ABSTRACT
@#Abstract: To report the diagnosis and treatment of Mucor infection in two cases of renal transplantation, and to provide reference for diagnosis and treatment of Mucor infection. Case 1, a male patient, who underwent allogeneic kidney transplantation due to increased creatinine for more than 8 years. The renal function had partially recovered 25 days after the operation, but then the patient suddenly got worse epigastric pain. Pathogen culture, smear microscopy, mass spectrometry identification and next-generation metagenomic sequencing (mNGS) were performed on the peritoneal drainage, with the result pointing to Rhizopus microsporus. The patient's condition improved after antifungal treatment using amphotericin B lipid complex (ABLC) and was discharged. Case 2, a male patient with hypertension and increased creatinine for more than 7 years was admitted to the hospital. After allograft kidney transplantation, tissue culture smear and histopathological examination suggested Mucor infection. The patient then underwent a "hand muscle debridement surgery + closed negative pressure drainage (VSD)" procedure, and amphotericin B was given postoperative treatment against Mucor infection and debridement. Subsequent retesting with mNGS showed no signs of Mucor infection. In the course of treatment, two patients developed abdominal pain after treatment with tegacycline, which was immediately diagnosed as pancreatitis and recovered after withdrawal. Both patients being male, with one case associated with hypertension. After initially guiding the diagnosis with traditional smear tests, final confirmation was done using histopathological examination, mNGS and mass spectrometry. One case was infected by Rhizopus microspora, and the other was infected by Rhizopus oryzae and Cunninghamia microbicans. The causes leading to Mucor infection in patients post renal transplantation varied greatly. Early diagnosis is the key to treatment of patients with Mucor infection after renal transplantation. Treatment with amphoteric B and its liposome is an effective means to improve mucormycosis patients after renal transplantation. The use of amphotericin B lipid complex treatment proved to be an effective treatment method for patients with Mucor infection after renal transplantation.
ABSTRACT
Aberrant energy metabolism is critical for cancer progression. Tumor-associated macrophages (TAMs) can stimulate tumor angiogenesis and enhance cancer metastasis; however, the metabolic interaction between cancer cells and macrophages characterized by lactate shuttles remains unclear. Here, we showed that lactate activated human macrophages to a TAM-like phenotype and stimulated the secretion of CCL5 by activation of Notch signaling in macrophages. Reciprocally, CCL5 increased cell migration, induced cancer cell EMT, and promoted aerobic glycolysis in breast cancer cells, suggesting a positive metabolic feedback loop in the co-culture system. Inhibition of CCR5, the cognate receptor of CCL5, or neutralization of CCL5, broke the metabolic loop and decreased cancer cell migration and EMT. Inhibition of aerobic glycolysis significantly reduced breast cancer cell EMT, indicated that aerobic glycolysis was necessary for the invasive phenotype of cancer cells. We further showed that TGF-ß signaling regulated the expression of CCR5 in the co-culture system, and CCL5 induced glycolysis by mediation of AMPK signaling. The expression of CCL5-CCR5 axis was highly associated with macrophage infiltration, TGF-ß and p-AMPK in clinical samples. CCL5-CCR5 axis promoted breast cancer metastasis in vivo. Our findings suggested a pivotal role of CCL5-CCR5 axis in the metabolic communication between cancer cells and macrophages.
