Indocyanine-Green-Loaded Liposomes for Photodynamic and Photothermal Therapies: Inducing Apoptosis and Ferroptosis in Cancer Cells with Implications beyond Oral Cancer.

Oral cancer represents a global health burden, necessitating novel therapeutic strategies. Photodynamic and photothermal therapies using indocyanine green (ICG) have shown promise due to their distinctive near-infrared (NIR) light absorption characteristics and FDA-approved safety profiles. This study develops ICG-loaded liposomes (Lipo-ICGs) to further explore their potential in oral cancer treatments. We synthesized and characterized the Lipo-ICGs, conducted in vitro cell culture experiments to assess cellular uptake and photodynamic/photothermal effects, and performed in vivo animal studies to evaluate their therapeutic efficacy. Quantitative cell apoptosis and gene expression variation were further characterized using flow cytometry and RNA sequencing, respectively. Lipo-ICGs demonstrated a uniform molecular weight distribution among particles. The in vitro studies showed a successful internalization of Lipo-ICGs into the cells and a significant photodynamic treatment effect. The in vivo studies confirmed the efficient delivery of Lipo-ICGs to tumor sites and successful tumor growth inhibition following photodynamic therapy. Moreover, light exposure induced a time-sensitive photothermal effect, facilitating the further release of ICG, and enhancing the treatment efficacy. RNA sequencing data showed significant changes in gene expression patterns upon Lipo-ICG treatment, suggesting the activation of apoptosis and ferroptosis pathways. The findings demonstrate the potential of Lipo-ICGs as a therapeutic tool for oral cancer management, potentially extending to other cancer types.

Coupling Zn2+ doping and rich oxygen vacancies in MnO2 nanowire toward advanced aqueous zinc-ion batteries.

Easy collapse of structure and sluggish reaction kinetics restrict the practical application of MnO2 in the field of aqueous Zn-ion batteries (ZIBs). To circumvent these obstacles, Zn2+ doping MnO2 nanowire electrode material with rich oxygen vacancies is prepared by one-step hydrothermal method combined with plasma technology. The experimental results indicate that Zn2+ doping MnO2 nanowire not only stabilizes the interlayer structure of MnO2, but also provide additional specific capacity as electrolyte ions. Meanwhile, plasma treatment technology induces the oxygen-deficient Zn-MnO2 electrode optimizing the electronic structure to improve the electrochemical behavior of the cathode materials. Especially, the optimized Zn/Zn-MnO2 batteries obtain outstanding specific capacity (546 mAh g-1 at 1 A g-1) and superior cycling durability (94% over 1000 continuous discharge/charge tests at 3 A g-1). Greatly, the H+ and Zn2+ reversible co-insertion/extraction energy storage system of Zn//Zn-MnO2-4 battery is further revealed by the various characterization analyses during the cycling test process. Further, from the perspective of reaction kinetics, plasma treatment also optimizes the diffusion control behavior of electrode materials. This research proposes a synergistic strategy of element doping and plasma technology, which has enhanced the electrochemical behaviors of MnO2 cathode and shed light on the design of the high-performance manganese oxide-based cathodes for ZIBs.

M1ARegpred: Epitranscriptome Target Prediction of N1-methyladenosine (m1A) Regulators Based on Sequencing Features and Genomic Features.

BACKGROUND: N1-methyladenosine (m1A) is a reversible post-transcriptional modification in mRNA, which has been proved to play critical roles in various biological processes through interaction with different m1A regulators. There are several m1A regulators existing in the human genome, including YTHDF1-3 and YTHDC1. METHODS: Several techniques have been developed to identify the substrates of m1A regulators, but their binding specificity and biological functions are not yet fully understood due to the limitations of wet-lab approaches. Here, we submitted the framework m1ARegpred (m1A regulators substrate prediction), which is based on machine learning and the combination of sequence-derived and genome-derived features. RESULTS: Our framework achieved area under the receiver operating characteristic (AUROC) scores of 0.92 in the full transcript model and 0.857 in the mature mRNA model, showing an improvement compared to the existing sequence-derived methods. In addition, motif search and gene ontology enrichment analysis were performed to explore the biological functions of each m1A regulator. CONCLUSIONS: Our work may facilitate the discovery of m1A regulators substrates of interest, and thereby provide new opportunities to understand their roles in human bodies.

Research Progress for RNA Modifications in Physiological and Pathological Angiogenesis.

