Yancheng First People's Hospital

BACKGROUND: We aimed to report the clinical characteristics of imported cases of coronavirus disease 2019 (COVID-19) in Jiangsu Province. METHODS: We retrospectively investigated the clinical, imaging, and laboratory characteristics of confirmed cases of COVID-19 with World Health Organization interim guidance in 3 grade IIIA hospitals of Jiangsu from 22 January to 14 February 2020. Real-time RT-PCR was used to detect the new coronavirus in respiratory samples. RESULTS: Of the 80 patients infected with COVID-19, 41 were female, with a median age of 46.1 years. Except for 3 severe patients, the rest of the 77 patients exhibited mild or moderate symptoms. Nine patients were unconfirmed until a third nucleic acid test; 38 cases had a history of chronic diseases. The main clinical manifestations of the patients were fever and cough, which accounted for 63 (78.75%) and 51 (63.75%) cases, respectively. Only 3 patients (3.75%) showed liver dysfunction. Imaging examination showed that 55 patients (68.75%) showed abnormal density shadow and 25 cases (31.25%) had no abnormal density shadow in the parenchyma of both lungs. Currently, 21 cases have been discharged from the hospital, and no patient died. The average length of stay for discharged patients was 8 days. CONCLUSIONS: Compared with the cases in Wuhan, the cases in Jiangsu exhibited mild or moderate symptoms and no obvious gender susceptibility. The proportion of patients having liver dysfunction and abnormal CT imaging was relatively lower than that in Wuhan. Notably, infected patients may be falsely excluded based on 2 consecutively negative respiratory pathogenic nucleic acid test results.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

BACKGROUND: At present, the severity of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a focal point. METHODS: To assess the factors associated with severity and prognosis of patients infected with SARS-CoV-2, we retrospectively investigated the clinical, imaging and laboratory characteristics of confirmed 280 cases of novel coronavirus disease (COVID-19) from 20 January to 20 February 2020. RESULTS: The median age of patients in the mild group was 37.55 years, whilst that in the severe group was 63.04 years. The proportion of patients aged over 65 years in the severe group was significantly higher than that of the mild group (59.04% vs. 10.15%, P < 0.05). 85.54% of severe patients had diabetes or cardiovascular diseases, which was significantly higher than that of the mild group (51.81% vs. 7.11%, P = 0.025; 33.73% vs. 3.05%, P = 0.042). Patients in the mild group experienced earlier initiation of antiviral treatment (1.19 ± 0.45 vs. 2.65 ± 1.06 days in the severe group, P < 0.001). Our study showed that comorbidity, time from illness onset to antiviral treatment and age >=65 were three major risk factors for COVID-19 progression, whilst comorbidity and time from illness onset to antiviral treatment were two major risk factors for COVID-19 recovery. CONCLUSIONS: The elderly and patients with underlying diseases are more likely to experience a severe progression of COVID-19. It is recommended that timely antiviral treatment should be initiated to slow the disease progression and improve the prognosis.

The emergence of disseminated metastases remains the primary cause of mortality in cancer patients. Formation of the pre-metastatic niche (PMN), which precedes the establishment of tumor lesions, is critical for metastases. Bone marrow-derived myeloid cells (BMDCs) are indispensable for PMN formation. Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells that accumulate in patients with cancer and appear in the early PMN. The mechanisms by which MDSCs establish the pre-metastatic microenvironment in distant organs are largely unknown, although MDSCs play an essential role in metastasis. Here, we summarize the key factors associated with the recruitment and activation of MDSCs in the PMN and review the mechanisms by which MDSCs regulate PMN formation and evolution. Finally, we predict the potential value of MDSCs in PMN detection and therapy.

