PTBP1 as a potential regulator of disease.

Polypyrimidine tract-binding protein 1 (PTBP1) is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, which plays a key role in alternative splicing of precursor mRNA and RNA metabolism. PTBP1 is universally expressed in various tissues and binds to multiple downstream transcripts to interfere with physiological and pathological processes such as the tumor growth, body metabolism, cardiovascular homeostasis, and central nervous system damage, showing great prospects in many fields. The function of PTBP1 involves the regulation and interaction of various upstream molecules, including circular RNAs (circRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These regulatory systems are inseparable from the development and treatment of diseases. Here, we review the latest knowledge regarding the structure and molecular functions of PTBP1 and summarize its functions and mechanisms of PTBP1 in various diseases, including controversial studies. Furthermore, we recommend future studies on PTBP1 and discuss the prospects of targeting PTBP1 in new clinical therapeutic approaches.

Mitochondrial targeted doxorubicin derivatives delivered by ROS-responsive nanocarriers to breast tumor for overcoming of multidrug resistance.

Multidrug resistance (MDR) is a serious challenge in chemotherapy and also a major threat to breast cancer treatment. As an intracellular energy factory, mitochondria provide energy for drug efflux and are deeply involved in multidrug resistance. Mitochondrial targeted delivery of doxorubicin can overcome multidrug resistance by disrupting mitochondrial function. By incorporating a reactive oxygen species (ROS)-responsive hydrophobic group into the backbone structure of hyaluronic acid - a natural ligand for the highly expressed CD44 receptor on tumor surfaces, a novel ROS-responsive and CD44-targeting nano-carriers was constructed. In this study, mitochondria-targeted triphenylphosphine modified-doxorubicin (TPP-DOX) and amphipathic ROS-responsive hyaluronic acid derivatives (HA-PBPE) were synthesized and confirmed by 1H NMR. The nanocarriers TPP-DOX @ HA-PBPE was prepared in a regular shape and particle size of approximately 200 nm. Compared to free DOX, its antitumor activity in vitro and tumor passive targeting in vivo has been enhanced. The ROS-responsive TPP-DOX@HA-PBPE nanocarriers system provide a promising strategy for the reverse of MDR and efficient delivery of doxorubicin derivatives into drug-resistant cancer cells.

Doxorubicin derivative loaded acetal-PEG-PCCL micelles for overcoming multidrug resistance in MCF-7/ADR cells.

Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor. Significance: Chemotherapy is one of the main treatments for breast cancer but is plagued by multidrug resistance (MDR). DOX-TPP-loaded micelles can enhance the specific concentration of drugs in the tumor and improve the efficacy and overcome MDR. Methods: In this study, DOX-TPP-loaded micelles based on acetal-PEG-PCCL were prepared and their physicochemical properties were characterized. The cellular uptake and ability to induce apoptosis of the micelles was confirmed by flow cytometry in MCF-7/ADR cells. In addition, cytotoxicity of the micelles was studied in MCF-7 cells and MCF-7/ADR cells. Confocal is used to study the subcellular distribution of DOX. Free DOX-TPP or DOX-TPP-loaded acetal-PEG-PCCL micelles were administered via intravenous injection in the tail vain for the biodistribution study in vivo. Results: The diameter of micelles was about 102.4 nm and their drug-loading efficiency is 61.8%. The structural characterization was confirmed by 1H NMR. The micelles exhibited better antitumor efficacy compared to free doxorubicin in MCF-7/ADR cells by MTT assay. The apoptotic rate and the cellular uptake of micelles were significantly higher than free DOX and DOX-TPP. Micelles can efficiently deliver mitochondria-targeting DOX-TPP to tumor cells. The result of bio-distribution showed that the micelles had stronger tumor infiltration ability than free drugs. Conclusions: In this study, mitochondriotropic DOX-TPP was conjugated to the nanocarrier acetal-PEG-PCCL via ionic interaction to form a polymer, which spontaneously formed spherical micelles. The cytotoxicity and cellular uptake of the micelles are superior to free DOX and exhibit mitochondrial targeting and passive tumor targeting, indicating that they have potential prospects.

Mitochondrial Targeted Doxorubicin-Triphenylphosphonium Delivered by Hyaluronic Acid Modified and pH Responsive Nanocarriers to Breast Tumor: in Vitro and in Vivo Studies.

