Nanocomposite Detection of Elemental Impurities and Process Correlation Analysis of Ceftriaxone Sodium for Injection

An inductively coupled plasma spectroscopy method was established to detect 29 elemental impurities in ceftriaxone sodium for injection by nanocomposite, and also used to detect the elemental impurities in the generic, domestic original and foreign original ceftriaxone sodium for injection. This paper for the first time analysed the possible sources of elemental impurities and their potential impacts on the drug quality based on the process. The results showed that zinc and potassium were detected in both the generic drug and the domestic original ceftriaxone sodium for injection, and zinc was not detected but potassium was detected in the foreign original drug; the content of zinc in the generic drug was significantly higher than that in the domestic original drug, and the content of potassium in generic drug and domestic original drug was higher than that in the foreign original drug, according to the process, the elemental impurities may come from the activated carbon or nanocarriers used in the process, and further stability analysis of the samples showed that the stability of the generic drug was slightly lower than that of the original drug, so it was speculated that impurity elements might also be one of the reasons for its instability.

The Effects of Nanometer Titanium Dioxide on Tumor Cells and in Rats with Nasopharyngeal Carcinoma

A drug delivery system based on nanomaterials has demonstrated a powerful function in disease treatment. In this study, a titanium-dioxide-nanotube-based cisplatin (nano-TiO2-DDP) delivery system was designed, and its effects in rats with nasopharyngeal carcinoma (NPC) and on tumor cells were analyzed. First, we obtained electrochemistry anodic oxidation (EAO) for the preparation of Nnano-TiO2, which was adopted as the carrier of cisplatin (CDDP). Then, we used a scanning electron microscope (SEM) to characterize and study the surface morphology of nano-TiO2. At the cellular level, flow cytometry, MTT, and Transwell assays were performed to analyze the apoptosis, proliferation, and invasion of cells treated by nano-TiO2-DDP, respectively. At the animal level, a xenotransplantation model was established for evaluating tumor growth and changes in experimental animals after injection of nano-TiO2-DDP. As a result, nano-TiO2-DDP strongly suppressed the invasion and vitality of tumor cells, induced their apoptosis, and delivered DDP more efficiently than did systems without a nano-TiO2 structure. In addition, injected nano-TiO2-DDP strongly inhibited the growth of solid tumors in vivo. Therefore, we believe that nano-TiO2-DDP can effectively suppress the growth of NPC, and it is more efficient than conventional drugs.

Ulinastatin-Gold Nanoparticles Reduce Sepsis-Induced Cardiomyocyte Apoptosis Through NF-κB Pathway Inactivation

Nanodrug delivery systems have recently become widely studied and applied in the medical field, and nanomaterials have greatly improved drugs’ efficacy. Ulinastatin has been confirmed to inhibit myocardial damage caused by sepsis. However, the effect and mechanism of ulinastatin-gold nanoparticles (UTI-GN) on sepsis-induced cardiomyocyte apoptosis are unknown. Here we explore the effect and mechanism of UTI-GN on sepsis-induced cardiomyocyte apoptosis. Lipopolysaccharide (LPS) was used to stimulate rat cardiomyocytes to construct an in vitro sepsis model. Enzymelinked immunosorbent assay detected cellular inflammatory factors NF-α, IL-1β, and IL-6. Western blots measured iNOS and COX-2 expression. Based on LPS-treated cells, different concentrations of UTI-GN were applied to cardiomyocytes. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) experiments and flow cytometry measured cell viability and apoptosis, respectively. Western blots evaluated apoptotic protein expression of NF-κB, iNOS, and COX-2. The NF-κB pathway inhibitor BAY11-7082 was further used to explore whether UTI-GN played a regulatory role through the NF-κB pathway. LPS promotes NF-α, IL-1β, and IL-6 production and iNOS and COX-2 expression in cardiomyocytes. The results of the MTT experiment showed that UTI-GN has little toxicity to cardiomyocytes. The flow cytometry and western blot experiments showed that UTI-GN promoted cell apoptosis and inhibited NF-κB expression. Additionally, the NF-κB pathway inhibitor BAY11-7082 counteracts the UTI-GN effect. UTI-GN inhibits sepsis-induced cardiomyocyte apoptosis through NF-κB pathway inhibition.