Cancer stem cells play a critical role in colorectal cancer (CRC) progression. Myeloid-derived suppressor cells (MDSCs) promote tumor progression through multiple mechanisms in CRC. The roles of MDSCs in CRC cell stemness are unclear. MDSC-derived exosomes are proposed to act as intercellular messengers. Herein, it is reported that granulocytic MDSCs (G-MDSCs) promote CRC cell stemness and progression in mice through exosomes. It is found that S100A9, is highly expressed in G-MDSC-derived exosomes, and its blockade suppresses CRC cell stemness and the susceptibility of mice to AOM/DSS-induced colitis-associated colon cancer. Hypoxia induces G-MDSCs to secrete more exosomes in a hypoxia-inducible factor 1α (HIF-1α)-dependent manner, and respiratory hyperoxia can reduce CRC cells stemness through the inhibition of GM-Exo production. Study-based CRC patients also show that human MDSCs enhance CRC cell stemness and growth via exosomal S100A9, and plasma exosomal S100A9 level in CRC patients is markedly higher than that in healthy subjects. Thus, this study suggests that G-MDSCs promote CRC cell stemness and growth through exosomal S100A9. Moreover, respiratory hyperoxia may be a beneficial strategy to reduce CRC cells stemness through the inhibition of GM-Exo production. MDSCs exosomal S100A9 may be a marker for predicting the development of CRC.

// Lingshuang L&uuml; 1, * , Jian Sun 2, * , Peiyi Shi 1 , Weimin Kong 2 , Kun Xu 3 , Biyu He 3 , Simin Zhang 1, 3 and Jianming Wang 1 1 Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China 2 Department of Thoracic Surgery, The First People&prime;s Hospital of Yancheng City, Yancheng, 224001, China 3 Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China * These authors have contributed equally to this work Correspondence to: Jianming Wang, email: jmwang@njmu.edu.cn Keywords: breast cancer, RNA, noncoding RNA, circRNA, biomarker Received: December 14, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: April 03, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: April 21, 2017 ABSTRACT Endogenous noncoding circular RNAs (circRNAs) have gained attention for their involvement in carcinogenesis, but their expression pattern in breast cancer has remained largely unknown. In this two-stage study, we first used an Arraystar Human circRNA Array to construct a genome-wide circRNA profile. We then selected candidate circRNAs for validation using a quantitative real-time polymerase chain reaction system. CircRNA/miRNA interactions were predicted and sequence analyses were performed. Among 1155 differentially expressed circRNAs, 715 were upregulated and 440 were downregulated in breast cancer tissues. The validation study demonstrated that hsa_circ_103110, hsa_circ_104689 and hsa_circ_104821 levels were elevated in breast cancer tissues, whereas hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were downregulated. These circRNAs targeted complementary miRNA response elements. The area under the receiver operating characteristic curve for distinguishing breast cancer was 0.82 (95% CI: 0.73-0.90) when hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were used in combination. This study provides evidence that circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs.

Human AlkB homolog H5 (ALKBH5) is a primary m6A demethylase, which is dysregulated and acts as a biological and pharmacological role in human cancers or non-cancers. ALKBH5 plays a dual role in various cancers through regulating kinds of biological processes, such as proliferation, migration, invasion, metastasis and tumor growth. In addition, it takes a great part in human non-cancer, including reproductive system diseases. The underlying regulatory mechanisms of ALKBH5 that relys on m6A-dependent modification are implicated with long non-coding RNA, cancer stem cell, autophagy and hypoxia. ALKBH5 is also an independent prognostic indicator in various cancers. In this review, we summarized the current evidence on ALKBH5 in diverse human cancers or non-cancers and its potential as a prognostic target.

This study aimed to analyze the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension. Randomized controlled trials (RCTs) that evaluated the effect of CPAP on BP in patients with OSA and resistant hypertension, indexed in MEDLINE, Embase, and the Cochrane Library from inception until March 20, 2015, were included in the meta-analysis. A total of five RCTs were identified to meet the inclusion criteria. The pooled changes after CPAP treatment for 24-hour ambulatory systolic BP and diastolic BP (DBP) were -4.78 mm Hg (95% confidence interval [CI], -7.95 to -1.61) and -2.95 mm Hg (95% CI, -5.37 to -0.53) in favor of the CPAP group. CPAP was also associated with reduction in nocturnal DBP (mean difference, -1.53 mm Hg, 95% CI, -3.07 to 0). The results indicated a favorable reduction in BP with CPAP treatment in patients with OSA and resistant hypertension.