As a critical layer of epigenetics, RNA modifications demonstrate various molecular functions and participate in numerous biological processes. RNA modifications have been shown to be essential for embryogenesis and stem cell fate. As high-throughput sequencing and antibody technologies advanced by leaps and bounds, the association of RNA modifications with multiple human diseases sparked research enthusiasm; in addition, aberrant RNA modification leads to tumor angiogenesis by regulating angiogenesis-related factors. This review collected recent cutting-edge studies focused on RNA modifications (N6-methyladenosine (m6A), N5-methylcytosine (m5C), N7-methylguanosine (m7G), N1-methyladenosine (m1A), and pseudopuridine (Ψ)), and their related regulators in tumor angiogenesis to emphasize the role and impact of RNA modifications.

Layered Co doped MnO2 with abundant oxygen defects to boost aqueous zinc-ion storage.

Zinc Manganese oxide (Zn/MnO2)-based aqueous battery is favored due to their high specific capacity, security and cost performance. Nevertheless, they usually problems of unstable cyclic structure and slow diffusion kinetics, restricting their practical application. Here, we have successfully synthesized a Co doped MnO2 cathode material with abundant defects on a carbon cloth substrate. Through a simple hydrothermal method, the Co element can be lightly intercalated in the two-dimensional (2D) layered α-MnO2 nanowires, inhibiting the structural transformation during the cycle and improve the stability of the material. Meanwhile, plasma technology facilitates the formation of oxygen vacancies in the electrode material, which not only accelerate electron diffusion but also improve the conductivity. Therefore, Zn/Co-MnO2 battery can reach a specific capacity of 511 mAh g-1 at 0.5A g-1 and the retention rate accomplish 98% at high current density. This research puts forward a strategy of element doping and physical preparation of oxygen vacancies, which provides the possibility to develop reversible Zn/MnO2-based aqueous battery cathode materials with high-performance.

An iron based organic framework coated with nickel hydroxide for energy storage, conversion and detection.

Although electrode materials based on metal organic frameworks (MOFs) were widely studied in the electrochemistry field, the origin of poor conductivity is still a bottleneck restricting their development. Herein, we constructed a conductive circuit by growing a layer of hydroxide on the surface of the Fe-MOF, and composite materials (Fe-MOF@Ni(OH)2) are applied in the fields of supercapacitor, OER, and electrochemical sensing. Fe-MOF@Ni(OH)2 not only maintains the intrinsic advantages of Fe-MOF, but also improves the electrical conductivity. Fe-MOF@Ni(OH)2 exhibits a high specific capacity of 188 mAh g-1 at 1 A g-1 . The energy density of the asymmetric supercapacitor (Fe-MOF@Ni(OH)2-20//AC) reaches 67.1 Wh kg-1. During the oxygen evolution reaction, the overpotential of the material is 280 mV at 10 mA cm-2, and the Tafel slope is 37.6 mV dec-1. The electrochemical sensing tests showed the detection limit of BPA is 5 µM. Hence, these results provide key insights into the design of multifunctional electrode materials.

Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma.

The present study was carried out to explore the effect of sinensetin in human T-cell lymphoma Jurkat cells and to reveal the underlying molecular mechanisms. We found that sinensetin significantly impeded Jurkat cell proliferation in a dose-dependent and time-dependent manner. Additionally, sinensetin treatment triggered apoptosis and autophagy in Jurkat cells. The apoptosis induction was related to a loss of mitochondrial membrane potential and to increased caspase-3/-8/-9 and poly(ADP-ribose) polymerase (PARP) cleavage. Sinensetin also induced autophagy, as evidenced by the formation of acidic vacuoles, the upregulation of LC3-II and beclin-1, and the downregulation of p62. In addition, the inhibition of autophagy by 3-methyladenine significantly enhanced the apoptosis rate and improved the sensitivity of the Jurkat cells to sinensetin. Moreover, sinensetin induced cell death, apoptosis, and autophagy through the activation of the reactive oxygen species/ c-Jun N-terminal kinase signaling pathway and the inhibition of the Akt/mTOR signaling pathways. In summary, our results revealed that sinensetin induced apoptosis and autophagy in human T-cell lymphoma Jurkat cells by activating reactive oxygen species/ c-Jun N-terminal kinase and blocking the Akt/mTOR signaling pathways. Thus, sinensetin might be a potential candidate in the development of antitumor drugs targeting T-cell leukemia.

