Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia.

INTRODUCTION: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML). METHODS: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection. RESULTS: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress. CONCLUSION: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future.

An adolescent with primary cutaneous follicle center lymphoma: a case report and literature review.

Primary cutaneous follicle center lymphoma (PCFCL) differs from follicular lymphoma in biological behavior and molecular profile and is treated as a distinct entity, according to the 5th edition of the World Health Organization classification of hematolymphoid tumors. It is an uncommon cutaneous B-cell lymphoma that is considerably rare in children and adolescents. To date, only 13 cases of individuals younger than 20 years of age have been reported in the literature. The lack of relevant clinical epidemiological data in this population has hampered the investigation of its clinical and diagnostic aspects. Here we report the case of a 17-year-old male with PCFCL, who may be the first PCFCL patient under 20 years of age reported in China. He was admitted to the hospital with a solitary nodule on his face. After complete surgical excision, the patient's facial mass was histologically identified as PCFCL. The patient's prognosis was favorable, with no recurrence at 17 months of follow-up after the surgical resection. We present a case of an adolescent PCFCL patient and systematically review the literature with a view to increase the awareness of the disease and inform the diagnosis and treatment of this age group.

Combined association of dietary fibre and cognitive function with all-cause and cause-specific mortality in older adults.

BACKGROUND: Dietary fibre and cognitive function are associated with the risk of mortality, respectively. Inadequate dietary fibre intake and cognitive impairment frequently co-occur in older adults, but the combined effect of dietary fibre and cognitive function on mortality remains unknown. The study was to investigate the combined effect of dietary fibre and cognitive function on mortality over a 13-year follow-up in a representative of older adults from the U.S. METHODS: We analyzed data from two cycles of the National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2001-2002 with mortality follow-up data through 13 December 2015 obtained from Public-use Linked Mortality Files. Low dietary fibre intake was defined as the lowest quartile of dietary fibre intake. Cognitive impairment was defined as below the median of Digit Symbol Substitution Test. The separate and combined effects of low dietary fibre intake and cognitive impairment on all-cause and cause-specific mortality were assessed in older adults using weighted Cox proportional hazard models adjusting for potential confounders. RESULTS: A total of 2012 participants (weighted sample was 32,765,094) aged 60 years and older were enrolled in the study. After a median follow-up of 13.4 years, 1017 participants (50.4%) were identified as all-cause deaths, including 183 (9.1%) participants dying from cancer, 199 (9.9%) participants dying from cardiovascular disease, and 635 (31.5%) participants dying from non-cancer/non-cardiovascular disease. Participants with low dietary fibre intake and cognitive impairment had nearly twice the risk of all-cause (HR, 2.030; 95% CI, 1.406-2.931) and non-cancer/non-cardiovascular (HR, 2.057; 95% CI, 1.297-3.262) mortality, and over triple cancer (HR, 3.334; 95% CI, 1.685-6.599) mortality, compared to those without both. CONCLUSIONS: The combination of low dietary fibre intake and cognitive impairment was associated with an increased risk of all-cause, cancer and non-cancer/non- cardiovascular mortality in older adults.

Key MessagesThe inadequate dietary fibre intake and cognitive impairment often coexist in older adults, but the combined effect of dietary fibre and cognitive function on mortality is still unknown.This study evaluated the combined effect of dietary fibre and cognitive impairment on mortality among older adults with a 13-year follow-up in the United States, based on the National Health and Nutrition Examination Survey (NHANES).The results provided evidence of the importance of early screening and intervention for dietary fibre intake and cognitive function, and suggested the joint effect of dietary fibre and cognitive function on mortality could be significant for public health in older adults.

Characterization, antioxidativity, and anti-carcinoma activity of exopolysaccharide extract from Rhodotorula mucilaginosa CICC 33013.

The water-soluble exopolysaccharide REPS2-A was isolated and characterized from R. mucilaginosa CICC 33013. REPS2-A was composed of galactose, arabinose, glucose, and mannose at a molar ratio of 63.1:0.2:18.3:18.3, respectively, with a molecular weight of 7.125×106Da. Based on FT-IR, NMR, and methylation analysis, REPS2-A was identified to be a highly branched polysaccharide with a backbone of (1→3)-linkedGal with Man, Gal, and Ara terminals. The branches were identified as (1→2)-linked Glc, (1→4)-linked Man, (1→3)-linked Glc, (1→4,6)-linked Man, and (1→2,3,4)-linked Ara. In addition, REPS2-A exhibited excellent free radical scavenging (DPPH, ABTS, and reducing power) and antitumor activities. These results indicate its activity against growth of the human hepatocarcinoma cell HepG2 with IC50 values of 1.0mg/mL, compared to lower cytotoxic effects on normal human hepatocyte cell L02. Studying the underlying mechanisms indicated that REPS2-A induced both dose- and time-dependent cell cycle arrest at the G1/S phase.

