LncRNA-Mediated TPI1 and PKM2 Promote Self-Renewal and Chemoresistance in GBM.

Temozolomide (TMZ) resistance is one of the major reasons for poor prognosis in patients with glioblastoma (GBM). Long noncoding RNAs (lncRNAs) are involved in multiple biological processes, including TMZ resistance. Linc00942 is a potential regulator of TMZ sensitivity in GBM cells is shown previously. However, the underlying mechanism of TMZ resistance induced by Linc00942 is unknown. In this study, the sequence of Linc00942 by rapid amplification of cDNA ends assay in TMZ-resistant GBM cells is identified and confirmed that Linc00942 contributes to self-renewal and TMZ resistance in GBM cells. Chromatin isolation by RNA purification followed by mass spectrometry (ChIRP-MS) and followed by Western blotting (ChIRP-WB) assays shows that Linc00492 interacted with TPI1 and PKM2, subsequently promoting their phosphorylation, dimerization, and nuclear translocation. The interaction of Linc00942 with TPI1 and PKM2 leads to increased acetylation of H3K4 and activation of the STAT3/P300 axis, resulting in the marked transcriptional activation of SOX9. Moreover, the knockdown of SOX9 reversed TMZ resistance induced by Linc00492 both in vitro and in vivo. In summary, Linc00942 strongly promotes SOX9 expression by interacting with TPI1 and PKM2 is found, thereby driving self-renewal and TMZ resistance in GBM cells. These findings suggest potential combined therapeutic strategies to overcome TMZ resistance in patients with GBM.

Successful Treatment of Eruptive Pruritic Papular Porokeratosis in the Elderly with Tofacitinib: A Case Report.

Eruptive pruritic papular porokeratosis (EPPP) is a rare subtype of porokeratosis that presents as an acute exacerbation of an annular papule with a distinct peripheral hyperkeratotic ridge border and severe pruritus. EPPP is mainly reported in elderly East Asian men. Its etiology and pathogenesis are unknown. We hereby present a case report of EPPP in a 68-year-old Chinese male with persistent circumscribed papules on the extremities, accompanied by severe pruritus for one year. After the patient was given conventional medication, a new rash appeared on the patient's extremities and he felt intense itching in the area of the rash. The patient was switched to oral tofacitinib treatment. The patient felt that the pruritus had largely disappeared after one month of oral dosing, leaving only brown pigmentation on the erythema of the extremities. The patient has been off the drug for 2 months. There was no pruritus or new rash during the follow-up period.

Pseudo-Kaposi's Sarcoma: A Rare Case and Review.

Our report concerns a 72-year-old female patient who presented with nodular ulcers on her right lower extremity and foot for a duration of 5 months. Based on the results of a dermatological examination, histopathological examination of the lesions, and immunohistochemical findings, we were able to diagnose the patient with Mari-type pseudocaposi sarcoma. Further research allowed us to clarify the distinction between this type of sarcoma and Kaposi's sarcoma, which will be crucial in devising an effective treatment plan for the patient as we continue to monitor her progress during clinical supervision.

Development and validation of a pyroptosis-related genes signature for risk stratification in gliomas.

Background: Glioma is a highly heterogeneous disease, causing the prognostic prediction a challenge. Pyroptosis, a programmed cell death mediated by gasdermin (GSDM), is characterized by cell swelling and the release of inflammatory factors. Pyroptosis occurs in several types of tumor cells, including gliomas. However, the value of pyroptosis-related genes (PRGs) in the prognosis of glioma remains to be further clarified. Methods: In this study, mRNA expression profiles and clinical data of glioma patients were acquired from TCGA and CGGA databases, and one hundred and eighteen PRGs were obtained from the Molecular Signatures Database and GeneCards. Then, consensus clustering analysis was performed to cluster glioma patients. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to establish a polygenic signature. Functional verification of the pyroptosis-related gene GSDMD was achieved by gene knockdown and western blotting. Moreover, the immune infiltration status between two different risk groups were analyzed through the "gsva" R package. Results: Our results demonstrated that the majority of PRGs (82.2%) were differentially expressed between lower-grade gliomas (LGG) and glioblastoma (GBM) in the TCGA cohort. In univariate Cox regression analysis, eighty-three PRGs were shown to be associated with overall survival (OS). A five-gene signature was constructed to divide patients into two risk groups. Compared with patients in the low-risk group, patients in the high-risk group had obviously shorter OS (p < 0.001). Also, we found that the high-risk group showed a higher infiltrating score of immune cells and immune-related functions. Risk score was an independent predictor of OS (HR > 1, p < 0.001). Furthermore, knockdown of GSDMD decreased the expression of IL-1ß and cleaved caspase-1. Conclusion: Our study constructed a new PRGs signature, which can be used to predict the prognosis of glioma patients. Targeting pyroptosis might serve as a potential therapeutic strategy for glioma.

