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Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CSsiRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted codelivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αv β3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1 α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of antitumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics. [ABSTRACT FROM AUTHOR]

Background: In secondary spinal cord injury (SCI), the immune microenvironment of the injured spinal cord plays an important role in spinal regeneration. Among the immune microenvironment components, macrophages/microglia play a dual role of pro-inflammation and anti-inflammation in the subacute stage of SCI. Therefore, discovering the immune hub genes and targeted therapeutic drugs of macrophages/microglia after SCI has crucial implications in neuroregeneration. This study aimed to identify immune hub genes and targeted therapeutic drugs for the subacute phase of SCI. Methods: Bulk RNA sequencing (bulk-RNA seq) datasets (GSE5296 and GSE47681) and single-cell RNA sequencing (scRNA-seq) dataset (GSE189070) were obtained from the Gene Expression Omnibus database. In the bulk RNA-seq, the R package 'limma,' 'WGCNA,' and 'CIBERSORT' were used to jointly screen key immune genes. Subsequently, the R package 'Seurat' and the R package 'celldex' were used to divide and annotate the cell clusters, respectively. After using the Autodock software to dock immune hub genes and drugs that may be combined, the effectiveness of the drug was verified using an in vivo experiment with the T9 SCI mouse model. Results: In the bulk-RNA seq, B2m, Itgb5, and Vav1 were identified as immune hub genes. Ten cell clusters were identified in scRNA-seq, and B2m and Itgb5 were mainly located in the microglia, while Vav1 was mainly located in macrophages. Molecular docking results showed that the proteins corresponding to these immune genes could accurately bind to decitabine. In decitabine-treated mice, the pro-inflammatory factor (TNF-a, IL-1b) levels were decreased while antiinflammatory factor (IL-4, IL-10) levels were increased at 2 weeks post-SCI, and macrophages/microglia transformed from M1 to M2. At 6 weeks post-SCI, the neurological function score and electromyography of the decitabine treatment group were also improved. Conclusion: In the subacute phase of SCI, B2m, Itgb5, and Vav1 in macrophages/microglia may be key therapeutic targets to promote nerve regeneration. In addition, low-dose decitabine may promote spinal cord regeneration by regulating the polarization state of macrophages/microglia. [ABSTRACT FROM AUTHOR]

Context: The effects of Rhodiola rosea L. (Crassulaceae) polysaccharides (RRPs) on haematopoiesis are poorly understood. Objective: To determine the effects of RRPs on haematopoiesis in mice with aplastic anaemia. Materials and methods: Aplastic anaemia was induced in Kunming mice by 60Coγ (2.0 Gy) irradiation and cyclophosphamide administration (50 mg/kg/day for 3 consecutive days; intraperitoneal injection). The in vivo effects of RRPs (10, 20, and 40 mg/kg; intraperitoneal injection) on haematopoiesis were analyzed using peripheral blood tests, histopathological examination of haematopoietic tissues, culture of haematopoietic progenitors and bone marrow stromal cells (BMSCs), and Western blotting of Fas and Fas ligand (FasL). The in vitro effects of RRPs on bone-marrow haematopoietic progenitors and BMSCs were also evaluated. Results: Compared to anaemic controls, high-dose RRPs (40 mg/kg) significantly increased red blood cells (8.21 ± 0.57835 versus 6.13 ± 1.34623 × 1012/L), white blood cells (5.11 ± 1.6141 versus l.54 ± 1.1539 × 109/L), and BMSCs (10.33 ± 1.5542 versus 5.87 ± 3.1567 × 1012/L) in mice with aplastic anaemia (all p < 0.01). High-dose RRPs significantly increased the formation of colony-forming unit-granulocyte macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-erythroid (CFU-E; p < 0.01). Fas and FasL protein expression in BMSCs decreased after RRPs administration. Especially at the high dose, RRPs (150 μg/mL) significantly promoted in vitro CFUs-E, BFUs-E, and CFUs-GM formation. RRPs (150-300 μg/mL) also promoted BMSC proliferation. Discussion and conclusions: RRPs helped to promote haematopoietic recovery in mice with aplastic anaemia, facilitating haematopoietic tissue recovery. This study indicated some mechanisms of the haematopoietic regulatory effects of RRPs. Our findings provide a laboratory basis for clinical research on RRPs. [ABSTRACT FROM AUTHOR]

