Enterococcal bloodstream infections in critically ill patients with COVID-19: a case series

BackgroundAn unexpected high prevalence of enterococcal bloodstream infection (BSI) has been observed in critically ill patients with COVID-19 in the intensive care unit (ICU).Materials and methodsThe primary objective was to describe the characteristics of ICU-acquired enterococcal BSI in critically ill patients with COVID-19. A secondary objective was to exploratorily assess the predictors of 30-day mortality in critically ill COVID-19 patients with ICU-acquired enterococcal BSI.ResultsDuring the study period, 223 patients with COVID-19 were admitted to COVID-19-dedicated ICUs in our centre. Overall, 51 episodes of enterococcal BSI, occurring in 43 patients, were registered. 29 (56.9%) and 22 (43.1%) BSI were caused by Enterococcus faecalis and Enterococcus faecium, respectively. The cumulative incidence of ICU-acquired enterococcal BSI was of 229 episodes per 1000 ICU admissions (95% mid-p confidence interval [CI] 172–298). Most patients received an empirical therapy with at least one agent showing in vitro activity against the blood isolate (38/43, 88%). The crude 30-day mortality was 42% (18/43) and 57% (4/7) in the entire series and in patients with vancomycin-resistant E. faecium BSI, respectively. The sequential organ failure assessment (SOFA) score showed an independent association with increased mortality (odds ratio 1.32 per one-point increase, with 95% confidence interval 1.04–1.66, p = .021).ConclusionsThe cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19. Our results suggest a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.

KEY MESSAGES

• The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19.
• The crude 30-day mortality of enterococcal BSI in critically ill patients with COVID-19 may be higher than 40%.
• There could be a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.

     

Effect of transforming growth factor-β1 on monocyte Toll-like receptor 4 expression in septic rats

BACKGROUND:

Sepsis is a tough problem in critical ill patients. This study aimed to investigate the dynamic changes of monocyte Toll-like receptor (TLR) 4 expression in peripheral blood of septic rats and to determine the effects of transforming growth factor (TGF)-β₁ on TLR4 expression.

METHODS:

Altogether 132 clean level SD rats were randomly divided into a control group (n=12), a sepsis model group (n=60), and a TGF-β₁ intervention group (n=60). In the sepsis model group and TGF-β₁ intervention group, the rats were subdivided into five groups (2-hour group, 6-hour group, 12-hour group, 24-hour group, and 48-hour group), with 12 rats in each group. Cecal ligation puncture (CLP) was performed in the sepsis model group and TGF-β₁ intervention group to establish models of sepsis. The rats in the sepsis model group were injected with 1 mL normal saline at the caudal vein 0.5 hour after the model establishment; the rats in the TGF-β₁ intervention group were injected with 20 ng/mL or 250 g TGF-β₁ 0.5 hour after the model establishment. Flow cytometry was used to detect the change of monocyte TLR4 in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) was used to detect the change of TNF-α level in peripheral blood.

RESULTS:

At 6-12 hours after CLP, the monocyte TLR4 in peripheral blood started to decrease, and reached the lowest level at 12 hours. Compared to the control group, the monocyte TLR4 expression at 6 and 12 hours was lowered significantly (P<0.05). Compared to the sepsis model group at 2, 24 and 48 hours after CLP, the monocyte TLR4 expression in the TGF-β₁ intervention group decreased dramatically (P<0.05), but there were no differences between the two groups at 6 and 12 hours respectively. Compared to the control group, the concentration of NF-κ in liver tissue increased significantly 6 hours after CLP (P<0.05). After use of TGF-β₁, the concentration of NF-κ was decreased significantly but still higher than that of the control group. Compared to the control group, the concentration of TNF-α in peripheral blood was increased significantly at 2-48 hours after CLP (P<0.05). After use of TGF-β₁, TNF-α was further increased.

