Trans-3, 5, 4'-trimethoxystilbene restrains non-small-cell lung carcinoma progression via suppressing M2 polarization through inhibition of m6A modified circPACRGL-mediated Hippo signaling.

BACKGROUND: Non-small-cell lung carcinoma (NSCLC) accounts for ∼85% of all lung carcinomas. Trans-3,5,4'-trimethoxystilbene (TMS) shows strong anti-tumor activity and induces tumor cell apoptosis. However, its function and mechanism in NSCLC still require investigation. METHODS: PMA was used to treated THP-1 cells for macrophage differentiation. The abundance and m6A modification of circPACRGL were examined with qRT-PCR and MeRIP. Colony forming, transwell, wound healing, and Western blotting assays were applied to analyze proliferation, invasion, migration, and EMT. Macrophage polarization was determined through flow cytometry analysis of M1 and M2 markers. The interplay between circPACRGL, IGF2BP2 and YAP1 was validated by RNA pull-down and RIP assays. Mice received subcutaneous injection of NSCLC cells as a mouse model of subcutaneous tumor. RESULTS: CircPACRGL was upregulated in NSCLC cells, but it was reduced by TMS treatment. CircPACRGL depletion blocked proliferation, migration, and invasion in H1299 and H1975 cells. TMS suppressed these malignant behaviors, but it was abolished by circPACRGL overexpression. In addition, NSCLC-derived exosomes delivered circPACRGL into THP-1 cells to promote its M2 polarization, but TMS inhibited these effects by downregulating exosomal circPACRGL. Mechanically, exosomal circPACRGL bound to IGF2BP2 to improve the stability of YAP1 mRNA and regulate Hippo signaling in polarized THP-1 cells. TMS inhibited NSCLC growth via suppressing Hippo signaling and M2 polarization in vivo. CONCLUSION: TMS restrains M2 polarization and NSCLC progression by reducing circPACRGL and inhibiting exosomal circPACRGL-mediated Hippo signaling. Thus, these findings provide a novel mechanism underlying NSCLC progression and potential therapeutic targets.

Temporal variations and trends prediction of water quality during 2010-2019 in the middle Yangtze River, China.

Water quality plays an important role in river habitats. This study revealed the annual and seasonal variations and trend prediction of water quality in the middle Yangtze River after the third impoundment stage of the Three Gorges Reservoir. Multivariate statistical methods including principal component analysis/factor analysis (PCA/FA), Mann-Kendall (M-K) tests, discriminant analysis (DA), rescaled range (R/S) analysis, and the Canadian Council of Ministers of the Environment Water Quality Index (CCME-WQI) were used. Herein, eight water quality constituents including pH, electrical conductivity (EC), chloride (Cl), dissolved oxygen (DO), ammonia nitrogen (NH3N), total phosphorus (TP), water temperature (T), and permanganate index (CODmn) were monthly monitored in the Jiujiang hydrological transaction during 2010-2019. The information of eight water quality constituents, related to salinity, nutrient status, and oxidation reactions efficiency, was extracted. Water quality status remained as fair-good during 2010-2019 based on the results of CCME-WQI, with the seasonal significance ranked as T > DO > Cl > pH > EC > TP > NH3N > CODmn. In the future decade, annual average T was predicted to continue to increase although it might decrease in the wet season. EC was predicted to continue increasing annually especially in the wet season while Cl might decrease. NH3N and TP might maintain a significant decreasing trend in the future wet and dry seasons. DO maintained significantly increasing especially in the future dry seasons, whereas CODmn will continue to decrease annually and seasonally. The continued alkalization trend of waterbody was predicted, which is more significant in the wet season. The results provide helpful references for the ecological protection of the middle Yangtze River.

Temporal and spatial variation in water quality in the Yangtze Estuary from 2012 to 2018.

