Xiaoliu Pingyi Pecipe Inhibits Lung Pre-Metastatic Niche Formation and Prevents Myeloid-Derived Suppressor Cells Recruitment.

BACKGROUND: Metastasis, a leading cause of cancer-related deaths, involves complex mechanisms. The premetastatic niche (PMN) is a crucial contributor to this process. Myeloid-derived suppressor cells (MDSCs) play an important role in PMN formation and promote tumor progression and metastasis. The Xiaoliu Pingyi recipe (XLPYR), a traditional Chinese medicine, is effective in preventing postoperative recurrence and metastasis in cancer patients. OBJECTIVE: This study investigated the effects of XLPYR on MDSCs recruitment and on the expression of PMN markers and elucidated the mechanisms involved in the prevention of tumor metastasis. METHODS: C57BL/6 mice were subcutaneously injected with Lewis cells and treated with cisplatin and XLPYR. Tumors were resected after 14 days after the establishment of a model of lung metastasis, and tumor volume and weight were measured. Lung metastases were observed 21 days after resection. MDSCs in the lung, spleen, and peripheral blood were detected by flow cytometry. Western blotting, qRT-PCR and ELISA were used to detect the expression of S100A8, S100A9, MMP9, LOX, and IL-6/STAT3 in premetastatic lung tissue. RESULTS: XLPYR treatment inhibited tumor growth and prevented lung metastasis. Compared to mice without subcutaneous tumor cell transplantation, the model group had an increased proportion of MDSCs, higher expression of S100A8, S100A9, MMP9, and LOX in the premetastatic lung. XLPYR treatment reduced the proportion of MDSCs, S100A8, S100A9, MMP9, and LOX expression, and downregulated the IL-6/STAT3 pathway. CONCLUSIONS: XLPYR may prevent MDSCs recruitment and reduce the expression of S100A8, MMP9, LOX, and IL6/STAT3 in premetastatic lung tissue, thus reducing lung metastases.

The combination of four main components in Xuebijing injection improved the preventive effects of Cyclosporin A in acute graft-versus-host disease mice by protecting intestinal microenvironment.

Acute graft-versus-host disease (aGVHD) is a major life-threatening complication after Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT). Although a series of immunosuppressant agents are routinely used as the first-line prevention, the morbidity and mortality rate remains high in allo-HSCT recipients. Our previous work indicated that combining Xuebijing (XBJ) with Cyclosporin A (CSA) is superior to CSA alone in preventing aGVHD. However, it was not clear which compounds in XBJ may prevent aGVHD. Whether the effective compounds in XBJ can be safely combined with CSA to prevent GVHD remain to be evaluated. Here, we accessed whether the combination of four main components in XBJ (C0127) had the same efficacy as XBJ in preventing aGVHD. In addition, the effectiveness of a novel combination therapy (C0127 + CSA) on aGVHD prophylaxis was evaluated using 16 s rRNA sequencing and RNA sequencing approaches in vitro and in vivo. In aGVHD mice, C0127 enhanced the preventive effects of CSA including decreasing mortality, maintaining weight, reducing GVHD score and reducing the expression of IL-6 and TNF-α in serum. Fatal GVHD is a frequent consequence of intestinal tract damage. We found combining C0127 with CSA alleviated the gut damage and maintained the normal physiological function of intestine by H&E staining, intestinal permeability and short chain fatty acid (SCFA) assays. Next, 16 S sequencing analysis of feces showed the combination treatment maintained the intestinal microbial diversity, normalized the intestinal microorganism and prevented flora disorder by reducing the relative abundances of Escherichia coli and Enterococcus. Further, RNA-seq analysis of colonic epithelium revealed C0127 combined with CSA chiefly regulated chemokines and cytokines in IL-17 signaling pathway. The combination treatment reduced the expression of G-CSF and its effector STAT3 (an axis that aggravated gut inflammation and flora disorder) in gut epithelium on mRNA and protein level. These findings indicated that C0127 improved the prevention of CSA in aGVHD mice partially by protecting the gut from damage through normalizing G-CSF signaling, which regulates the intestinal microbiota and the integrity of the epithelial barrier.

Association of 25-hydroxyvitamin D level with survival outcomes in female breast cancer patients: A meta-analysis.

