Impact of macrophage differentiation on hematopoietic function enhancement by Shenzhu ErKang Syrup.

Shenzhu Erkang Syrup (SZEK) is a traditional Chinese medicine that improves spleen and stomach function, tonifying the Qi and activating the blood; however, its therapeutic effects in hematopoietic dysfunction and their underlying mechanism remain unexplored. In this study, mice were given cyclophosphamide (100 mg/kg) by intraperitoneal injections for three days to produce hematopoietic dysfunction model. We investigated the hematopoietic effect and mechanism of SZEK in mice with hematopoietic dysfunction via histopathological examination, flow cytometry, enzyme-linked immunosorbent assay, and Western blotting combined with intestinal flora and serum metabolomics analysis. In mice with hematopoietic dysfunction, SZEK (gavage, 0.3 mL/25 g) alleviated pathological damage to the bone marrow and spleen; increased the number of naïve cells (Lin-), hematopoietic stem cells (Lin-Sca-1+c-Kit+), long-term self-renewing hematopoietic stem cells (Lin-Sca-1+c-Kit+CD48-CD150+), B lymphocytes (CD45+CD19+), and macrophages (CD11b+F4/80+) in the bone marrow; and reduced inflammation. Preliminary intestinal flora and serum metabolome analyses indicated that the pro-hematopoietic mechanism of SZEK was associated with macrophage differentiation. Further validation revealed that SZEK promoted hematopoiesis by decreasing the number of M2 macrophages and inhibiting the secretion of negative hematopoietic regulatory factors in mice with hematopoietic dysfunction.

Identification of an Immune-Related BAT Signature for Predicting Adjuvant Chemotherapy Response and Overall Survival in Patients with Resected Ductal Adenocarcinoma of the Pancreas.

BACKGROUND: Adjuvant chemotherapy (ACT) is widely accepted in patients with pancreatic ductal adenocarcinoma (PDAC) after surgery; however, effective models for predicting ACT response are scarce. Thus, the objective of this study was to develop a novel signature for predicting its response and overall survival (OS) in resected PDAC patients. METHODS: A total of 50 PDAC patients with the transcriptome expression profiles, information about chemotherapy, and relevant clinical data were retrieved from the Cancer Genome Atlas (TCGA), and twenty-nine patients with tissue specimens and clinical data from our hospital were included as a validation. A novel gene signature was developed using bioinformatic differentially expressed genes (DEGs) analysis, Lasso-penalized Cox regression, and multivariate Cox regression studies. RESULTS: Between chemotherapy-resistant and chemotherapy-sensitive cohorts, 569 DEGs were identified, with 490 upregulated and 79 downregulated genes mainly specialized in the regulation of peptide/protein/hormone secretion, calcium ion homeostasis, and T cell activation regulation in biological processes. After Lasso-penalized Cox and multivariate Cox regression analysis, BAT (BCHE, ADH1A, and TNS4) signature was established to predict ACT response and OS. Moreover, BAT signature was verified as an independent risk factor for ACT response (p = 0.042) and OS (median OS: 17.5 months vs. 34.8 months, p = 0.040) and significantly associated with immune infiltrations (p < 0.05). Then, this signature was further validated as the independent risk factor for recurrence-free survival (RFS) in PDAC patients receiving postoperative ACT (median RFS: 9.0 months vs. not reached, p = 0.014), and tumor-infiltrating CD4+ and CD8+ T cells were further validated to be significantly decreased in tissues with higher BAT signature scores (p = 0.015 and 0.021, respectively). CONCLUSION: The BAT signature is a novel formulated and independent risk factor for predicting ACT response and long-term survival in patients with resected PDAC. This signature could comprehensively reflect local immune-related response, tumor purity, potential biological behavior, and chemo drug susceptibility.

A molybdenum oxide-based degradable nanosheet for combined chemo-photothermal therapy to improve tumor immunosuppression and suppress distant tumors and lung metastases.

Molybdenum oxide (MoOx) nanosheets have drawn increasing attention for minimally invasive cancer treatments but still face great challenges, including complex modifications and the lack of efficient accumulation in tumor. In this work, a novel multifunctional degradable FA-BSA-PEG/MoOx nanosheet was fabricated (LA-PEG and FA-BSA dual modified MoOx): the synergistic effect of PEG and BSA endows the nanosheet with excellent stability and compatibility; the FA, a targeting ligand, facilitates the accumulation of nanosheets in the tumor. In addition, DTX, a model drug for breast cancer treatment, was loaded (76.49%, 1.5 times the carrier weight) in the nanosheets for in vitro and in vivo antitumor evaluation. The results revealed that the FA-BSA-PEG/MoOx@DTX nanosheets combined photothermal and chemotherapy could not only inhibit the primary tumor growth but also suppress the distant tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%), which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, which co-contributes towards effective suppression of tumor and lung metastasis. Our experiments demonstrated that this novel multifunctional nanosheet is a promising platform for combined chemo-photothermal therapy.

Experience of Treatments of Amanita phalloides-Induced Fulminant Liver Failure with Molecular Adsorbent Recirculating System and Therapeutic Plasma Exchange.

Ingestion of the mushroom containing Amanita phalloides can induce fulminant liver failure and death. There are no specific antidotes. Blood purifications, such as molecular adsorbent recirculating system (MARS) and therapeutic plasma exchange (TPE), are potential therapies. However, the extent to which these technologies avert the deleterious effects of amatoxins remains controversial; the optimal intensity, duration, and initiation criteria have not been determined yet. This study aimed to retrospectively observe the effects of MARS and TPE on nine patients with A. phalloides-induced fulminant liver failure. The survival rate for the nine patients was 66.7%. Both TPE and MARS might remove toxins and improve liver functions. However, a single session of TPE produced immediately greater improvements in alanine aminotransferase (-60% vs. -16.3%), aspartate aminotransferase (-47.6% vs. -15.4%), and total bilirubin (-37.3% vs. -17.1%) (compared with the values of pretreatment, all p < 0.05) than MARS compared with MARS. Early intervention may be more effective than delayed therapy. Additionally, the presence of severe liver failure and renal failure indicated worse outcome. Although these findings are promising, additional case-controlled, randomized studies are required to confirm our results.