Silencing UBE2K inhibits the growth of glioma cells by inducing the autophagy-related apoptosis.

Glioma is a central nervous system (CNS) malignant tumor with high heterogeneity and mortality, which severely threatens the health of patients. The overall survival of glioma patients is relatively short and it is critical to identify new molecular targets for developing effective treatment strategies. UBE2K is a ubiquitin conjugating enzyme with oncogenic function in several malignant tumors. However, whether UBE2K participates in gliomas remains unknown. Herein, in glioma cells, UBE2K was found highly expressed in U87 and U251 cells. Subsequently, U87 and U251 cells were transfected with si-UBE2K to silence UBE2K, with the si-NC transfection as the negative control. In both U87 and U251 cells, the cell viability was sharply reduced by transfecting si-UBE2K for 48 and 72 h. Markedly decreased colony number, reduced number of migrated cells and invaded cells, and declined relative wound healing rate were observed in si-UBE2K transfected U87 and U251 cells. Moreover, the Bcl-2 level was markedly reduced, while the Bax and cleaved-caspase-3 levels were sharply increased in U87 and U251 cells after the si-UBE2K transfection. Furthermore, the p62 level was signally declined, while the Beclin-1 and LC-3 II/I levels were greatly increased in U87 and U251 cells by the si-UBE2K transfection. Furthermore, the facilitating effect of si-UBE2K on the apoptosis and autophagy in U87 and U251 cells was abolished by the coculture of 3-MA, an inhibitor of autophagy. Collectively, UBE2K facilitated the in vitro growth of glioma cells, possibly by inhibiting the autophagy-related apoptosis, which might be a promising target for treating glioma.

Audiological outcomes after revision stapes surgeries: a systematic review.

PURPOSE: Revision stapes surgery is a challenging procedure performed in relatively small numbers compared to other middle ear procedures. Despite numerous data on hearing results of different middle ear surgeries, the audiological standards for successful outcome of this procedure are still not clarified. On the basis of well-documented data, we wanted to determine what the expected audiological results and complications are after revision stapes surgery in order to set a realistic threshold for surgical success. METHODS: After the protocol registration in the PROSPERO database, a systematic review was performed in multiple databases (PubMed, Cochrane, Web of Science, Scopus, ScienceOpen, ClinicalTrials.gov, Google Scholar) according to PRISMA guidelines. Twelve articles were reviewed according to the inclusion criteria. A total of 1032 cases were obtained for evaluation. A modified version of Newcastle-Ottawa Scale (NOS) was used to assess publication quality. RESULTS: Average air-bone gap (ABG) gain was 17.3 dB, average air conduction (AC) gain was 17.5 dB. The average postoperative air-bone gap was 11.1 dB. The postoperative ABG distribution was the following 0-10 dB: 53.3%, > 10-20 dB: 28.2%, > 20 dB: 18.5%. SNHL as a surgical complication was described in a total of 17 cases (1.6%), no equilibrium disorder was reported. CONCLUSION: The pooled data suggest that revision stapes surgery is an effective solution after failure of previous stapes surgery. However, the results are clearly inferior to those of primary stapedotomies. Hence, we need to apply different expectations and use different standards in the indication and evaluation of this type of surgery.

Distinct roles of vaccine-induced SARS-CoV-2-specific neutralizing antibodies and T cells in protection and disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) lack cross-reactivity between SARS-CoV species and variants and fail to mediate long-term protection against infection. The maintained protection against severe disease and death by vaccination suggests a role for cross-reactive T cells. We generated vaccines containing sequences from the spike or receptor binding domain, the membrane and/or nucleoprotein that induced only T cells, or T cells and NAbs, to understand their individual roles. In three models with homologous or heterologous challenge, high levels of vaccine-induced SARS-CoV-2 NAbs protected against neither infection nor mild histological disease but conferred rapid viral control limiting the histological damage. With no or low levels of NAbs, vaccine-primed T cells, in mice mainly CD8+ T cells, partially controlled viral replication and promoted NAb recall responses. T cells failed to protect against histological damage, presumably because of viral spread and subsequent T cell-mediated killing. Neither vaccine- nor infection-induced NAbs seem to provide long-lasting protective immunity against SARS-CoV-2. Thus, a more realistic approach for universal SARS-CoV-2 vaccines should be to aim for broadly cross-reactive NAbs in combination with long-lasting highly cross-reactive T cells. Long-lived cross-reactive T cells are likely key to prevent severe disease and fatalities during current and future pandemics.

The D ~ Sense ex-vivo viability assay application in a patient with stage IV lung adenocarcinoma: a case report.

BACKGROUND: The treatment resistance is a problem for lung cancer. In this study, we used a vitro tissue culturing system to select a new therapy strategy for a patient with tyrosine kinase inhibitors (TKIs) resistance. CASE PRESENTATION: A 42-year-old male Asian patient was diagnosed with advanced lung adenocarcinoma harboring an exon 19 deletion in the epidermal growth factor receptor (EGFR) gene. The patient was treated with Gefitinib, resulting in an almost complete remission for over a year. The patient relapsed after 13 months treatment, and received four cycles of chemotherapy. At 20 months, the patient had developed multiple lung metastases and a solitary cerebellar metastasis. An EGFR T790M mutation was identified in the peripheral blood sample. Subsequent treatment with Osimertinib resulted in a complete response of the intracranial metastasis. By 33 months, the patient had developed a mediastinal tumor mass that responded well to local radiotherapy. By 39 months, an EGFR C797S cis-mutation had been identified and the patient was treated with Brigatinib and Cetuximab. By 44 months, the tumor cells from the pleural effusion had been tested for sensitivity against 30 targeted and cytostatic drugs using the D ~ Sense ex-vivo viability assay. The assay identified 8 drugs with moderate to high sensitivity. Combination therapy of Gemcitabin and Lobaplatin had resulted in disease stabilization. CONCLUSIONS: The case showed that individualized treatment aided by D ~ Sense ex-vivo viability assay can be a viable option for patients with advanced lung adenocarcinoma with pleural effusions.

Revision Stapedotomies: The Role of Periprosthetic Scar Tissue Formation in the Development of Unsatisfactory Hearing Results after Stapedotomy

Abstract Introduction Revision stapes surgeries are difficult to perform, and their audiological results are inferior to primary surgeries. Objective Our goal was to identify the most common and most influential postoperative reasons that cause persistent air-bone gap (ABG) after the primary surgery. Our focus was concentrated on the mechanical dysfunctions in the middle ear, with special regard to postoperative adhesion formation. Methods We performed a retrospective case series study with 23 cases that underwent revision stapedotomies. Results A significant improvement was seen in ABG and air conduction levels after surgery. The periprosthetic adhesion formation was seen in 65% of the cases, and it was the primary cause behind the unsatisfactory hearing result in 30% of cases. There was no significant difference in the level of persistent ABGs after the primary surgery, in case of the intratympanic adhesion presence, compared with the presence of other surgical failures. Concerning hearing and ABG gain after revision surgery, the non-inferiority of the negative effect associated with adhesion was shown compared with the other reasons. Conclusion The revision stapedotomy is an efficient treatment option in case of persistent ABG. Periprosthetic adhesions are the most common intratympanic reasons for compromised audiological outcomes after stapedotomy.