Conflicting results have been reported on the association of blood vitamin D level with prognosis in women with breast cancer. This meta-analysis aimed to evaluate the association between blood 25-hydroxyvitamin D level and survival outcomes in female breast cancer patients. Two authors independently searched PubMed and Embase databases from their inception to August 25, 2020. Prospective or retrospective cohort studies evaluating the association between blood 25-hydroxyvitamin D level and survival outcomes in women with breast cancer were included. Outcome measures included overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). Twelve studies involving 8574 female breast cancer patients were identified and analyzed. When compared the lowest with the highest category of 25-hydroxyvitamin D level, the pooled adjusted hazard ratio (HR) was 1.57 (95 % confidence interval [CI] 1.35-1.83) for OS, 1.98 (95 % CI 1.55-2.53) for DFS, and 1.44 (95 % CI 1.14-1.81) for BCSS. This meta-analysis indicates that lower blood 25-hydroxyvitamin D level is significantly associated with reduced survival among female breast cancer patients. Additional clinical trials are required to investigate whether vitamin D supplement can improve survival outcomes in these patients.

Protecting Intestinal Microenvironment Alleviates Acute Graft-Versus-Host Disease.

Acute gut graft-versus-host disease (aGVHD) is a leading threat to the survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Abnormal gut microbiota is correlated with poor prognosis in allo-HSCT recipients. A disrupted intestinal microenvironment exacerbates dysbiosis in GVHD patients. We hypothesized that maintaining the integrity of the intestinal barrier may protect gut microbiota and attenuate aGVHD. This hypothesis was tested in a murine aGVHD model and an in vitro intestinal epithelial culture. Millipore cytokine array was utilized to determine the expression of proinflammatory cytokines in the serum. The 16S rRNA sequencing was used to determine the abundance and diversity of gut microbiota. Combining Xuebijing injection (XBJ) with a reduced dose of cyclosporine A (CsA) is superior to CsA alone in improving the survival of aGVHD mice and delayed aGVHD progression. This regimen also reduced interleukin 6 (IL-6) and IL-12 levels in the peripheral blood. 16S rRNA analysis revealed the combination treatment protected gut microbiota in aGVHD mice by reversing the dysbiosis at the phylum, genus, and species level. It inhibited enterococcal expansion, a hallmark of GVHD progression. It inhibited enterococcal expansion, a hallmark of GVHD progression. Furthermore, Escherichia coli expansion was inhibited by this regimen. Pathology analysis revealed that the combination treatment improved the integrity of the intestinal tissue of aGVHD mice. It also reduced the intestinal permeability in aGVHD mice. Besides, XBJ ameliorated doxorubicin-induced intestinal epithelial death in CCK-8 assay. Overall, combining XBJ with CsA protected the intestinal microenvironment to prevent aGVHD. Our findings suggested that protecting the intestinal microenvironment could be a novel strategy to manage aGVHD. Combining XBJ with CsA may reduce the side effects of current aGVHD prevention regimens and improve the quality of life of allo-HSCT recipients.

Protective effects of fucoidan against hyperoxic lung injury via the ERK signaling pathway.

High oxygen mechanical ventilation is widely used to treat various lung diseases; however, it may result in hyperoxia, which induces inflammation and lung injury. Fucoidan is an extract of the seaweed Fucus vesiculosus, which has previously been reported to exert effects against diabetic nephropathy. The present study is the first, to the best of our knowledge, to investigate the protective effects of fucoidan against hyperoxic lung injury. Balb/c mice were ventilated with 100% oxygen, with or without the atomization inhalation of fucoidan, for 36 h. Hyperoxia reduced the body weight and increased the relative lung weight of the mice. In addition, cell quantity and differentiation were determined using a hemocytometer, hyperoxia increased the total number of cells, and the number of macrophages, neutrophils and lymphocytes in the bronchoalveolar lavage fluid. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) demonstrated that hyperoxia also increased the mRNA expression levels of cluster of differentiation (CD)68, F4/80, CD64 and CD19 in lung tissue, and induced lung morphological alterations. Furthermore, western blotting assay demonstrated that hyperoxia increased the expression levels of interleukin (IL)­1, IL­6 and tumor necrosis factor (TNF)­α, and the phosphorylation of extracellular signal­regulated kinase (ERK)1/2. Conversely, hyperoxia­induced inflammation and morphological alterations were significantly attenuated in the mice treated with fucoidan. Atomization inhalation of fucoidan also reduced the hyperoxia­induced expression of IL­1, IL­6 and TNF­α, and the phosphorylation of ERK1/2. These findings suggested that fucoidan may attenuate hyperoxic lung injury via the ERK1/2 signaling pathway.

Treatment of multiple ceramic alloys before recasting.