Multidrug resistance (MDR) is the major obstacle for chemotherapy. In a previous study, we have successfully synthesized a novel doxorubicin (DOX) derivative modified by triphenylphosphonium (TPP) to realize mitochondrial delivery of DOX and showed the potential of this compound to overcome DOX resistance in MDA-MB-435/DOX cells. (1) To introduce specificity for DOX-TPP to cancer cells, here we report on the conjugation of DOX-TPP to hyaluronic acid (HA) by hydrazone bond with adipic acid dihydrazide (ADH) as the acid-responsive linker, producing HA- hydra-DOX-TPP nanoparticles. Hyaluronic acid (HA) is a natural water-soluble linear glycosaminoglycan, which was hypothesized to increase the accumulation of nanoparticles containing DOX-TPP in the mitochondria of tumor cells upon systemic administration, overcoming DOX resistance, in vivo. Our results showed HA- hydra-DOX-TPP to self-assemble to core/shell nanoparticles of good dispersibility and effective release of DOX-TPP from the HA- hydra-DOX-TPP conjugate in cancer cells, which was followed by enhanced DOX mitochondria accumulation. The HA- hydra-DOX-TPP nanoparticles also showed improved anticancer effects, better tumor cell apoptosis, and better safety profile compared to free DOX in MCF-7/ADR bearing mice.

Delivery of mitochondriotropic doxorubicin derivatives using self-assembling hyaluronic acid nanocarriers in doxorubicin-resistant breast cancer.

Breast cancer is the leading cause of cancer-related death for women, and multidrug resistance (MDR) is the major obstacle faced by chemotherapy for breast cancer. We have previously synthesized a doxorubicin (DOX) derivative by conjugating DOX with triphenylphosphonium (TPP) to achieve mitochondrial delivery, which induced higher cytotoxicity in drug-resistant breast cancer cells than DOX itself. Due to its amphiphilicity, TPP-DOX is difficult to physically entrap in nanocarriers. Thus, we linked it to hyaluronic acid (HA) by a novel ionic bond utilizing the specific bromide ion of TPP to form supra-molecular self-assembled structures (HA-ionic-TPP-DOX). The product was analyzed uisng 1H-NMR, 13C-NMR and mass spectrometry. The HA nanocarriers (HA-ionic-TPP-DOX) were shown to self-assemble into spherical nanoparticles, and sensitive to acidic pH in terms of morphology and drug release. Compared with free DOX, HA-ionic-TPP-DOX produced much greater intracellular DOX accumulation and mitochondrial localization, leading to increased ROS production, slightly decreased mitochondrial membrane potential, increased cytotoxicity in MCF-7/ADR cells and enhanced tumor targeting in vivo. In xenotransplant zebrafish model with the MCF-7/ADR cell line, both TPP-DOX and HA-ionic-TPP-DOX inhibited tumor cell proliferation without inducing significant side effects compared with free DOX. In addition, we observed a better anti-tumor effect of HA-ionic-TPP-DOX on MCF-7/ADR cells in zebrafish than that of TPP-DOX treatment. Furthermore, HA-ionic-DOX-TPP exhibited favorable biocompatibility and anti-tumor effects in MCF-7/ADR tumor-bearing nude mice in comparison with the effects of TPP-DOX and DOX, suggesting the potential of HA-ionic-TPP-DOX for the targeted delivery and controlled release of TPP-DOX, which can lead to the sensitization of resistant breast tumors.

Evaluation of a Self-Management Program for Gastroesophageal Reflux Disease in China.

Gastroesophageal reflux disease is a chronic disease with a high incidence worldwide. The various symptoms have substantial impact on the quality of life of affected individuals. A long-term self-management program can increase the ability of patients to make behavioral changes, and health outcomes can improve as a consequence. This study's aim was to evaluate the effectiveness of a self-management program for gastroesophageal reflux disease. A total of 115 patients with gastroesophageal reflux disease were allocated to the experimental group and the control group. The former received self-management intervention along with conventional drug therapy, whereas the latter received standard outpatient care and conventional drug therapy. After the clinical trial, the control group also received the same self-management intervention. The levels of self-management behaviors, self-efficacy, gastroesophageal reflux disease symptoms, and psychological condition were compared. Those in the experimental group demonstrated significantly higher self-efficacy for managing their illness, showed positive changes in self-management behaviors, and had comparatively better remission of symptoms and improvement in psychological distress. The program helped patients with gastroesophageal reflux disease self-manage their illness as possible.

