DcR1 and DcR2 showed lower levels compared to the noninfected group. Although receptor expression was altered, there was no difference detected in TRAIL expression. The observed altered expression of TRAIL receptors in C trachomatis-infected rats compared to noninfected rats during the embryo implantation phase suggests a possible mechanism for spontaneous abortion due to apoptosis and therefore failed embryo implantation. In addition, the observed increase in caspase-3 levels in infected cells further supports this finding. Taken together, the data presented in this study suggests C trachomatis infection altered the expression of TRAIL receptors, thus representing a general mechanism for C trachomatis-induced spontaneous abortion in C trachomatis-infected rats during early pregnancy loss.

Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles.

Developing novel approaches to reverse the drug resistance of tumor-repopulating cells (TRCs) or stem cell-like cancer cells is an urgent clinical need to improve outcomes of cancer patients. Here we show an innovative approach that reverses drug resistance of TRCs using tumor cell-derived microparticles (T-MPs) containing anti-tumor drugs. TRCs, by virtue of being more deformable than differentiated cancer cells, preferentially take up T-MPs that release anti-tumor drugs after entering cells, which in turn lead to death of TRCs. The underlying mechanisms include interfering with drug efflux and promoting nuclear entry of the drugs. Our findings demonstrate the importance of tumor cell softness in uptake of T-MPs and effectiveness of a novel approach in reversing drug resistance of TRCs with promising clinical applications.

Mild oxidative stress induced by a low dose of cisplatin contributes to the escape of TRAIL-mediated apoptosis in the ovarian cancer SKOV3 cell line.

Tumor necrosis factor (TNF)-related apoptosis­inducing ligand (TRAIL) is expressed in ovarian tissue and is widely thought to exhibit strong antitumor activity in a variety of tumor cell types. Therefore, we hypothesized that the cisplatin resistance of ovarian cancer is linked to the ability to escape from TRAIL-mediated apoptosis. We demonstrated that cisplatin-resistant ovarian cancer cell line SKOV3/DDP tolerated treatment with TRAIL, in contrast to the cisplatin­sensitive ovarian cancer cell line SKOV3. SKOV3/DDP cells exhibited a much higher cell viability and a lower apoptosis rate than SKOV3 cells after treatment with TRAIL. To determine whether cisplatin induced the tolerance of TRAIL, we pretreated the SKOV3 cells with cisplatin in the presence of TRAIL. This revealed that a low dose of cisplatin (1 µM) increased the TRAIL tolerance of SKOV3 cells. Furthermore, cisplatin induced oxidative stress in both the SKOV3/DDP and SKOV3 cells, although the oxidative stress level of the SKOV3/DDP cells was generally much higher than that noted in the SKOV3 cells. Similarly, a low dose of hydrogen peroxide increased the TRAIL tolerance in SKOV3 cells. Notably, the TRAIL tolerance in the SKOV3 and SKOV3/DDP cells could be abrogated by the oxidative stress scavenger N-acetyl-cysteine. These results suggest that a low dose of cisplatin induces the tolerance of TRAIL in SKOV3 cells at least partly, depending on the oxidative stress signaling pathway.

Cell-free tumor microparticle vaccines stimulate dendritic cells via cGAS/STING signaling.

Tumor antigens and innate signals are vital considerations in developing new therapeutic or prophylactic antitumor vaccines. The role or requirement of intact tumor cells in the development of an effective tumor vaccine remains incompletely understood. This study reveals the mechanism by which tumor cell-derived microparticles (T-MP) can act as a cell-free tumor vaccine. Vaccinations with T-MPs give rise to prophylactic effects against the challenge of various tumor cell types, while T-MP-loaded dendritic cells (DC) also exhibit therapeutic effects in various tumor models. Such antitumor effects of T-MPs are perhaps attributable to their ability to generate immune signaling and to represent tumor antigens. Mechanically, T-MPs effectively transfer DNA fragments to DCs, leading to type I IFN production through the cGAS/STING-mediated DNA-sensing pathway. In turn, type I IFN promotes DC maturation and presentation of tumor antigens to T cells for antitumor immunity. These findings highlight a novel tumor cell-free vaccine strategy with potential clinical applications.

Astragalus polysaccharide induces anti-inflammatory effects dependent on AMPK activity in palmitate-treated RAW264.7 cells.

