Supramolecular Nanoparticles of Histone and Hyaluronic Acid for Co-Delivery of siRNA and Photosensitizer In Vitro.

Small interfering RNA (siRNA) has significant potential as a treatment for cancer by targeting specific genes or molecular pathways involved in cancer development and progression. The addition of siRNA to other therapeutic strategies, like photodynamic therapy (PDT), can enhance the anticancer effects, providing synergistic benefits. Nevertheless, the effective delivery of siRNA into target cells remains an obstacle in cancer therapy. Herein, supramolecular nanoparticles were fabricated via the co-assembly of natural histone and hyaluronic acid for the co-delivery of HMGB1-siRNA and the photosensitizer chlorin e6 (Ce6) into the MCF-7 cell. The produced siRNA-Ce6 nanoparticles (siRNA-Ce6 NPs) have a spherical morphology and exhibit uniform distribution. In vitro experiments demonstrate that the siRNA-Ce6 NPs display good biocompatibility, enhanced cellular uptake, and improved cytotoxicity. These outcomes indicate that the nanoparticles constructed by the co-assembly of histone and hyaluronic acid hold enormous promise as a means of siRNA and photosensitizer co-delivery towards synergetic therapy.

Phosphorus addition increases stability and complexity of co-occurrence network of soil microbes in an artificial Leymus chinensis grassland.

Introduction: Understanding the response of cross-domain co-occurrence networks of soil microorganisms to phosphorus stability and the resulting impacts is critical in ecosystems, but the underlying mechanism is unclear in artificial grassland ecosystems. Methods: In this study, the effects of four phosphorus concentrations, P0 (0 kg P ha-1), P1 (15.3 kg P ha-1), P2 (30.6 kg P ha-1), and P3 (45.9 kg P ha-1), on the cross-domain co-occurrence network of bacteria and fungi were investigated in an artificial Leymus chinensis grassland in an arid region. Results and discussion: The results of the present study showed that phosphorus addition significantly altered the stem number, biomass and plant height of the Leymus chinensis but had no significant effect on the soil bacterial or fungal alpha (ACE) diversity or beta diversity. The phosphorus treatments all increased the cross-domain co-occurrence network edge, node, proportion of positively correlated edges, edge density, average degree, proximity to centrality, and robustness and increased the complexity and stability of the bacterial-fungal cross-domain co-occurrence network after 3 years of continuous phosphorus addition. Among them, fungi (Ascomycota, Basidiomycota, Mortierellomycota and Glomeromycota) play important roles as keystone species in the co-occurrence network, and they are significantly associated with soil AN, AK and EC. Finally, the growth of Leymus chinensis was mainly due to the influence of the soil phosphorus content and AN. This study revealed the factors affecting the growth of Leymus chinense in artificial grasslands in arid areas and provided a theoretical basis for the construction of artificial grasslands.

Arsenic trioxide suppresses lung adenocarcinoma stem cell stemness by inhibiting m6A modification to promote ferroptosis.

Arsenic trioxide (ATO) is well known for its inhibitory effects on cancer progression, including lung adenocarcinoma (LUAD), but the molecular mechanism remains elusive. This study aimed to investigate the roles of ATO in regulating LUAD stem cells (LASCs) and the underlying mechanisms. To induce LASCs, cells cultured in an F12 medium, containing B27, epidermal growth factor, and basic fibroblast growth factor, induced LASCs. LASCs stemness was assessed through tumor sphere formation assay, and percentages of CD133+ cells were detected by flow cytometry. The Cell Counting Kit-8 method was used to assess LASCs viability, while reactive oxygen species (ROS) and iron ion levels were quantitated by fluorescence microscopy and spectrophotometry, respectively, and total m6A levels were measured by dot blot. Additionally, LASCs mitochondrial alterations were analyzed via transmission electron microscopy. Finally, the tumorigenicity of LASCs was assessed using a cancer cell line-based xenograft model. Tumor sphere formation and CD133 expression were used to validate the successful induction of LASCs from A549 and NCI-H1975 cells. ATO significantly inhibited proliferation, reduced ZC3H13 expression and total m6A modification levels, and increased ROS and iron ion content, but repressed sphere formation and CD133 expression in LASCs. ZC3H13 overexpression or ferrostatin-1 treatment abrogated LASCs stemness inhibition caused by ATO treatment, and interference with ZC3H13 inhibited LASCs stemness. Furthermore, the promotion of LASCs ferroptosis by ATO was effectively mitigated by ZC3H13 overexpression, while interference with ZC3H13 further promoted ferroptosis. Moreover, si-ZC3H13 promoted ferroptosis and impaired stemness in LASCs, which ferrostatin-1 abrogated. Finally, ZC3H13 overexpression alleviated the inhibitory effects of ATO on LASCs tumorigenicity. Taken together, ATO treatment substantially impaired the stemness of LUAD stem cells by promoting the ferroptosis program, which was mediated by its ZC3H13 gene expression inhibition to suppress m6A medication.

