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1.
Clin Nutr ESPEN ; 50: 326-329, 2022 08.
Article in English | MEDLINE | ID: covidwho-1959410

ABSTRACT

BACKGROUND & AIMS: Obesity courses with metabolic and inflammatory changes that include, among others, higher expression of the renin-angiotensin-aldosterone system. The pathophysiology of the new coronavirus suggests an affinity for angiotensin-2 converting enzyme receptors, cytokine storm, and systemic hypercoagulability. Thus, obesity could contribute to the worse evolution of individuals with COVID-19. Here we evaluated the clinical outcome and age of SARS-CoV-2 infection in patients with higher BMI compared with normal BMI at the São Francisco de Assis University Hospital (HUSF), in Bragança Paulista, SP. METHODS: Retrospective observational study with a review of medical records from June of 2020 to May of 2021 of patients positive for SARS-CoV-2 from HUSF. Demographic, anthropometric, and metabolic data were collected for correlation analysis. The study was approved by the Ethical Committee under CAAE: 34121820.3.0000.5514. RESULTS: 360 medical records were analyzed, of which 125 were included. The mean age of patients with obesity was significantly lower than overweight and normal weight, both in the overall mean (p-value 0.002-66 versus 56 and 56) and in the mean age of mortality (p-value 0.003-59 versus 61 and 76). The mean plasma calcium in the last sample collected during hospitalization of patients with obesity was significantly higher than that of overweight and normal weight (p-value < 0.001-7.8 versus 8.1 and 8.6). The mean hemoglobin in the first admission sample was also significantly higher in patients with obesity compared to the other groups (p-value 0.041-12.5 versus 12.9 and 13.6). On the other hand, the plasma concentration of urea in the first sample of hospitalization of patients with normal weight was higher than in patients with overweight and obesity (p-value 0.036-90.4 versus 64.8 and 57.1). CONCLUSION: Our findings suggest that age is not a determining factor for the death outcome in patients with obesity. However, obesity contributes to metabolic changes and mortality in SARS-CoV-2 infected patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Calcium , Humans , Obesity , Observational Studies as Topic , Overweight , Urea
2.
Cells ; 11(15)2022 Jul 23.
Article in English | MEDLINE | ID: covidwho-1957236

ABSTRACT

S100 is a broad subfamily of low-molecular weight calcium-binding proteins (9-14 kDa) with structural similarity and functional discrepancy. It is required for inflammation and cellular homeostasis, and can work extracellularly, intracellularly, or both. S100 members participate in a variety of activities in a healthy cell, including calcium storage and transport (calcium homeostasis). S100 isoforms that have previously been shown to play important roles in the immune system as alarmins (DAMPs), antimicrobial peptides, pro-inflammation stimulators, chemo-attractants, and metal scavengers during an innate immune response. Currently, during the pandemic, it was found that several members of the S100 family are implicated in the pathophysiology of COVID-19. Further, S100 family protein members were proposed to be used as a prognostic marker for COVID-19 infection identification using a nasal swab. In the present review, we compiled the vast majority of recent studies that focused on the multifunctionality of S100 proteins in the complex immune system and its associated activities. Furthermore, we shed light on the numerous molecular approaches and signaling cascades regulated by S100 proteins during immune response. In addition, we discussed the involvement of S100 protein members in abnormal defense systems during the pathogenesis of COVID-19.


Subject(s)
COVID-19 , S100 Proteins , Alarmins , Calcium/metabolism , Humans , Immune System/metabolism , Inflammation/metabolism , S100 Proteins/metabolism
3.
Einstein (Sao Paulo) ; 20: eAO6953, 2022.
Article in English | MEDLINE | ID: covidwho-1955457