Syringotropic mycosis fungoides responding well to VELP chemotherapy: A case report.

Mycosis fungoides (MF), a low-malignant lymphoproliferative disorder, is the most common type of cutaneous T-cell lymphoma. The current study reported a case of syringotropic MF, a rare variant of MF, which presented with reactive B cell proliferation, lymphoid follicle formation, hair loss and lymphadenopathy. The clinical manifestations of the patient were MF-like lumps. Immunohistochemical staining of AE1/AE3 showed that there were abundant infiltrated lymphocytes surrounding the syringocystadenoma. In addition, the direction of the lymphocyte arrangement was consistent with the meandering direction of syringocystadenoma. The patient did not respond to 1-month narrowband (311-nm) ultraviolet therapy; however, a good response was obtained subsequent to one cycle of chemotherapy with vincristine sulfate, etoposide, L-asparaginase and prednisone acetate (know as the VELP regimen). After 7 days of VELP chemotherapy, the skin lesions were ameliorated, hair loss was improved and lymphadenopathy disappeared. No lymphadenopathy or new skin lesions were observed during 6 months of follow-up.

Relationship between low-density lipoprotein levels on admission and 1-year outcome in patients with acute ST-segment-elevation myocardial infarction.

This study assessed the relationship between low-density lipoprotein cholesterol (LDL-C) levels on admission and the incidence of major adverse cardiovascular events (MACE) in patients with acute ST-segment-elevation myocardial infarction (ASTEMI). Patients with ASTEMI who had a lipid profile tested within 24 hours of symptom onset were enrolled. They were stratified into high and low LDL-C groups according to whether their LDL-C was above (n = 501) or below (n = 575) the median level, respectively. The incidence of MACE, cardiovascular death, non-fatal MI, revascularization, and stroke was compared between the groups at 1 month, 6 months, and 1 year. Survival analysis and Cox proportional hazard analysis were performed. In-hospital use of beta blockers was better in the high than in the low LDL-C group (76.6% vs. 69.7%, p = 0.01). Statin use was significantly higher in the high than in the low LDL-C group during follow-up (86.8% vs. 80.0%, p = 0.003 at1 month; 71.6% vs. 62.4%, p = 0.002 at 6 months; 67.8% vs. 61.2%, p = 0.03 at 1 year). The incidence of MACE on follow-up at 1 month was higher in the low than in the high LDL-C group (12.0% vs. 8.1%, p = 0.04). At 1 year, survival was not significantly different between the groups. Cox proportional hazards analysis indicated that the incidence of MACE was significantly associated with hypertension, current smoking, high-density lipoprotein cholesterol (HDL-C), in-hospital use of beta blockers, and statin use on follow-up (p < 0.01). LDL-C levels on admission in patients with ASTEMI had no significant effect on the 6-month and 1-year incidence of MACE, but the incidence of MACE was significantly higher in the low LDL-C group at 1 month. It would be relevant to further investigate the HDL-C level on admission, in-hospital use of beta blockers, and statin use during follow-up in relation to MACE.

Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in female patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Early loading statin therapy before percutaneous coronary intervention (PCI) is associated with reduced mortality and periprocedural myocardial injury. The aim of this study was to study the effect of rosuvastatin loading therapy before PCI in female patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). METHODS: Consecutive 117 female patients with NSTEACS were randomly assigned to either the group of rosuvastatin loading before PCI (20 mg 12 hours before angioplasty procedure, with a further 10 mg dose 2 hours before procedure, the loading dose group, n = 59) or the no rosuvastatin treatment group before PCI (control group, n = 58). Periprocedural myocardial injury, periprocedural changes of high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-a in serum and the incidence of major adverse cardiac events (MACE) 3 months and 6 months later were assessed. RESULTS: The incidence of periprocedural myocardial injury was higher in control group than loading dose group (CKMB: 10.17% vs. 25.86%, P = 0.027; Troponin I: 11.86% vs. 29.31%, P = 0.019). MACE occurred in 1.69% of patients in loading dose group and 12.07% of those in control group 3 months after procedure (P = 0.026), 3.39% vs. 17.24% at 6 months (P = 0.014). The levels of hs-CRP, IL-1, IL-6, and TNF-a in serum were not significantly different between the two groups before PCI, but after PCI they were significantly higher in control group. CONCLUSIONS: High-dose rosuvastatin loading before PCI significantly reduced periprocedural myocardial injury and periprocedural inflammation cytokines release and improved 3-month and 6-month clinical outcomes in female patients with NSTEACS who underwent PCI.