Water quality plays an important role in estuarine habitats and affects aquatic organisms. The focus of this study was to understand the temporal-spatial variation of water quality and reveal the natural and anthropogenic drivers by using multiple analysis approaches. Herein, during 2012-2018, six water quality constituents (pH, electrical conductivity (EC), dissolved oxygen (DO), ammonia nitrogen (NH3N), total nitrogen (TN), and total phosphorus (TP) were examined for eight sites in the Yangtze Estuary, and the hydro-sediment data, i.e., discharge (Q) and sediment transport rate (STR), was collected from the upstream hydrological station Datong. The cluster analysis (CA), principal component analysis (PCA)/factor analysis (FA), Canadian Council of Ministers of the Environment Water Quality Index (CCME-WQI), and the Mann-Kendall (MK) test were applied. The eight sampling sites were geographically grouped into cluster I, cluster II, and cluster III based on the characteristics of water quality changes, which are under the influence of the upstream runoff, the anthropogenic activities, and seawater. The results are as follows: (1) NH3N, TN, and DO were key constituents representing the water quality of cluster I and cluster III, and those were EC, TN, and DO for cluster II; (2) The monthly-average Q and STR of Datong were negatively correlated to water quality constituents with seasonal variation except for pH; (3) The impact of anthropogenic activities on water quality was especially reflected in cluster III which is close to the Huangpu River Estuary; upstream runoff was the natural driver of water quality changes for cluster I while that was seawater for cluster II. Seawater acts a key role in affecting the water quality of cluster II situated at the North Branch. Revealing the key drivers of water quality change in the Yangtze Estuary provides a reference for water quality management.

Lipid-coated CaCO3-PDA nanoparticles as a versatile nanocarrier to enable pH-responsive dual modal imaging-guided combination cancer therapy.

Development of an intelligent and versatile delivery system to achieve tumor-targeted delivery and controlled release of diverse functional moieties is of great significance to realize precise cancer theranostics. In this study, we use pH-dissociable calcium carbonate-polydopamine (pCaCO3) nanocomposites as a template to guide the formation of a lipid bilayer on their surface, yielding lipid-coated pCaCO3 nanoparticles with high loading efficacies towards gadolinium ions (Gd3+), doxorubicin (DOX) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR). The obtained liposomal nanotheranostics show excellent physiological stability and pH-dependent release of DOX and Gd3+; the latter could lead to pH-dependent T1 signal enhancement under magnetic resonance (MR) imaging, as well as efficient photothermal conversion efficacy. Then, we found that tumors in mice with intravenous injection of DiR-DOX-Gd@pCaCO3-PEG could be clearly visualized in a real-time manner by recording their near-infrared (NIR) fluorescence and T1 MR signal. Furthermore, treatment with such liposomal nanotheranostics injection and NIR laser irradiation could enable collective suppression of the growth of 4T1 tumors in Balb/c mice via combined chemo- and photothermal therapies. Therefore, this work highlights the concise preparation of lipid-coated pCaCO3 nanocomposites, which could be utilized for the construction of diverse cancer nanotheranostics by exploiting their versatile loading capacities.

Self-Assembled Hybrid Nanocomposites for Multimodal Imaging-Guided Photothermal Therapy of Lymph Node Metastasis.

Multimodal imaging-guided therapy holds great potential for precise theranostics of cancer metastasis. However, imaging agents enabling the convergence of complementary modalities with therapeutic functions to achieve perfect theranostics have been less exploited. This study reports the construction of a multifunctional nanoagent (FIP-99mTc) that comprises Fe3O4 for magnetic resonance imaging, radioactive 99mTc for single-photon-emission computed tomography, and IR-1061 to serve for the second near-infrared fluorescence imaging, photoacoustic imaging, and photothermal therapy treatment of cancer metastasis. The nanoagent possessed superior multimodal imaging capability with high sensitivity and resolution attributing to the complement of all the imaging modalities. Moreover, the nanoagent showed ideal photothermal conversion ability to effectively kill tumor cells at low concentration and power laser irradiation. In the in vivo study, FIP-99mTc confirmed the fast accumulation and clear delineation of metastatic lymph nodes within 1 h after administration. Attributing to the efficient uptake and photothermal conversion, FIP-99mTc could raise the temperature of metastatic lymph nodes to 54 °C within 10 min laser irradiation, so as to facilitate tumor cell ablation. More importantly, FIP-99mTc not only played an active role in suppressing cancer growth in metastatic lymph nodes with high efficiency but also could effectively prevent further lung metastasis after resection of the primary tumor. This study proposes a simple but effective theranostic approach toward lymph node metastasis.

Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis.

Cannabinoid receptor 2 (CB2) has been implicated as an important clinical regulator of inflammation and malignant osteolysis. Here, we observed that CB2 expression was markedly higher in the collagen-induced arthritis (CIA) mice synovium and bone tissues than in the noninflamed synovium and bone tissues. The CB2 selective agonist (JWH133) but not antagonist (SR144528) suppressed CIA in mice without toxic effects, as demonstrated by the decreased synovial hyperplasia, inflammatory responses, cartilage damage, and periarticular and systemic bone destruction. JWH133 treatment decreased the infiltration of pro-inflammatory M1-like macrophages and repolarized macrophages from the M1 to M2 phenotype. Similarly, activation of CB2 increased the expression of anti-inflammatory cytokine interleukin (IL)-10 and reduced the expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6. In addition, JWH133 treatment attenuated osteoclast formation and osteoclastic bone resorption, and reduced the expression of receptor activators of the nuclear factor-κB (NF-κB) ligand (RANKL), matrix metallopeptidase-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and nuclear factor of activated T-cells 1 (NFAT-1) in CIA mice and osteoclast precursors, which were obviously blocked by pretreatment with SR144528. Mechanistically, JWH133 inhibited RANKL-induced NF-κB activation in the osteoclast precursors. We found that JWH133 ameliorates pathologic bone destruction in CIA mice via the inhibition of osteoclastogenesis and modulation of inflammatory responses, thereby highlighting its potential as a treatment for human rheumatoid arthritis. © 2018 American Society for Bone and Mineral Research.

Synchronous colorectal cancer and multiple myeloma with chest wall involvement: Is this a coincidence?

Multiple primary malignant neoplasms (MPMNs) are rare malignant neoplasms that simultaneously or successively occur in the same patient as 2 or more primary malignancies. Currently, an increasing number of cases are being reported. In general, MPMNs more commonly occur as 2 solid tumors or 2 hematological malignancies. Cases of MPMN that involve a solid tumor and a hematological malignancy are rare. Here, we report a case of synchronous colorectal cancer (CRC) and multiple myeloma (MM) with chest wall involvement. After reviewing the literature, we believe that there may be a distinct syndrome involving CRC and MM. The patient in our case study suffered refractory anemia following surgery and 2 cycles of chemotherapy. Initially, the anemia was considered to be a common manifestation of CRC in this patient. Interestingly, although he received a blood transfusion, his hemoglobin levels remained low. He later developed hematuria, proteinuria, multiple osteoporosis in the costal bones, and thrombocytopenia. These new symptoms drew our attention, and we considered a diagnosis of synchronous primary CRC and MM, with the anemia as a symptom of MM. Based on the results of a bone marrow aspirate, MM was confirmed. Therefore, when CRC is associated with refractory anemia, we should not only assume that anemia is a classical symptom of CRC, a result of chronic blood loss, nutritional deficiencies, or myelosuppression due to chemotherapy, but we should also consider that it may reflect the possibility of a coexisting hematologic malignancy. As the treatment of these 2 malignancies is different, early diagnosis and treatment based on definitive diagnosis as early as possible will be beneficial to overall prognosis.

Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Results of an open-label, single-arm, multicenter trial.

BACKGROUND: The purpose of this study was to assess the efficacy, safety, and pharmacokinetics of cisplatin-based chemotherapy plus cetuximab as first-line treatment in Chinese and Korean patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients (n = 68) received cetuximab weekly plus 3-week cycles of cisplatin/5-fluorouracil (5-FU) chemotherapy for up to 6 cycles. The primary endpoint was overall response rate. RESULTS: The overall response rate was 55.9%, including 2 complete responses (CRs). Median overall survival (OS) was 12.6 months and median progression-free survival (PFS) was 6.6 months. Grade 3/4 adverse events (AEs) were reported in 41 (60.3%) patients. The safety profile was in line with previous clinical experience. The pharmacokinetic profile was in line with that observed with cetuximab in white and Japanese patients. CONCLUSION: The efficacy, safety, and pharmacokinetic findings from this study support the use of first-line platinum-based chemotherapy plus cetuximab in Chinese and Korean patients with recurrent and/or metastatic SCCHN (ClinicalTrials.gov NCT01177956).