CONCLUSION:

During sepsis, TGF-β₁ can decrease the monocyte TLR4 expression and NF-κ in liver tissue, but facilitate the formation of proinflammatory mediator TNF-α. This finding indicates that TGF-β₁ may play a role in promoting inflammatory response during sepsis, but this regulation is not via direct regulation of monocyte TLR4 in peripheral blood.KEY WORDS: Sepsis, TGF-β₁, TLR4, Monocyte, TNF-α     

Puerarin induces platinum-resistant epithelial ovarian cancer cell apoptosis by targeting SIRT1

ObjectivePrevious investigations indicated the anticancer activity of puerarin. The current study aimed to evaluate the effect and molecular mechanisms of puerarin in chemotherapy-resistant ovarian cancer cells.MethodsWe examined the effects of puerarin in platinum-resistant epithelial ovarian cancer cells in vitro and in vivo. We also analyzed the molecular mechanism underlying Wnt/β-catenin inhibition and sirtuin 1 (SIRT1) regulation following puerarin treatment.ResultsOur study demonstrated that puerarin effectively inhibited cell growth in vitro and in vivo by increasing apoptosis in ovarian cancer cells. More importantly, puerarin sensitized cisplatin-resistant ovarian cancer cells to chemotherapy. Puerarin treatment decreased SIRT1 expression, which attenuated the nuclear accumulation of β-catenin to inhibit Wnt/β-catenin signaling. In addition, SIRT1 overexpression diminished the effects of puerarin treatment on cisplatin-resistant ovarian cancer cells. Further analysis supported SIRT1/β-catenin expression as a candidate biomarker for the disease progression of epithelial ovarian cancer.ConclusionsPuerarin increased the apoptosis of platinum-resistant ovarian cancer cells. The mechanism is partly related to the downregulation of SIRT1 and subsequent inhibition of Wnt/β-catenin signaling.     

Comparative study of hematological and radiological feature of severe/critically ill patients with COVID‐19, influenza A H7N9, and H1N1 pneumonia

ObjectivesThis study aimed to explore clinical indexes for management of severe/critically ill patients with COVID‐19, influenza A H7N9, and H1N1 pneumonia by comparing hematological and radiological characteristics.MethodsSevere/critically ill patients with COVID‐19, H7N9, and H1N1 pneumonia were retrospectively enrolled. The demographic data, clinical manifestations, hematological parameters, and radiological characteristics were compared.ResultsIn this study, 16 cases of COVID‐19, 10 cases of H7N9, and 13 cases of H1N1 who met severe/critically ill criteria were included. Compared with COVID‐19, H7N9 and H1N1 groups had more chronic diseases (80% and 92.3% vs. 25%, p < 0.05), higher APACHE Ⅱ scores (16.00 ± 8.63 and 15.08 ± 6.24, vs. 5.50 ± 2.58, p < 0.05), higher mortality rates (40% and 46.2% vs. 0%, p < 0.05), significant lymphocytopenia (0.59 ± 0.31 × 10⁹/L and 0.56 ± 0.35 × 10⁹/L vs. 0.97 ± 0.33 × 10⁹/L, p < 0.05), and elevated neutrophil‐to‐lymphocyte ratio (NLR; 14.67 ± 6.10 and 14.64 ± 10.36 vs. 6.29 ± 3.72, p < 0.05). Compared with the H7N9 group, ground‐glass opacity (GGO) on chest CT was common in the COVID‐19 group (p = 0.028), while pleural effusion was rare (p = 0.001).ConclusionsThe NLR can be used as a clinical parameter for the predication of risk stratification and outcome in COVID‐19 and influenza A pneumonia. Manifestations of pleural effusion or GGO in chest CT may be helpful for the identification of different viral pneumonia.     

Expression of β1 adrenergic receptor in vascular anomalies in children

ObjectiveControversial, heterogeneous, and inconsistent responses to beta-blockers have been reported in some cases of infantile proliferative hemangiomas. On the basis of these clinical observations, we aimed to examine the β1 adrenergic receptor (β1-AR) protein expression distribution among different types of pediatric vascular anomalies.MethodsImmunohistochemistry (IHC) was performed for β1-AR on 43 surgical specimens.ResultsWe found positive β1-AR IHC staining in all intramuscular hemangiomas, capillary–lymphatic, lymphatic, venous, and combined malformations, and Masson’s tumor cases, as well as in 7 of 10 cases of proliferative infantile hemangiomas.ConclusionsOur research demonstrates, for the first time, the degree of heterogeneous expression of β1-AR among pediatric vascular malformations. Our results support the need for β1-AR assessment in pediatric vascular anomalies to select cases with a robust response to β1-selective blockers. β1-AR assessment may have a strong impact on therapeutic refinement for pediatric vascular anomalies by selecting cases with a stronger response to beta-blockers.     

