Field performance of 15 rain gardens in different cities in Taiwan.

Rain gardens are widely used for low impact development (LID) or as a nature-based solution (NbS). They help to reduce runoff, mitigate hot temperatures, create habitats for plants and insects, and beautify landscapes. Rain gardens are increasingly being established in urban areas. In Taiwan, the Ministry of Environment (MoE) initiated a rain garden project in Taipei city in 2018, and 15 rain gardens have since been constructed in different cities. These Taiwanese-style rain gardens contain an underground storage tank to collect the filtrated rainwater, which can be used for irrigation. Moreover, the 15 rain gardens are equipped with sensors to monitor temperature, rainfall, and underground water levels. The monitoring data were transmitted with Internet of Things (IoT) technology, enabling the capture and export of real-time values. The water retention, temperature mitigation, water quality, and ecological indices of the rain gardens were quantified using field data. The results from the young rain gardens (1-3 years) showed that nearly 100 % of the rainfall was retained onsite and did not flow out from the rain gardens; however, if the stored water was not used and the tanks were full, the rainwater from subsequent storms could not be stored, and the tanks overflowed. The surface temperatures of the rain garden and nearby impermeable pavement differed by an average of 2-4 °C. This difference exceeded 20 °C in summer at noon. The water in the underground storage tanks had very low levels of SS and BOD, with averages of 1.6 mg/L and 5.6 mg/L, respectively. However, the E. coli concentrations were high, and the average was 6283 CFU/100 mL; therefore, washing or drinking water is not recommended. The ecological indices, i.e., the Shannon and Simpson indices, demonstrated the good flora status of the rain gardens after one year. Although the weather differed by city, the performance of the rain gardens in terms of water retention, temperature mitigation, rainwater harvesting, and providing biological habitats was consistent. However, maintenance influences rain garden performance. If the stored water is not frequently used, the stored volume is reduced, and the stored water quality degrades.

Protein lipoylation: mitochondria, cuproptosis, and beyond.

Protein lipoylation, a crucial post-translational modification (PTM), plays a pivotal role in mitochondrial function and emerges as a key player in cell death through cuproptosis. This novel copper-driven cell death pathway is activated by excessive copper ions binding to lipoylated mitochondrial proteins, disrupting energy production and causing lethal protein aggregation and cell death. The intricate relationship among protein lipoylation, cellular energy metabolism, and cuproptosis offers a promising avenue for regulating essential cellular functions. This review focuses on the mechanisms of lipoylation and its significant impact on cell metabolism and cuproptosis, emphasizing the key genes involved and their implications for human diseases. It offers valuable insights into targeting dysregulated cellular metabolism for therapeutic purposes.

A novel long non-coding RNA MIR4500HG003 promotes tumor metastasis through miR-483-3p-MMP9 axis in triple-negative breast cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is over 90% in BC patients, but once BC cells metastasis into distal organs, it is dramatically decreasing to less than 30%. Especially, triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. Understanding the underline mechanisms of TNBC metastasis is a critical issue. Non-coding RNAs, including of lncRNAs and microRNAs, are non-protein-coding transcripts and have been reported as important regulators in TNBC metastasis. However, the underline mechanisms for non-coding RNAs regulating TNBC metastasis remain largely unclear. Here, we found that lncRNA MIR4500HG003 was highly expressed in highly metastatic MDA-MB-231 TNBC cells and overexpression of MIR4500HG003 enhanced metastasis ability in vitro and in vivo and promoted MMP9 expression. Furthermore, we found MIR4500HG003 physically interacted with miR-483-3p and reporter assay showed miR-483-3p attenuated MMP9 expression. Importantly, endogenous high expressions of MIR4500HG003 were correlated with tumor recurrence in TNBC patients with tumor metastasis. Taken together, our findings suggested that MIR4500HG003 promotes metastasis of TNBC through miR-483-3p-MMP9 signaling axis and may be used as potential prognostic marker for TNBC patients.

A game-based multimedia application to improve the ability of clinical nurses to perform geriatric care: A randomized controlled trial.