A better method to evaluate the reliability of echocardiography for assessment of pulmonary hypertension: comparison of tricuspid regurgitant spectrum quality grading and tricuspid valve regurgitation degree.

Background: Transthoracic echocardiography (TTE) is recommended as the most important noninvasive screening tool for the diagnosis of pulmonary hypertension (PH), sonographers usually measure the volume of regurgitant flow rather than evaluating the spectral quality, so physicians will determine whether the ultrasound measurements of pulmonary arterial systolic pressure (US-PASP) are reliable based on the volume of tricuspid regurgitation (TR). Therefore, for the first time, we grade the quality of TR spectrum (TRS) based on its integrity and clarity, aiming to assess clinical application value of different tricuspid regurgitant spectrum quality grades (TR-SQG), and investigate whether the accuracy of US-PASP is more trustworthy than TR. Methods: We retrospectively analyzed 108 patients with chronic thromboembolic PH (CTEPH) to compare the correlation and agreement between US-PASP and right heart catheterization measurements of PASP (RHC-PASP). TR area (TRA) and TRS were measured in each patient, and TR-SQG was performed. Results: The correlation coefficients between US-PASP and RHC-PASP were r=0.622 (P<0.001), r=0.754 (P<0.001), r=0.595 (P<0.001) in mild, moderate, severe TR, and r=0.301 (P=0.135), r=0.747 (P<0.001), r=0.739 (P<0.001), r=0.828 (P<0.001) in TR-SQG I-IV, respectively. Bland-Altman analysis revealed the mean biases of 5.05, 3.06, 7.62 mmHg in mild, moderate, severe TR, and -16.47, -8.07, 1.82, 6.09 mmHg in TR-SQG I-IV, respectively. In mild TR with the TR-SQG III and IV, the correlation coefficients between US-PASP and RHC-PASP were r=0.779 (P<0.001), intraclass correlation coefficient (ICC) =0.774, paired t-test P=0.160, respectively; and the consistency was significantly higher than that of mild TR without considering TR-SQG. In moderate TR with the TR-SQG III and IV, the r=0.749, ICC =0.746, paired t-test P=0.298 between US-PASP and RHC-PASP. Conclusions: The US-PASP with TR-SQG III or IV is trustworthy, and its accuracy and consistency are better than those predicted by the traditional severity of TR. The establishment of the ultrasound evaluation system of TR-SQG helps clinicians to judge whether the US-PASP is accurate, credible, and reliable.

Marine biodegradation of plastic films by Alcanivorax under various ambient temperatures: Bacterial enrichment, morphology alteration, and release of degradation products.