In Vitro and In Vivo Antitumor Effects of Pyrimethamine on Non-small Cell Lung Cancers.

BACKGROUND/AIM: Pyrimethamine (PYR), an anti-malarial drug is known to inhibit various types of human cancer cells. The aim of this study was to investigate the anti-tumour effects of pyrimethamine (PYR) and its underlying molecular mechanisms using the human NSCLC cell line A549. MATERIALS AND METHODS: PYR was dissolved in dimethyl sulfoxide to determine its apoptotic activity on A549 cells. Cell viability was determined by the MTT assay. Cell cycle, mitochondrial membrane potential, and Annexin V-FITC early apoptosis detection were evaluated by flow cytometry. Cyclin-dependent kinase (CDK) and Bcl-2 family protein expression was determined by western blotting. RESULTS: PYR reduced cell viability percentage and induced G0/G1 arrest, which was associated with down-regulation of cyclins D1 and E, CDK4, and CDK2, and up-regulation of p21. PYR induced sub-G1 accumulation, Annexin-V binding, caspase-9 and -3 activation, poly (ADPribose) polymerase cleavage, and mitochondrial dysfunction in A549 cells. Moreover, PYR effectively inhibited NSCLC tumour growth in an A549 xenograft model. CONCLUSION: PYR demonstrated anti-tumour effects on NSCLC in vitro and in vivo, indicating its therapeutic potential against human NSCLC.

Lobocrassin B Induces Apoptosis of Human Lung Cancer and Inhibits Tumor Xenograft Growth.

Lobocrassin B, a natural cembrane-type compound isolated from the soft coral Lobophytum crassum, has been shown to have significant biological effects, including anticancer activity. As the most common cause of cancer mortality worldwide, lung cancer remains a major concern threatening human health. In the current study, we conducted in vitro experiments to demonstrate the inhibiting effect of Lobocrassin B on CL1-5 and H520 human lung cancer cells growth and to explore the underlying mechanisms, as well as in nude mice bearing CL1-5 tumor xenografts. Lobocrassin B exerted cytotoxic effects on lung cancer cells, as shown by decreasing cell viability, and inducing apoptosis, oxidative stress and mitochondrial dysfunction. In addition, the increased level of Bax, cleaved caspase-3, -9 and -8, and the suppression of Bcl-2 were observed in the Lobocrassin B treated cells. Moreover, in vivo assays verified the significance of these results, revealing that Lobocrassin B inhibited CL1-5 tumor xenograft growth and that inhibitory effects were accompanied by a marked increase in tumor cell apoptosis. In conclusion, the results suggested that Lobocrassin B could be a potential anticancer compound for its propensity to inhibit growth and induce apoptosis in human lung cancer cells.

Plasma levels of high-mobility group box 1 and soluble receptor for advanced glycation end products in primary antiphospholipid antibody syndrome patients.

INTRODUCTION: Many studies have demonstrated elevated circulating levels of high-mobility group box 1 (HMGB1) and decreased circulating levels of soluble receptor for advanced glycation end products (sRAGE) in patients with autoimmune diseases. In the present study, we investigated plasma levels of both HMGB1 and sRAGE in primary antiphospholipid syndrome (pAPS) patients. METHODS: We prospectively recruited 11 pAPS patients, 17 antiphospholipid antibody (APA)-positive SLE patients without APS manifestations (APA+SLE) and 12 SLE patients with secondary APS (APS+SLE). We also recruited 10 healthy controls (HCs). Plasma levels of HMGB1 and sRAGE were determined using sandwich ELISA kits. In addition, plasma levels of HMGB1 were also determined using Western blot in 6 pAPS patients and 6 HCs. RESULTS: There was no significant difference in plasma levels of HMGB1 measured by ELISA among subgroups of the enrolled subjects. In addition, there was no significant difference in plasma levels of HMGB1 measured by Western blot between pAPS patients and HCs. On the other hand, we observed a trend toward lower plasma levels of sRAGE in APA+SLE or APS+SLE patients when compared with HCs. However, there was no significant difference in plasma levels of sRAGE between pAPS patients and HCs, or between APA+SLE patients and APS+SLE patients. CONCLUSION: There was no significant difference in plasma levels of sRAGE or HMGB1 between pAPS patients and HCs. Plasma levels of sRAGE/HMGB1 could not be utilized to differentiate between APA+SLE and APS+SLE patients.