BACKGROUND: Given the realities of global aging, maintaining Comprehensive Geriatric Assessment (CGA) abilities among clinical nurses is very important. Newer methods of continuing education are needed to engage nurses in CGA education. Using multimedia and game-based applications in CGA education (CGA APP) may be an effective method for continuing education. OBJECTIVES: To test the effectiveness of CGA APP in improving nurses' confidence in their abilities to perform geriatric care. DESIGN: A randomized, controlled trial were adopted. SETTING: An 1343-bed tertiary-care medical center in southern Taiwan. PARTICIPANTS: A total of 1250 nurses met inclusion criteria in 35 adult wards. We employed stratified sampling to recruit a total of 132 nurses proportional to the number of nurses in each ward, from January to March 2019. METHODS: Based on the Octalysis gamification framework, the CGA APP was developed. Participants were randomly assigned to either an CGA APP or a control group, which received traditional classroom learning of the same content. The main outcome was improvement in confidence in geriatric care ability were measured before and end of the training session, and six months later. RESULTS: There were no differences in baseline characteristics (except years of experience as a registered nurse), knowledge, attitudes or confidence of geriatric care between the two groups. Clinical nurses in the CGA APP group demonstrated significantly higher confidence in their geriatric care abilities than control group immediately after the intervention (75.85 ± 10.71 vs. 65.93 ± 8.49, p < 0.001) and six-months later (71.13 ± 9.69 vs. 63.57 ± 8.78, p < 0.001). After using GEE to control the confounding variable, the CGA APP group remained significantly higher confidence in their geriatric care abilities than control group. CONCLUSIONS: Use of multimedia game-based applications my better engage and teach practicing clinical than traditional learning methods. Our findings suggest that such interventions be further developed and tested for a larger variety of continuing education needs.

Continuous microalgal culture module and method of culturing microalgae containing macular pigment.

This study established and investigated continuous macular pigment (MP) production with a lutein (L):zeaxanthin (Z) ratio of 4-5:1 by an MP-rich Chlorella sp. CN6 mutant strain in a continuous microalgal culture module. Chlorella sp. CN6 was cultured in a four-stage module for 10 days. The microalgal culture volume increased to 200 L in the first stage (6 days). Biomass productivity increased to 0.931 g/L/day with continuous indoor white light irradiation during the second stage (3 days). MP content effectively increased to 8.29 mg/g upon continuous, indoor white light and blue light-emitting diode irradiation in the third stage (1 day), and the microalgal biomass and MP concentrations were 8.88 g/L and 73.6 mg/L in the fourth stage, respectively. Using a two-step MP extraction process, 80 % of the MP was recovered with a high purity of 93 %, and its L:Z ratio was 4-5:1.

Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II.

Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis (S. baicalensis) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis, respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

Intelligent Evacuation Sign Control Mechanism in IoT-Enabled Multi-Floor Multi-Exit Buildings.

In contemporary evacuation systems, the evacuation sign typically points fixedly towards the nearest emergency exit, providing guidance to evacuees. However, this static approach may not effectively respond to the dynamic nature of a rapidly evolving fire situation, in particular if the closest emergency exit is compromised by fire. This paper introduces an intelligent evacuation sign control mechanism that leverages smoke and temperature sensors to dynamically adjust the direction of evacuation signs, ensuring evacuees are guided to the quickest and safest emergency exit. The proposed mechanism is outlined through a rigorous mathematical formulation, and an ESP heuristic is devised to determine temperature-safe, smoke-safe, and congestion-aware evacuation paths for each sign. This algorithm then adjusts the direction light on the evacuation sign to align with the identified evacuation path. To validate the effectiveness of this approach, fire simulations using FDS software 6.7.1 were conducted in the Taipei 101 shopping mall. Temperature and smoke data from sensor nodes were utilized by the ESP algorithm, demonstrating superior performance compared to that of the existing FEL algorithm. Specifically, the ESP algorithm exhibited a notable increase in the probability of evacuation success, surpassing the FEL algorithm by up to 34% in methane fire scenarios and 14% in PVC fire scenarios. The significance of this improvement is more pronounced in densely congested evacuation scenarios.

Fabrication and application of glutathione biosensing SPCE strips with gold nanoparticle modification.