Serum profiling by mass spectrometry combined with bioinformatics for the biomarkers discovery in diffuse large B-cell lymphoma.

The aim of this study was to identify potential serum biomarkers of diffuse large B-cell lymphoma (DLBCL) and to detect DLBCL therapy response biomarkers. DLBCL serum proteomic analysis was performed using the CM10 ProteinChip mass spectrometry (SELDI-TOF-MS) approach combined with bioinformatics. A total of 178 samples were analyzed in this study from untreated early stage DLBCL patients (38), patients with inflammatory lymphadenopathy (13), healthy donors (35), post-treatment non-relapsed DLBCL patients (53), and relapsed DLBCL patients (39). Model 1 formed by nine protein peaks (m/z: 6443, 5913, 6198, 4098, 7775, 9293, 5946, 5977, and 4628) could be used to distinguish DLBCL patients from healthy individuals with an accuracy of 95.89% (70/73). The diagnostic pattern constructed using the support vector machine including the nine proteins of model 1, showed a maximum Youden's Index. Model 2 formed by three protein peaks (m/z: 3942, 6639, and 4121) could be used to distinguish DLBCL patients from those with inflammatory lymphadenopathy with an accuracy of 94.12% (48/51). Model 3 formed by six protein peaks could distinguish patients with inflammatory lymphadenopathy from healthy individuals with an accuracy of 97.92% (47/48). Model 4 could be used to distinguish non-relapsed DLBCL patients from relapsed DLBCL patients with an accuracy of 84.78% (78/92). The four patterns were validated by leave-one-out cross-validation. These data demonstrate that the CM10 ProteinChip and SELDI-TOF-MS approach combined with bioinformatics can be used effectively to screen for the differential protein expression profiles of DLBCL patients and to predict the response to therapy.

Cardiac mitochondrial proteome dynamics with heavy water reveals stable rate of mitochondrial protein synthesis in heart failure despite decline in mitochondrial oxidative capacity.

We recently developed a method to measure mitochondrial proteome dynamics with heavy water ((2)H2O)-based metabolic labeling and high resolution mass spectrometry. We reported the half-lives and synthesis rates of several proteins in the two cardiac mitochondrial subpopulations, subsarcolemmal and interfibrillar (SSM and IFM), in Sprague Dawley rats. In the present study, we tested the hypothesis that the mitochondrial protein synthesis rate is reduced in heart failure, with possible differential changes in SSM versus IFM. Six to seven week old male Sprague Dawley rats underwent transverse aortic constriction (TAC) and developed moderate heart failure after 22weeks. Heart failure and sham rats of the same age received heavy water (5% in drinking water) for up to 80days. Cardiac SSM and IFM were isolated from both groups and the proteins were separated by 1D gel electrophoresis. Heart failure reduced protein content and increased the turnover rate of several proteins involved in fatty acid oxidation, electron transport chain and ATP synthesis, while it decreased the turnover of other proteins, including pyruvate dehydrogenase subunit in IFM, but not in SSM. Because of these bidirectional changes, the average overall half-life of proteins was not altered by heart failure in both SSM and IFM. The kinetic measurements of individual mitochondrial proteins presented in this study may contribute to a better understanding of the mechanisms responsible for mitochondrial alterations in the failing heart.

Targeting the organelle for radiosensitization in cancer radiotherapy.

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

Reprogramming of astrocytes and glioma cells into neurons for central nervous system repair and glioblastoma therapy.

Central nervous system (CNS) damage is usually irreversible owing to the limited regenerative capability of neurons. Following CNS injury, astrocytes are reactively activated and are the key cells involved in post-injury repair mechanisms. Consequently, research on the reprogramming of reactive astrocytes into neurons could provide new directions for the restoration of neural function after CNS injury and in the promotion of recovery in various neurodegenerative diseases. This review aims to provide an overview of the means through which reactive astrocytes around lesions can be reprogrammed into neurons, to elucidate the intrinsic connection between the two cell types from a neurogenesis perspective, and to summarize what is known about the neurotranscription factors, small-molecule compounds and MicroRNA that play major roles in astrocyte reprogramming. As the malignant proliferation of astrocytes promotes the development of glioblastoma multiforme (GBM), this review also examines the research advances on and the theoretical basis for the reprogramming of GBM cells into neurons and discusses the advantages of such approaches over traditional treatment modalities. This comprehensive review provides new insights into the field of GBM therapy and theoretical insights into the mechanisms of neurological recovery following neurological injury and in GBM treatment.