Identification of Immune-Related Prognostic Biomarkers in Pancreatic Cancer

Immunotherapy for pancreatic cancer (PC) faces significant challenges. It is urgent to find immunerelated genes for targeted therapy. We aimed to identify immune-related messenger ribonucleic acids (mRNAs) with multiple methods of comprehensive immunoenrichment analysis in predicting survival of PC. PC genomics and clinical data were downloaded from TCGA. We analyzed relative enrichment of 29 immune cells using ssGSEA and classified PC samples into three immuneinfiltrating subgroups. Immune cell infiltration level and pathways were evaluated by ESTIMATE data and KEGG. Independent risk factors were derived from the combined analysis of WGCNA, LASSO regression and Cox regression analyses. Immune risk score was calculated according to four mRNAs to identify its value in predicting survival. PPI analysis was used to analyze the connections and potential pathways among genes. Finally, PC samples were classified into three immuneinfiltrating subgroups. Immunity high subgroup had higher immune score, soakage of immune cells, HLA/PD-L1 expression level, immune-related pathways enrichment and better survivability. Four potential prognostic immune-related genes (ITGB7, RAC2, DNASE1L3, and TRAF1) were identified. Immune risk score could be a potential survival prediction indictor with high sensitivity and specificity (AUC values = 0.708, HR = 1.445). A PPI network with seven nodes and five potential targeted pathways were generated. In conclusion, we estimated the state of immune infiltration in the PC tumor microenvironment by calculating stromal and immune cells enrichment with ssGSEA algorithms, and identified four prognostic immune-related genes that affect the proportion and distribution of immune cells infiltration in the tumor microenvironment. They lay a theoretical foundation to be important immunity targets of individual treatment in PC.

Effect of Low-Carbohydrate Diet on Metabolism in Type 2 Diabetes Patients with the Aid of Intelligent Administration of Insulin-Loaded Nanoparticle

Nanoparticles play a major role in drug delivery. We investigated the effects of the intelligent administration of insulin-loaded nanoparticles (ILNP) when combined with a low-carbohydrate diet (LCD) on the metabolism of patients with type 2 diabetes. ILNP and smart vesicle polymers were developed, and their properties were studied in vitro. Further clinical trials were performed, during which body mass index (BMI), fasting blood glucose (FBG) levels, and glycated hemoglobin (HbA1c) levels were compared between type 2 diabetes patients on LCDs those on normal diets. The results demonstrated that ILNP resisted protease degradation due to steric hindrance, and remained relatively stable at a pH range of 5.0 to 7.4. The nanoparticle enteric-coated capsules resisted the gastric juice acidity (pH = 2.5) and ensured the stable embedding of the insulin. The insulin was then released at a slightly higher pH (pH = 6.6), which mimicked the small intestine. Smart vesicle polymers further embedded the insulin and glucose oxidase simultaneously in nano polymer compounds, which allowed for a dose-dependent response to the concentration of glucose. Thus, the insulin was not released in a low-concentration glucose solution, but rather in a high-concentration glucose solution. Based on these results, we concluded that the clinical trial results showed that the intelligent administration of ILNP combined with a LCD reduced BMI, FBG, and HbA1c levels in patients with type 2 diabetes.

Precision Control of Micromechanical Automatic Manufacturing Based on Nanotechnology

Segment precision affects the accuracy level of micro machine manufacturing, only for the linear change is not big, more straight segment control, easy to cause dimensional deviation, so a precision control method of micro machine automatic manufacturing based on nanotechnology is proposed. The white noise is selected as random sequence to eliminate the concentrated trend and high frequency components in the input and output data. The precision control parameters of micromechanical automatic manufacturing are adjusted by setting the current loop, speed loop and position loop. According to the setting results, the contact area of micromechanical automation manufacturing is established in the coordinate system o-xy, and the equivalent curvature radius of the contact surface is calculated. Through coordinate transformation, the pressure distribution in the circular contact area is obtained, and the precision control area model of micromanical automation manufacturing is established. According to the model and the finite element analysis method, the control flow is designed to realize the precision control of the automatic manufacturing of micromachines. The experimental results show that the design method can reduce the precision control error of the automatic manufacturing of micromachines and improve the construction level of micromachines.

Method of Adhesion Cell Segmentation Based on Mathematical Morphology in the Preparation of Micro Nanowood Powder

As a new type of environmental protection material, micro nanowood powder has a great relationship with mesh number and wood species, and the premise of wood property recognition is accurate extraction of cell parameters. Adhesion often exists in the cell images of coniferous wood, and the right segmentation of adhesion cells constitutes the prerequisite to ensure the accuracy of the identification of species. In this paper, we have put forward a method based on mathematical morphology for the segmentation of adherent cells, and we have compared the method with that of parallel cells and series cells respectively. As shown by the experimental results, the method proposed in this study proves to be effective for two ordinary adherent cells thanks to its optimal stability and robustness.

miR-199a-3p Inhibitor Delivered Through Nano-Drug Delivery Systems Suppresses Tumor Cell Survival and Metastasis