Expression of caspase-3 and hypoxia inducible factor 1α in hepatocellular carcinoma complicated by hemorrhage and necrosis

BACKGROUNDHepatocellular carcinoma (HCC) is a malignant tumor that occurs in the liver. Its onset is latent, and it shows high heterogeneity and can readily experience intrahepatic metastasis or systemic metastasis, which seriously affects patients’ quality of life. Numerous studies have shown that hypoxia inducible factor1α (HIF-1α) plays a significant role in the occurrence and development of tumors, as it promotes the formation of intratumoral vessels and plays a key role in their metastasis and invasion. Some studies have reported that caspase-3, which is induced by various factors, is involved in the apoptosis of tumor cells.AIMTo investigate the expression of caspase-3 and HIF-1α and their relationship to the prognosis of patients with primary HCC complicated by pathological changes of hemorrhage and necrosis.METHODSA total of 88 patients with HCC complicated by pathological changes of hemorrhage and necrosis who were treated at our hospital from January 2017 to December 2019 were selected. The expression of caspase-3 and HIF-1α in HCC and paracancerous tissues from these patients was assessed.RESULTSThe positive expression rate of caspase-3 in HCC tissues was 27.27%, which was significantly lower than that in the paracancerous tissues (P < 0.05), while the positive expression rate of HIF-1α was 72.73%, which was significantly higher than that in the paracancerous tissues (P < 0.05). The positive expression rates for caspase-3 in tumor node metastasis (TNM) stage III and lymph node metastasis tissues were 2.78% and 2.50%, respectively, which were significantly lower than those in TNM stage I-II and non-lymph node metastasis tissues (P < 0.05). The positive expression rates of HIF-1α in TNM stage III, lymph node metastasis, and portal vein tumor thrombus tissues were 86.11%, 87.50%, and 88.00%, respectively, and these values were significantly higher than those in TNM stage I-II, non-lymph node metastasis, and portal vein tumor thrombus tissues (P < 0.05). The expression of caspase-3 and HIF-1α in HCC tissues were negatively correlated (r_s = − 0.426, P < 0.05). The median overall survival time of HCC patients was 18.90 mo (95% CI: 17.20–19.91). The results of the Cox proportional risk regression model analysis showed that TNM stage, portal vein tumor thrombus, lymph node metastasis, caspase-3 expression, and HIF-1α expression were the factors influencing patient prognosis (P < 0.05).CONCLUSIONThe expression of caspase-3 decreases and HIF-1α increases in HCC tissues complicated by pathological changes of hemorrhage and necrosis, and these are related to clinicopathological features and prognosis.     

Alarmins,COVID-19 and comorbidities

The coronavirus SARS-CoV-2, the aetiological agent of COVID-19 disease, is representing a worldwide threat for the medical community and the society at large so that it is being defined as “the twenty-first-century disease”. Often associated with a severe cytokine storm, leading to more severe cases, it is mandatory to block such occurrence early in the disease course, to prevent the patients from having more severe, sometimes fatal, outcomes. In this framework, early detection of “danger signals”, possibly represented by alarmins, can represent one of the most promising strategies to effectively tailor the disease and to better understand the underlying mechanisms eventually leading to death or severe consequences. In light of such considerations, the present article aims at evaluating the role of alarmins in patients affected by COVID-19 disease and the relationship of such compounds with the most commonly reported comorbidities. The conducted researches demonstrated yet poor literature on this specific topic, however preliminarily confirming a role for danger signals in the amplification of the inflammatory reaction associated with SARS-CoV-2 infection. As such, a number of chronic conditions, including metabolic syndrome, gastrointestinal and respiratory diseases, in turn, associated with higher levels of alarmins, both foster the infection and predispose to a worse prognosis. According to these preliminary data, prompt detection of high levels of alarmins in patients with COVID-19 and co-morbidities could suggest an immediate intense anti-inflammatory treatment.