BACKGROUND: Both outdoor air pollution and extreme temperature have been associated with daily mortality; however, the effect of their interaction is not known. METHODS: This time-series analysis examined the effect of the interaction between outdoor air pollutants and extreme temperature on daily mortality in Shanghai, China. A generalized additive model (GAM) with penalized splines was used to analyze mortality, air pollution, temperature, and covariate data. The effects of air pollutants were stratified by temperature stratum to examine the interaction effect of air pollutants and extreme temperature. RESULTS: We found a statistically significant interaction between PM₁₀/O₃ and extreme low temperatures for both total nonaccidental and cause-specific mortality. On days with "normal" temperatures (15th-85th percentile), a 10-µg/m³ increment in PM₁₀ corresponded to a 0.17% (95% CI: 0.03%, 0.32%) increase in total mortality, a 0.23% (0.02%, 0.44%) increase in cardiovascular mortality, and a 0.26% (-0.07%, 0.60%) increase in respiratory mortality. On low-temperature days (<15th percentile), the estimates changed to 0.40% (0.21%, 0.58%) for total mortality, 0.49% (0.13%, 0.86%) for cardiovascular mortality, and 0.24% (-0.33%, 0.82%) for respiratory mortality. The interaction pattern of O₃ with lower temperature was similar. The interaction between PM₁₀/O₃ and lower temperature remained robust when alternative cut-points were used for temperature strata. CONCLUSIONS: The acute health effects of air pollution might vary by temperature level.

Over the past several years, long non-coding RNAs (lncRNAs) have attracted more and more attention due to their special functions. They are vital biomarkers in multiple diseases. LncRNA HOMEOBOX A11 (HOXA11) has been found to be aberrantly expressed in some kinds of malignant tumors. In this study, we mainly discuss the oncogenic role of it in promoting malignant progression and chemoresistance in lung adenocarcinoma (LUAD) cells. The expression of HOXA11-AS was much stronger in cisplatin-resistant LUAD cells. Based on The Cancer Genome Atlas database, patients with high expression of HOXA11-AS had shorter survival time. Additionally, knockdown of HOXA11-AS caused positive changes in cell activities of LUAD. For example, cell proliferation and migration were weakened, the epithelial mesenchymal transition process was reversed, and apoptosis was induced. These changes were more obvious in cells treated with cisplatin. Next, the HOXA11-AS/miR-454-3p/Stat3 (signal transducer and activator of transcription 3) pathway was found to influence the cisplatin resistance of LUAD cells. HOXA11-AS specifically acted as a competing endogenous RNA (ceRNA) in LUAD cells. The combinations among these three genes were demonstrated. Finally, rescue assays were applied to demonstrate the ceRNA pattern consisting of HOXA11-AS, miR-454-3p and Stat3. In conclusion, lncRNA HOXA11-AS acted as a ceRNA to promote cisplatin resistance of human LUAD cells via the miR-454-3p/Stat3 axis.

Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3 (STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-κB) and 22q13.1 (RPL3/SYNGR1). We also identified variants in IL21, IL21R, CD28/CTLA4/ICOS, CD58, ARID3A and IL16 as novel PBC risk loci. These new findings and histochemical studies showing enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic portal tracks) support a disease mechanism in which the deregulation of the IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation are critical components in the development of PBC.