ABSTRACT

OBJECTIVE: To evaluate anthropometric and clinical data, muscle mass, subcutaneous fat, spine bone mineral density, extent of acute pulmonary disease related to COVID-19, quantification of pulmonary emphysema, coronary calcium, and hepatic steatosis using chest computed tomography of hospitalized patients with confirmed diagnosis of COVID-19 pneumonia and verify its association with disease severity. METHODS: A total of 123 adults hospitalized due to COVID-19 pneumonia were enrolled in the present study, which evaluated the anthropometric, clinical and chest computed tomography data (pectoral and paravertebral muscle area and density, subcutaneous fat, thoracic vertebral bodies density, degree of pulmonary involvement by disease, coronary calcium quantification, liver attenuation measurement) and their association with poorer prognosis characterized through a combined outcome of intubation and mechanical ventilation, need of intensive care unit, and death. RESULTS: Age (p=0.013), body mass index (p=0.009), lymphopenia (p=0.034), and degree of pulmonary involvement of COVID-19 pneumonia (p<0.001) were associated with poor prognosis. Extent of pulmonary involvement by COVID-19 pneumonia had an odds ratio of 1,329 for a poor prognosis and a cutoff value of 6.5 for increased risk, with a sensitivity of 64.9% and specificity of 67.1%. CONCLUSION: The present study found an association of high body mass index, older age, extent of pulmonary involvement by COVID-19, and lymphopenia with severity of COVID-19 pneumonia in hospitalized patients.


Subject(s)
COVID-19 , Lymphopenia , Adult , COVID-19/diagnostic imaging , Calcium , Humans , Prognosis , Retrospective Studies , Tomography, X-Ray Computed/methods
4.
Int J Mol Sci ; 21(16)2020 Aug 06.
Article in English | MEDLINE | ID: covidwho-1934101

ABSTRACT

The recently discovered 340-cavity in influenza neuraminidase (NA) N6 and N7 subtypes has introduced new possibilities for rational structure-based drug design. However, the plasticity of the 340-loop (residues 342-347) and the role of the 340-loop in NA activity and substrate binding have not been deeply exploited. Here, we investigate the mechanism of 340-cavity formation and demonstrate for the first time that seven of nine NA subtypes are able to adopt an open 340-cavity over 1.8 µs total molecular dynamics simulation time. The finding that the 340-loop plays a role in the sialic acid binding pathway suggests that the 340-cavity can function as a druggable pocket. Comparing the open and closed conformations of the 340-loop, the side chain orientation of residue 344 was found to govern the formation of the 340-cavity. Additionally, the conserved calcium ion was found to substantially influence the stability of the 340-loop. Our study provides dynamical evidence supporting the 340-cavity as a druggable hotspot at the atomic level and offers new structural insight in designing antiviral drugs.


Subject(s)
Antiviral Agents/pharmacology , Drug Development , Neuraminidase/chemistry , Orthomyxoviridae/enzymology , Binding Sites , Calcium/chemistry , Ions , Models, Molecular , Molecular Dynamics Simulation , N-Acetylneuraminic Acid/chemistry , Principal Component Analysis , Protein Structure, Secondary , Thermodynamics
5.
Int J Mol Sci ; 23(13)2022 Jun 22.
Article in English | MEDLINE | ID: covidwho-1934118

ABSTRACT

A decrease in skeletal muscle contractile activity or its complete cessation (muscle unloading or disuse) leads to muscle fibers' atrophy and to alterations in muscle performance. These changes negatively affect the quality of life of people who, for one reason or another, are forced to face a limitation of physical activity. One of the key regulatory events leading to the muscle disuse-induced changes is an impairment of calcium homeostasis, which leads to the excessive accumulation of calcium ions in the sarcoplasm. This review aimed to analyze the triggering mechanisms of calcium homeostasis impairment (including those associated with the accumulation of high-energy phosphates) under various types of muscle unloading. Here we proposed a hypothesis about the regulatory mechanisms of SERCA and IP3 receptors activity during muscle unloading, and about the contribution of these mechanisms to the excessive calcium ion myoplasmic accumulation and gene transcription regulation via excitation-transcription coupling.


Subject(s)
Calcium , Quality of Life , Adenosine Triphosphate , Humans , Muscle Contraction , Muscle, Skeletal/pathology , Muscular Atrophy/pathology
6.
Int J Mol Sci ; 23(13)2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1917525

ABSTRACT

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.