Glioblastoma Cell-Derived lncRNA-Containing Exosomes Induce Microglia to Produce Complement C5, Promoting Chemotherapy Resistance.

Glioblastoma (GBM), the most common malignant primary brain cancer in adults, nearly always becomes resistant to current treatments, including the chemotherapeutic temozolomide (TMZ). The long noncoding RNA (lncRNA) TMZ-associated lncRNA in GBM recurrence (lnc-TALC) promotes GBM resistance to TMZ. Exosomes can release biochemical cargo into the tumor microenvironment (TME) or transfer their contents, including lncRNAs, to other cells as a form of intercellular communication. In this study, we found that lnc-TALC could be incorporated into exosomes and transmitted to tumor-associated macrophages (TAM) and could promote M2 polarization of the microglia. This M2 polarization correlated with secretion of the complement components C5/C5a, which occurred downstream of lnc-TALC binding to ENO1 to promote the phosphorylation of p38 MAPK. In addition, C5 promoted the repair of TMZ-induced DNA damage, leading to chemotherapy resistance, and C5a-targeted immunotherapy showed improved efficacy that limited lnc-TALC-mediated TMZ resistance. Our results reveal that exosome-transmitted lnc-TALC could remodel the GBM microenvironment and reduce tumor sensitivity to TMZ chemotherapy, indicating that the lnc-TALC-mediated cross-talk between GBM cells and microglia could attenuate chemotherapy efficacy and pointing to potential combination therapy strategies to overcome TMZ resistance in GBM.See related Spotlight by Zhao and Xie, p. 1372.

Epidemiological analysis of 67 local COVID-19 clusters in Sichuan Province, China.

BACKGROUND: This study was intended to investigate the epidemiological characteristics of COVID-19 clusters and the severity distribution of clinical symptoms of involved cases in Sichuan Province, so as to provide information support for the development and adjustment of strategies for the prevention and control of local clusters. METHODS: The epidemiological characteristics of 67 local clusters of COVID-19 cases in Sichuan Province reported as of March 17, 2020 were described and analyzed. Information about all COVID-19 clusters and involved cases was acquired from the China Information System for Disease Control and Prevention and analyzed with the epidemiological investigation results taken into account. RESULTS: The clusters were temporally and regionally concentrated. Clusters caused by imported cases from other provinces accounted for 73.13%; familial clusters accounted for 68.66%; the average attack rate was 8.54%, and the average secondary attack rate was 6.11%; the median incubation period was 8.5 d; a total of 28 cases met the criteria for incubation period determination, and in the 28 cases, the incubation period was > 14 d in 21.43% (6/28). a total of 226 confirmed cases were reported in the 67 clusters. Ten cases were exposed before the confirmed cases they contacted with developed clinical symptoms, and the possibility of exposure to other infection sources was ruled out; two clusters were caused by asymptomatic carriers; confirmed cases mainly presented with fever, respiratory and systemic symptoms; a gradual decline in the severity of clinical symptoms was noted with the increase of the case generation. CONCLUSIONS: Population movement and gathering restrictions and strict close contact management measures will significantly contribute to the identification and control of cases. Transmission during the incubation period and asymptomatic infections have been noted. Studies on the pathogenicity and transmissibility in these populations and on COVID-19 antibody levels and protective effects in healthy people and cases are required.

Immunogenomic analysis reveals LGALS1 contributes to the immune heterogeneity and immunosuppression in glioma.

Mutualistic and dynamic communication between tumour cells and the surrounding microenvironment accelerates the initiation, progression, chemoresistance and immune evasion of glioblastoma (GBM). However, the immunosuppressive mechanisms of GBM has not been thoroughly elucidated to date. We enrolled six microenvironmental signatures to identify glioma microenvironmental genes. The functional enrichment analysis such as ssGSEA, ESTIMATE algorithm, Gene Ontology, Pathway analysis is conducted to discover the potential function of microenvironmental genes. In vivo and in vitro experiments are used to verify the immunologic function of LGALS1 in GBM. We screen eight glioma microenvironmental genes from glioma databases, and discover a key immunosuppressive gene (LGALS1 encoding Galectin-1) exhibiting obviously prognostic significance among glioma microenvironmental genes. Gliomas with different LGALS1 expression have specific genomic variation spectrums. Immunosuppression is a predominate characteristic in GBMs with high expression of LGALS1. Knockdown of LGALS1 remodels the GBM immunosuppressive microenvironment by down regulating M2 macrophages and myeloid-derived suppressor cells (MDSCs), and inhibiting immunosuppressive cytokines. Our results thus implied an important role of microenvironmental regulation in glioma malignancy and provided evidences of LGALS1 contributing to immunosuppressive environment in glioma and that targeting LGALS1 could remodel immunosuppressive microenvironment of glioma.