Comparative analysis of anxiety/depression scores in COVID-19 patients with disease severity, sleep patterns, and certain laboratory test results.

Introduction: Coronavirus disease 2019 (COVID-19) is associated with severe emotional changes. This research aims to investigate the prevalence of anxiety and depression in COVID-19 patients and its relationship with disease severity, sleep patterns, lifestyle, and specific laboratory test results. Material and methods: An observational study of 52 Chinese patients with COVID-19 was conducted to assess the relation between anxiety and depression (evaluated with the Hospital Anxiety and Depression Scale) and laboratory findings (lymphocytes, C-reactive proteins, leukocytes, alanine aminotransferase, aspartate aminotransferase). The relationships between the severity of COVID-19 in patients, the Insomnia Severity Index (ISI) score, and the Hospital Anxiety and Depression Scale (HADS) score were also investigated. Results: There were statistically significant associations between disease, smoking, and HADS-A scores (p = 0.011/0.020). The HADS-D score of patients with the disease was higher than in those without a past medical history (p = 0.008). The difference in C-reactive protein (CRP) between different lung infections, the HADS-A and HADS-D scores between different ages and ISI groups, and the correlation between the two scores were statistically significant. Conclusions: Anxiety and depression are associated with poor sleep quality, smoking, and past medical history in patients with COVID-19. Additionally, anxiety and depression were seen to coexist, and there was a positive correlation between them. Further, the inflammatory index CRP was significantly increased in bilateral lung infections.

Investigating the inotropic effect of pyruvic acid on the isolated rat heart and its underlying mechanism.

Pyruvic acid is important organic chemical intermediates that plays a role in cardiomyocyte pathophysiology and therapy. This study sought to explore the inotropic effects of pyruvic acid on the function of the isolated rat hearts and investigate its underlying mechanism. Pyruvic acid produced a greater negative inotropic effect compared to HCl and sodium pyruvate in a concentration-dependent pattern in the hearts. The role of low dose of pyruvic acid on heart function was regulated by pyruvic acid molecules and high dose pyruvic acid may be influenced by pyruvic acid molecules and pH. Kv channels may be involved in the pyruvic acid-induced negative inotropic effect. Finally, pyruvic acid markedly increased the level of LDH and CK and reduced the level of Ca2+Mg2+-ATPase and Na+K+-ATPase. These results suggest that pyruvic acid may modulate cardiac function at physiological or low doses but can cause damage to cardiomyocytes at high doses.

Formaldehyde regulates vascular tensions through nitric oxide-cGMP signaling pathway and ion channels.

Formaldehyde (FA) has been linked to the detrimental cardiovascular effects. Here, we explored the effects and mechanisms of FA on rat aortas both in vivo and in vitro. The results presented that FA evidently lowered the blood pressures of rats. The expression levels of BKCa subunits α and ß1 and iNOS of the aortas were up-regulated by FA in vivo. However, FA markedly reduced the levels of Cav1.2 and Cav1.3, which are the subunits of L-Ca2+ channel. Furthermore, the contents of NO, cGMP and iNOS in the aortas were augmented by FA. To further confirm these findings, the mechanisms accredited to these effects were examined in vitro. The data showed that FA contracted the isolated aortic rings at low concentrations (<300 µM), while it relaxed the rings at high concentrations (>500 µM). The FA-induced vasoconstriction at low concentrations was blocked partly by an inhibitor of ACE. The relaxation caused by FA at high concentrations was attenuated by the inhibitors of NO-cGMP pathway, L-Ca2+ channel and BKCa channel, respectively. Similarly, the expression of iNOS was strongly enhanced by FA in vitro. The effects of FA on the aortic rings with endothelium were significantly greater than those on the rings without endothelium. Our results indicate that the vasoconstriction of FA at low concentrations might be partially pertinent to endothelin, and the FA-caused vasorelaxation at high concentrations is possibly associated with the NO-cGMP pathway, L-Ca2+ channel and BKCa channel. This study will improve our understanding of the pathogenic mechanisms for FA-related cardiovascular diseases.

The molecular mechanisms of sodium metabisulfite on the expression of K ATP and L-Ca2+ channels in rat hearts.