Subject(s)
Acute Kidney Injury , COVID-19 , Vitamin D Deficiency , Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , COVID-19/complications , COVID-19/drug therapy , Calcium , Humans , SARS-CoV-2 , Vitamin D/metabolism , Vitamin D/therapeutic use , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapy , Vitamins/therapeutic use
7.
J Nanobiotechnology ; 20(1): 314, 2022 Jul 06.
Article in English | MEDLINE | ID: covidwho-1916963

ABSTRACT

Acute respiratory distress syndrome (ARDS), caused by noncardiogenic pulmonary edema (PE), contributes significantly to Coronavirus 2019 (COVID-19)-associated morbidity and mortality. We explored the effect of transmembrane osmotic pressure (OP) gradients in PE using a fluorescence resonance energy transfer-based Intermediate filament (IF) tension optical probe. Angiotensin-II- and bradykinin-induced increases in intracellular protein nanoparticle (PN)-OP were associated with inflammasome production and cytoskeletal depolymerization. Intracellular protein nanoparticle production also resulted in cytomembrane hyperpolarization and L-VGCC-induced calcium signals, which differed from diacylglycerol-induced calcium increment via TRPC6 activation. Both pathways involve voltage-dependent cation influx and OP upregulation via SUR1-TRPM4 channels. Meanwhile, intra/extracellular PN-induced OP gradients across membranes upregulated pulmonary endothelial and alveolar barrier permeability. Attenuation of intracellular PN, calcium signals, and cation influx by drug combinations effectively relieved intracellular OP and pulmonary endothelial nonselective permeability, and improved epithelial fluid absorption and PE. Thus, PN-OP is pivotal in pulmonary edema in ARDS and COVID-19, and transmembrane OP recovery could be used to treat pulmonary edema and develop new drug targets in pulmonary injury.


Subject(s)
COVID-19 , Nanoparticles , Pulmonary Edema , Respiratory Distress Syndrome , COVID-19/drug therapy , Calcium , Humans , Osmotic Pressure , Proteins , Pulmonary Edema/complications , Pulmonary Edema/drug therapy , Respiratory Distress Syndrome/drug therapy
8.
Cell Calcium ; 101: 102524, 2022 01.
Article in English | MEDLINE | ID: covidwho-1914206

ABSTRACT

A recent publication proposes that T cell receptor activation elicits formation of the Ca2+ releasing messenger NAADP from NAADPH, catalysed by the NADPH oxidase DUOX. This is in contrast to the hitherto prevailing view that CD38 is critical for NAADP formation. Is it time to reassess the role of CD38?


Subject(s)
Calcium , Membrane Glycoproteins , ADP-ribosyl Cyclase 1/metabolism , Calcium/metabolism , Calcium Signaling , Membrane Glycoproteins/metabolism , NADP/metabolism , Receptors, Antigen, T-Cell
9.
Curr Cancer Drug Targets ; 22(5): 351-360, 2022.
Article in English | MEDLINE | ID: covidwho-1910830

ABSTRACT

BACKGROUND: The hypothesis that hypertension is clinically associated with an enhanced risk of developing cancer has been highlighted. However, the working principles involved in this link are still under intensive discussion. A correlation among inflammation, hypertension, and cancer could accurately describe the clinical link between these diseases. In addition, dyshomeostasis of Ca2+ has been considered to be involved in both cancer and hypertension, and inflammation. There is a strong link between Ca2+ signalling, e.g. enhanced Ca2+ signals, and inflammatory outcomes. cAMP also modulates pro- and anti-inflammatory outcomes; pharmaceuticals, which increase intracellular cAMP levels, can decrease the production of proinflammatory mediators and enhance the production of antiinflammatory outcomes. OBJECTIVE: This article highlights the participation of Ca2+/cAMP signalling in the clinical association among inflammation, hypertension, and an enhanced risk for the development of cancer. In addition, considering that research on coronavirus disease 2019 (COVID-19) is a rapidly evolving field, this article also reviews recent reports related to the role of Ca2+ channel blockers in restoring Ca2+ signalling disruption due to COVID-19, including the relationship among COVID-19, cancer, and hypertension. CONCLUSION: An understanding of the association among these diseases could expand current pharmacotherapy, involving Ca2+ channel blockers and pharmaceuticals that facilitate a rise in cAMP levels.


