The long-chain fatty acyl CoA synthetase (ACSLs) family of enzymes contributes significantly to lipid metabolism and produces acyl-coenzyme A by catalyzing fatty acid oxidation. The dysregulation of ACSL3 and ACSL4, which belong to the five isoforms of ACSLs, plays a key role in cancer initiation, development, metastasis, and tumor immunity and may provide several possible therapeutic strategies. Moreover, ACSL3 and ACSL4 are crucial for ferroptosis, a non-apoptotic cell death triggered by the accumulation of membrane lipid peroxides due to iron overload. Here, we present a summary of the current knowledge on ACSL3 and ACSL4 and their functions in various cancers. Research on the molecular mechanisms involved in the regulation of ferroptosis is critical to developing targeted therapies for cancer.
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. Methods: In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. Results: To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. Conclusions: Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.
Erianin, a natural product derived from Dendrobium chrysotoxum Lindl, has been proved to play antitumor activity in various cancers. However, the effects and molecular mechanisms of erianin in bladder cancer cells remain unexplored. In this study, we found that erianin triggered cell death and cell cycle arrest in bladder cancer cells. Then we demonstrated that erianin could promote the accumulation of lethal lipid-based reactive oxygen species (ROS) and the depletion of glutathione (GSH), suggesting the induction of ferroptosis. In the further study, the ferroptosis inhibitor deferoxamine (DFO), N-Acetylcysteine (NAC) and GSH but not necrostatin-1, CQ or Z-VAD-FMK rescued erianin-caused cell death, showing ferroptosis played a major role in erianin-caused cell death. In vivo, we also showed that erianin suppressed the tumor growth by inducing ferroptosis. Mechanistically, we demonstrated that nuclear factor E2-related factor 2 (NRF2) inactivation was a key determinant of ferroptosis caused by erianin. In bladder cancer cells, the compound tert-butylhydro-quinone (TBHQ), an activator of NRF2, suppressed erianin-induced ferroptosis. Whereas, NRF2 inhibition used shRNA augmented the ferroptosis response induced by erianin treatment. In conclusion, our data provide the first evidence that erianin can initiate ferroptosis-like cell death and lipid peroxidation in bladder cancer, which will hopefully become a promising anticancer compound for the treatment of bladder cancer.
Background: We aim to investigate the profile of acute antibody response in COVID-19 patients, and provide proposals for the usage of antibody test in clinical practice. Methods: A multi-center cross-section study (285 patients) and a single-center follow-up study (63 patients) were performed to investigate the feature of acute antibody response to SARS-CoV-2. A cohort of 52 COVID-19 suspects and 64 close contacts were enrolled to evaluate the potentiality of the antibody test. Results: The positive rate for IgG reached 100% around 20 days after symptoms onset. The median day of seroconversion for both lgG and IgM was 13 days after symptoms onset. Seroconversion of IgM occurred at the same time, or earlier, or later than that of IgG. IgG levels in 100% patients (19/19) entered a platform within 6 days after seroconversion. The criteria of ‘IgG seroconversion’ and ‘> 4-fold increase in the IgG titers in sequential samples’ together diagnosed 82.9% (34/41) of the patients. Antibody test aided to confirm 4 patients with COVID-19 from 52 suspects who failed to be confirmed by RT-PCR and 7 patients from 148 close contacts with negative RT-PCR. Conclusion: IgM and IgG should be detected simultaneously at the early phase of infection. The serological diagnosis criterion of seroconversion or the ‘>; 4-fold increase in the IgG titer’ is suitable for a majority of COVID-19 patients. Serologic test is helpful for the diagnosis of SARS-CoV-2 infection in suspects and close contacts.
Docetaxel-based chemotherapy can lead to fluid retention and secondary peripheral edema of the extremities, but its association with lymphedema remains unclear. In this study, we retrospectively investigated the relationship between adjuvant docetaxel-based chemotherapy and breast cancer-related lymphedema. Patients with stage II/III breast cancer who received adjuvant chemotherapy were evaluated for lymphedema on the basis of arm circumference measurements. The incidence and risk factors of lymphedema were determined by Kaplan–Meier and Cox proportional hazard analyses. A total of 320 patients were included. Specifically, 182 patients received docetaxel and 138 patients did not receive docetaxel. Compared with docetaxel-free chemotherapy, docetaxel-based chemotherapy significantly increased the 2.5-year cumulative incidence of all-grade lymphedema (19.91 vs. 32.09%; P=0.011), which was further verified in grade 1–2 (P=0.012), but not in grade 3 lymphedema (P=0.448). Similar results were found in a comparison between docetaxel and nontaxane, but not in a comparison between docetaxel and other taxanes. Multivariate analysis showed that docetaxel-based chemotherapy is an independent risk factor for both all-grade (hazard ratio=1.73; P=0.017) and grade 1–2 lymphedema (hazard ratio=1.87; P=0.022). In conclusion, adjuvant docetaxel-based chemotherapy significantly increased the risk of breast cancer-related lymphedema.
Oesophageal cancer is a malignant tumor with high morbidity and mortality. Surgical treatment, radiotherapy, and chemotherapy are the most common treatment methods for oesophageal cancer. However, traditional chemotherapy drugs have poor targeting performance and cause serious adverse drug reactions. In this study, a GSH-sensitive material, ATRA-SS-HA, was developed and self-assembled with curcumin, a natural polyphenol antitumor drug, into nanomicelles Cur@ATRA-SS-HA. The micelles had a suitable particle size, excellent drug loading, encapsulation rate, stability, biocompatibility, and stable release behaviour. In the tumor microenvironment, GSH induced disulfide bond rupture in Cur@ATRA-SS-HA and promoted the release of curcumin, improving tumor targeting. Following GSH-induced release, the curcumin IC50 value was significantly lower than that of free curcumin and better than that of 5-FU. In vivo pharmacokinetic experiments showed that the drug-loaded nanomicelles exhibited better metabolic behaviour than free drugs, which greatly increased the blood concentration of curcumin and increased the half-life of the drug. The design of the nanomicelle provides a novel clinical treatment for oesophageal cancer.