Gastric cancer (GC) is a life-threatening malignant tumor present in the digestive tract. In this study the connection of miR-199a-3p, which is a gene abnormally expressed in GC, was analyzed along with the pathological parameters as well as the prognosis of GC patients. Moreover, the influence of miR-199a-3p inhibitor delivered through the nano-drug delivery system (NDDS) was studied in regard of GC cell survival and metastasis, seeking to reveal its potential treatment effect. During the conduction of the study, high miR-199a-3p expression was detected in GC tissues, sera, and cells along with its value for GC screening and pathological progression. In molecular research, polylactic-glycolic acid (PLGA) nanoparticles (NPs)-miRNA complexes that shaped like symmetrical spheres under the scanning electron microscope (SEM) were prepared to increase or decrease the levels of miR-199a-3p. The GC cell survival and metastasis was remarkably facilitated by the elevated miR-199a-3p, and its knockdown produced an opposite effect to markedly inhibit GC cell survival and metastasis. In conclusion, the expression in GC patients was increased by miR-199a-3p and the ability of its inhibitor delivered through the NDDS was demonstrated to control the survival and metastasis of GC cells.

Uptake and Transport Mechanisms of Ginkgolide B Niosomal Composite Drug Through the Blood-Brain Barrier

Cerebrovascular and functional neurological lesions are the major disorders threatening human health and quality of life. The presence of the blood-brain barrier seriously affects the distribution and efficacy of various drugs in the brain. Ginkgolide B (GB) and Puerarin (Pue) are active pharmaceutical ingredients for the treatment of Parkinson’s disease. Here, we have developed a novel strategy to construct a GB-Pue niosomal composite drug. The in vitro cytology study of the niosomal composite drug showed that 20 mmol/L glutamate resulted in a mortality of 50–60% in the SHSY-5Y cells, while 30 μmol/L niosomal composite drug resulted in a survival rate of 95.2% in the SHSY-5Y cells with a maximum uptake value of 3.5 μg/mg and a peak uptake time at 2 hr. The monolayer cells reached a maximum transepithelial/endothelial electrical resistance (TEER) value of 626 Ω*cm2 at 36 hr in culture, and the cellular integrity was negatively correlated with the amount of drug accumulated in the cells. The accumulated GB and Pue in cells reached 86.53% and 76.49%, respectively. The 30 μmol/L composite drug preparation provided a higher cell survival rate in the glutamate (Glu) injured cells compared to the single drug preparations. Therefore, the composite preparation of the two drugs generated a synergistic effect, meeting the requirement for a combined use. The cell transmembrane transport experiments demonstrated that the pharmaceutical preparations traversed the blood-brain barrier through the active transport of cells.

Astragalus Polysaccharide Nano-Liposomes Modulate the Inflammatory Response and Oxidative Stress in Stroke-Associated Pneumonia by Increasing OIP5-AS1 to Regulate the miR-128-3p/SIRT1 Pathway

Stroke-associated pneumonia (SAP) is major reason for the poor prognosis of stroke patients. Astragalus polysaccharide (APS) is a commonly used Chinese herbal extract that regulates the inflammatory response, however, its therapeutic effects on APS as well as its underlying mechanism of action are unclear. In this study, we evaluated the effects of APS nano-liposomes on SAP, including regulation of the inflammatory response and oxidative stress, as well as the underlying molecular mechanism. Serum samples of SPA were collected from patients and healthy controls and the expression of OIP5-AS1 and miR-128-3p was measured. Lipopolysaccharide (LPS) was used to construct an in vitro lung injury model using RLE-6TN lung epithelial cells and APS nanoliposomes were used for treatment. Several cellular processes were evaluated including OIP5-AS1, miR-128-3p, and SIRT1 expression by RT-PCR, SIRT1 protein expression by western blot analysis, IL-1β, TNF-α, and IL-6 expression by ELISA, a bioinformatics analysis for downstream molecular targets of OIP5-AS1, and dual luciferase and RNA immunoprecipitation (RIP) assays to identify interactions between miR-128-3p, OIP5-AS1, and SIRT1. Our results revealed low expression of OIP5-AS1 and high expression of miR-128-3p in SAP. Treatment with APS nano-liposomes reduced LPS-induced apoptosis of RLE-6TN cells, inhibited the inflammatory response and oxidative stress, and increased OIP5-AS1 and SIRT1 expression. Furthermore, the overexpression of miR-128-3p reversed the protective effect of APS nano-liposomes on LPS-induced RLE-6TN cells. In summary, OIP5-AS1 is an endogenous competitor that inhibits miR-128-3p targeting of SIRT1. APS nanoliposomes significantly reduced miR-128-3p expression resulting in increased OIP5-AS1 expression.