The aim of this meta-analysis is to examine the effects of dexmedetomidine on serum inflammatory markers when administered perioperatively. We searched multiple electronic databases for relevant research papers, and carried out meta-analyses of weighted mean differences and interpreted in the light of statistical heterogeneity (I(2)). Fifteen RCTs recruiting 641 patients were included. Dexmedetomidine treatment significantly decreased interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-α) levels with mean differences [95% CI] in the changes from baseline between dexmedetomidine treated and controls of -25.14 [-35.29, -15.00]; P < 0.00001 (for IL-6), -5.69 [-10.77, -0.60]; P < 0.04 (for IL-8), and -20.30 [-30.93, -9.67]; P < 0.0002 (for TNF-α) immediately after surgery; and -41.55 [-57.41, -25.70]; P < 0.00001 (IL-6), -6.46 [-10.83, -2.08]; P < 0.005 (IL-8), and -14.67 [-22.61, -6.73]; P < 0.0003 (TNF-α) on postoperative day 1 (random effects). IL-10 levels were found to increase significantly a day after surgery (8.33 [3.31, 13.36]; P = 0.001). Subgroup analyses did not reveal significant differences. In conclusion, perioperative adjunctive use of dexmedetomidine substantially decreases serum IL-6, IL-8 and TNF-α levels.

Glioblastoma (GBM) is a complex ecosystem that includes a heterogeneous tumor population and the tumor-immune microenvironment (TIME), prominently containing tumor-associated macrophages (TAM) and microglia. Here, we demonstrated that β2-microglobulin (B2M), a subunit of the class I major histocompatibility complex (MHC-I), promotes the maintenance of stem-like neoplastic populations and reprograms the TIME to an anti-inflammatory, tumor-promoting state. B2M activated PI3K/AKT/mTOR signaling by interacting with PIP5K1A in GBM stem cells (GSC) and promoting MYC-induced secretion of transforming growth factor-β1 (TGFβ1). Inhibition of B2M attenuated GSC survival, self-renewal, and tumor growth. B2M-induced TGFβ1 secretion activated paracrine SMAD and PI3K/AKT signaling in TAMs and promoted an M2-like macrophage phenotype. These findings reveal tumor-promoting functions of B2M and suggest that targeting B2M or its downstream axis may provide an effective approach for treating GBM. SIGNIFICANCE: β2-microglobulin signaling in glioblastoma cells activates a PI3K/AKT/MYC/TGFβ1 axis that maintains stem cells and induces M2-like macrophage polarization, highlighting potential therapeutic strategies for targeting tumor cells and the immunosuppressive microenvironment in glioblastoma.

N6-methyladenosine (m6A) modification is the most abundant modification on eukaryotic RNA. In recent years, lots of studies have reported that m6A modification and m6A RNA methylation regulators were involved in cancer progression. However, the m6A level and its regulators in esophageal cancer (ESCA) remain poorly understood. In this study, we analyzed the expression of m6A regulators using The Cancer Genome Atlas (TCGA) data, and found 14 of 19 m6A regulators are significantly increased in ESCA samples. Then we performed a univariate Cox regression analysis and LASSO Cox regression model to investigate the prognostic role of m6A regulators in ESCA, and the results indicated that a two-gene prognostic signature including ALKBH5 and HNRNPA2B1 could predict overall survival (OS) of ESCA patients. Moreover, HNRNPA2B1 is higher expressed in high risk scores subtype of ESCA, indicating that HNRNPA2B1 may be involved in ESCA development. Subsequently, we confirmed that the level of m6A and HNRNPA2B1 was significantly increased in ESCA. We also found that HNRNPA2B1 expression positively correlated with tumor diameter and lymphatic metastasis of ESCA. Moreover, functional study showed that knockdown of HNRNPA2B1 inhibited the proliferation, migration and invasion of ESCA. Mechanistically, we found that knockdown of HNRNPA2B1 inhibited the expression of de novo fatty acid synthetic enzymes, ACLY and ACC1, and subsequently suppressed cellular lipid accumulation. In conclusion, our study provides critical clues to understand the role of m6A and its regulators in ESCA. Moreover, HNRNPA2B1 functions as an oncogenic factor in promoting ESCA progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1, and it may be a promising prognostic biomarker and therapeutic target for human ESCA.

