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BACKGROUND: Since its first outbreak, coronavirus disease 2019 (COVID-19) has led to a great deal of published literature highlighting the short-term determinants of morbidity and mortality. Recently, several studies have reported radiological and functional sequelae from 3 months to 1 year among hospitalized COVID-19 survivors; however, long-term (more than 1 year) respiratory consequences in this population remain to be evaluated. OBJECTIVE: To assess the long-term radiological and pulmonary function outcomes of patients with COVID-19 2 years after resolution of the initial infection. METHODS: Hospitalized COVID-19 patients with moderate to severe disease who survived acute illness were included in this prospective and partially retrospective study. Clinical assessment, laboratory tests, high-resolution computed tomography scans, and pulmonary function tests (PFTs) were performed at baseline, followed by radiological and lung function assessments at 6 and 24 months. RESULTS: Among 106 enrolled participants (mean age 62 ± 13.5 years; males: 61), 44 (41.5%) and 27 (25.4%) underwent radiological assessment at 6 and 24 months, respectively. Overall, 22.6% (24) of patients had residual radiological abnormalities. Overt fibrosis was observed in 12.2% of patients. Computed tomography disease severity and extent diminished significantly at 6 (13 ± 6, P < 0.001) and 24 months (11 ± 6, P < 0.001) from baseline. PFTs were performed in 65 (61.3%), 22 (20.7%), and 34 (32%) patients at baseline, 6 and 24 months, respectively. Impaired diffusion capacity (median diffusion capacity for carbon monoxide: 60%, interquartile range [IQR]: 51–80), restrictive lung defect (mean total lung capacity: 73.4% ± 18% predicted), and reduced exercise tolerance (median 6-min walk distance: 360 m, IQR: 210–400) were the predominant features at baseline. With the exception of exercise tolerance, a statistically significant improvement was observed in lung function parameters at the extended follow-up (2 years). CONCLUSIONS: Hospitalized COVID-19 survivors are at increased risk of developing long-term pulmonary complications, including lung fibrosis. A protocol-based approach to the management of post-COVID-19 patients is mandatory to improve future outcomes.

BackgroundRetinal degenerative diseases such as diabetic retinopathy and diabetic macular edema are characterized by impaired retinal endothelial cells (RECs) functionality. While the role of glycolysis in glucose homeostasis is well-established, its contributions to REC barrier assembly and cell spreading remain poorly understood. This study aimed to investigate the importance of upper glycolytic components in regulating the behavior of human RECs (HRECs).MethodsElectric cell-substrate impedance sensing (ECIS) technology was employed to analyze the real-time impact of various upper glycolytic components on maintaining barrier functionality and cell spreading of HRECs by measuring cell resistance and capacitance, respectively. Specific inhibitors were used: WZB117 to inhibit Glut1/3, lonidamine to inhibit hexokinases, PFK158 to inhibit the PFKFB3-PFK axis, and TDZD-8 to inhibit aldolases. Additionally, the viability of HRECs was evaluated using the lactate dehydrogenase (LDH) cytotoxicity assay.ResultsThe most significant reduction in electrical resistance and increase in capacitance of HRECs resulted from the dose-dependent inhibition of PFKFB3/PFK using PFK158, followed by aldolase inhibition using TDZD-8. LDH level analysis at 24- and 48-hours post-treatment with PFK158 (1 μM) or TDZD-8 (1 and 10 μM) showed no significant difference compared to the control, indicating that the disruption of HRECs functionality was not attributed to cell death. Conversely, inhibiting Glut1/3 with WZB117 had minimal impact on HREC behavior, except at higher concentrations (10 μM) and prolonged exposure. Lastly, inhibiting hexokinase with lonidamine did not noticeably alter HREC cell behavior.ConclusionThis study illustrates the unique impacts of components within upper glycolysis on HREC functionality, emphasizing the crucial role of the PFKFB3/PFK axis in regulating HREC behavior. Understanding the specific contributions of each glycolytic component in preserving normal REC functionality will facilitate the development of targeted interventions for treating endothelial cell dysfunction in retinal disorders while minimizing effects on healthy cells.

[This corrects the article DOI: 10.1371/journal.pone.0134156.].

Iron overload is now recognized as a health problem in industrialized countries, as excessive iron is highly toxic for liver and spleen. The potential use of curcumin as an iron chelator has not been clearly identified experimentally in iron overload condition. Here, we evaluate the efficacy of curcumin to alleviate iron overload-induced hepatic and splenic abnormalities and to gain insight into the underlying mechanisms.Three groups of male adult rats were treated as follows: control rats, rats treated with iron in a drinking water for 2 months followed by either vehicle or curcumin treatment for 2 more months. Thereafter, we studied the effects of curcumin on iron overload-induced lipid peroxidation and anti-oxidant depletion.Treatment of iron-overloaded rats with curcumin resulted in marked decreases in iron accumulation within liver and spleen. Iron-overloaded rats had significant increases in malonyldialdehyde (MDA), a marker of lipid peroxidation and nitric oxide (NO) in liver and spleen when compared to control group. The effects of iron overload on lipid peroxidation and NO levels were significantly reduced by the intervention treatment with curcumin (P

PURPOSE: The incidence of Hepatocellular carcinoma (HCC) is on the rise, but what is causing that trend has remained a mystery. Mycotoxins are almost entirely ignored health problems, and sometimes actually naively belittled in advanced medical care. Ochratoxin A (OTA) is one of the most abundant food contaminating mycotoxins worldwide that is carcinogenic, but no studies have evaluated its levels in HCC patients. Therefore, this study was designed to monitor the presence of OTA in the serum of HCC patients and to quantify the strength of the association between OTA and HCC. METHODS: We conducted a case control-based study on 61 participants. Thirty-nine were HCC cases identified between 2010 and 2012 and individually matched by age, sex, residence and date of recruitment to 22 healthy controls. Serum OTA and alpha-fetoprotein levels were measured by using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay, respectively. RESULTS: HPLC analysis of 61 serum samples indicated that the highest incidence of elevated OTA was found in the HCC group and was 5-fold higher than in the control group. The concentration of OTA in the HCC group ranged between 0.129 and 10.93 ng/mL with a mean value±SD of 1.1±0.3 ng/mL, while in the normal group it ranged between 0.005 and 0.50 ng/mL with a mean value±SD of 0.201±0.02 ng/mL. The odds ratio for HCC patients presenting OTA levels above the cut-off of 0.207 (calculated by the receiver operating characteristic curve) was 9.78 (95% confidence interval = 2.9095-32.9816, P = 0.0002) with respect to normal controls, suggesting that HCC is 9.8 times as frequent in the exposed group to OTA. CONCLUSION: Our results reveal a strong association between the presence of OTA and HCC, which may offer a coherent explanation for much of the descriptive epidemiology of HCC and suggest new avenues for analytical research.