Role of histone modifications in neurogenesis and neurodegenerative disease development.

Progressive neuronal dysfunction and death are key features of neurodegenerative diseases; therefore, promoting neurogenesis in neurodegenerative diseases is crucial. With advancements in proteomics and high-throughput sequencing technology, it has been demonstrated that histone post-transcriptional modifications (PTMs) are often altered during neurogenesis when the brain is affected by disease or external stimuli and that the degree of histone modification is closely associated with the development of neurodegenerative diseases. This review aimed to show the regulatory role of histone modifications in neurogenesis and neurodegenerative diseases by discussing the changing patterns and functional significance of histone modifications, including histone methylation, acetylation, ubiquitination, phosphorylation, and lactylation. Finally, we explored the control of neurogenesis and the development of neurodegenerative diseases by artificially modulating histone modifications.

Enhanced resistance to permeability transition in interfibrillar cardiac mitochondria in dogs: effects of aging and long-term aldosterone infusion.

Functional differences between subsarcolemmal and interfibrillar cardiac mitochondria (SSM and IFM) have been observed with aging and pathological conditions in rodents. Results are contradictory, and there is little information from large animal models. We assessed the respiratory function and resistance to mitochondrial permeability transition (MPT) in SSM and IFM from healthy young (1 yr) and old (8 yr) female beagles and in old beagles with hypertension and left ventricular (LV) wall thickening induced by 16 wk of aldosterone infusion. MPT was assessed in SSM and IFM by Ca(2+) retention and swelling. Healthy young and old beagles had similar mitochondrial structure, respiratory function, and Ca(2+)-induced MPT within SSM and IFM subpopulations. On the other hand, oxidative capacity and resistance to Ca(2+)-induced MPT were significantly greater in IFM compared with SSM in all groups. Old beagles treated with aldosterone had greater LV wall thickness and worse diastolic filling but normal LV chamber volume and systolic function. Treatment with aldosterone did not alter mitochondrial respiratory function but accelerated Ca(2+)-induced MPT in SSM, but not IFM, compared with healthy old and young beagles. In conclusion, in a large animal model, oxidative capacity and resistance to MPT were greater in IFM than in SSM. Furthermore, aldosterone infusion increased susceptibility to MPT in SSM, but not IFM. Together this suggests that SSM are less resilient to acute stress than IFM in the healthy heart and are more susceptible to the development of pathology with chronic stress.

The crosstalk: Tumor-infiltrating lymphocytes rich in regulatory T cells suppressed cancer-associated fibroblasts.

BACKGROUND: The interactions between cancer-associated fibroblasts (CAFs) and cancer cells or tumor-infiltrating lymphocytes (TILs) and cancer cells play important roles in cancer progression and metastasis. However, studies related to the crosstalk between CAFs and TILs in tumor microenvironment (TME) are still lacking. In this study, we mainly investigated the interactions between CAFs and TILs. MATERIAL AND METHODS: The distribution of TILs rich in regulatory T cells (Tregs) in breast cancer tissues was evaluated using hematoxylin-eosin staining and immunohistochemistry with anti-CD3, anti-Foxp3, and anti-α-smooth muscle actin antibodies. Homologous CAFs/normal fibroblasts (NFs) and TILs cultured in vitro were identified and detected using immunocytochemistry and flow cytometry (FCM). The direct interaction among these cell types was studied via a factorial design in a co-cultured system. Their indirect interaction was assayed using Transwell plates. The cell cycle and apoptosis of CAFs/NFs co-cultured with TILs was analyzed using propidium iodide staining. RESULTS: Histochemistry demonstrated most of the TILs including Tregs, were distributed in the cancer stroma, adjoining to CAFs. This finding implies that both cell types interact closely in the TME. Identification of the cultured cells showed that CAFs maintained their activated phenotype within limited passages in vitro, and that the TILs population contained a high percentage of Tregs. Data analysis of the factorial design suggests significant interactions among CAFs, NFs, and TILs in both direct and indirect contact ways. The CAFs and NFs were suppressed signally by TILs, which are probably induced by the secretory cytokines derived from TILs or Tregs. Although apoptosis was not detected in CAFs/NFs, the cell cycle assay suggested that the CAFs/NFs were arrested in the G2/M phase by the TILs and their secretory cytokines. CONCLUSION: CAFs and NFs were dramatically suppressed by Tregs-rich TILs. This suggests the interaction between TILs and CAFs might modify the TME in an unknown manner.