Aptamers are short RNA or DNA oligonucleotides which can bind with different targets. Typically, they are selected from a large number of random DNA sequence libraries. The main strategy to obtain aptamers is systematic evolution of ligands by exponential enrichment (SELEX). Low efficiency is one of the limitations for conventional PCR amplification of random DNA sequence library in aptamer selection because of relative low products and high by-products formation efficiency. Here, we developed emulsion PCR for aptamer selection. With this method, the by-products formation decreased tremendously to an undetectable level, while the products formation increased significantly. Our results indicated that by-products in conventional PCR amplification were from primer-product and product-product hybridization. In emulsion PCR, we can completely avoid the product-product hybridization and avoid the most of primer-product hybridization if the conditions were optimized. In addition, it also showed that the molecule ratio of template to compartment was crucial to by-product formation efficiency in emulsion PCR amplification. Furthermore, the concentration of the Taq DNA polymerase in the emulsion PCR mixture had a significant impact on product formation efficiency. So, the results of our study indicated that emulsion PCR could improve the efficiency of SELEX.

Abstract Given that traditional anticancer therapies fail to significantly improve the prognoses of triple negative breast cancer (TNBC), new modalities with high efficiency are urgently needed. Herein, by mixing the metal‐phenolic network formed by tannic acid (TA), bleomycin (BLM), and Fe 3+ with glutathione peroxidase 4 (GPX4) inhibitor (ML210) loaded hollow mesoporous Prussian blue (HMPB) nanocubes, the HMPB/ML210@TA‐BLM‐Fe 3+ (HMTBF) nanocomplex is prepared to favor the ferroptosis/apoptosis synergism in TNBC. During the intracellular degradation, Fe 3+ /Fe 2+ conversion mediated by TA can initiate the Fenton reaction to drastically upregulate the reactive oxygen species level in cells, subsequently induce the accumulation of lipid peroxidation, and thereby cause ferroptotic cell death; meanwhile, the released ML210 efficiently represses the activity of GPX4 to activate ferroptosis pathway. Besides, the chelation of Fe 2+ with BLM leads to in situ BLM toxification at tumor site, then triggers an effective apoptosis to synergize with ferroptosis for tumor therapy. As a result, the superior in vivo antitumor efficacy of HMTBF is corroborated in a 4T1 tumor‐bearing mice model regarding tumor growth suppression, indicating that the nanoformulations can serve as efficient ferroptosis and apoptosis inducers for use in combinatorial TNBC therapy.

Abstract Background Colorectal cancer (CRC) remains one of the leading causes of cancer-related death. The current study aimed to elucidate the mechanism by which exosomes carrying KRAS mutant contribute to neutrophil recruitment as well as the formation of the neutrophil extracellular trap (NET) in CRC. Methods APC-WT and APC-KRAS G12D mouse models were initially developed. Peripheral blood, spleen, bone marrow (BM) and mesenteric lymph nodes (mLN) were isolated to detect neutrophil content. Then, APC-WT and APC-KRAS G12D mice were injected with exosomes isolated from APC-WT and APC-KRAS G12D mice. The ratio of neutrophils, NETs formation and IL-8 protein content were subsequently quantified in colon tissues. DKs-8 (wild type) and DKO-1 (KRAS mutant) cells were employed for in vitro experimentation. Then, DKs-8 cells were cultured with exosome-treated PMA stimulated neutrophil-forming NETs culture medium, with cell viability, invasion, migration, and adhesion evaluated. Results Compared with APC-WT mice, the numbers of polyps and neutrophils in the peripheral blood, spleen and mLNs were increased in APC-KRAS G12D mice, accompanied with increased NET formation, IL-8 expression and exosomes. Meanwhile, IL-8 upregulation, neutrophil recruitment and NET formation were observed in the mice injected with exosomes derived from APC-KRAS G12D . The in vitro investigation results revealed that more NETs were formed in the presence of DKO-1-Exos, which were inhibited by DNAse. In addition, DKs-8- and DKO-1 cells-derived exosomes could adhere to NETs under static conditions in vitro. Exosomal KRAS mutants were noted to exert stimulatory effects on the IL-8 production and NET formation to promote the growth of CRC cells. Conclusion The results provide evidence suggesting that exosomes may transfer mutant KRAS to recipient cells and trigger increases in IL-8 production, neutrophil recruitment and formation of NETs, eventually leading to the deterioration of CRC.