Key message

• Alarmins have a role in the amplification of the inflammatory reaction associated with SARS-CoV-2 infection
• a prompt detection of high levels of alarmins in patients with COVID-19 could suggest an immediate intense anti-inflammatory treatment

     

Efficacy and safety of three new oral antiviral treatment (molnupiravir,fluvoxamine and Paxlovid) for COVID-19：a meta-analysis

BackgroundThe coronavirus disease (COVID-19) epidemic has not been completely controlled. Although great achievements have been made in COVID-19 research and many antiviral drugs have shown good therapeutic effects against COVID-19, a simple oral antiviral drug for COVID-19 has not yet been developed. We conducted a meta-analysis to investigate the improvement in mortality or hospitalization rates and adverse events among COVID-19 patients with three new oral antivirals (including molnupiravir, fluvoxamine and Paxlovid).MethodsWe searched scientific and medical databases, such as PubMed, Web of Science, Embase and Cochrane Library for relevant articles and screened the references of retrieved studies on COVID-19.ResultsA total of eight studies were included in this study. The drug group included 2440 COVID-19 patients, including 54 patients who died or were hospitalized. The control group included a total of 2348 COVID-19 patients, including 118 patients who died or were hospitalized. The overall odds ratio (OR) of mortality or hospitalization was 0.33 (95% confidence interval [CI], 0.22–0.49) for COVID-19 patients in the drug group and placebo group, indicating that oral antiviral drugs were effective for COVID-19 patients and reduced the mortality or hospitalization by approximately 67%.ConclusionsThis study showed that three novel oral antivirals (molnupiravir, fluvoxamine and Paxlovid) are effective in reducing the mortality and hospitalization rates in patients with COVID-19. In addition, the three oral drugs did not increase the occurrence of adverse events, thus exhibiting good overall safety. These three oral antiviral drugs are still being studied, and the available data suggest that they will bring new hope for COVID-19 recovery and have the potential to be a breakthrough and very promising treatment for COVID-19.

KEY MESSAGES

• Many antiviral drugs have shown good therapeutic effects, and there is no simple oral antiviral drug for COVID-19 patients.
• Meta-analysis was conducted for three new oral antivirals to evaluate the improvement in mortality or hospitalization rates and adverse events among COVID-19 patients.
• We focussed on three new oral Coronavirus agents (molnupiravir, fluvoxamine and Paxlovid) and hope to provide guidance for the roll-out of oral antivirals.

     

HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism

Background and aimPathogenesis of COVID-19 -related headache is unknown, though the induction of the trigeminal neurons through inflammation is proposed. We aimed to investigate key systemic circulating inflammatory molecules and their clinical relations in COVID-19 patients with headache.MethodsThis cross-sectional study enrolled 88 COVID-19 patients, hospitalized on a regular ward during the second wave of the pandemic. Clinical characteristics of COVID-19 patients were recorded, and laboratory tests were studied.ResultsThe mean ages of 48 COVID-19 patients with headache (47.71 ± 10.8) and 40 COVID-19 patients without headache (45.70 ± 12.72) were comparable. COVID-19 patients suffered from headache had significantly higher serum levels of HMGB1, NLRP3, ACE2, and IL-6 than COVID-19 patients without headache, whereas CGRP and IL-10 levels were similar in the groups. Angiotensin II level was significantly decreased in the headache group. COVID-19 patients with headache showed an increased frequency of pulmonary involvement and increased D- dimer levels. Furthermore, COVID-19 was more frequently associated with weight loss, nausea, and diarrhea in patients with headache. Serum NLRP3 levels were correlated with headache duration and hospital stay, while headache response to paracetamol was negatively correlated with HMGB1 and positively associated with IL-10 levels.ConclusionStronger inflammatory response is associated with headache in hospitalized COVID-19 patients with moderate disease severity. Increased levels of the circulating inflammatory and/or nociceptive molecules like HMGB1, NLRP3, and IL-6 may play a role in the potential induction of the trigeminal system and manifestation of headache secondary to SARS-CoV-2 infection.     