STATEMENT OF PROBLEM: Dental laboratories often reuse dental casting alloys by recasting them, but the processing methods before recasting require further research. PURPOSE: The purpose of the study was to determine the treatment methods to remove the surface contamination of the previously melted alloys before recasting. MATERIAL AND METHODS: Cobalt-chromium (Co-Cr), commercially pure titanium (CP Ti), palladium-copper-gallium (Pd-Cu-Ga), and gold-platinum (Au-Pt) ceramic alloys were investigated in the present study. Field emission scanning electron microscopy, energy-dispersive x-ray spectroscopy (EDAX), and x-ray photoelectron spectroscopy (XPS) were used to evaluate the changes in the surface structures and compositions of Co-Cr, CP Ti, Pd-Cu-Ga, and Au-Pt ceramic alloys after airborne-particle abrasion and immersion in various chemical solutions for different time periods. The data obtained by EDAX and XPS were statistically analyzed by Kruskal-Wallis and Nemenyi tests (α=.05). RESULTS: By using appropriate mechanical and chemical treatment procedures, the contamination content of previously cast ceramic alloys was found to be below the detection limits of EDAX and XPS. The statistical results showed that, compared to the control group (new alloys after polishing), the impurity element was not detected after being treated with these methods, which was not statistically different to control group. CONCLUSIONS: The surface contamination of ceramic alloys was effectively removed by using certain mechanical and/or chemical treatment methods. Within the limitations of the present study, the most appropriate ways to treat ceramic alloys before recasting were as follows: (1) for Co-Cr ceramic alloys: Al2O3 airborne-particle abrasion and immersion in aqua regia for 15 min; (2) for CP Ti ceramic alloys: Al2O3 airborne-particle abrasion and immersion in 65% HNO3 and 40% HF 1:7 (V/V) for 60 min; (3) for Pd-Cu-Ga ceramic alloys: glass bead airborne-particle abrasion and immersion in 40% HF solution for 30 min; and (4) for Au-Pt ceramic alloys: glass bead airborne-particle abrasion.

Protective effects of emodin combined with danshensu on experimental severe acute pancreatitis.

OBJECTIVE AND DESIGN: In the present experiment, we aimed to determine the feasibility and curative effects of emodin combined with danshensu on experimental severe acute pancreatitis (SAP) and the mutual benefit of this synergistic strategy by a prospective animal study. MATERIAL: Eighty Wistar rats were randomly divided into four groups (n = 20). TREATMENT: SAP was elicited by a retrograde infusion of 5.0% sodium taurocholate into the pancreatic main duct. SAP rats in each group received no further intervention, emodin alone, danshensu (DSS) alone, and emodin combined with DSS (EDSS), respectively. METHODS: 48 h after SAP induction, all surviving animals were sacrificed to collect blood and tissue samples for the following measurements: serum levels of amylase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), endotoxin and D-lactate. Pancreatic levels of TNF-alpha, IL-1beta, maleic dialdehyde (MDA), myeloperoxidase (MPO) activity, nuclear factor-kappaappaB (NF-kappaB) activation as well as wet-dry weight ratio were also evaluated. Ascitic fluid was quantified and the severity of pancreatic damage was analyzed by pathological grading and scoring. RESULTS: Compared with the SAP group, the emodin, DSS and EDSS groups had significant differences in every index. Furthermore, EDSS obviously improved all the parameters mentioned above so as to counteract inflammatory response and oxidative stress, as well as most effectively abating pancreatic and intestinal barrier injury. CONCLUSIONS: EDSS exerted protective effects on SAP rats and remarkably alleviated the severity of experimental SAP. Mechanisms that might account for the beneficial effects include protecting the intestinal barrier, inhibiting over-inflammatory reaction and abating oxidative stress. The combined strategy proved to be more effective than either emodin or DSS alone and may cause synergistic effects in combination in the early stage of SAP. Broad potential for future clinical practice is foreseeable.

[Feasibility for inhibiting tumor metastasis with Chinese herbal medicines as angiogenesis inhibitors].

Anti-angiogenesis is one of the important ways to control tumor growth and metastasis, and searching for anti-angiogenesis herbs targeting tumor angiogenesis has become a hot topic in both basic and clinical research for tumor. Utilizing the traditional Chinese medicine theory, authors of this article discussed the feasibility and research of anti-angiogenesis effect of Chinese medicine on tumor. To develop new drugs inhibiting tumor angiogenesis from the Chinese native herbal medicine has an extremely vital significance in blocking tumor invasion and metastasis, as well as improving the patients' prognosis and their survival rates.