Liriogerphines E-U, further unique sesquiterpene-alkaloid hybrids from the rare Chinese tulip tree.

Seventeen undescribed sesquiterpene-alkaloid hybrids (liriogerphines E-U, 1-17) were isolated and identified during a further phytochemical investigation on the branches and leaves of Chinese tulip tree (Liriodendron chinense), a rare medicinal and ornamental plant endemic to China. These unique heterodimers are conjugates of germacranolide-type sesquiterpenoids with structurally diverse alkaloids [i.e., aporphine- (1-15), proaporphine- (16), and benzyltetrahydroisoquinoline-type (17)] via the formation of a C-N bond. The previously undescribed structures were elucidated by comprehensive spectroscopic data analyses and electronic circular dichroism calculations. Such a class of sesquiterpene-alkaloid hybrids presumably biosynthesized via an aza-Michael addition is quite rare from terrestrial plants. In particular, the sesquiterpene-benzyltetrahydroisoquinoline hybrid skeleton has never been reported until the present study. All the isolates were evaluated for their cytotoxic effects against a small panel of leukemia cell lines (Raji, Jeko-1, Daudi, Jurkat, MV-4-11 and HL-60), and some of them exhibited considerable activities.

Exosome-Mediated Immunosuppression in Tumor Microenvironments.

Exosomes are membranous structures secreted by nearly all cell types. As critical messengers for intercellular communication, exosomes deliver bioactive cargoes to recipient cells and are involved in multiple physiopathological processes, including immunoregulation. Our pioneering study revealed that cancer cells release programmed death-ligand 1-positive exosomes into the circulation to counter antitumor immunity systemically via T cells. Tumor cell-derived exosomes (TDEs) also play an immunosuppressive role in other immunocytes, including dendritic cells (DCs), macrophages, natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs). Moreover, exosomes secreted by nontumor cells in the tumor microenvironments (TMEs) also exert immunosuppressive effects. This review systematically provides a summary of the immunosuppression induced by exosomes in tumor microenvironments, which modulates tumor growth, invasion, metastasis, and immunotherapeutic resistance. Additionally, therapeutic strategies targeting the molecular mechanism of exosome-mediated tumor development, which may help overcome several obstacles, such as immune tolerance in oncotherapy, are also discussed. Detailed knowledge of the specific functions of exosomes in antitumor immunity may contribute to the development of innovative treatments.

Liriogerphines A-D, a Class of Sesquiterpene-Alkaloid Hybrids from the Rare Chinese Tulip Tree Plant.

Liriogerphines A-D (1-4, respectively), an unprecedented class of hybrids of germacranolide-type sesquiterpenoids and aporphine-type alkaloids, were isolated from the rare medicinal plant Liriodendron chinense. Their structures were elucidated by comprehensive spectroscopic analyses combined with electronic circular dichroism calculations and X-ray crystallographic data. Biosynthetically, an aza-Michael addition reaction is proposed to be involved in the assemblies of this class of hybrids. Compound 4 exhibited cytotoxicity against leukemia cells via inducing apoptosis and inhibiting Bcl-2 expression.

[Single-dose ceftriaxone versus multiple-dose cefuroxime for prophylaxis of surgical site infection].

OBJECTIVE: To compare the effects and pharmacoeconomics of single-dose of ceftriaxone versus 3-day cefuroxime prophylaxis in patients undergoing gastric or colorectal resection. METHODS: Three hundred and five consecutive patients with gastric or colorectal cancer from 5 medical centers were randomly divided into ceftriaxone group (n = 153, receiving intravenously 1 g ceftriaxone 0.5 - 1 h prior to operation only) and cefuroxime group (n = 152, receiving 0.75 g cefuroxime preoperatively and the same dose q8h for 3 d). The patients' intra- and postoperative status, adverse responses and infectious complications were observed and documented, and pharmacoeconomic parameters were analyzed. RESULTS: The disease distribution, operative procedures and patients' conditions in the 2 groups were comparable. No adverse responses to the test antibiotics were observed. Postoperative infectious complications occurred in 7 cases in the ceftriaxone group (4.58%) and 14 cases in the cefuroxime group (9.21%), respectively (P = 0.992), among which, 12 cases were surgical site infections (incisional, intra-abdominal): 2 cases in the ceftriaxone group (1.31%), and 10 cases in the cefuroxime group (6.58%), (chi(2) = 5.607, P = 0.018). The direct cost related to prevention and treatment of surgical site infections was 283.5 RMB in the ceftriaxone group and 811.1 RMB in the cefuroxime group (Z = 14.51, P = 0.000). CONCLUSION: Both ceftriaxone and cefuroxime are safe and effective for prevention of surgical site infections. Single-dose ceftriaxone prophylaxis is sufficient for gastric and colorectal operations, with a better cost-effectiveness ratio.