Knockdown of lncRNA MALAT1 ameliorates acute kidney injury by mediating the miR‐204/APOL1 pathway

BackgroundAcute kidney injury (AKI) was characterized by loss of renal function, associated with chronic kidney disease, end‐stage renal disease, and length of hospital stay. Long non‐coding RNAs (lncRNAs) participated in AKI development and progression. Here, we aimed to investigate the roles and mechanisms of lncRNA MALAT1 in AKI.MethodsAKI serum samples were obtained from 129 AKI patients. ROC analysis was conducted to confirm the diagnostic value of MALAT1 in differentiating AKI from healthy volunteers. After hypoxic treatment on HK‐2 cells, the expressions of inflammatory cytokines, MALAT1, miR‐204, APOL1, p65, and p‐p65, were measured by RT‐qPCR and Western blot assays. The targeted relationship between miR‐204 and MALAT1 or miR‐204 and APOL1 was determined by luciferase reporter assay and RNA pull‐down analysis. After transfection, CCK‐8, flow cytometry, and TUNEL staining assays were performed to evaluate the effects of MALAT1 and miR‐204 on AKI progression.ResultsFrom the results, lncRNA MALAT1 was strongly elevated in serum samples from AKI patients, with the high sensitivity and specificity concerning differentiating AKI patients from healthy controls. In vitro, we established the AKI cell model after hypoxic treatment. After experiencing hypoxia, we found significantly increased MALAT1, IL‐1β, IL‐6, and TNF‐α expressions along with decreased miR‐204 level. Moreover, the targeted relationship between MALAT1 and miR‐204 was confirmed. Silencing of MALAT1 could reverse hypoxia‐triggered promotion of HK‐2 cell apoptosis. Meanwhile, the increase of IL‐1β, IL‐6, and TNF‐α after hypoxia treatment could be repressed by MALAT1 knockdown as well. After co‐transfection with MALAT1 silencing and miR‐204 inhibition, we found that miR‐204 could counteract the effects of MALAT1 on HK‐2 cell progression and inflammation after under hypoxic conditions. Finally, NF‐κB signaling was inactivated while APOL1 expression was increased in HK‐2 cells after hypoxia treatment, and lncRNA MALAT1 inhibition reactivated NF‐κB signaling while suppressed APOL1 expression by sponging miR‐204.ConclusionsCollectively, these results illustrated that knockdown of lncRNA MALAT1 could ameliorate AKI progression and inflammation by targeting miR‐204 through APOL1/NF‐κB signaling.     

The lower expression of circulating miR‐210 and elevated serum levels of HIF‐1α in ischemic stroke; Possible markers for diagnosis and disease prediction

Background Stroke, either due to ischemia or hemorrhage, causes acute neurological damages to the brain. There is shortage of reliable biomarkers for ischemic stroke (IS), and we therefore investigated the serum concentrations of microRNA‐210 (miR‐210) and hypoxia inducible factor‐1α (HIF‐1α), as possible diagnostic and/or prognostic markers for IS.MethodsSerum samples were acquired from 52 IS patients and their healthy counterparts at five time points: upon admission, 24 and 48 h after admission, upon discharge and 3 months later. Serum levels of miR‐210 and HIF‐1α were respectively analyzed using real time RT‐PCR and ELISA. Diagnostic and prognostic accuracy tests were performed to assess the value of suggested biomarkers.ResultsIS patients demonstrated higher levels of serum HIF‐1α and lower miR‐210 in comparison to the healthy subjects. MiR‐210 was suggested to be a weak diagnostic biomarker at the time of admission (AUC = 0.61; p = 0.05), while HIF‐1α was an acceptable diagnostic marker for IS (AUC = 0.73; p < 0.0001). The higher expression of miR‐210 and lower levels of HIF‐1α were associated with better survivals in IS patients.ConclusionsSerum miR‐210 is a weak diagnostic marker of IS. Serum HIF‐1α is a better biomarker in diagnosing IS patients but further work in larger groups, including those with hemorrhagic stroke is necessary to confirm its diagnostic utility. Similarly, the prognostic potentiality of miR‐210 and HIF‐1α was acceptable but needs bigger sample size and longer follow‐up to be statistically confirmed.     

