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.     

Association between reactogenicity and SARS-CoV-2 antibodies after the second dose of the BNT162b2 COVID-19 vaccine

High vaccine reactogenicities may reflect stronger immune responses, but the epidemiological evidence for coronavirus disease 2019 (COVID-19) vaccines is sparse and inconsistent. We observed that a fever of ≥38℃ after two doses of the BNT162b2 vaccine was associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG titers.     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

Impact of COVID-19 and malaria coinfection on clinical outcomes: a retrospective cohort study

ObjectivesDespite the possibility of concurrent infection with COVID-19 and malaria, little is known about the clinical course of coinfected patients. We analysed the clinical outcomes of patients with concurrent COVID-19 and malaria infection.MethodsWe conducted a retrospective cohort study that assessed prospectively collected data of all patients who were admitted between May and December 2020 to the Universal COVID-19 treatment center (UCTC), Khartoum, Sudan. UCTC compiled demographic, clinical, laboratory (including testing for malaria), and outcome data in all patients with confirmed COVID-19 hospitalized at that clinic. The primary outcome was all-cause mortality during the hospital stay. We built proportional hazard Cox models with malaria status as the main exposure and stepwise adjustment for age, sex, cardiovascular comorbidities, diabetes, and hypertension.ResultsWe included 591 patients with confirmed COVID-19 diagnosis who were also tested for malaria. Mean (SD) age was 58 (16.2) years, 446/591 (75.5%) were males. Malaria was diagnosed in 270/591 (45.7%) patients. Most malaria patients were infected by Plasmodium falciparum (140/270; 51.9%), while 121/270 (44.8%) were coinfected with Plasmodium falciparum and Plasmodium vivax. Median follow-up was 29 days. Crude mortality rates were 10.71 and 5.87 per 1000 person-days for patients with and without concurrent malaria, respectively. In the fully adjusted Cox model, patients with concurrent malaria and COVID-19 had a greater mortality risk (hazard ratio 1.43, 95% confidence interval 1.21-1.69).DiscussionCoinfection with COVID-19 and malaria is associated with increased all-cause in-hospital mortality compared to monoinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).     

Más difícil todavía: tratar una glomerulonefritis rápidamente progresiva grave en el seno de una neumonía por COVID-19

We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.     

Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection

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Rehabilitation in long COVID-19: A mini-review

We have been experiencing multiple waves of the coronavirus disease 2019 (COVID-19) pandemic. With these unprecedented waves, we have entered into an era of ‘new normal’. This pandemic has enforced us to rethink the very basics of childhood learning: Habits, health etiquette, and hygiene. Rehabilitation has immense importance during this pandemic considering a few aspects. Multidisciplinary COVID-19 rehabilitation clinics are essential to address the demand. The equitable distribution of COVID-19 rehabilitation services for differently-abled individuals during the pandemic is an important aspect. Rehabilitation needs identification and further studies on various rehabilitation interventions are among the key unmet future research needs.     

基于网络药理学和分子对接技术分析筒鞘蛇菰多糖治疗肝损伤的作用机制及体内实验研究＊

目的 基于网络药理学探讨并分析筒鞘蛇菰（Balanophora involucrata Hook. f.，BIH）治疗肝损伤的作用及分子机制，并通过大鼠体内实验验证相关预测靶点及筒鞘蛇菰提取物-蛇菰多糖（Polysaccharides of Balanophora involucrata Hook. f.，BPS）对实验性肝损伤的保护作用。方法 化学专业数据库、TCMID和TCMSP平台检索筒鞘蛇菰组成的化合物及可能靶点，以肝损伤为关键词检索GeneCards和网站，获得相关靶点，绘制Venn图，选交集靶点，将“化合物-靶点和疾病-靶点”关系导入Cytoscape V3.7.2软件，获得化合物-靶点-疾病的三重网络，对化合物及相关靶点蛋白行分子对接，并用交集靶点绘制蛋白互作网络图及进行GO生物功能和KEGG信号途径富集分析。结果 筒鞘蛇菰主要成分有11个化合物，其中与肝损伤有37个交集靶点，高度关联靶点包括NOS3、ESR1、TNF、MAOA、PTGS2、IL10等，GO和KEGG富集分析发现筒鞘蛇菰治疗肝损伤的分子机制，可能与调节肾上腺素能信号通路、cGMP-PKG信号及神经活性配体-受体交互通路等有关，而且ADRA1B、ADRA2A、ADRA2C、ADRB1/2等基因高度富集于这些通路中。动物体内实验发现BPS灌胃处理可减轻肝组织损伤、调控血清炎症因子肿瘤坏死因子α（Tumor necrosis factor， TNF-α）和白细胞介素10（IL-10）水平、提高抗氧化酶超氧化物歧化酶（superoxide dismutase，SOD）活性，并增强肝组织内氧化应激相关蛋白核因子E2相关因子2（NF-E2-related factor 2，NRF2）和醌NADH脱氢酶1（NQO1）的表达，从而抑制大鼠体内氧化应激损伤、减轻炎症反应和细胞凋亡，达到保护实验性肝损伤的作用。结论 本研究初步确定筒鞘蛇菰治疗肝损伤的有效成分、“化合物-蛋白-靶点”关联网络及发挥作用的分子机制，并通过动物体内实验证实蛇菰多糖保护肝损伤的机制与上调NRF2/NQO1通路来减轻氧化应激反应性损伤、减轻肝细胞凋亡有关。