Glutathione (GSH) is a major antioxidant in organisms. An alteration in GSH concentration has been implicated in a number of pathological conditions. Therefore, GSH sensing has become a critical issue. In this study, a disposable strip used for tyrosinase-modified electrochemical testing was fabricated for the detection of GSH levels in vivo. The system is based on tyrosinase as a biorecognition element and a screen-printed carbon electrode (SPCE) as an amperometric transducer. On the tyrosinase-SPCE strips, the oxidation reaction from catechol to o-quinone was catalyzed by tyrosinase. The tyrosinase-SPCE strips were modified with gold nanoparticles (AuNPs). In the presence of AuNPs of 25 nm diameter, the cathodic peak current of cyclic voltammetry (CV) was significantly enhanced by 5.2 fold. Under optimized conditions (250 µM catechol, 50 mM phosphate buffer, and pH 6.5), the linear response of the tyrosinase-SPCE strips ranged from 31.25 to 500 µM GSH, with a detection limit of approximately 35 µM (S/N > 3). The tyrosinase-SPCE strips have been used to detect real samples of plasma and tissue homogenates in a mouse experiment. The mice were orally administrated with N-acetylcysteine (NAC) 100 mg kg-1 once a day for 7 days; the plasma GSH significantly enhanced 2.8 fold as compared with saline-treated mice (1123 vs. 480 µM µg-1 protein). NAC administration also could alleviate the adverse effect of GSH reduction in the mice treated with doxorubicin.

Relationship Between Rectal Swab and Tissue Samples in Mucosa-associated Microbiota in Patients With Inflammatory Bowel Disease.

BACKGROUND: Gut mucosa-associated microbiota is more closely correlated with disease phenotypes than fecal microbiota; however sampling via tissue biopsy is more invasive and uncomfortable. Rectal swab may be a suitable substitute for tissue biopsy, but its effectiveness is controversial. This study aimed to evaluate differences in the microbiota at these sites in patients with inflammatory bowel disease (IBD). METHODS: Inflammatory bowel disease patients and a control group were enrolled when surveillance colonoscopy was scheduled. Samples of colon biopsy tissues, rectal swabs during colonoscopy, and feces before bowel preparation were collected to analyze microbial composition. To explore the short-term effects of bowel preparation on swab microbiota, prepreparation swab samples were also collected from 27 IBD patients. RESULTS: A total of 33 Crohn's disease, 54 ulcerative colitis, and 21 non-IBD patients were enrolled. In beta diversity analysis, fecal microbiota clearly differed from swab and tissue microbiota in the 3 disease groups. The swab microbiota was closer to, but still different from, the tissue microbiota. Consistently, we identified that swab samples differed more in abundant genera from feces than from tissue. Beta diversity analysis did not reveal a difference in swab microbiota before and after bowel preparation, but the genus composition of most individuals varied markedly. CONCLUSIONS: Swab microbiota more closely resembled tissue microbiota relative to fecal microbiota, but there were still differences. Bowel preparation did not alter the overall swab microbiota in the short term but markedly changed the microbial composition in most patients.

ACE2 and a Traditional Chinese Medicine Formula NRICM101 Could Alleviate the Inflammation and Pathogenic Process of Acute Lung Injury.

COVID-19 is a highly transmittable respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major complication of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6 and TNF-α) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

Fucoidan Enhances Cisplatin-induced Effects on SCC-25 Human Oral Cancer Cells by Inhibiting the PI3K/AKT Pathway.