Background. Psoriasis is a chronic immune-mediated inflammatory dermatosis. Long noncoding RNAs (lncRNAs) play an important role in immune-related diseases. This study aimed to identify potential immune-related lncRNA biomarkers for psoriasis. Methods. We screened differentially expressed immune-related lncRNAs biomarkers using GSE13355 (skin biopsy samples of 180 cases) from Gene Expression Omnibus (GEO). Moreover, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were performed to explore biological mechanisms in psoriasis. In addition, we performed LASSO logistic regression to identify potential diagnostic lncRNAs and further verify the diagnostic value and relationship with drug response using two validation sets: GSE30999 (skin biopsy samples of 170 cases) and GSE106992 (skin biopsy samples of 192 cases). Furthermore, we estimated the degree of infiltrated immune cells and investigated the correlation between infiltrated immune cells and diagnostic lncRNA biomarkers. Results. A total of 394 differentially expressed genes (DEGs) were extracted from gene expression profile. GO and KEGG analysis of target genes found that immunerelated lncRNAs were primarily associated with epidermis development, skin development, collagen-containing extracellular matrix, and glycosaminoglycan binding and mainly enriched in cytokine-cytokine receptor interaction and influenza A and chemokine signaling pathway. We found that LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1, CARMN, CCDC18-AS1, EPB41L4A-AS, and LINC01214 exhibited well diagnostic efficacy. The ROC and ROC CI were 0.944 (0.907-0.982), 0.953 (0.919-0.987), 0.822 (0.758-0.887), 0.854 (0.797-0.911), 0.957(0.929-0.985), 0.894 (0.846-0.942), and 0.964 (0.937-0.991) for LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1, CARMN, CCDC18-AS1, EPB41L4A-AS1, and LINC01214. LINC01137, LINC01215, and LINC01214 were correlated with drug response. LINC01137, CCDC18-AS1, and CARMN were positively correlated with activated memory CD4 T cell, activated myeloid dendritic cell (DC), neutrophils, macrophage M1, and T follicular helper (Tfh) cells, while negatively correlated with T regulatory cell (Treg). LINC01215, MAPKAPK5-AS1, TPT1-AS1, EPB41L4A-AS, and LINC01214 were negatively correlated with activated memory CD4 T cell, activated myeloid DC, neutrophils, macrophage M1, and Tfh, while positively correlated with Treg. Conclusions. These findings indicated that these immune-related lncRNAs may be used as potential diagnostic and predictive biomarkers for psoriasis. [ABSTRACT FROM AUTHOR]

Background: Shen-ling-bai-zhu-san (SLBZS) regulates inflammation and gut microbiota which are associated with Streptococcus pneumoniae (Spn)-induced pneumonia. So, we studied the therapeutic effect of SLBZS and evaluated whether gut microbiota is associated with the effects of SLBZS in improving Spn-induced pneumonia. Methods: Spn-induced pneumonia NIH mice were treated by SLBZS and cefixime. A CT scan was performed and Myeloperoxidase (MPO) activity in lung homogenates was determined using the MPO Colorimetric Assay Kit. Inflammation levels in lung homogenates were measured using ELISA. Bacterial load was coated on a TSAII sheep blood agar. Intestinal gut microbiota information was analyzed according to sequencing libraries. Results: SLBZS decreased bacterial load, reduced wet/dry weight ratio, inhibited myeloperoxidase activity, reduced the neutrophils count, and ameliorated lung injury. Furthermore, SLBZS inhibited interleukin (IL)-1ß, IL-6, tumor necrosis factor-a, IL-2, IL-8, IL-12, and interferon-? secretion and enhanced IL-10 secretion. These results suggest that SLBZS ameliorates lung injury in mice with Spn-induced pneumonia. Moreover, SLBZS reduced inflammatory cytokine levels in a concentration-dependent manner and increased gut microbiota abundance and diversity. After SLBZS treatment, bacteria such as Epsilonbacteraeota, Bacteroidetes, Actinobacteria, Proteobacteria, and Patescibacteria were significantly reduced, while Tenericutes and Firmicutes were significantly increased. Conclusion: SLBZS ameliorates inflammation, lung injury, and gut microbiota in mice with S. pneumoniaeinduced pneumonia. [ABSTRACT FROM AUTHOR]

Objectives] The study aims to explore the protective effect of Shenlingbaizhu powder on peroxidation injury and inflammatory response in mice with pneumonia. [Methods] 60 NIH mice were randomly divided into the blank group, model group, control group, large dose group, medium dose group and small dose group of Shenlingbaizhu powder. The mice in the control group were given cefixime granules, while the mice in each group of Shenlingbaizhu powder were given corresponding concentrations of Shenlingbaizhu powder water decoction by gavage. After 7 d, the content of MAD, SOD and CRP in the mice were detected by ELISA, while the content of NO was detected by fluorescence, and lung index was also detected. [Results] The medium dose and large dose of Shenlingbaizhu powder can effectively reduce the concentration of MAD and improve the level of SOD in mice with pneumonia. The effect of the large dose of Shenlingbaizhu powder is more obvious than that of the control group. Moreover, the large dose of Shenlingbaizhu powder can effectively reduce the level of NO in mice with pneumonia. In addition, the medium dose and large dose of Shenlingbaizhu powder can reduce the lung index and CRP level of mice with pneumonia, and the results are statistically significant. [Conclusions] The medium dose and large dose of Shenlingbaizhu powder can effectively reduce the concentration of MAD and improve the level of SOD in mice with pneumonia. The effect of the large dose of Shenlingbaizhu powder is more obvious than that of the control group. Moreover, the large dose of Shenlingbaizhu powder can effectively reduce the level of NO in mice with pneumonia. In addition, the medium dose and large dose of Shenlingbaizhu powder can reduce the lung index and CRP level of mice with pneumonia, and the results are statistically significant. [ABSTRACT FROM AUTHOR]