BACKGROUND: Epithelial cell transformation sequence 2 (ECT2) is upregulated in glioma and promotes glioma cell proliferation. A preliminary experiment showed a positive correlation between ECT2 and pituitary tumor-transforming gene 1 (PTTG1). The aim of this study was to explore how ECT2 affects PTTG1 to influence the proliferation of glioma cells. METHODS: The expression of ECT2 in glioma was detected by western blot and reverse transcription PCR. The effect of ECT2 on glioma proliferation was examined using cell proliferation-related assays and in vivo experiments. The effect of ECT2 on the stability of E2F transcription factor 1 (E2F1) and the expression of PTTG1 were examined by western blot, co-immunoprecipitation, and in vivo ubiquitination assays. RESULTS: ECT2 was upregulated in gliomas and was negatively correlated with prognosis; its downregulation inhibited glioma cell proliferation. Furthermore, ECT2 regulated PTTG1 expression by affecting the stability of E2F1, thereby affecting the glioma cell proliferation. In addition, the deubiquitinating enzyme proteasome 26S subunit, non-ATPase 14 (PSMD14) affected the degradation of E2F1 and regulated the stability of E2F1. Interestingly, ECT2 regulated the expression of PSMD14. CONCLUSION: In this study, we clarify a new mechanism by which ECT2 regulates the expression of PTTG1 and thus affects the proliferation of glioma cells: ECT2 influences the stability of E2F1 by regulating the expression of the deubiquitinating enzyme PSMD14, thereby affecting the expression of PTTG1. Intensive and extensive understanding of the mechanism of ECT2 in glioma proliferation may provide an opportunity for the development of new molecular therapeutic targets for glioma treatment.

Ulcerative colitis (UC) is a chronic, relapsing, remitting, and inflammatory disorder that afflicts millions of people around the world. It carries a substantial economic burden, reducing the quality of life, ability to work, and increasing disability. Conventional medical treatment of UC includes the use of aminosalicylates, corticosteroids, and immunosuppressive drugs. However, these medicines are not always effective due to some serious side effects. Nuclear factor-kappa B (NF-κB) is a key factor in the inflammatory setting and strongly affects the course of mucosal inflammation in UC. This review aims to describe the complex role of NF-κB in UC and discuss existing pharmacological attempts by curcumin for blocking NF-κB activation to develop new therapeutic strategies in UC. Several studies have shown intriguing pharmacologic effects associated with curcumin, which inhibits NF-κB expression by regulating NF-κB/IkB pathway and down-regulation expression of pro-inflammatory cytokines, such as Interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α. The efficacy of curcumin has been confirmed in several experimental models of UC. Furthermore, curcumin significantly induced clinical remission in active mild-to-moderate UC patients and reduced clinical relapse in quiescent UC patients. The inhibitory effects of curcumin on NF-κB and its unrivaled safety profile indicate that it remains effective for the treatment of UC. In addition, curcumin is a nontoxic, inexpensive, and easily available natural polyphenol. In conclusion, curcumin can be used as a potential and safe drug in the management of patients with remission and mild-to-moderate UC.

AIMS: Acyl-CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post-SAH EBI using a rat model of SAH. METHODS: The rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin-1 and Liproxstatin-1) to investigate the role of ferroptosis in EBI. RESULTS: We found that ACSL4 levels in brain tissue increased significantly in post-SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood-brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis. CONCLUSIONS: ACSL4 exacerbated SAH-induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post-SAH EBI.