Subject(s)
COVID-19 , Hypertension , Neoplasms , COVID-19/complications , Calcium/metabolism , Calcium Signaling , Cyclic AMP/metabolism , Cyclic AMP/therapeutic use , Humans , Hypertension/complications , Hypertension/drug therapy , Inflammation , Pharmaceutical Preparations
10.
Sci Rep ; 12(1): 11078, 2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1908298

ABSTRACT

Immune cell chemotaxis to the sites of pathogen invasion is critical for fighting infection, but in life-threatening conditions such as sepsis and Covid-19, excess activation of the innate immune system is thought to cause a damaging invasion of immune cells into tissues and a consequent excessive release of cytokines, chemokines and neutrophil extracellular traps (NETs). In these circumstances, tempering excessive activation of the innate immune system may, paradoxically, promote recovery. Here we identify the antimalarial compound artemisinin as a potent and selective inhibitor of neutrophil and macrophage chemotaxis induced by a range of chemotactic agents. Artemisinin released calcium from intracellular stores in a similar way to thapsigargin, a known inhibitor of the Sarco/Endoplasmic Reticulum Calcium ATPase pump (SERCA), but unlike thapsigargin, artemisinin blocks only the SERCA3 isoform. Inhibition of SERCA3 by artemisinin was irreversible and was inhibited by iron chelation, suggesting iron-catalysed alkylation of a specific cysteine residue in SERCA3 as the mechanism by which artemisinin inhibits neutrophil motility. In murine infection models, artemisinin potently suppressed neutrophil invasion into both peritoneum and lung in vivo and inhibited the release of cytokines/chemokines and NETs. This work suggests that artemisinin may have value as a therapy in conditions such as sepsis and Covid-19 in which over-activation of the innate immune system causes tissue injury that can lead to death.


Subject(s)
Artemisinins , COVID-19 , Extracellular Traps , Macrophages , Neutrophils , Sepsis , Animals , Artemisinins/pharmacology , COVID-19/drug therapy , Calcium/metabolism , Calcium-Transporting ATPases/metabolism , Chemotaxis/drug effects , Cytokines/biosynthesis , Cytokines/metabolism , Extracellular Traps/metabolism , Macrophages/drug effects , Macrophages/metabolism , Mice , Neutrophils/drug effects , Neutrophils/metabolism , Thapsigargin/pharmacology
11.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(5): 502-508, 2022 May.
Article in Chinese | MEDLINE | ID: covidwho-1903520

ABSTRACT

OBJECTIVE: To analyze the relationship between blood electrolytes and the prognosis of patients with severe coronavirus disease 2019 (COVID-19) and to provide assistance for clinical decision-making. METHODS: The clinical data of patients with severe COVID-19 admitted to intensive care unit (ICU) of the Wuhan Third Hospital by the Shanghai aid-Hubei medical team from January 21 to March 4, 2020 were collected. Excluding ineligible patients, 110 patients were finally enrolled. The patients' gender, age, temperature, heart rate, systolic and diastolic blood pressure, clinical symptoms at admission, time of symptom onset, duration of fever, and relevant indicators at admission to ICU (including blood potassium, chloride, sodium, calcium, phosphorus, and magnesium, etc.) and prognosis were analyzed. The patients were grouped by blood potassium or calcium levels or blood potassium/calcium ratio. The Kaplan-Meier survival curves were used to analyze the survival of patients in each group. The relationship between the potassium/calcium ratio and the prognosis was analyzed using restricted cubic spline plots. The relationship between each index in the different models and the prognosis was analyzed using Cox regression models. RESULTS: Among 110 severe COVID-19 patients, 78 cases survived, and 32 cases died. Compared with the surviving group, patients in the death group had higher blood potassium levels [mmol/L: 4.25 (3.80, 4.65) vs. 3.90 (3.60, 4.20), P < 0.05] and lower blood calcium levels (mmol/L: 2.00±0.14 vs. 2.19±0.18, P < 0.05). The Kaplan-Meier survival curves showed that patients in the potassium > 4.2 mmol/L group had a worse prognosis than the potassium < 3.8 mmol/L group and the potassium 3.8-4.2 mmol/L group (P = 0.011), patients in the calcium > 2.23 mmol/L group had a better prognosis than the calcium < 2.03 mmol/L group and the calcium 2.03-2.23 mmol/L group, and the lower calcium group had a worse prognosis (P = 0.000 15). Cox regression analysis showed that the hazard ratio (HR) of blood potassium and calcium were 2.08 and 0.01, respectively, in model 1 (single blood potassium or calcium) and in model 2 (model 1 plus age and gender), the HR of blood potassium and calcium were 1.98 and 0.01 respectively, which were significantly associated with patient prognosis (all P < 0.05). Patients in the group with the potassium/calcium ratio > 1.9 had higher blood potassium levels and a higher proportion of mechanical ventilation, lower calcium levels and lower proportion of survival, and longer time of ICU admission compared with the groups with the potassium/calcium ratio < 1.7 and 1.7-1.9. The Kaplan-Meier survival curves showed that the survival rate of the potassium/calcium ratio > 1.9 group was the lowest (P < 0.000 1), and there was no statistically significant difference in survival between the potassium/calcium ratio < 1.7 group and the potassium/calcium ratio 1.7-1.9 group. A restricted cubic spline plot corrected for age and gender showed that patients in the potassium/calcium ratio > 1.8 group had HR values > 1. Cox regression analysis corrected for other indicators showed that the potassium/calcium ratio was still associated with patient prognosis (HR = 4.85, P = 0.033). CONCLUSION: Blood potassium, calcium, and the potassium/calcium ratio at ICU admission are related to the prognosis of patients with severe COVID-19, and the potassium/calcium ratio is an independent risk factor for the death of patients. The higher the potassium/calcium ratio, the worse the prognosis of patients.