BACKGROUND/AIM: Cisplatin is a drug for treating oral cancer. However, several previous studies indicate that oral cancer cells can develop resistance to cisplatin, which may result in a poor prognosis for patients with oral cancer. Fucoidan, a natural health product extracted from brown seaweed, has anticancer abilities against various types of cancer cell. This study evaluated whether fucoidan can enhance the sensitivity of oral cancer cells to cisplatin and explored the underlying mechanism. MATERIALS AND METHODS: SCC-25 cells were used in the present study and treated with 0.3125 mg/ml fucoidan, 12.5 µg/ml cisplatin, or 0.3125 mg/ml fucoidan plus 12.5 µg/ml cisplatin for 48 h, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, enzyme-linked immunosorbent, and immunoblotting assays were performed to evaluate cell survival, cytokeratin-18 fragment release, and expression of markers of apoptosis and autophagy, respectively. RESULTS: Cotreatment with fucoidan enhanced cisplatin-induced reduction of SCC-25 cell survival compared to cisplatin alone. In addition, cotreatment also increased the expression of apoptosis markers, including activated caspase-8, activated caspase-9, activated caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP), but did not increase the expression of the two autophagy markers studied, beclin and autophagy-related 12-autophagy-related 5 conjugate. Fucoidan significantly inhibited cisplatin-induced AKT serine/threonine kinase 1 activation, which promoted PARP cleavage, caspase-3 activation, and cytokeratin-18 fragment expression in SCC-25 cells. CONCLUSION: Fucoidan promoted cisplatin-induced effects by inhibiting phosphatidylinositol 4,5 bisphosphate 3 kinase/AKT serine/threonine kinase 1 activation induced by cisplatin. The results of this study may provide a basis for the possible application of the combination of fucoidan and cisplatin in the clinical treatment of oral cancer in the future to improve the prognosis of patients with oral cancer.

What nature has to offer: Opportunities for immuno-oncology.

Recent rapid development of cancer therapy has come about with the paradigm shift from the traditional goal of targeting cancer cells themselves, to reprograming the immune tumor microenvironment. Accumulating evidence shows that compounds that target epigenetic regulation, called epidrugs, play a crucial role in mediating the immunogenicity of cancer cells and in reshaping antitumor immunity. A large body of literature has recognized natural compounds as epigenetic modulators for their immunomodulatory effects and anticancer potential. Unifying our understanding of the role of these biologically active compounds in immuno-oncology may open new avenues for more effective cancer therapies. In this review, we explore how natural compounds modulate the epigenetic machinery to shape antitumor immune response, highlighting the promise offered by the Mother Nature that could be exploited therapeutically to improve outcomes for cancer patients.

A Low-Cost Fertilizer Medium Supplemented with Urea for the Lutein Production of Chlorella sp. and the Ability of the Lutein to Protect Cells against Blue Light Irradiation.

This study aimed to investigate the use of organic fertilizers instead of modified f/2 medium for Chlorella sp. cultivation, and the extracted lutein of the microalga to protect mammal cells against blue-light irradiation. The biomass productivity and lutein content of Chlorella sp. cultured in 20 g/L fertilizer medium for 6 days were 1.04 g/L/d and 4.41 mg/g, respectively. These values are approximately 1.3- and 1.4-fold higher than those achieved with the modified f/2 medium, respectively. The cost of medium per gram of microalgal biomass reduced by about 97%. The microalgal lutein content was further increased to 6.03 mg/g in 20 g/L fertilizer medium when supplemented with 20 mM urea, and the cost of medium per gram lutein reduced by about 96%. When doses of ≥1 µM microalgal lutein were used to protect mammal NIH/3T3 cells, there was a significant reduction in the levels of reactive oxygen species (ROS) produced by the cells in the following blue-light irradiation treatments. The results show that microalgal lutein produced by fertilizers with urea supplements has the potential to develop anti-blue-light oxidation products and reduce the economic challenges of microalgal biomass applied to carbon biofixation and biofuel production.

Serum Starvation Induces Matrix Metalloproteinase 9 Expression in Nasopharyngeal Carcinoma Cells Through the ERK-AP1 Pathway In Vitro.

BACKGROUND/AIM: Although clinical medicine has significantly progressed in treating nasopharyngeal carcinoma (NPC) in recent years, many patients still have poor prognoses due to distant metastasis. It is still relatively unclear why NPC has a highly metastatic ability. Especially whether the tumor microenvironment affects the invasion and metastasis of NPC still needs to be cleared. In this study, serum starvation was used to simulate nutrient deficiency in the tumor microenvironment to explore whether nutrient deficiency affects the malignancy of NPC cells. MATERIALS AND METHODS: Semiquantitative reverse transcription-polymerase chain reaction, ELISA, immunoblotting assay, reporter gene assay, and Matrigel invasion assay were carried out. RESULTS: Under serum starvation, NPC cells could induce the mRNA expression and protein secretion of matrix metalloproteinase 9 (MMP9). The ERK-AP1 pathway was activated under serum starvation in NPC cells, resulting in the expression of MMP9. In contrast, treatment with an MMP9 inhibitor or an MMP9 siRNA inhibited serum starvation-induced invasion. CONCLUSION: Serum starvation could up-regulate MMP9 expression in NPC cells, contributing to NPC invasion. Therefore, serum starvation may promote malignancy of NPC cells but also support MMP9 as a potential therapeutic target to prevent NPC cell invasion and metastasis.