Ligation of TLR9 induced on human IL-10–secreting Tregs by 1α,25-dihydroxyvitamin D3 abrogates regulatory function

Signaling through the TLR family of molecular pattern recognition receptors has been implicated in the induction of innate and adaptive immune responses. A role for TLR signaling in the maintenance and/or regulation of Treg function has been proposed, however its functional relevance remains unclear. Here we have shown that TLR9 is highly expressed by human Treg secreting the antiinflammatory cytokine IL-10 induced following stimulation of blood and tissue CD3⁺ T cells in the presence of 1α,25-dihydroxyvitamin D3 (1α25VitD3), the active form of Vitamin D, with or without the glucocorticoid dexamethasone. By contrast, TLR9 was not highly expressed by naturally occurring CD4⁺CD25⁺ Treg or by Th1 and Th2 effector cells. Induction of TLR9, but not other TLRs, was IL-10 dependent and primarily regulated by 1α25VitD3 in vitro. Furthermore, ingestion of calcitriol (1α25VitD3) by human volunteers led to an increase of both IL-10 and TLR9 expression by CD3⁺CD4⁺ T cells analyzed directly ex vivo. Stimulation of 1α25VitD3-induced IL-10–secreting Treg with TLR9 agonists, CpG oligonucleotides, resulted in decreased IL-10 and IFN-γ synthesis and a concurrent loss of regulatory function, but, unexpectedly, increased IL-4 synthesis. We therefore suggest that TLR9 could be used to monitor and potentially modulate the function of 1α25VitD3-induced IL-10–secreting Treg in vivo, and that this has implications in cancer therapy and vaccine design.     

Inflammatory markers in acute myocardial infarction and the correlation with the severity of coronary heart disease

IntroductionThe inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established.ObjectivesThe study investigates the levels of C reactive protein (CRP), interleukin 1β (IL-1β) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group.ResultsIn the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1β showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p=.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= −0.43, p=.05). IL-1β weakly correlated with the severity of coronary lesions (rho =0.29, p=.02) and strongly with LVEF (rho= −0.8, p=.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p=.01) and with the severity of coronary atherosclerosis (rho= −0.41, p=.003).ConclusionsCRP, IL-1β and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.     

Evaluating red blood cell distribution width from community blood tests as a predictor of hospitalization and mortality in adults with SARS-CoV-2: a cohort study

BackgroundRed blood cell distribution width (RDW) has been assessed during COVID-19 patient hospitalization, however, further research should be done to evaluate RDW from routine community blood tests, before infection, as a risk factor for COVID-19 related hospitalization and mortality.Patients and methodsRDW was measured as a predictor along with age, sex, chronic illnesses, and BMI in logistic regressions to predict hospitalization and mortality. Hospitalization and mortality odds ratios (ORs) were estimated with 95% confidence intervals (CI). RDW was evaluated separately as continuous and discrete (High RDW ≥ 14.5) variables.ResultsFour thousand one hundred and sixty-eight patients were included in this study, where 824 patients (19.8%) had a high RDW value ≥14.5% (High RDW: 64.7% were female, mean age 58 years [±22] vs. Normal RDW: 60.2% female, mean age 46 years [±19]). Eight hundred and twenty-nine patients had a hospitalization, where the median time between positive PCR and hospital entry was 5 [IQR 1–18] days. Models were analyzed with RDW (continuous) and adjusted for age, sex, comorbidities, and BMI suggested an OR of 1.242 [95% CI = 1.187–2.688] for hospitalization and an OR of 2.911 [95% CI = 1.928–4.395] for mortality (p < .001). RDW (discrete) with the same adjustments presented an OR of 2.232 [95% CI = 1.853–1.300] for hospitalization and an OR of 1.263 [95% CI = 1.166–1.368] for mortality (p < .001).ConclusionsHigh RDW values obtained from community blood tests are associated with greater odds of hospitalization and mortality for patients with COVID-19.

KEY MESSAGES

• RDW measures before SARS-CoV-2 infection is a predictive factor for hospitalization and mortality.
• RDW threshold of 14.5% provides high sensitivity and specificity for COVID-19 related mortality, comparatively to other blood tests.
• Patient records should be accessed by clinicians for prior RDW results, if available, followed by further monitoring.

