Natural and revolutionary tumor-specific T-cell therapy.

Recently the FDA conducted a risk investigation and labeled the Boxed Warning for all BCMA- and CD19-directed CAR-T cell therapy, so does it mean that the public must take risk of secondary cancer to receive cell therapy? Here, without lentivirus and professional antigen presenting cell application, a novel tumor-specific T-cell therapy was successfully developed only by co-culturing MHC+ cancer cells and Naïve-T cells under the CD28 co-stimulatory signals. These tumor-specific T-cells could be separated through cell size and abundantly produced from peripheral blood, and would spontaneously attack target cells that carrying the same tumor antigen while avoiding others in vitro test. Moreover, it markedly decreased 90% tumor nodules companying with greatly improving overall survival (76 days vs 30 days) after twice infusion back to mice. This work maximally avoided the risks of secondary cancer and non-specific killing, and might open a revolutionary beginning of natural tumor-specific T-cell therapy.

Structural diversity and biological activities of indole-diterpenoids from Penicillium janthinellum by co-culture with Paecilomyces formosus.

Co-culturing the marine-derived fungi Penicillium janthinellium with Paecilomyces formosus led to the isolation of nine new indole-diterpenes, janthinellumines A-I (1-9), along with twelve known analogues (10-21). The chemical structures including their absolute configurations of them were assigned by the analysis of extensive spectroscopic data and calculated ECD and VCD methods. These indole-diterpenoids displayed extensive biological activities, including anti-influenza A virus, protein tyrosine phosphatase (PTP) inhibitory, and anti-Vibrio activities. Among them, the anti-influenza mechanism of compounds 1, 2, and 7 was further investigated using neuraminidase inhibitory assay, molecular docking, and reverse genetics methods, suggesting that 1, 2, and 7 could interact with Arg371 of the viral neuraminidase. The structure-activity relationship (SAR) of PTPs inhibitory activity for indole-diterpene derivatives (1, 2, 4, 5, 9-16, and 19-21) was also summarized.

Application of stereotactic biopsy for diagnosing intracranial lesions in patients with AIDS in China: Report of 7 cases.

RATIONALE: The aim of the study was to evaluate stereotactic biopsy for diagnosing intracranial lesions in patients with AIDS. PATIENT CONCERNS: Seven AIDS patients with an intracranial lesion who underwent stereotactic biopsy were included in this retrospective study (4 males and 3 females, 15 to 49 years old). The patients' disease history ranged from 1 month to 1 year. The samples were examined by hematoxylin-eosin (HE) staining and immunohistochemical examination. DIAGNOSES, INTERVENTIONS AND OUTCOMES: All patients were successfully sampled, and the histological results showed inflammation in 4 cases, toxoplasma gondii infection in 1 case, astrocytoma in 1 case, and abscess in 1 case. The clinical diagnosis included toxoplasma encephalitis (TE) in 2 cases, cryptococcus encephalitis in 2 cases, cytomegalovirus (CMV) encephalitis in 2 case, tubercular abscess in 1 case, astrocytoma in 1 case, and co-infection of TE with Cryptococcus infection in 1 patient. The clinical diagnosis was made according to the plasma and cerebrospinal fluid (CSF) laboratory testing, the imaging data and the histological findings. The diagnostic yield was 100%, and the post-operation morbidity was 14.3% (1/7) with an asymptomatic haemorrhage and seizure in 1 case. There was no operation-related mortality. Patients were followed up for 6 months to 6 years; 1 case fully recovered, 4 cases significantly improved in symptoms, and 2 died. LESSONS: Stereotactic biopsy is a safe and effective way of diagnosing intracranial lesions in patient with AIDS. It is helpful for the differential diagnosis and for choosing a suitable therapy. Due to the broad spectrum of nervous system abnormalities in AIDS, histological findings are very valuable. However, histology is not a unique tool for making a definite diagnosis, whereas the combination of molecular pathology and stereotactic biopsy should play a more important role in the future.