[Objectives] To explore the effect of Shenling Baizhu San combined with routine treatment on the clinical efficacy, gastrointestinal function protection, inflammatory response and immune function of children with bacterial pneumonia. [Methods] From July 2017 to January 2018, 80 children with bacterial pneumonia were randomly selected and divided into observation group and control group with 40 cases in each group. The control group was treated with conventional Western medicine, while the observation group was treated with Shenling Baizhu San on the basis of conventional treatment, with a period of 10 d. Then, we compared the clinical efficacy, incidence of gastrointestinal symptoms, WBC, CRP, CD4+ and CD8+ levels between the two groups. [Results] The clinical efficacy of the observation group was better than that of the control group（P<0.05）. After treatment, the levels of WBC and CRP in the two groups decreased, especially in the observation group（P<0.05）. After treatment, the level of CD4+ in both groups increased significantly, while the level of CD8+ decreased significantly, and the level of CD4+ in the observation group was significantly higher than that in the control group after treatment. The incidence of gastrointestinal symptoms in the observation group was significantly lower than that in the control group（P<0.01）. [Conclusions] Shenling Baizhu San can obviously improve the clinical effect of bacterial pneumonia in children and has the protective effect of gastrointestinal tract, and its mechanism may be related to its anti-inflammatory and immunomodulatory effects. [ABSTRACT FROM AUTHOR]

Background: A lot of time and money was needed during the diagnosis and treatment process of leprosy, the delayed leprosy would also impair the labor capability of patients as well, and these put a heavy burden for the leprosy patients. The migrant leprosy patient is a special group and need more concern. Our goal was to assess the economic burden of leprosy on migrant and resident patient populations in Guangdong province, China.Methods: We conducted a population-based cross-sectional survey from February to July of 2016. A self-designed questionnaire was administered to leprosy patients who: (1) had registered in Leprosy Management Information System in China (LEPMIS) by the end of February 2016, (2) had received multiple drug treatment (MDT) drugs at a local leprosy control institution for three consecutive months or had had at least one physical check in the past half year, and (3) were willing to take part in the investigation and give informed written consent. Demographic characteristics, Financial and disease information, and costs before and after leprosy diagnosis were collected and compared using t-test and χ2 test.Results: A total of 254 participants completed the questionnaires, including 168 males and 86 females. Migrants and residents accounted for 33.9% and 66.1% of patients, respectively. Among migrant patients, the median cost before diagnosis was $131.6 (39.2-450.9), the median yearly cost of leprosy treatment after diagnosis was $300.6 (158.4-868.5), and the median yearly cost of leprosy complications was $69.5 (11-178.4). In comparison, among residents the median yearly costs were $152.4 (30.7-770.9) pre-diagnosis, $309.7 (103.2-1016.7) after diagnosis, and $91.9 (32.6-303.1) for leprosy complications. Base on this, we determined that the median yearly total expense after diagnosis amounted to 15% of migrant and 38% of resident patients' annual income.Conclusion: Leprosy places a heavy economic burden on both migrant and resident leprosy patients and governmental policies and programs could substantially alleviate this. Measures to implement more active surveillance and early diagnosis would benefit both populations, while labor protection and medical insurance are urgently needed for migrant patients and easier access to medical services and social aids could substantially decrease the burden of leprosy for resident patients. [ABSTRACT FROM AUTHOR]

Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development. [ABSTRACT FROM AUTHOR]

Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the intermediate zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the intermediate zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin-mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription. [ABSTRACT FROM AUTHOR]

In the multicarrier direct-sequence code-division multiple access with repetition code system, decreasing the code rate can result in greater frequency diversity. However, to keep the same transmit bit rate, the spreading factor in each subcarrier needs to be reduced. In this paper, we use the outage probability as a criterion for these two system parameters' design. We first examine the condition on code rate for the uncorrelated fading channel assumption. The system performance is derived and the outage probability is obtained in closed forms for equal unequal transmit bit energy scenarios. The relation between the spreading factor and the rate of the repetition code is investigated by observing the outage probability equation. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 36-year-old man with multiple, disseminated, violaceous nodules and maculopapules on the skin of his extremeties and trunk. Physical examination revealed disseminated solid, nodules, multiple and violaceous plaques on the skin of the trunk and on the lower and upper limbs as well as the face. Treatment with prednisone 30 milligrams (mg)/day was administered for five days and the lesions nearly disappeared.