Docosahexaenoic acid supplementation alters key properties of cardiac mitochondria and modestly attenuates development of left ventricular dysfunction in pressure overload-induced heart failure.

PURPOSE: Supplementation with the n3 polyunsaturated fatty acid docosahexaenoic acid (DHA) is beneficial in heart failure patients, however the mechanisms are unclear. DHA is incorporated into membrane phospholipids, which may prevent mitochondrial dysfunction. Thus we assessed the effects of DHA supplementation on cardiac mitochondria and the development of heart failure caused by aortic pressure overload. METHODS: Pathological cardiac hypertrophy was generated in rats by thoracic aortic constriction. Animals were fed either a standard diet or were supplemented with DHA (2.3 % of energy intake). RESULTS: After 14 weeks, heart failure was evident by left ventricular hypertrophy and chamber enlargement compared to shams. Left ventricle fractional shortening was unaffected by DHA treatment in sham animals (44.1 ± 1.6 % vs. 43.5 ± 2.2 % for standard diet and DHA, respectively), and decreased with heart failure in both treatment groups, but to a lesser extent in DHA treated animals (34.9 ± 1.7 %) than with the standard diet (29.7 ± 1.5 %, P < 0.03). DHA supplementation increased DHA content in mitochondrial phospholipids and decreased membrane viscosity. Myocardial mitochondrial oxidative capacity was decreased by heart failure and unaffected by DHA. DHA treatment enhanced Ca(2+) uptake by subsarcolemmal mitochondria in both sham and heart failure groups. Further, DHA lessened Ca(2+)-induced mitochondria swelling, an index of permeability transition, in heart failure animals. Heart failure increased hydrogen peroxide-induced mitochondrial permeability transition compared to sham, which was partially attenuated in interfibrillar mitochondria by treatment with DHA. CONCLUSIONS: DHA decreased mitochondrial membrane viscosity and accelerated Ca(2+) uptake, and attenuated susceptibility to mitochondrial permeability transition and development of left ventricular dysfunction.

Dedollarization as a Direction of Russia's Financial Policy in Current Conditions.

Under financial sanctions imposed on it by the US and the EU, Russia accelerated dedollarization of the economy in order to protect its sovereignty in strategic rivalry with the US. To this end, a set of strategies has been developed, such as reducing the direct use of US dollars, cutting the share of the dollar in foreign exchange reserves, expanding nondollar funding, increasing gold reserves, as well as reserving and creating its own systems of payment and exchange of financial information. This practice is of great importance for reorganizing the dollar-dominated international monetary system and establishing a new economic and financial system.

A Model of Long-Term Ventricular Fibrillation in Isolated Rat Hearts.

Ventricular fibrillation (VF) is a fatal arrhythmia with a high incidence in cardiac patients, but VF arrest under perfusion is a neglected method of intraoperative arrest in the field of cardiac surgery. With recent advances in cardiac surgery, the demand for prolonged VF studies under perfusion has increased. However, the field lacks simple, reliable, and reproducible animal models of chronic ventricular fibrillation. This protocol induces long-term VF through alternating current (AC) electrical stimulation of the epicardium. Different conditions were used to induce VF, including continuous stimulation with a low or high voltage to induce long-term VF and stimulation for 5 min with a low or high voltage to induce spontaneous long-term VF. The success rates of the different conditions, as well as the rates of myocardial injury and recovery of cardiac function, were compared. The results showed that continuous low-voltage stimulation induced long-term VF and that 5 min of low-voltage stimulation induced spontaneous long-term VF with mild myocardial injury and a high rate of recovery of cardiac function. However, the low-voltage, continuously stimulated long-term VF model had a higher success rate. High-voltage stimulation provided a higher rate of VF induction but showed a low defibrillation success rate, poor recovery of cardiac function, and severe myocardial injury. On the basis of these results, continuous low-voltage epicardial AC stimulation is recommended for its high success rate, stability, reliability, reproducibility, low impact on cardiac function, and mild myocardial injury.

CLDN6 inhibits colorectal cancer proliferation dependent on restraining p53 ubiquitination via ZO-1/PTEN axis.

Colorectal cancer (CRC) is one of the most common cancers in the world. Abnormal proliferation is a chief characteristic of cancer and is the initiation of CRC progression. As an important component of tight junctions, CLDN6 regulates the proliferation of multiple tumors. Our previous study showed that CLDN6 was low expressed in CRC, and CLDN6 overexpression inhibited CRC proliferation. However, the specific mechanism of how CLDN6 works remains unclear. This research aimed to reveal the relationship between CLDN6 and clinical features, as well as the molecular mechanism by which CLDN6 inhibited CRC proliferation. We found that low expression of CLDN6 was associated with pathological grade and prognosis of CRC patients, and confirmed that CLDN6 inhibited CRC proliferation dependent on p53. Mechanically, we elucidated that CLDN6 regulated ubiquitination to enhance p53 stability and nuclear import by PTEN/AKT/MDM2 pathway. Through the PDZ-binding motif (PBM), CLDN6 bound to ZO-1 to interact with PTEN, and regulate AKT/MDM2 pathway. Collectively, our data enriched the theoretical basis for CLDN6 as a potential biomarker for diagnosis, therapy and prognosis of CRC.

Double layer spherical nanoparticles with hyaluronic acid coating to enhance oral delivery of exenatide in T2DM rats.

Soybean phospholipid was used as an amphiphilic material to form reverse micelles (RMs) in medium glycerol monolinoleate (Maisine) with Exenatide (EXT.) encapsulated in the polar core formed by the hydrophilic part of phospholipid. Cremopher RH40 and caprylocaproyl macrogol-8 glycerides EP/caprylocaproyl polyoxyl-8 glycerides NF (Labrasol) were added as surfactants to prepare reverse micelles-self emulsifying drug delivery system (RMs-SEDDS). On this basis, oil in water (O/W) emulsion was further prepared. By adding DOTAP, the surface of the emulsion was positively charged. Finally, hyaluronic acid wrapping in the outermost layer by electrostatic adsorption and reverse micelles-O/W-sodium hyaluronate (RMs-O/W-HA) nanoparticles containing Exenatide were prepared. RMs-SEDDS was spherical with an average particle size of 213.6 nm and RMs-O/W-HA was double-layered spherical nanoparticle with an average particle size of 309.2 nm. HA coating enhanced the adhesion of nanoparticles (NPs), and RMs-O/W-HA increased cellular uptake through CD44-mediated endocytosis. Pharmacodynamics results showed that RMs-SEDDS and RMs-O/W-HA could reduce blood glucose in type 2 diabetic rats, protect pancreatic ß cells to a certain extent, and relieve insulin resistance and hyperlipemia complications with good safety.

Mitochondrial targeted drug delivery combined with manganese catalyzed Fenton reaction for the treatment of breast cancer.

In previous studies, we found that triphenylphosphine-modified doxorubicin (TPP-DOX) can effectively kill drug-resistant tumor cells, but its effect on sensitive tumor cells is weakened. In this research, with albumin from Bovine Serum (BSA) as a carrier, TPP-DOX@MnBSA (TD@MB) nanoparticles were prepared by co-loading TPP-DOX and manganese which can realize the combination of chemotherapy and chemodynamic therapy (CDT). The uniform and stable nano-spherical nanoparticle can promote drug uptake, achieve mitochondrial-targeted drug delivery, increase intracellular reactive oxygen species (ROS) and catalyze the production of highly toxic oxidative hydroxyl radicals (OH·), further inhibiting the growth of both sensitive and drug-resistant MCF-7 cells. Besides, TD@MB can down-regulate the stemness-related proteins and the metastasis-related proteins, potentially decreasing the tumor stemness and metastasis. In vivo experiment indicated that TD@MB was able to exert desired antitumor effect, good tumor targeting and biocompatibility.