Subject(s)
COVID-19 , Sepsis , Calcium , China , Electrolytes , Humans , Potassium , Prognosis , Retrospective Studies
12.
Poult Sci ; 101(6): 101849, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1900091

ABSTRACT

Influence of marine mineral complex (CeltiCal) as a partial substitute for limestone on growth efficiency, carcass traits, meat quality, bone strength, calcium (Ca) retention, and immune response was investigated in broilers fed low-Ca diets with or without phytase (PHY) addition for a 35-d trial period. A total of 300 one-day-old Ross 308 straight-run broilers were randomly allocated to: T1 (positive control), recommended Ca levels + PHY; T2 (negative control), 0.2% below the recommended Ca levels + PHY; T3, 0.1% below the recommended Ca levels + 0.2% CeltiCal + PHY; T4, 0.2% below the recommended Ca levels + 0.4% CeltiCal + PHY; T5, 0.2% below the recommended Ca levels + 0.4% CeltiCal. PHY was added at 500 phytase units/kg diets. Each dietary treatment had 10 replications of 6 chicks each. Results revealed that production efficiency factor was greater for T4 compared to T2 and T5 during 22-35 d and for T1, T3, and T4 compared to T2 during 0 to 35 d (P < 0.05). Feed conversion ratio was lower for T3 and T4 compared to T2 and T5 during 0 to 35 d (P < 0.05). T4 had a greater (P < 0.05) dressing percentage than T2, which had a lighter (P < 0.01) small intestinal relative weight than all other treatments. Breast meat temperature at 15 min postmortem was highest for T1 and lowest for T3 (P < 0.001). Breast meat pH was greater for T1 compared to T5 at 15 min postmortem and for T3 compared to T4 at 24 h postmortem (P < 0.05). T5 had a lower breast meat redness than all other treatments at 15 min postmortem and then T1 and T3 at 24 h postmortem (P < 0.01). Tibia and femur weights were greater (P < 0.05) for T3, T4, and T5 compared to T2, which had the lowest tibia ash content (P < 0.05) and femur geometric properties (P < 0.001). Greater antibodies to infectious bronchitis virus (P < 0.01) and Ca retention (P < 0.001) were observed for T3 and T4 in comparison to T2. Based on the findings of this research, CeltiCal can adequately replace a considerable portion of limestone in broiler reduced-Ca diets containing PHY.