Astragalus polysaccharide (APS) has been reported to increase insulin sensitization and to ameliorate diabetes in animal models, and studies have demonstrated that this effect may be correlated with its anti-inflammatory roles in vivo and in vitro. However, the potential pharmacological mechanisms of APS in anti-inflammatory regulation are still poorly understood. Herein, RAW264.7 cells treated with APS showed anti-inflammatory effects. Interleukin (IL)-10 protein levels and expression of most of the anti-inflammatory genes, including IL-10, macrophage mannose receptor (MMR), arginase, Dectin-1, YM-1 and YM-2, were significantly increased after treatment with APS for 24 h. Furthermore, to determine whether APS plays a potential role in RAW264.7 cell inflammation, we pretreated RAW264.7 cells with APS in the presence of palmitate. The results showed that APS markedly recovered the impairment of AMPK activity induced by palmitate. Furthermore, APS induced IL-10 protein production and anti-inflammatory gene expression of IL-10, MMR, Dectin-1, arginase, YM-1 and YM-2. Additionally, APS inhibited IL-1ß protein production and expression of most of the pro-inflammatory genes, such as IL-1ß, iNOS, MCP-1, IL-6 and CD11c but not tumor necrosis factor (TNF)-α. Notably, the effect of APS on inflammatory genes, except for TNF-α, was abrogated when AMPK activity was inhibited using a DN-AMPK plasmid. These results suggest that APS effectively ameliorates palmitate-induced pro-inflammatory responses through AMPK activity.

Astragalus polysaccharide stimulates glucose uptake in L6 myotubes through AMPK activation and AS160/TBC1D4 phosphorylation.

AIM: To establish the mechanism responsible for the stimulation of glucose uptake by Astragalus polysaccharide (APS), extracted from Astragalus membranaceus Bunge, in L6 myotubes in vitro. METHODS: APS-stimulated glucose uptake in L6 myotubes was measured using the 2-deoxy-[(3)H]-D-glucose method. The adenine nucleotide contents in the cells were measured by HPLC. The phosphorylation of AMP-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) was examined using Western blot analysis. The cells transfected with 4P mutant AS160 (AS160-4P) were constructed using gene transfer approach. RESULTS: Treatment of L6 myotubes with APS (100-1600 µg/mL) significantly increased glucose uptake in time- and concentration-dependent manners. The maximal glucose uptake was reached in the cells treated with APS (400 µg/mL) for 36 h. The APS-stimulated glucose uptake was significantly attenuated by pretreatment with Compound C, a selective AMPK inhibitor or in the cells overexpressing AS160-4P. Treatment of L6 myotubes with APS strongly promoted the activation of AMPK. We further demonstrated that either Ca(2+)/calmodulin-dependent protein kinase kinase ß (CaMKKß) or liver kinase B1 (LKB1) mediated APS-induced activation of AMPK in L6 myotubes, and the increased cellular AMP: ATP ratio was also involved. Treatment of L6 myotubes with APS robustly enhanced the phosphorylation of AS160, which was significantly attenuated by pretreatment with Compound C. CONCLUSION: Our results demonstrate that APS stimulates glucose uptake in L6 myotubes through the AMP-AMPK-AS160 pathway, which may contribute to its hypoglycemic effect.

[Transplantation of atrial natriuretic peptide-expressing fibroblasts reduces blood pressure and increases urine volume in spontaneously hypertensive rats].

To investigate the potential of gene therapy for the treatment of chronic diseases such as hypertension, chronic heart failure, and chronic renal failure, we established the neonatal rat fibroblast line engineered to secrete the mutant human atrial natriuretic peptide (mhANP), and then transplanted the cell line into young spontaneously hypertensive rats (SHR) subcutaneously. We found that a single transplantation of the cell line caused an obvious rise in the concentration of mhANP in serum 7 d after transplantation ((135 +/- 8) vs (106 +/- 7) pg/mL, P < 0.01). The animals' blood pressure in test group was always remarkably lower than that of empty vector group within 42 d after transplantation, even though the blood pressure in all groups was constantly increasing in the process of ontogeny ((175 +/- 10) mm Hg vs (189 +/- 12) mm Hg, P < 0.05). A maximal blood pressure reduction of 33 mm Hg ((157 +/- 9) mm Hg vs (124 +/- 112) mm Hg, P < 0.01) was observed 14 d post cell transplantation. There was a marked increase in urine volume in test group from second week after treatment beginning ((5.9 +/- 0.7) mL/6 h vs (4.3 +/- 0.8) mL/6 h, P < 0.01) and the effect lasted 14 d ((6.1 +/- 1.1) mL/6 h vs (4.0 +/- 0.8) mL/6 h, P < 0.01), however the statistical difference in concentration of K+ and Na+ in serum and urine was not observed. The results suggested that subcutaneous implantation of fibroblasts-expressing mhANP significantly reduced blood pressure in young SHR during the period of ontogeny and efficiently improved their renal function and the somatic gene transfer of mhANP may have potential value in the treatment of human chronic diseases such as hypertension, chronic heart failure, and chronic renal failure.