The global ocean has been receiving massive amounts of plastic wastes. Marine biodegradation, influenced by global climate, naturally breaks down these wastes. In this study, we systematically compared the biodegradation performance of petroleum- and bio-based plastic films, i.e., low-density polyethylene (LDPE), polylactic acid (PLA), and polyhydroxyalkanoates (PHAs) under three ambient temperatures (4, 15, and 22 °C). We deployed the our previously isolated cold-tolerant plastic-degrading Alcanivorax to simulate the accelerated marine biodegradation process and evaluated the alteration of bacterial growth, plastic films, and released degradation products. Notably, we found that marine biodegradation of PHA films enriched more bacterial amounts, induced more conspicuous morphological damage, and released more microplastics (MPs) and dissolved organic carbon (DOC) under all temperatures compared to LDPE and PLA. Particularly, MPs were released from film edges and cracks with a mean size of 2.8 µm under all temperatures. In addition, the degradation products released by biodegradation of PHA under 22 °C induced the highest acute toxicity to Vibrio fischeri. Our results highlighted that: (1) marine biodegradation of plastics would release millions of MPs per cm2 exposed surface area even in cold environments within 60 days; (2) different marine biodegradation scenarios of these plastics may raise disparate impacts and mitigation-related studies.

Effect of platelet concentrates for pain and symptom management in oral lichen planus: an evidence-based systematic review.

BACKGROUND: Platelet Concentrate (PC) injection therapy has shown potential as a local therapy for oral lichen planus (OLP). However, its safety and efficacy have not yet been fully established. Our research compared the efficacy of PC with topical steroid treatment in alleviating pain and symptoms related to OLP. We aims to present evidence-based alternatives that dentists can use to improve patient outcomes while reducing potential side effects. METHODS: We conducted a systematic search of five electronic databases up to April 2023, including Embase, Cochrane Central Register of Controlled Trials, PubMed, OVID Medline, and WanFang, to evaluate PCs' efficacy compared to topical corticosteroid therapy for OLP. The literature quality was assessed using the Cochrane ROB tool. A fixed-effects model was used to determine the Weighted Mean Difference (WMD) and Mean Difference (MD) at a 95% confidence interval (CI) for pain severity and other relevant clinical indicators. RESULTS: The comparison between topical corticosteroid therapy and PCs showed no significant difference for pain relief (WMD = -0.07, CI = 95% -0.34 to 0.19), symptom improvement (MD = -0.21, CI = 95% -0.55 to 0.13), or the severity of included lesions measured by REU scores (MD = -0.25, CI = 95% -0.32 to 0.82). CONCLUSIONS: Locally injected PC have been found efficient in managing oral lichen planus, indicating that they are a promising alternative option to steroid therapy for OLP patients, particularly those who have not responded favorably to steroid therapy. However, further research is needed to establish determining the recurrence rate and long-term adverse effects. TRIAL REGISTRATION: The systematic review protocol has been registered in advance with the PROSPERO database (CRD42023415372).

circRNA-miRNA Complex Participates in the Apoptosis of Myocardial Cells in Myocardial Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion (I/R) injury is a common condition. This study aimed to investigate the potential mechanisms of circ_Ddx60 in the mouse model of I/R injury. Cardiac tissues were used to extract RNA for subsequent RNA sequencing analysis. Bioinformatic analysis was performed and circ_Ddx60 and Bcl2a1a (B cell leukemia/lymphoma 2 related protein A1a) were selected for further validation. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to detect the gene expression level. The effect of circ_Ddx60 on cardiac cell apoptosis was examined. The function of miR-302a-3p in cell apoptosis was further explored in circ_Ddx60-overexpressed HL-1 cells under hypoxia/reoxygenation (H/R) treatment. We have revealed a number of differentially expressed circRNAs and mRNAs between the I/R group and sham groups, with circ_Ddx60 being among them. Treatment of HL-1 cells with hypoxia/reoxygenation (H/R) led to an overexpression of circ_Ddx60, which then inhibited apoptosis and promoted the Bcl2a1a expression. Furthermore, circ_Ddx60 directly binds with miR-302a-3p, which could reverse the effect of circ_Ddx60 overexpression on cellular apoptosis and Bcl2a1a expression. Our study revealed that circ_Ddx60 inhibits apoptosis in myocardial cells by regulating the miR-302a-3p/Bcl2a1a axis, which provides novel insights into the prevention of myocardial I/R injury.

Novel active stealth micelles based on ß2M achieved effective antitumor therapy.