Subject(s)
6-Phytase , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Calcium , Calcium Carbonate , Calcium, Dietary , Chickens , Diet/veterinary , Dietary Supplements , Immunity , Meat , Minerals
13.
Int J Mol Sci ; 23(11)2022 May 27.
Article in English | MEDLINE | ID: covidwho-1892895

ABSTRACT

Identification of alternative attenuation targets of Mycobacterium tuberculosis (Mtb) is pivotal for designing new candidates for live attenuated anti-tuberculosis (TB) vaccines. In this context, the CtpF P-type ATPase of Mtb is an interesting target; specifically, this plasma membrane enzyme is involved in calcium transporting and response to oxidative stress. We found that a mutant of MtbH37Rv lacking ctpF expression (MtbΔctpF) displayed impaired proliferation in mouse alveolar macrophages (MH-S) during in vitro infection. Further, the levels of tumor necrosis factor and interferon-gamma in MH-S cells infected with MtbΔctpF were similar to those of cells infected with the parental strain, suggesting preservation of the immunogenic capacity. In addition, BALB/c mice infected with Mtb∆ctpF showed median survival times of 84 days, while mice infected with MtbH37Rv survived 59 days, suggesting reduced virulence of the mutant strain. Interestingly, the expression levels of ctpF in a mouse model of latent TB were significantly higher than in a mouse model of progressive TB, indicating that ctpF is involved in Mtb persistence in the dormancy state. Finally, the possibility of complementary mechanisms that counteract deficiencies in Ca2+ transport mediated by P-type ATPases is suggested. Altogether, our results demonstrate that CtpF could be a potential target for Mtb attenuation.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Animals , Calcium , Calcium-Transporting ATPases , Cell Membrane/pathology , Mice , Tuberculosis/microbiology , Virulence/genetics
14.
Cells ; 11(11)2022 06 05.
Article in English | MEDLINE | ID: covidwho-1892776

ABSTRACT

All human life starts with a calcium (Ca2+) wave. This ion regulates a plethora of cellular functions ranging from fertilisation and birth to development and cell death. A sophisticated system is responsible for maintaining the essential, tight concentration of calcium within cells. Intricate components of this Ca2+ network are store-operated calcium channels in the cells' membrane. The best-characterised store-operated channel is the Ca2+ release-activated Ca2+ (CRAC) channel. Currents through CRAC channels are critically dependent on the correct function of two proteins: STIM1 and Orai1. A disruption of the precise mechanism of Ca2+ entry through CRAC channels can lead to defects and in turn to severe impacts on our health. Mutations in either STIM1 or Orai1 proteins can have consequences on our immune cells, the cardiac and nervous system, the hormonal balance, muscle function, and many more. There is solid evidence that altered Ca2+ signalling through CRAC channels is involved in the hallmarks of cancer development: uncontrolled cell growth, resistance to cell death, migration, invasion, and metastasis. In this work we highlight the importance of Ca2+ and its role in human health and disease with focus on CRAC channels.


Subject(s)
Calcium Release Activated Calcium Channels , Calcium , Calcium/metabolism , Calcium Release Activated Calcium Channels/metabolism , Calcium Signaling/physiology , Humans , Literacy , ORAI1 Protein/metabolism
15.
Elife ; 112022 06 07.
Article in English | MEDLINE | ID: covidwho-1879632

ABSTRACT

TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using trophoblasts as a model for cell fusion, we demonstrate that Ca2+ influx through the Ca2+ permeable transient receptor potential vanilloid channel TRPV4 is critical for TMEM16F activation and plays a role in subsequent human trophoblast fusion. GSK1016790A, a TRPV4 specific agonist, robustly activates TMEM16F in trophoblasts. We also show that TRPV4 and TMEM16F are functionally coupled within Ca2+ microdomains in a human trophoblast cell line using patch-clamp electrophysiology. Pharmacological inhibition or gene silencing of TRPV4 hinders TMEM16F activation and subsequent trophoblast syncytialization. Our study uncovers the functional expression of TRPV4 and one of the physiological activation mechanisms of TMEM16F in human trophoblasts, thus providing us with novel strategies to regulate CaPLSase activity as a critical checkpoint of physiologically and disease-relevant cell fusion events.


