A review of epidemic investigation on cold-chain food-mediated SARS-CoV-2 transmission and food safety consideration during COVID-19 pandemic.

COVID-19 has brought speculations on potential transmission routes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the pandemic. It is reported that the main route of virus transmission to be person-to-person by respiratory droplets; however, people have raised concerns on the possible transmission of SARS-CoV-2 to humans via food and packaging and its potential effects on food safety. This review discusses food safety issues in the COVID-19 pandemic and reveals its possible transmission in cold-chain food. The first outbreak of COVID-19 in late 2019 was associated with a seafood market in Wuhan, China, while the second outbreak of COVID-19 in June 2020 was also related to a seafood market in Beijing, China. As of 2020, several frozen seafood products linked with SARS-CoV-2 have been reported in China. According to the current survey and scientific studies, the risk of infection by SARS-CoV-2 from cold-chain food, food products, and food packaging is thought to be very low. However, studies on food cold chain contamination have shown that SARS-CoV-2 remained highly stable under refrigerated (4°C) and even in freezing conditions (-10 to -80°C). Since one mode of SARS-CoV-2 transmission appears to be touching contaminated surfaces, it is important to clean and sanitize food contact surfaces properly. Understanding food safety hazard risks is essential to avoid potential negative health effects and SARS-CoV-2 transmission in the food supply chain during the COVID-19 pandemic.

Renal chymase-dependent pathway for angiotensin II formation mediated acute kidney injury in a mouse model of aristolochic acid I-induced acute nephropathy.

Angiotensin-converting enzyme (ACE) is the primary enzyme that converts angiotensin I (Ang I) to angiotensin II (Ang II) in the renin-angiotensin system (RAS). However, chymase hydrates Ang I to Ang II independently of ACE in some kidney diseases, and it may play an important role. The present study investigated whether chymase played a crucial role in aristolochic acid I (AAI)-induced nephropathy. C57BL/6 mice were treated with AAI via intraperitoneal injection for an accumulated AAI dosage of 45 mg/kg body weight (BW) (15 mg/kg BW per day for 3 days). The animals were sacrificed after acute kidney injury development, and blood, urine and kidneys were harvested for biochemical and molecular assays. Mice exhibited increased serum creatinine, BUN and urinary protein after the AAI challenge. Significant infiltrating inflammatory cells and tubular atrophy were observed in the kidneys, and high immunocytokine levels were detected. Renal RAS-related enzyme activities were measured, and a significantly increased chymase activity and slightly decreased ACE activity were observed in the AAI-treated mice. The renal Ang II level reflected the altered profile of RAS enzymes and was significantly increased in AAI-treated mice. Treatment of AAI-induced nephropathic mice with an ACE inhibitor (ACEI) or chymase inhibitor (CI; chymostatin) reduced renal Ang II levels. The combination of ACEI and CI (ACEI+CI) treatment significantly reversed the AAI-induced changes of Ang II levels and kidney inflammation and injuries. AAI treatment significantly increased renal p-MEK without increasing p-STAT3 and p-Smad3 levels, and p-MEK/p-ERK1/2 signalling pathway was significantly activated. CI and ACEI+CI treatments reduced this AAI-activated signaling pathway. AAI-induced nephropathy progression was significantly mitigated with CI and ACEI+CI treatment. This study elucidates the role of RAS in the pathogenesis of AAI-induced nephropathy.

Imbalanced plasma ACE and ACE2 level in the uremic patients with cardiovascular diseases and its change during a single hemodialysis session.