Micelles have been extensively investigated as drug delivery systems for loading of antitumor drugs with the advantages of good dispersibility, controllable size distribution, and high loading capacity. However, phagocytic clearance by the mononuclear phagocyte system remains a major impediment that inhibits blood circulation and thus tumor accumulation of micelles. Inspired by the antiphagocytic properties of ß2-microglobulin (ß2M), here we developed a ß2M-derived peptide for the surface functionalization of micelles. A ß2M-derived sequence was integrated with a matrix metalloproteinase-2 (MMP-2) cleavable sequence and then modified on the surface of poly(ethylene glycol)-b-poly(caprolactone) (PEG-PCL) micelles, endowing the micelles with both antiphagocytic and MMP-2-responsive properties. Compared to pristine PEG-PCL micelles, micelles modified with the dual-functional peptide exhibited higher inhibition of phagocytosis by macrophages in the absence of MMP-2, and enhanced internalization by tumor-associated macrophages in the presence of MMP-2, leading to enhanced tumor accumulation of the loaded photosensitizer, thus enabling antitumor therapy. These results demonstrated that antiphagocytic peptides derived from endogenous proteins are promising for functionalization of micelles in smart drug delivery.

Lnc00892 competes with c-Jun to block NCL transcription, reducing the stability of RhoA/RhoC mRNA and impairing bladder cancer invasion.

Metastasis of bladder cancer is a complex process and has been associated with poor clinical outcomes. However, the mechanisms of bladder cancer metastasis remain largely unknown. The present study found that the long noncoding RNA lnc00892 was significantly downregulated in bladder cancer tissues, with low lnc00892 expression associated with poor prognosis of bladder cancer patients. Lnc00892 significantly inhibited the migration, invasion, and metastasis of bladder cancer cells in vitro and in vivo. In-depth analysis showed that RhoA/C acted downstream of lnc00892 to inhibit bladder cancer metastasis. Mechanistically, lnc00892 reduces nucleolin gene transcription by competitively binding the promoter of nucleolin with c-Jun, thereby inhibiting nucleolin-mediated stabilization of RhoA/RhoC mRNA. Taken together, these findings provide novel insights into understanding the mechanisms of bladder cancer metastasis and suggest that lnc00892 can serve as a potential therapeutic target in patients with invasive bladder cancer.

Biomimetic regulation of dentine remineralization by amino acid in vitro.

OBJECTIVE: The aim of this study was to evaluate the effect of conditioning solutions containing DL-aspartic amino (Asp) on dentine remineralization induced by bioactive glass 45S5 (BAG) in a simulated oral environment. METHODS: Sixty dentine discs from human third molars were used. Dentine specimens were treated with ethylene diamine tetraacetic acid (EDTA) to create a partially demineralization model and randomly divided to 4 groups: Artificial saliva (AS) group, Asp group (pretreated with Asp and remineralized with distilled water), BAG group (pretreated with distilled water and remineralized by BAG), Asp-BAG group (pretreated with Asp and remineralized by BAG). Each samples were measured at various time points, and at the end of the experiment, 6% citric acid challenge were taken. The remineralization characteristics were analyzed by using the spectroscopic data from attenuated total reflectance spectroscopy (ATR-IR) and Raman spectroscopy. The micro-morphology and structure were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Dentine permeability was measured before and after each treatment to evaluate the resistance of remineralized layer to acid and simulated oral environment. RESULTS: Both BAG and Asp-BAG groups significantly reduced dentine permeability and formed enamel-like apatite layers on dentine surface. For the mineralization of BAG, Asp showed inhibition effect. The 7-day mineral matrix area ratio in BAG group (12.54±2.29) was lower than the value in the Asp-BAG group (17.77±2.27) (p<0.05) and the Raman intensity (RI%) in Asp-BAG Group (1.49±0.26) was also significantly higher than that of BAG group (1.34±0.14) (p<0.05). According to permeability test, the apatite layer in BAG group and Asp-BAG group effectively occluded the dentinal tubules (p<0.05) and had certain acidic resistance (p>0.05). Furthermore, adsorbed acidic amino acid on hydroxyapatite (HAP) altered the crystal to increase into a larger size in diameter during crystal growth. SIGNIFICANCE: The study demonstrated that a superior remineralization efficacy of BAG with Asp pretreatment on dentine.