[Therapeutic effect of whole body hyperthermia combined with chemotherapy in patients with advanced cancer].

OBJECTIVE: To determine the short-term efficacy and security of whole body hyperthermia (WBH) combined with chemotherapy for advanced cancer. METHODS: Different chemotherapy regimens were applied in 138 patients with advanced cancer. Among them, 68 patients (Group A) didn't receive any other therapies. The other 70 patients (Group B) received WBH together with chemotherapy. WBH was maintained at 40 degrees C approximately 42 degrees C for 50 approximately 60 min (once or twice every week and 4 times a cycle). RESULTS: In Group A, the rate of complete remission (CR) was 2.9%, partial remission (PR) was 36.8%, stable disease was 35.3%, progressive disease was 25.0%, the overall response rate (CR + PR) was 39.7%; while in Group B, the corresponding figures were 5.7%, 52.9%, 25.7%, 25.0%, and 58.6%, respectively. There was significant difference between the two groups (P < 0.05). The rates of III + IV gastrointestinal tract andmyelosuppression toxicities were 26.5% and 16.2% in Group A, while 27.1% and 18.6% in Group B. No significant difference was found. CONCLUSION: WBH combined with chemotherapy is efficient and safe for advanced cancer, and is worth generalizing extensively.

[Nutrient cycling in Castanea mollissima B1 forest at the Miyun reservoir watershed, Beijing].

Studies on the nutrient cycling in Castanea mollissima B1 forest at the Miyun reservoir watershed, Beijing, showed that the total biomass of the Castanea mollissima B1 stands at age 22 was 38,638 kg.hm-2, and the biomass of their stem, branch, leaf, blossom, chestnut, seed capsule and root was 20,160, 8,430, 1429, 873, 1024, 800 and 5,922 kg.hm-2, occupying 52.18%, 21.82%, 3.70%, 2.26%, 2.65%, 2.07%, 15.33% of the total biomass, respectively. The annual average growth amount of stem, branch, and root was 916, 383, and 269 kg.hm-2, respectively, and the total annual average growth amount was 5,694 kg.hm-2. The nutrient contents in different organs of Castanea mollissima B1 stands showed that the N content sequence was leaf > blossom > chestnut > seed capsule > branch > stem, P content sequence was leaf > blossom > branch > stem > seed capsule > chestnut, K content sequence was chestnut > blossom > leaf > chestnut > branch > stem, Ca content sequence leaf > seed capsule > branch > stem > blossom > chestnut, and Mg content sequence was leaf > blossom > branch > chestnut > seed capsule > stem. The storage of N, P, K, Ca and Mg in Castanea mollissima B1 forest was 89.47, 17.34, 74.68, 105.49 and 28.40 kg.hm-2, respectively. The nutrient annual assimilation was 79.17 kg.hm-2, the total annual returning amount 106.55 kg.hm-2, and the annual retention amount was 11.25 kg.hm-2. Among of the total returning, atmospheric dry and wet deposition was 38.36 kg.hm-2, and the litter returning was 58.08 kg.hm-2. The nutrient input was a little more than the output. The storage of the five nutrient elements in 0(-)-30 cm soil layer was 206,427.59 kg.hm-2, and their storage amount in stands only occupied about 0.15% of the total storage in soil. The absorption coefficient of the stands was N > P > K > Ca > Mg, the utilization coefficient was K > N > Mg > P > Ca, and the cycling coefficient was K > N > P > Mg > Ca. The turnover period of the N, P, K, Ca and Mg was 4.34, 7.51, 3.31, 12.90 and 6.45 yr, respectively.