Subject(s)
Anoctamins/metabolism , COVID-19 , HIV Infections , Phospholipid Transfer Proteins/metabolism , Calcium/metabolism , Female , Humans , Placenta/metabolism , Pregnancy , RNA, Viral , SARS-CoV-2 , TRPV Cation Channels/genetics , TRPV Cation Channels/metabolism , Trophoblasts/metabolism
16.
Arch Cardiovasc Dis ; 115(5): 276-287, 2022 May.
Article in English | MEDLINE | ID: covidwho-1878028

ABSTRACT

BACKGROUND: Coronary artery calcium (CAC) is an independent risk factor for major adverse cardiovascular events; however, its impact on coronavirus disease 2019 (COVID-19) mortality remains unclear, especially in patients without known atheromatous disease. AIMS: To evaluate the association between CAC visual score and 6-month mortality in patients without history of atheromatous disease hospitalized with COVID-19 pneumonia. METHODS: A single-centre observational cohort study was conducted, involving 293 consecutive patients with COVID-19 in Paris, France, between 13 March and 30 April 2020, with a 6-month follow-up. Patients with a history of ischaemic stroke or coronary or peripheral artery disease were excluded. The primary outcome was all-cause mortality at 6 months according to CAC score, which was assessed by analysing images obtained after the first routine non-electrocardiogram-gated computed tomography scan performed to detect COVID-19 pneumonia. RESULTS: A total of 251 patients (mean age 64.8±16.7 years) were included in the analysis. Fifty-one patients (20.3%) died within 6 months. The mortality rate increased with the magnitude of calcifications, and was 10/101 (9.9%), 15/66 (22.7%), 10/34 (29.4%) and 16/50 (32.0%) for the no CAC, mild CAC, moderate CAC and heavy CAC groups, respectively (p=0.004). Compared with the no calcification group, adjusted risk of death increased progressively with CAC: hazard ratio (HR) 2.37 (95% confidence interval [CI] 1.06-5.27), HR 3.1 (95% CI 1.29-7.45) and HR 4.02 (95% CI 1.82-8.88) in the mild, moderate and heavy CAC groups, respectively. CONCLUSIONS: Non-electrocardiogram-gated computed tomography during the initial pulmonary assessment of patients with COVID-19 without atherosclerotic cardiovascular disease showed a high prevalence of mild, moderate and heavy CAC. CAC score was related to 6-month mortality, independent of conventional cardiovascular risk factors. These results highlight the importance of CAC scoring for patients hospitalized with COVID-19, and calls for attention to patients with high CAC.


Subject(s)
Brain Ischemia , COVID-19 , Coronary Artery Disease , Stroke , Vascular Calcification , Aged , Aged, 80 and over , Calcium , Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Coronary Vessels , Humans , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Vascular Calcification/diagnostic imaging
17.
Heart ; 108(12): 899-901, 2022 05 25.
Article in English | MEDLINE | ID: covidwho-1874629

Subject(s)
Calcium , Heart , Heart Rate , Humans
18.
J Bone Miner Metab ; 40(4): 663-669, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1872444

ABSTRACT

INTRODUCTION: Despite the high prevalence of hypocalcemia in patients with COVID-19, very limited studies have been designed to evaluate etiologies of this disorder. This study was designed to evaluate the status of serum parameters involved in calcium metabolism in patients with COVID-19 and hypocalcemia. MATERIALS AND METHODS: This cross-sectional study was conducted on 123 hospitalized patients with COVID-19. Serum concentrations of PTH, 25 (OH) D, magnesium, phosphate, and albumin were assessed and compared across three groups of moderate/severe hypocalcemia (serum total calcium < 8 mg/dl), mild hypocalcemia (8 mg/dl ≤ serum total calcium < 8.5 mg/dl) and normocalcemia (serum total calcium ≥ 8.5 mg/dl). Multivariate analyses were performed to evaluate the independent roles of serum parameters in hypocalcemia. RESULTS: In total, 65.9% of the patients had hypocalcemia. Vitamin D deficiency was found in 44.4% and 37.7% of moderate/severe and mild hypocalcemia cases, respectively, compared to 7.1% in the normal serum total calcium group (P = 0.003). In multivariate analysis, vitamin D deficiency was independently associated with 6.2 times higher risk of hypocalcemia (P = 0.001). Only a minority of patients with hypocalcemia had appropriately high PTH (15.1% and 14.3% in mild and moderate/severe hypocalcemia, respectively). Serum PTH was low/low-normal in 40.0% of patients with moderate/severe low-corrected calcium group. Magnesium deficiency was not associated with hypocalcemia in univariate and multivariate analysis. CONCLUSION: Vitamin D deficiency plays a major role in hypocalcemia among hospitalized patients with COVID-19. Inappropriately low/low-normal serum PTH may be a contributing factor in this disorder.