High incidence of trigger finger after carpal tunnel release: a systematic review and meta-analysis.

INTRODUCTION: Trigger finger (TF) often occurs after carpal tunnel release (CTR), but the mechanism and outcomes remain inconsistent. This study evaluated the incidence of TF after CTR and its related risk factors. MATERIALS AND METHODS: ​PubMed, Embase, and Scopus databases were searched up to 27 August 2022, with the following keywords: "carpal tunnel release" and "trigger finger". Studies with complete data on the incidence of TF after CTR and published full text. The primary outcome was the association between CTR and the subsequent occurrence of the TF and to calculate the pooled incidence of post-CTR TF. The secondary outcomes included the potential risk factors among patients with and without post-CTR TF as well as the prevalence of the post-CTR TF on the affected digits. RESULTS: Ten studies with total 10,399 participants in 9 studies and 875 operated hands in one article were included for meta-analysis. CTR significantly increases the risk of following TF occurrence (odds ratio=2.67; 95% CI 2.344-3.043; P <0.001). The pooled incidence of TF development after CTR was 7.7%. Women were more likely to develop a TF after CTR surgery (odds ratio=2.02; 95% CI 1.054-3.873; P =0.034). Finally, the thumb was the most susceptible fingers, followed by middle and ring fingers. CONCLUSIONS: High incidence of TF comes after CTR, and women were more susceptible than man. Clinicians were suggested to notice the potential risk of TF after CTR in clinical practice. LEVEL OF EVIDENCE: Level III, meta-analysis.

Short-term effects of Chlorhexidine mouthwash and Listerine on oral microbiome in hospitalized patients.

Introduction: Chlorhexidine (CHX) and essential oil containing mouthwashes like Listerine® can improve oral hygiene via suppressing oral microbes. In hospitalized patients, CHX mouthwash reduces the incidence of ventilator-associated pneumonia. However, CHX use was also associated with increased mortality, which might be related to nitrate-reducing bacteria. Currently, no study determines oral bacteria targeted by essential oils mouthwash in hospitalized patients using a metagenomic approach. Methods: We recruited 87 hospitalized patients from a previous randomized control study, and assigned them to three mouthwash groups: CHX, Listerine, and normal saline (control). Before and after gargling the mouthwash twice a day for 5-7 days, oral bacteria were examined using a 16S rDNA approach. Results: Alpha diversities at the genus level decreased significantly only for the CHX and Listerine groups. Only for the two groups, oral microbiota before and after gargling were significantly different, but not clearly distinct. Paired analysis eliminated the substantial individual differences and revealed eight bacterial genera (including Prevotella, Fusobacterium, and Selenomonas) with a decreased relative abundance, while Rothia increased after gargling the CHX mouthwash. After gargling Listerine, seven genera (including Parvimonas, Eubacterium, and Selenomonas) showed a decreased relative abundance, and the magnitudes were smaller compared to the CHX group. Fewer bacteria targeted by Listerine were reported to be nitrate-reducing compared to the CHX mouthwash. Discussion: In conclusion, short-term gargling of the CHX mouthwash and Listerine altered oral microbiota in our hospitalized patients. The bacterial genera targeted by the CHX mouthwash and Listerine were largely different and the magnitudes of changes were smaller using Listerine. Functional alterations of gargling CHX and Listerine were also different. These findings can be considered for managing oral hygiene of hospitalized patients.

Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer.

Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway.

Studying the Roles of the Renin-Angiotensin System in Accelerating the Disease of High-Fat-Diet-Induced Diabetic Nephropathy in a db/db and ACE2 Double-Gene-Knockout Mouse Model.

Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity can cause the over-accumulation of angiotensin II (Ang II). Angiotensin-converting enzyme inhibitor (ACEI) administration has been proposed as a therapy, but previous studies have also indicated that chymase, the enzyme that hydrolyzes angiotensin I to Ang II in an ACE-independent pathway, may play an important role in the progression of DN. Therefore, this study established a model of severe DN progression in a db/db and ACE2 KO mouse model (db and ACE2 double-gene-knockout mice) to explore the roles of RAS factors in DNA and changes in their activity after short-term (only 4 weeks) feeding of a high-fat diet (HFD) to 8-week-old mice. The results indicate that FD-fed db/db and ACE2 KO mice fed an HFD represent a good model for investigating the role of RAS in DN. An HFD promotes the activation of MAPK, including p-JNK and p-p38, as well as the RAS signaling pathway, leading to renal damage in mice. Blocking Ang II/AT1R could alleviate the progression of DN after administration of ACEI or chymase inhibitor (CI). Both ACE and chymase are highly involved in Ang II generation in HFD-induced DN; therefore, ACEI and CI are potential treatments for DN.

PRMT1 is an important factor for medulloblastoma cell proliferation and survival.

Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of brain tumors, but the role of PRMT1 in medulloblastoma, the most common malignant pediatric brain tumor, remains unexplored. By examining the publicly available databases of pediatric brain tumor collection, we found that PRMT1 was predominantly expressed in medulloblastomas across all the pediatric brain tumors and that the high-level expression of PRMT1 correlated with poor survival of medulloblastoma patients. To determine the role of PRMT1 in medulloblastoma cells, we established an inducible knockdown system and demonstrated that PRMT1 depletion decreased medulloblastoma cell proliferation and induced cell apoptosis. Furthermore, the diamidine compounds, previously shown to exhibit selective PRMT1 inhibition, suppressed medulloblastoma cell viability in a dose-dependent manner. Finally, we observed induction of medulloblastoma cell apoptosis by the potent diamidine compounds at low micromolar concentrations. Together, our results suggest that PRMT1 could be an actionable therapeutic target in medulloblastoma.

Multifunctional magnetic nanocarriers for delivery of siRNA and shRNA plasmid to mammalian cells: Characterization, adsorption and release behaviors.

Nucleic acids are promising candidates for treating various diseases. Nucleic acid is negatively charged and hydrophilic; therefore, it is not efficiently taken up by cells. Successful gene therapy requires the development of carriers for efficient delivery of gene-expressing DNA plasmid and small interfering RNA (siRNA) duplex. In this study, we developed MNP-CA-PEI, a citric acid (CA)-modified magnetic nanoparticle (MNP) cross-linked with polyethyleneimine (PEI), using carbonyldiimidazole as the crosslinker. The physical properties of MNP-CA-PEI (particle size, morphologies, surface coating, surface potentials, magnetic hystereses, superparamagnetic behaviors, and infrared spectra) were systematically characterized by transmission electron microscopy imaging, dynamic light scattering, thermogravimetric analysis, superconducting quantum interference device, and Fourier transform infrared spectroscopy. The adsorption isotherm and kinetics were determined by the Langmuir model, the Freundlich model, a pseudo-first-order equation, and a pseudo-second-order equation. MNP-CA-PEI could form polyelectrolyte complexes with negatively charged nucleic acids, enabling the efficient delivery of nucleic acids into cells. Using MNP-CA-PEI nanoparticles, we magnetically triggered the intracellular delivery of green fluorescence protein (GFP)-expressing DNA plasmid, plasmid-expressing short hairpin RNA (shRNA) against GFP, or siRNA targeting GFP into different cell lines. Nucleic acid/MNP-CA-PEI displayed the enhanced cellular uptake of GFP-expressing DNA plasmid, and it improved the silencing efficiency of shRNA and siRNA, determined by fluorescence imaging. Gene knockdowns mediated by shRNA and siRNA were also confirmed by a quantitative real-time polymerase chain reaction. MNP-CA-PEI delivered nucleic acids into cytosol through caveolae-mediated endocytosis. This study introduces a new MNP functionalization that can be used for the magnetically driven intracellular delivery of nucleic acids.