Targeting tissue-resident memory CD8+ T cells in the kidney is a potential therapeutic strategy to ameliorate podocyte injury and glomerulosclerosis

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Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

Comment on “Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis”

The present letter to the editor is in response to the research “Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis” by Elshaarawy et al in World J Gastroenterol 2021; 13(5): 424–439. The preoperative assessment of the liver reserve function in hepatocellular carcinoma (HCC) patients with cirrhosis is crucial, and there is no universal consensus on how to assess it. Based on a retrospective study, Elshaarawy et al investigated the impact of various classical clinical indicators on liver failure and the prognosis after hepatectomy in HCC patients with cirrhosis. We recommend that we should strive to explore new appraisal indicators, such as the indocyanine green retention rate at 15 min.     

一测多评法同时测定艾纳香油中5种成分

目的建立一测多评法同时测定艾纳香Blumea balsamifera(L.)DC.油中β⁃蒎烯、β⁃石竹烯、樟脑、α⁃石竹烯和龙脑5种成分的含有量。方法艾纳香油乙酸乙酯提取物的分析采用PEG⁃20 M柱(30 m×0.32 mm,1.0μm);程序升温;载气为高纯氮气(99.999%);FID检测器温度240℃,进样口温度240℃。以龙脑为内标,计算其他4种成分的相对校正因子,再测定其含有量。结果蒎烯、β⁃石竹烯、樟脑、α⁃石竹烯和龙脑分别在1.49~59.5μg/mL(r=0.9996)、2.22~88.8μg/mL(r=0.9996)、6.48~259μg/mL(r=0.9997)、3.64~146μg/mL(r=0.9991)和16.4~656μg/mL(r=0.9998)范围内线性关系良好,平均加样回收率(RSD)分别为97.4%(0.9%)、99.0%(1.3%)、98.9%(0.9%)、97.6%(0.9%)和99.7%(1.0%)。一测多评法所得结果接近于外标法。结论该方法准确稳定,重复性好,可用于艾纳香油的质量控制。     

Interplay between bile acids and the gut microbiota promotes intestinal carcinogenesis

The gut microbiota and the bile acid pool play pivotal roles in maintaining intestinal homeostasis. Bile acids are produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. Gut dysbiosis has been reported to be associated with colorectal cancer. However, the interplay between bile acid metabolism and the gut microbiota during intestinal carcinogenesis remains unclear. In the present study, we investigated the potential roles of bile acids and the gut microbiota in the cholic acid (CA; a primary bile acid)‐induced intestinal adenoma‐adenocarcinoma sequence. Apc ^min/+ mice, which spontaneously develop intestinal adenomas, were fed a diet supplemented with 0.4% CA for 12 weeks. Mice that were fed a normal diet were regarded as untreated controls. In CA‐treated Apc ^min/+ mice, the composition of the gut microbiota was significantly altered, and CA was efficiently transformed into deoxycholic acid (a secondary bile acid) by the bacterial 7α‐dehydroxylation reaction. The intestinal adenoma‐adenocarcinoma sequence was observed in CA‐treated Apc ^min/+ mice and was accompanied by an impaired intestinal barrier function and IL‐6/STAT3‐related low‐grade inflammation. More importantly, microbiota depletion using an antibiotic cocktail globally compromised CA‐induced intestinal carcinogenesis, suggesting a leading role for the microbiota during this process. Overall, our data suggested that the crosstalk between bile acids and the gut microbiota mediated intestinal carcinogenesis, which might provide novel therapeutic strategies against intestinal tumor development.     

Targeting an RNA-Binding Protein Network in Acute Myeloid Leukemia

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