Human umbilical cord mesenchymal stem cells combined with pirfenidone upregulates the expression of RGS2 in the pulmonary fibrosis in mice.

OBJECTIVE: The therapeutic effect of umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in combination with pirfenidone (PFD) on pulmonary fibrosis in mice and its possible mechanism were investigated. METHODS: C57BL/6 mice were randomly divided into six groups: control group, model group, P10 group, P30 group, P100 group, and P300 group. Modeled by tracheal intubation with 3 mg/kg bleomycin drip, each dose of PFD was administered daily by gavage from day 7 onwards. The mice were observed continuously for 21 days and survival was recorded. Lung tissues were collected on day 21, and hematoxylin-eosin (HE) and Masson staining were performed to assess morphological changes and collagen deposition in the lungs. Collagen content was measured by the Sircol method, and fibrosis marker levels were detected by PCR and Western blot. Another batch of C57BL/6 mice was then randomly divided into five groups: hUC-MSC control group, model group, P100 group, hUC-MSC treatment group, and hUC-MSCs + P30 group. On day 7, 5 × 105 hUC-MSCs were injected into the tail vein, the mice were administered PFD gavage daily from day 7 onwards, and their survival was recorded. Lung tissues were collected on day 21 to detect pathological changes, the collagen content, and the expression of regulator of G protein signaling 2 (RGS2). Pulmonary myofibroblasts (MFBs) were divided into an MFB group and an MFB + hUC-MSCs group; different doses of PFD were administered to each group, and the levels of RGS2, intracellular Ca2+, and fibrosis markers were recorded for each group. RESULTS: Compared with other PFD group doses, the P100 group had significantly improved mouse survival and lung pathology and significantly reduced collagen and fibrosis marker levels (p < 0.05). The hUC-MSCs + P30 group had significantly improved mouse survival and lung pathology, significantly reduced collagen content and fibrosis marker levels (p < 0.05), and the efficacy was better than that of the P100 and hUC-MSCs groups (p < 0.05). RGS2 expression was significantly higher in the MSCs + P30 group compared with the P100 and hUC-MSCs groups (p < 0.05). PFD increased RGS2 expression in MFBs (p < 0.05) in a dose-dependent manner. Compared with PFD and hUC-MSCs treatment alone, combination of hUC-MSCs and PFD increased RGS2 protein levels, significantly decreased intracellular Ca2+ concentration, and significantly reduced fibrosis markers. CONCLUSION: The findings suggest that hUC-MSCs combined with low-dose PFD have a therapeutic effect better than that of the two treatments used separately. Its effect on attenuating bleomycin-induced pulmonary fibrosis in mice is related to the increase of RGS2.

Castleman disease of the pancreas mimicking pancreatic malignancy on 68Ga-DOTATATE and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: A case report.

BACKGROUND: Castleman disease is an uncommon nonclonal lymphoproliferative disorder, which frequently mimics both benign and malignant abnormalities in several regions. Depending on the number of lymph nodes or regions involved, Castleman disease (CD) varies in diagnosis, treatment and prognosis. It rarely occurs in the pancreas alone without any distinct clinical feature and tends to be confused with pancreatic paraganglioma (PGL), neuroendocrine tumors (NETs), and primary tumors, thus impeding proper diagnosis and treatment. CASE SUMMARY: A 28-year-old woman presented with a lesion on the neck of the pancreas, detected by ultrasound during a health examination. Physical examination and laboratory findings were normal. The mass showed hypervascularity on enhanced computed tomography (CT), significantly increased 18F-fluorodeoxyglucose uptake on positron emission tomography (PET)/CT, and slightly increased somatostatin receptor (SSTR) expression on 68Ga-DOTATATE PET/CT, suggesting no distant metastases and subdiagnoses such as pancreatic PGL, NET, or primary tumor. Intraoperative pathology suggested lymphatic hyperplasia, and only simple tumor resection was performed. The patient was diagnosed with the hyaline vascular variant of CD, which was confirmed by postoperative immunohistochemistry. The patient was discharged successfully, and no recurrence was observed on regular review. CONCLUSION: High glucose uptake and slightly elevated SSTR expression are potentially new diagnostic features of CD of the pancreas.

Design of dual targeting immunomicelles loaded with bufalin and study of their anti-tumor effect on liver cancer.

OBJECTIVE: Bufalin is an effective drug for the treatment of liver cancer. But its high toxicity, poor water-solubility, fast metabolism and short elimination half-life limit its use in tumor treatment. How to make the drug accumulate in the tumor and reduce side effects while maintaining its efficacy are urgent problems to be solved. The goal of this study is to solve these problems. METHODS: A copolymer with tunable poly-N-isopropylacrylamide and polylactic acid was designed and synthesized. The corresponding dual targeting immunomicelles (DTIs) loaded with bufalin (DTIs-BF) were synthesized by copolymer self-assembly in an aqueous solution. The size and structure of DTIs-BF were determined by ZetaSizer Nano-ZS and transmission electron microscopy. Then, its temperature sensitivity, serum stability, critical micelle concentration (CMC), entrapment efficiency (EE), drug release and non-cytotoxicity of blank block copolymer micelles (BCMs) were evaluated. Next, the effects of DTIs-BF on cellular uptake, cytotoxicity, and tumor cell inhibition were evaluated. Finally, the accumulation of DTIs-fluorescein isothiocyanate (FITC) and the in vivo anti-tumor effect were observed using an interactive video information system. RESULTS: DTIs-BF had a small size, spherical shape, good temperature sensitivity, high serum stability, low CMC, high EE, and slow drug release. The blank BCMs had very low cytotoxicity. Compared with free bufalin, the in vitro cellular internalization and cytotoxicity of DTIs-BF against SMMC-7721 cells were significantly enhanced, and the effects were obviously better at 40 °C than 37 °C. In addition, the therapeutic effect on SMMC-7721 cells was further enhanced by the programmed cell death specifically caused by bufalin. When DTIs-FITC were injected intravenously in BALB/c nude mice bearing liver cancer, the accumulation of FITC was significantly increased in tumors. CONCLUSION: DTIs-BF is a potentially effective nano-formulation and has broad prospects in the clinical treatment of liver cancer.