Subject(s)
COVID-19 , Hypocalcemia , Hypoparathyroidism , Vitamin D Deficiency , COVID-19/complications , Calcium , Cross-Sectional Studies , Humans , Hypocalcemia/epidemiology , Magnesium , Parathyroid Hormone , Vitamin D , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology
19.
BMJ Open ; 12(4): e055123, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1868733

ABSTRACT

INTRODUCTION: Identifying and excluding coronary artery disease (CAD) in patients with atypical angina pectoris (AP) and non-specific thoracic complaints is a challenge for general practitioners (GPs). A diagnostic and prognostic tool could help GPs in determining the likelihood of CAD and guide patient management. Studies in outpatient settings have shown that the CT-based coronary calcium score (CCS) has high accuracy for diagnosis and exclusion of CAD. However, the CT CCS test has not been tested in a primary care setting. In the COroNary Calcium scoring as fiRst-linE Test to dEtect and exclude coronary artery disease in GPs patients with stable chest pain (CONCRETE) study, the impact of direct access of GPs to CT CCS will be investigated. We hypothesise that this will allow for early diagnosis of CAD and treatment, more efficient referral to the cardiologist and a reduction of healthcare-related costs. METHODS AND ANALYSIS: CONCRETE is a pragmatic multicentre trial with a cluster randomised design, in which direct GP access to the CT CCS test is compared with standard of care. In both arms, at least 40 GP offices, and circa 800 patients with atypical AP and non-specific thoracic complaints will be included. To determine the increase in detection and treatment rate of CAD in GP offices, the CVRM registration rate is derived from the GPs electronic registration system. Individual patients' data regarding cardiovascular risk factors, expressed chest pain complaints, quality of life, downstream testing and CAD diagnosis will be collected through questionnaires and the electronic GP dossier. ETHICS AND DISSEMINATION: CONCRETE has been approved by the Medical Ethical Committee of the University Medical Center of Groningen. TRIAL REGISTRATION NUMBER: NTR 7475; Pre-results.


Subject(s)
Coronary Artery Disease , General Practitioners , Angina Pectoris/complications , Angina Pectoris/diagnosis , Calcium , Chest Pain/diagnosis , Chest Pain/etiology , Coronary Angiography/methods , Coronary Artery Disease/complications , Coronary Artery Disease/diagnosis , Humans , Multicenter Studies as Topic , Pragmatic Clinical Trials as Topic , Predictive Value of Tests , Quality of Life , Randomized Controlled Trials as Topic
20.
J Trace Elem Med Biol ; 73: 127015, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1867436

ABSTRACT

OBJECTIVE: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), a worldwide health problem, is the cause of 2019 coronavirus disease. This study aimed to compare the trace element (selenium and iron), electrolyte (calcium and sodium), and physical activity levels of COVID-19 patients before and after COVID-19 treatment. METHOD: This prospective study was conducted in patients diagnosed with COVID-19 (n = 15). Trace element (selenium and iron), electrolyte (calcium and sodium), and physical activity levels of the patients were compared before and after the treatment. RESULT: Most of patients had selenium deficiency (86.7 %), iron deficiency (73.3 %), calcium deficiency (66.7 %) and sodium deficiency (46.7 %) before COVID-19 treatment. The most important improvements were seen in iron deficiency (from 73.3 % to 26.7 %) and sodium deficiency (from 46.7 % to 13.3 %) after the treatment. Selenium, iron, calcium, and sodium levels of the patients were significantly higher after the treatment (p < 0.05). The patients had low physical activity before and after COVID-19 treatment. In addition, no statistically significant difference was found in the comparison of physical activity levels (p > 0.05). CONCLUSION: This study indicated that selenium, iron, calcium, and sodium levels and deficiencies might improve after treating patients with COVID-19. However, the results of this study showed that the physical activity levels of COVID-19 patients might remain stable and low throughout the treatment process.


Subject(s)
COVID-19 , Selenium , Trace Elements , COVID-19/drug therapy , Calcium , Electrolytes , Exercise , Humans , Ions , Iron , Prospective Studies , SARS-CoV-2 , Selenium/therapeutic use , Sodium , Trace Elements/therapeutic use
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