Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

The level of urinary albumin is a critical indicator for the early diagnosis and management of chronic kidney disease (CKD). However, existing methods for detecting albumin are not conducive to point-of-care testing due to the complexity of reagent addition and incubation processes. This study presents a smartphone-integrated handheld automated biochemical analyzer (sHABA) designed for point-of-care testing of urinary albumin. The sHABA features a pre-loaded, disposable reagent cassette with reagents for the albumin assay arranged in the order of their addition within a hose. The smartphone-integrated analyzer can drive the reagents following a preset program, to enable automatic sequential addition. The sHABA has a detection limit for albumin of 5.9 mg/L and a linear detection range from 7 to 450 mg/L. The consistency of albumin level detection in 931 urine samples using sHABA with clinical tests indicates good sensitivity (95.78%) and specificity (90.16%). This research advances the field by providing an automated detection method for albumin in a portable device, allowing even untrained individuals to monitor CKD in real time at the patient's bedside. In the context of promoting tiered diagnosis and treatment, the sHABA has the potential to become an essential tool for the early diagnosis and comprehensive management of CKD and other chronic conditions.

Arsenic compounds are widely used for the therapeutic intervention of multiple diseases.Ancient pharmacologists discovered the medicinal utility of these highly toxic substances,and modern phar-macologists have further recognized the specific active ingredients in human diseases.In particular,Arsenic trioxide(ATO),as a main component,has therapeutic effects on various tumors(including leukemia,hepatocellular carcinoma,lung cancer,etc.).However,its toxicity limits its efficacy,and con-trolling the toxicity has been an important issue.Interestingly,recent evidence has pointed out the pivotal roles of arsenic compounds in phase separation and membraneless organelles formation,which may determine their toxicity and therapeutic efficacy.Here,we summarize the arsenic compounds-regulating phase separation and membraneless organelles formation.We further hypothesize their potential involvement in the therapy and toxicity of arsenic compounds,highlighting potential mecha-nisms underlying the clinical application of arsenic compounds.

Cryptococcal meningitis is a common and refractory central nervous system infection,with high rates of mortality and disability.The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion.Based on the current situation of cryptococcal meningitis in China,the management of cryptococcal meningitis includes 6 aspects:introduction,microorganism identification,clinical manifestations and diagnosis,principles of antifungal therapy,treatment of refractory and recurrent meningitis,treatment of intracranial hypertension.There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis.This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines.The importance of early diagnosis,combined long-term antifungal therapy,control of intracranial hypertension are emphasized.

OBJECTIVETo investigate the effect of amphotericinB (AmB) on migration and invasion of esophageal carcinoma Eca109 cells exposed to hypoxia and explore the molecular mechanisms.

METHODSRoutinely cultured esophageal carcinoma Eca109 cells were treated with 0, 1.25, 2.5, or 5 µg/ml AmB in hypoxic condition (3% O2, 5% CO2, and 92% N2) for 24 h. The cell migration and invasion were assessed by cell scratch test and Transwell chamber assay, respectively. Real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-2 (MMP-2), and E-cadherin in the cells, respectively.

RESULTSCompared with the control cells, the cells treated with different doses of AmB showed attenuated ability of migration and invasion (P<0.05). AmB treatment resulted in significantly lowered mRNA and protein expressions of MMP-2 (P<0.05) and increased expressions of E-cadherin (P<0.05); the protein expression of HIF-1α decreased significantly in cells after AmB treatment (P<0.05) but its mRNA levels showed no significant changes (P>0.05).

CONCLUSIONAmB can suppress the migration and invasion of esophageal carcinoma Eca109 cells in hypoxic microenvironment possibly by regulating the expressions of HIF-1α, MMP-2 and E-cadherin.

Amphotericin B ; pharmacology ; Cadherins ; metabolism ; Cell Hypoxia ; Cell Line, Tumor ; drug effects ; Cell Movement ; drug effects ; Down-Regulation ; Esophageal Neoplasms ; metabolism ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Matrix Metalloproteinase 2 ; metabolism ; RNA, Messenger

Objective:To study the effect of immunological molecules expressive state upon the telomerase activation ( TA) of bone marrow mononuclear cells ( BMMNC ) in the hemopoietic microenvironment of patients with immune related hematocytopenia ( IRHS) ,and to explore the immunologic mechanism as well as the clinical significance of hematoclasis in marrow of IRHS patients .Methods:①TRAP-PCR-ELISA method was performed to detect the TA of BMMNC in marrow of 366 IRHS patients before and after therapy.②The molecules HLA-DR,anti-hunman IgG,FcγⅡR,mannose receptor ( MR),IL-17A and its receptor ( IL-17AR) were analysed by immunochemistry and immunofluorescence staining .③The flow cytometric ( FCM) was used to analyse the proportion of CD3+CD4+T cells as well as CD3+CD8+T cells ,CD3-CD19+B cells and CD3-CD16/56+NK cells in peripheral blood lymphocyte.60 cases of health examination were selected as the control group , and 30 cases hypoferric anemia patients were selected as disease control.The differences between patient group and control group were analysed with statistic method .Immunochemistry and immunofluo-rescence staining were performed to in situ analyze the activation-characteristics of immunocyte in bone marrow slides of IRHS ,and the dependablity of cellular immunologic injury was also checked.Results: ①The levels of TA was 0.261 7 ±0.021 6 before treatment , higher than the disease control group (0.061 6±0.031 3 ,P<0.01).Among of them HLA-B27+patients were higher than HLA-B27-patients (0.301 3±0.020 6 vs.0.192 3±0.012 9,P<0.05).Serious IRP patients with HLA-B27+IgG+were obviously higher than HLA-B27-IgG+patients (0.401 6±0.017 2 vs.0.221 1±0.011 0,P<0.01).②In marrow of HLA-B27+IgG+patients,both cell immunity and humoral immunity were in disorder in the hemopoietic microenvironment ,and immonocyte in marrow expressed HLA-DR, FcγⅡR,IL-17A,IL-17RA and MR,and Th,Ts,B cell and NK cell in peripheral blood increased in different degree ,inducing the in-flammation of haemocyte and lead to destruction.③Humoral immunity was in the dominant level in morrow;humoral immunity of HLA-B27-IgG+patients,immonocyte expressed FcγⅡR in high level,but IL-17A was seldom expressed,only CD19+B cell was increased slightly ,the antibody dependent cellular cytotoxicity ( ADCC) was the main mode of destruction.After therapy glucocorticoids associated with ciclosporin A ,the TA level of BMMNC decreased to 0 with devitalization.Conclusion: The telomerase activation of bone marrow mononuclear cells in IRHS is related with the immune state of hemopoietic microenvironment and the pathologic lesion degree of hema -topoietic cell in marrow.It is viral infection and immunological activation as well as a variety of inflammatory factors play a part in the immunologic injury that might be an important factor of the enhancement in TA.

Objective To investigate the effect of amphotericinB (AmB) on migration and invasion of esophageal carcinoma Eca109 cells exposed to hypoxia and explore the molecular mechanisms. Methods Routinely cultured esophageal carcinoma Eca109 cells were treated with 0, 1.25, 2.5, or 5μg/ml AmB in hypoxic condition (3%O2, 5%CO2, and 92%N2) for 24 h. The cell migration and invasion were assessed by cell scratch test and Transwell chamber assay, respectively. Real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-2 (MMP-2), and E-cadherin in the cells, respectively. Results Compared with the control cells, the cells treated with different doses of AmB showed attenuated ability of migration and invasion (P<0.05). AmB treatment resulted in significantly lowered mRNA and protein expressions of MMP-2 (P<0.05) and increased expressions of E-cadherin (P<0.05); the protein expression of HIF-1α decreased significantly in cells after AmB treatment (P<0.05) but its mRNA levels showed no significant changes (P>0.05). Conclusion AmB can suppress the migration and invasion of esophageal carcinoma Eca109 cells in hypoxic microenvironment possibly by regulating the expressions of HIF-1α, MMP-2 and E-cadherin.

Objective To investigate the effect of amphotericinB (AmB) on migration and invasion of esophageal carcinoma Eca109 cells exposed to hypoxia and explore the molecular mechanisms. Methods Routinely cultured esophageal carcinoma Eca109 cells were treated with 0, 1.25, 2.5, or 5μg/ml AmB in hypoxic condition (3%O2, 5%CO2, and 92%N2) for 24 h. The cell migration and invasion were assessed by cell scratch test and Transwell chamber assay, respectively. Real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-2 (MMP-2), and E-cadherin in the cells, respectively. Results Compared with the control cells, the cells treated with different doses of AmB showed attenuated ability of migration and invasion (P<0.05). AmB treatment resulted in significantly lowered mRNA and protein expressions of MMP-2 (P<0.05) and increased expressions of E-cadherin (P<0.05); the protein expression of HIF-1α decreased significantly in cells after AmB treatment (P<0.05) but its mRNA levels showed no significant changes (P>0.05). Conclusion AmB can suppress the migration and invasion of esophageal carcinoma Eca109 cells in hypoxic microenvironment possibly by regulating the expressions of HIF-1α, MMP-2 and E-cadherin.

Objective To investigate the biological effect of anti-leukemic cells induced by eosinophilic granulocyte (EOS) in bone marrow of patients with chronic myelogenous leukemia (CML).Methods The BCR-ABL fusion gene as well as the expression of IL-12 and IL-17 mRNA were performed by RT-PCR.The serum concentrations of cytokine IL-12 and IL-17 were determined by enzyme-linked immuno sorbent assay (ELISA).Immunochemistry staining and cytochemistry staining were used to observe the peroxydase (POX) and human Leukocyte antigen (HLA)-DR expression of EOS in bone marrow.Immunofluorescence staining was used to observe mannose receptor (MR),IL-12,IL-17A and IL-17receptor A (IL-17RA) expression of EOS.The results between the CML patients and the healthy controls were compared.Results Serum levels of IL-12 and IL-17 were higher in the 60 CML patients [(196.33 ±21.79) ng/L and (36.55-±3.01) ng/L] than those in the controls [(96.60 ±4.92) ng/L and (23.74 ±1.36) ng/L].In the 32 patients with activated EOS,the levels of IL-12 and IL-17 were (273.12 ± 17.16)ng/L and (40.11 ± 6.13) ng/L,which were significantly higher than those in the non-activated EOS [(126.16 ± 14.27) ng/L and (28.14 ±5.29) ng/L] (P values ＜0.01).IL-12 and IL-17 mRNA were expressed in activated EOS,while BCR-ABL fusion gene was not found.The amounts of EOS were increased abnormally in the bone marrow and peripheral blood of the CML patients with POX positive staining in the cytoplasm and weakly positive HLA-DR staining.It was observed easily by a microscope that EOS could attack leukemic cells in bone marrow through adhesion,capture and phagocytosis.Activated EOS could express IL-12,IL-17A and MR,which was related with the serum levels of these cytokines.Conclusions Activated EOS in bone marrow of CML patients could express IL-12 and IL-17.Activated EOS could induce coup injury to leukemic cell by releasing POX and expressing IL-12 and IL-17.It can also capture or swallow target cells via the expression of MR on the membrane.EOS may play an important role in the anti-tumor immunologic function in bone marrow of CML patients.

Objective To describe the clinical features of invasive fungal disease in Huashan Hospital,Fudan University from January 2004 to December 2006.Methods The medical data were reviewed retrospectively for the patients with fungal infection, which was confirmed by positive fungal culture or microscopic examination with blood,sterile body fluid,deep tissue,sputum specimen or isolation of Aspergillus spp.and Cryptococcus spp.from bronchoalveolar lavage.The proven and probable cases of invasive fungal disease were included in this analysis.Results A total of 111 patients were diagnosed as invasive fungal dis-ease,including 104 proven cases and 7 probable cases.Sixty-one cases were community-acquired and the other 50 were nosoco-mial.The most common site of infection was bloodstream (51,45.9%),followed by central nervous system (44,39.6%)and respiratory system (14,12.6%).The most common pathogens were Candida spp.(50,45%),Cryptococcus (47,42.3%) and Aspergillus spp. (12, 10.8%). The community-acquired fungal infections were mostly found in central nervous system (44,72.1%),and respiratory system (12, 19.7%),mainly caused by Cryptococcus and Aspergillus. The nosocomial fungal infections occurred primarily in blood-stream (96.0%),mainly due to Candida spp.No underlying disease or risk factor was identified in more than half of the pa-tients with community-acquired infection,while almost all the patients with nosocomial fungal infection had underlying disease and predisposing factors.Indwelling venous catheter was closely associated with nosocomial bloodstream infection.Indwelling venous catheter lasted for more than 1 week in 64.7% of the patients with Candida bloodstream infection.The same fungal strain was isolated from both the cather and blood of the same patient in 11 cases.The overall mortality of these invasive fungal diseases was 14.4% (16/111).The mortality rate was 18.0% (9/50)in the patients with nosocomial invasive fungal infection, and 11.5% (7/61)in the patients with community-acquired invasive fungal infection.Conclusions The most common site of in-vasive fungal infection is bloodstream,followed by central nervous system,and respiratory system.Majority of the fungal patho-gens are Candida spp.,Cryptococcus and Aspergillus spp.The community-acquired invasive fungal disease is primarily meningitis caused by Cryptococcus.The nosocomial invasive fungal disease is mainly bloodstream infection caused by Candida spp.