BACKGROUND: The renin-angiotensin system (RAS) has significant influences on heart and renal disease progression. Angiotensin converting enzyme (ACE) and angiotensin converting enzyme II (ACE2) are major peptidases of RAS components and play counteracting functions through angiotensin II (Ang II)/ATIR and angiotensin-(1-7) (Ang-(1-7))/Mas axis, respectively. METHODS: There were 360 uremic patients on regular hemodialysis (HD) treatment (inclusive of 119 HD patients with cardiovascular diseases (CVD) and 241 HD patients without CVD and 50 healthy subjects were enrolled in this study. Plasma ACE, ACE2, Ang II and Ang-(1-7) levels of the HD patients were determined. RESULTS: We compared pre-HD levels of plasma ACE, ACE2, Ang II and Ang-(1-7) in the HD patients with and without CVD to those of the controls. The HD patients, particularly those with CVD, showed a significant increase in the levels of ACE and Ang II, whereas ACE2 and Ang-(1-7) levels were lower than those in the healthy controls. Therefore, imbalanced ACE/ACE2 was observed in the HD patients with CVD. In the course of a single HD session, the plasma ACE, ACE/ACE2 and Ang II levels in the HD patients with CVD were increased from pre-HD to post-HD. On the contrary, ACE2 levels were decreased after the HD session. These changes were not detected in the HD patients without CVD. CONCLUSIONS: Pathogenically imbalanced circulating ACE/ACE2 was detected in the HD patients, particularly those with CVD. HD session could increase ACE/Ang II/AT1R axis and decrease ACE2/Ang-(1-7)/Mas axis activity in the circulation of HD patients with CVD.

Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice.

Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2(-/-)) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2(-/-) mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2(-/-) mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2(-/-) mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2(-/-) mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury.

Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis.

BACKGROUND: Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) play important roles in the pathophysiology of renal diseases. Imbalanced MMPs/TIMPs are implicated in the vascular alterations of uremic patients on hemodialysis (HD). We have investigated the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in uremic patients and the effects of a course of HD on the changes in these factors. METHODS: There were 382 uremic patients on regular HD treatment and 50 healthy controls enrolled in this study. The plasma MMP-2 and MMP-9 levels were detected by gelatin zymography, and TIMP-1 and TIMP-2 concentrations were determined by ELISA assay. RESULTS: Significantly higher plasma MMP-2 and MMP-9 and decreased TIMP-1 in the uremic patients were detected compared with those in the controls. Therefore, there were markedly higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in the uremic patients. In the course of a single HD session, the plasma MMP-2 level was significantly decreased from pre-HD to post-HD. TIMP-1 concentration was significantly increased from pre-HD to post-HD. Although the HD session did not have a significant effect on the levels of plasma MMP-9 and TIMP-2, both plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios were significantly decreased from pre-HD to post-HD levels. CONCLUSION: HD session could decrease MMP-2 and increase TIMP-1 level in the circulation of uremic patients. The physiological significance of reduced MMPs/TIMPs ratio due to a single HD session is required to further validate.

Gold nanoparticles conjugates-amplified aptamer immunosensing screen-printed carbon electrode strips for thrombin detection.

Thrombin plays the role in cardiovascular diseases and regulates many processes in inflammation and could be a feature of many pathological conditions, including the thromboembolic disease, cancer and neurodegenerative diseases. An ultrasensitive and amplified electrochemical sandwich assay using screen-printed carbon electrode (SPCE) strips for thrombin detection was established in this study. The conductivity and sensing performance of the carbon electrodes were enhanced by using gold nanoparticles (AuNPs). The aptamer addressed on the strips was used as a primary probe to capture thrombin in the detected samples. An amplifier was invented for recognizing thrombin captured on the SPCE, which is the multiple molecules of anti-thrombin antibody (Ab) and horseradish peroxidase (HRP) co-modified AuNPs (AuNPs/Ab-HRP). Hydrogen peroxide was used as the substrate for HRP and then the response current (RC) could be detected. The optimization of these AuNPs conjugates-amplified aptamer immunosensing SPCE strips was conducted for thrombin detection. The detection sensitivity showed a linear relation between RC and thrombin concentration in the range of 10 pM-100 nM, and limit of detection (LOD) was 1.5 pM. The fabricated AuNPs/Ab-HRP-amplified aptamer immunosensing SPCE strips were further used to detect thrombin in human serum with a linear range of 100 pM-100 nM. This study provided the promising SPCE strips with highly sensitive and rapid detection for thrombin by the electrochemical aptasensor combined with AuNPs conjugates for amplifying the detection signal.