Although the telomeric sequence has been reported to form various G-quadruplex topologies in vitro and in Xenopus laevis oocytes, in living human cells, the topology of telomeric DNA G-quadruplex ...remains a challenge. To investigate the human telomeric DNA G-quadruplex in a more realistic human cell environment, in the present study, we demonstrated that the telomeric DNA sequence can form two hybrid-type and two-tetrad antiparallel G-quadruplex structures by in-cell 19F NMR in living human cells (HELA CELLS). This result provides valuable information for understanding the structures of human telomeric DNA in living human cells and for the design of new drugs that target telomeric DNA.
Cadmium is an endocrine disruptor, impairing male reproduction. The objective of this study is to investigate whether cadmium affects rat Leydig cell regeneration and to dissect the underlying ...mechanism. Adult male Sprague-Dawley rats received a single intraperitoneal injection (i.p.) of 0, 0.5 or 1.0 mg/kg of cadmium chloride, followed by ethane dimethane sulfonate (EDS) treatment to eliminate adult Leydig cells 20 days later. Compared to control (0 dose), cadmium treatment reduced serum testosterone levels by days 21, 35, and 56 after EDS treatment. Serum luteinizing hormone (LH) levels were also affected by day 56, the only time point examined. There were fewer regenerated Leydig cells in the cadmium-treated testis on days 35 and 56 after EDS treatment. Further studies demonstrated that the mRNA or protein levels of Leydig (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, and Hsd11b1), non-Leydig (Fshr and Dhh), and gonadotroph (Lhb) cells were also significantly lower in cadmium-treated animals. Since LH and desert hedgehog (DHH) are critical factors for Leydig cell differentiation, our result demonstrated that the lower doses of cadmium exposure, even briefly, may permanently damage Leydig cell regeneration.
This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase.
A retrospective study of COVID-19 patients at the Fifth Affiliated Hospital ...of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-min walking distance (6MWD) and high resolution CT being collected at 30 days after discharged.
Fifty-seven patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p = 0.019), higher lung total severity score (TSS) and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit.
Impaired diffusing-capacity, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.
Background Long noncoding RNAs (lncRNAs) have emerged as critical players in cancer progression, but their functions in colorectal cancer (CRC) metastasis have not been systematically clarified. ...Methods lncRNA expression profiles in matched normal and CRC tissue were checked using microarray analysis. The biological roles of a novel lncRNA, namely RP11-138 J23.1 (RP11), in development of CRC were checked both in vitro and in vivo. Its association with clinical progression of CRC was further analyzed. Results RP11 was highly expressed in CRC tissues, and its expression increased with CRC stage in patients. RP11 positively regulated the migration, invasion and epithelial mesenchymal transition (EMT) of CRC cells in vitro and enhanced liver metastasis in vivo. Post-translational upregulation of Zeb1, an EMT-related transcription factor, was essential for RP11-induced cell dissemination. Mechanistically, the RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m.sup.6A methylation was involved in the upregulation of RP11 by increasing its nuclear accumulation. Clinical analysis showed that m.sup.6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of CRC. Conclusions m.sup.6A-induced lncRNA RP11 can trigger the dissemination of CRC cells via post-translational upregulation of Zeb1. Considering the high and specific levels of RP11 in CRC tissues, our present study paves the way for further investigations of RP11 as a predictive biomarker or therapeutic target for CRC. Keywords: LncRNA RP11, CRC, Zeb1, m.sup.6A, hnRNPA2B1, Cell dissemination
ObjectiveTo study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients.DesignWe analysed epidemiological, demographic, clinical and laboratory data of 95 ...cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues.ResultsAmong the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients.ConclusionsGI tract may be a potential transmission route and target organ of SARS-CoV-2.
Autophagy is a genetically well-controlled cellular process that is tightly controlled by a set of core genes, including the family of autophagy-related genes (ATG). Autophagy is a "double-edged ...sword" in tumors. It can promote or suppress tumor development, which depends on the cell and tissue types and the stages of tumor. At present, tumor immunotherapy is a promising treatment strategy against tumors. Recent studies have shown that autophagy significantly controls immune responses by modulating the functions of immune cells and the production of cytokines. Conversely, some cytokines and immune cells have a great effect on the function of autophagy. Therapies aiming at autophagy to enhance the immune responses and anti-tumor effects of immunotherapy have become the prospective strategy, with enhanced antigen presentation and higher sensitivity to CTLs. However, the induction of autophagy may also benefit tumor cells escape from immune surveillance and result in intrinsic resistance against anti-tumor immunotherapy. Increasing studies have proven the optimal use of either ATG inducers or inhibitors can restrain tumor growth and progression by enhancing anti-tumor immune responses and overcoming the anti-tumor immune resistance in combination with several immunotherapeutic strategies, indicating that induction or inhibition of autophagy might show us a prospective therapeutic strategy when combined with immunotherapy. In this article, the possible mechanisms of autophagy regulating immune system, and the potential applications of autophagy in tumor immunotherapy will be discussed.
Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can ...promote or suppress tumor development, so it is a "double-edged sword" in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.
Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal ...hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and the TCA cycle, therefore suppressing the growth of leukemia cells. High PMI expression was also a poor prognostic factor for acute myeloid leukemia. Our findings reveal a new mechanism for glucose starvation resistance in leukemia. Furthermore, the combination of PMI suppression and mannose loading has potential as a novel treatment for driver oncogene‐independent leukemia.
Leukemia cells utilize mannose as a glycolytic energy source under glucose starvation. High PMI expression is associated with poor prognosis in acute myeloid leukemia due to energy starvation resistance and anticancer drug resistance. Mannose load that exceeds the processing capacity of PMI inhibits leukemia cell proliferation and energy metabolism.
In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 novel coronavirus (2019-nCoV) were reviewed, with emphasis on identifying and ...characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease, as manifested by increasing extent and density of lung opacities.
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