     

Cardiorespiratory and metabolic fitness indicators in novice volleyball trainees: effect of 1-week antioxidant supplementation with N-acetyl-cysteine/zinc/vitamin C

ObjectivesThis study aimed to determine the effect of 7-day dietary supplementation of N-acetylcysteine (NAC)/zinc/vitamin C on the time-to-exhaustion (TTE), the cardiorespiratory fitness (CRF) index, and metabolic indicators.MethodsThis study enrolled volleyball student trainees (n = 18 men) who took NAC/zinc/vitamin C (750 mg/5 mg/100 mg) for 7 days at Jouf University, Saudi Arabia. The CRF index and TTE were determined. Serum concentrations of metabolic regulators (insulin, betatrophin, and hepatocyte growth factor), biomarkers of cellular damage/hypoxia, and indicators of lipid and glycemic control were measured.ResultsSupplementation improved the TTE and CRF index, and lowered cytochrome c, C-reactive protein, hypoxia-inducible factor-1α (HIF-1α), total cholesterol, insulin, and glycated hemoglobin values. Before and after supplementation, the CRF index was negatively correlated with body mass index and positively correlated with the TTE. Before supplementation, the CRF index was positively correlated with betatrophin concentrations, and hepatocyte growth factor concentrations were positively correlated with betatrophin concentrations and negatively correlated with the homeostasis model assessment of insulin resistance index. After supplementation, the CRF index was negatively correlated with HIF-1α concentrations and metabolites. Additionally, the TTE was negatively correlated with HIF-1α, cytochrome c, and triacylglycerol concentrations.ConclusionSupplementation of NAC/zinc/vitamin C improves metabolic and CRF performance.     

Long non-coding (lnc)RNA profiling and the role of a key regulator lnc-PNRC2-1 in the transforming growth factor-β1-induced epithelial–mesenchymal transition of CNE1 nasopharyngeal carcinoma cells

ObjectivesTo identify key long non-coding (lnc)RNAs responsible for the epithelial–mesenchymal transition (EMT) of CNE1 nasopharyngeal carcinoma cells and to investigate possible regulatory mechanisms in EMT.MethodsCNE1 cells were divided into transforming growth factor (TGF)-β1-induced EMT and control groups. The mRNA and protein expression of EMT markers was determined by real-time quantitative PCR and western blotting. Differentially expressed genes (DEGs) between the two groups were identified by RNA sequencing analysis, and DEG functions were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. EMT marker expression was re-evaluated by western blotting after knockdown of a selected lncRNA.ResultsTGF-β1-induced EMT was characterized by decreased E-cadherin and increased vimentin, N-cadherin, and Twist expression at both mRNA and protein levels. Sixty lncRNA genes were clustered in a heatmap, and mRNA expression of 14 dysregulated lncRNAs was consistent with RNA sequencing. Knockdown of lnc-PNRC2-1 increased expression of its antisense gene MYOM3 and reduced expression of EMT markers, resembling treatment with the TGF-β1 receptor inhibitor LY2109761.ConclusionVarious lncRNAs participated indirectly in the TGF-β1-induced EMT of CNE1 cells. Lnc-PNRC2-1 may be a key regulator of this and is a potential target to alleviate CNE1 cell EMT.     

Identification of C-C Chemokine Receptor 1 (CCR1) as the Monocyte Hemofiltrate C-C Chemokine (HCC)-1 Receptor

Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1α. Unlike most chemokines, it is constitutively secreted by tissues and is present at high concentrations in normal human plasma. Also atypical for chemokines, HCC-1 is reported not to be chemotactic for leukocytes. In this paper, we have investigated the chemokine receptor usage and downstream signaling pathways of HCC-1. Cross-desensitization experiments using THP-1 cells suggested that HCC-1 and MIP-1α activated the same receptor. Experiments using a panel of cloned chemokine receptors revealed that HCC-1 specifically activated C-C chemokine receptor (CCR)1, but not closely related receptors, including CCR5. HCC-1 competed with MIP-1α for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC₅₀ = 93 nM versus 1.3 nM for MIP-1α). Similarly, HCC-1 was less potent than MIP-1α in inducing inhibition of adenylyl cyclase in CCR1-transfected cells. HCC-1 induced chemotaxis of freshly isolated human monocytes, THP-1 cells, and CCR1-transfected cells, and the optimal concentration for cell migration (100 nM) was ∼100-fold lower than that of MIP-1α (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes.