Tumor immunotherapy boosted by R837 nanocrystals through combining chemotherapy and mild hyperthermia.

Melanoma is a malignant skin cancer that is prone to metastasis in the early stage and has a poor prognosis. Immunomodulatory therapy for melanoma has been a hot research topic in recent years. However, low immune cell infiltration and loss of tumor immunogenicity may occur in tumors, resulting in low response rates to immunotherapy. Thus, immunomodulatory therapy is usually used in combination with chemotherapy and radiotherapy. Development of combined therapeutic strategies with low systemic toxicity, high immune responsiveness and long-term inhibition of metastasis and recurrence of melanoma is the goal of current research. In this study, the insoluble immune adjuvant imiquimod (R837) was prepared as nanocrystals and coated with polydopamine (PDA) to form R837@PDA, which was then loaded into chitosan hydrogel (CGP) to form the drug-loaded gel system, R837@PDA@CGP (RPC), to combine immunomodulation effects, induction of immunogenic cell death (ICD) effects and immune-enhancement effects. After treatment with RPC, ICD in melanoma was induced, and the infiltration rate of cytotoxic T cells (CTLs) in melanoma was also significantly enhanced, which turned the tumor itself into an in situ vaccine and boosted the cancer-immunity cycle at the tumor site. Therefore, melanoma growth, metastasis and recurrence were notably inhibited.

Ancient Chinese Medicine Herbal Formula Huanglian Jiedu Decoction as a Neoadjuvant Treatment of Chemotherapy by Improving Diarrhea and Tumor Response.

BACKGROUND: Diarrhea is a major gastrointestinal complication in cancer patients receiving chemotherapy. Prognosis and treatment of chemotherapy-induced diarrhea (CID) remain unsatisfactory. This study aims to explore the potential of an ancient Chinese Medicine herbal formula Huanglian Jiedu Decoction (HLJDD) as an adjuvant treatment on CID. METHOD: HLJDD extract was prepared by GMP manufacturing standard with quality and stability being checked. 5-fluorouracil (5-Fu) and irinotecan (CPT-11)-induced diarrhea model in mice was established and pre-, co- and post-treatment of HLJDD was implemented. Mechanism of action was explored by detecting related protein expression. In addition, the effect of HLJDD on diarrhea and tumor response induced by clinical regimens FOLFOX and FOLFIRI was measured in murine orthotopic colorectal cancer model. RESULTS: HLJDD exhibited consistency in quality and stability after 24-month storage. Pre-treatment of HLJDD, but not co-treatment or post-treatment, could significantly improve the diarrhea score, body weight loss and intestinal damage in 5-Fu- and CPT-11-treated mice. Pre-treatment of HLJDD reduced cell apoptosis in the intestine of chemotherapy-treated mice, and promoted renewal of intestinal cell wall. CD44 was predicted as the potential target of HLJDD-containing compounds in CID. HLJDD pre-treatment induced presentation of CD44-postive cells in the intestine of chemotherapy-treated mice, and initiated expression of stemness-associated genes. Transcriptional products of the downstream Wnt signaling of CD44 were elevated. Furthermore, pre-treatment of HLJDD could significantly improve the tumor response of clinical chemotherapy regimens FOLFOX and FOLFIRI in orthotopic colorectal cancer, and reduce diarrhea and intestinal damage. Conclusion: Our study suggests the potential of HLJDD as a neoadjuvant treatment of chemotherapy by reducing diarrhea and improving tumor response.

Multi-Component Herbal Products in the Prevention and Treatment of Chemotherapy-Associated Toxicity and Side Effects: A Review on Experimental and Clinical Evidences.

Chemotherapy is nowadays the main treatment of human cancers. Chemotherapeutic agents target rapidly dividing cancer cells to suppress tumor progression, however, their non-specific cytotoxicity often leads to significant side effects that might be intolerable to cancer patients. Multi-component herbal products have been used for thousands of years for the treatment of multiple human diseases. This study aims to systematically summarize and evaluate the experimental and clinical evidences of the efficacy of multi-component herbal products in improving chemotherapy-induced side effect. Literature was retrieved from PubMed database and evaluated based on the side effects described. Multi-component herbal products were found to be effective in ameliorating the neurotoxicity, gastrointestinal toxicity, hematological toxicity, cardiotoxicity, hepatotoxicity and nephrotoxicity. Both experimental and clinical evidences were found, indicating the potential of applying multicomponent herbal products in the clinical treatment of chemotherapy-induced side effects. However, the lack of mechanistic and pharmacokinetic studies, inconsistency in product quality, as well as insufficient clinical evidence suggested that more investigations are urgently necessary. In all, our review shed light on the potential of using multi-component herbal products in the clinical management of chemotherapy-induced toxicity and side effects. We also discussed the potential threats of natural products for cancer treatment and compared the advantages of using herbs to conventional chemical drugs.

Allicin improves the function of cardiac microvascular endothelial cells by increasing PECAM-1 in rats with cardiac hypertrophy.

OBJECTIVE: Cardiac microvascular damage is significantly associated with the development of cardiac hypertrophy (CH). Researchers found that allicin could inhibit CH, but the relationship between cardiac microvessel and the inhibition of allicin on CH has not been reported. We aimed to investigate the effect of allicin on the function of cardiac microvascular endothelial cells (CMECs) in CH rat. MATERIALS AND METHODS: The hemodynamic parameters were measured by BL-420F biological function experimental system and the indicators of the ventricular structure and function were measured by echocardiographic system. MTT assay was performed to assess the cell viability. Nitrite detection was performed to detect nitric oxide content. The morphology and molecular characteristics were detected by electron micrographs, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), western blot. Wound healing experiment, analysis of tube formation and shear adaptation were performed to assess CMECs migration ability, angiogenesis and shear-responsiveness respectively. RESULT: Our findings have identified that microvascular density was decreased by observing the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) in CH rats. Interestingly, allicin improved the distribution and expression of PECAM-1. Meanwhile, allicin enhanced the migration and angiogenesis ability of CMECs, activated PECAM-1-PI3K-AKT-eNOS signaling pathway, however, the role of allicin was disappear after PECAM-1 was silenced. Allicin decreased the expression of caspase-3 and receptor interacting protein 3 (RIP3), inhibited necroptosis, and increased the levels of Angiopoietin-2 (Ang-2) and platelet-derived growth factor receptor-ß (PDGFR-ß). Under 10 dyn/cm2 condition, allicin advanced the modification ability of CMECs's shear-adaptation by activating PECAM-1. CONCLUSION: Allicin provided cardioprotection for CH rats by improving the function of CMECs through increasing the expression of PECAM-1.

[Law of Pollutant Erosion and Deposition in Urban Sewage Network].

In order to investigate the scouring and deposition law of pollutants in urban sewer systems, the investigation of sewer systems was carried out in Xi'an. The results showed that the thickness of sediment in the branch pipe and the main pipe varied obviously. At the peak of the drainage, the velocity increased gradually, and the thickness of the pipeline sediment decreased. At the bottom of the drainage trough, the changes of the velocity and the thickness of the pipeline sediment were opposite, with variations of 0-24 mm and 0-12 mm, respectively. And the probability of granular contaminants sedimentation and scouring in sewer systems was high, while the thickness of sediment in sewage main pipe was less than the above mentioned pipes, the variation of which was 0-7 mm. In addition, the sedimentation and scouring in the main pipeline kept relatively balanced and the thickness of sediment remained stable. In order to clarify the relationship between the concentration of pollutants and the flow velocity, a pilot sewer system was established. The effects of different flow rates, which were 0.1, 0.3, 0.6, 0.9, 1.2 m·s-1, respectively, on the contents of carbon (organic), nitrogen and phosphorus in the pipeline were studied. The results showed that with the increase of the flow velocity, the scour intensity increased and the concentration of pollutants in the pipeline also increased sharply. As shown by the monitoring results of the static light scattering particle size analyzer, the carbon organic pollutants in the pipeline were easily adsorbed on the larger particles, while nitrogen and phosphorus pollutants were easily adsorbed on the particles with smaller size. Analysis on the change of the urban sewage pipeline showed, when the flow rate was less than 0.6 m·s-1, the sedimentation of granular pollutants in the sewage was greater than the scouring effect. When the flow velocity was higher than 0.6 m·s-1, the water scouring intensity increased and the scouring action was greater than the sedimentation, meanwhile, the sediments were carried by the water and the thickness of the sediments was reduced. The increase of the organic pollutants in the sewage was bigger than the nitrogen and phosphorus pollutants, so that the existing sewage carbon source was improved.