MicroRNA-411 Downregulation Enhances Tumor Growth by Upregulating MLLT11 Expression in Human Bladder Cancer.

Although several previous studies have reported the implication of various microRNAs (miRNAs) in regulation of human bladder cancer (BC) development, alterations and function of many miRNAs in bladder cancer growth are not explored yet at present. Here, we screened 1,900 known miRNAs and first discovered that miR-411 was one of the major miRNAs, which was down-regulated in n-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced BCs. This miR-411 down-regulation was also observed in human BC tissues and cell lines. The results from evaluating the relationship between miR-411 and patient survival in BC using the TCGA (The Cancer Genome Atlas) database indicated that miR-411 was positively correlated with DFS (disease-free survival). Our studies also showed that miR-411 inhibited tumor growth of human BC cells in a xenograft animal model. Mechanistic studies revealed that overexpression of miR-411 repressed the expression of ALL1-fused gene from the chromosome 1q (AF1q) (MLLT11) by binding to the 3' untranslated region (UTR) of mllt11 mRNA and in turn induced p21 expression and caused cell cycle arrest at the G2/M phase, further inhibiting BC tumor growth. Collectively, our results improve our understanding of the role of miR-411 in BC tumor growth and suggest miR-411 and MLLT11 as potential new targets for the treatment of BC patients.

Phenolic compositions and antioxidant capacities of Chinese wild mandarin (Citrus reticulata Blanco) fruits.

As one of the most important centres of origin for the genus Citrus L., China is rich in wild mandarin germplasm. In this study, phenolic compounds in the peels of 14 wild mandarin genotypes native to China were determined and their antioxidant capacities were evaluated using DPPH, FRAP, ABTS and ORAC methods. We found that Nieduyeju had the highest total phenol content (51.14 mg/g DW), and Wulongsuanju had the highest total flavonoid content (20.66 mg/g DW). Hesperidin, the dominant flavonoid, was observed to be highest in Guangxihongpisuanju (55.98 mg/g DW). Ferulic acid was the most abundant phenolic acid analyzed, and Nieduyeju (7780.17 µg/g DW) and Guangxihongpisuanju (13,607.19 µg/g DW) had the highest contents of extractable and bound phenolic acid, respectively. Antioxidant potency composite (APC) index showed obvious variations ranging from 58.84 to 98.89 in the studied wild mandarins, among them, Nieduyeju had the highest APC index. Overall, Guangxihongpisuanju, Nieduyeju, Cupigoushigan and Daoxianyeju contained more phenolics and exhibited higher antioxidant capacities than the mandarin cultivars Satsuma and Ponkan.

Different responses of tumor and normal cells to low-dose radiation.

AIM OF THE STUDY: We demonstrated stimulation of both erythrocyte immune function and superoxide dismutase activity in tumor-bearing mice in response to whole-body 75 mGy X-rays. In addition, we enhanced the chemotherapeutic effect by exposing tumor-bearing mice to low-dose radiation (LDR). This study aims to investigate the different responses of tumor cells and normal cells to LDR. MATERIAL AND METHODS: Survival fraction, micronucleus frequency, and cell cycle of Lewis cells and primary human fibroblast AG01522 cells were measured. S180 sarcoma cells were implanted in mice, and tumor sizes were measured in vivo. RESULTS: In response to LDR exposure in vitro, a stimulating effect was observed in AG01522 cells but not in Lewis cells. Low-dose radiation did not cause an adaptive response in the Lewis cell cycle. Lack of an LDR-induced radioadaptive response in tumor cells was observed in tumor-bearing mouse models. Furthermore, a higher apoptotic effect and lower expression of the anti-apoptosis gene Bcl-2 were found in tumor cells of tumor-bearing mice exposed to D1 + D2 than those in tumor cells of tumor-bearing mice exposed to D2 alone. CONCLUSIONS: Different responses of tumor cells and normal cells to LDR were found. Low-dose radiation was found to stimulate the growth of normal cells but not of tumor cells in vitro and in vivo, which is a very important and clinically relevant phenomenon.