Sodium metabisulfite (SMB) is used as an antioxidant and antimicrobial agent in a variety of drugs and foods. However, there are few reported studies about its side effects. This study is to investigate the SMB effects on the expression of ATP-sensitive K(+) (KATP) and L-type calcium (L-Ca(2+)) channels in rat hearts. The results show that the mRNA and protein levels of the KATP channel subunits Kir6.2 and SUR2A were increased by SMB; on the contrary, SMB at 520 mg/kg significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. This suggests that SMB can activate the expression of KATP channel by increasing the mRNA and protein levels of Kir6.2 and SUR2A, while it inhibits the expression of L-Ca(2+) channels by decreasing the mRNA and protein levels of Cav1.2 and Cav1.3 in rat hearts. Therefore, the molecular mechanism of the SMB effect on rat hearts might be related to the increased expression of KATP channels and the decreased expression of L-Ca(2+) channels.

Effect of sulfur dioxide inhalation on the expression of KATP and L-Ca(2+) channels in rat hearts.

Epidemiological studies have revealed an association between sulfur dioxide (SO2) exposure and cardiovascular diseases. This study is designed to investigate the SO2 effect on the expression of ATP-sensitive K(+) (KATP) channel and L-type calcium (L-Ca(2+)) channel in rat hearts. The results show that the mRNA and protein levels of the KATP channel subunits Kir6.2 and SUR2A of rat hearts in SO2 groups were higher than those in control group. SO2 at 14mg/m(3) significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. This suggests that SO2 can activate the KATP channels by up-regulating the expression of Kir6.2 and SUR2A, while it inhibits the L-Ca(2+) channels by down-regulating the expression of Cav1.2 and Cav1.3 in rat hearts. The molecular mechanism of SO2-induced negative inotropic effect might be linked to the expression changes of these subunits, which may contribute to the pathogenesis of SO2-associated cardiovascular diseases.

Effects of sodium metabisulfite on the expression of BK(Ca), K(ATP), and L-Ca(2+) channels in rat aortas in vivo and in vitro.

Sodium metabisulfite (SMB) is most commonly used as the preservative in many food preparations and drugs. So far, few studies about its negative effects were reported. The purpose of this study was to investigate the effect of SMB on the expression of big-conductance Ca(2+)-activated K(+) (BKCa), ATP-sensitive K(+) (KATP), and L-type calcium (L-Ca(2+)) channels in rat aorta in vivo and in vitro. The results showed that the mRNA and protein levels of the BKCa channel subunits α and ß1 of aorta in rats were increased by SMB in vivo and in vitro. Similarly, the expression of the KATP channel subunits Kir6.1, Kir6.2, and SUR2B were increased by SMB. However, SMB at the highest concentration significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. These results suggest that SMB can activate BKCa and KATP channels by increasing the expression of α, ß1, and Kir6.1, Kir6.2, SUR2B respectively, while also inhibit L-Ca(2+) channels by decreasing the expression of Cav1.2 and Cav1.3 of aorta in rats. The molecular mechanism of SMB-induced vasorelaxant effect might be related to the expression changes of BKCa, KATP, and L-Ca(2+) channels subunits. Further work is needed to determine the relative contribution of each channel in SMB-mediated vasorelaxant effect.

Effects of gaseous sulfur dioxide and its derivatives on the expression of KATP, BKCa and L-Ca(2+) channels in rat aortas in vitro.

Epidemiological investigations have revealed that sulfur dioxide (SO2) exposure is linked to cardiovascular diseases. Our previous study indicated that the vasorelaxant effect of SO2 might be partly related to ATP-sensitive K(+) (KATP), big-conductance Ca(2+)-activated K(+) (BKCa) and L-type calcium (L-Ca(2+)) channels. The present study was designed to further investigate the effects of gaseous SO2 and its derivatives on the gene and protein expression of these channels in the rat aortas in vitro. The results showed that the mRNA and protein levels of the KATP channel subunits Kir6.1, Kir6.2 and SUR2B of the rat aortas in SO2 and its derivatives groups were higher than those in control group. Similarly, the expression of the BKCa channel subunits α and ß1 was increased by SO2 and its derivatives. However, SO2 and its derivatives at 1500µM significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. Histological examination of the rat aorta tissues showed moderate injury of tunica media induced by SO2 and its derivatives at 1500µM. These results suggest that SO2 and its derivatives can activate the KATP and BKCa channels by increasing the expression of Kir6.1, Kir6.2, SUR2B and α, ß1, respectively, while also inhibiting the L-Ca(2+) channels by decreasing the expression of Cav1.2 and Cav1.3 of the rat aortas. The molecular mechanism of the vasorelaxant effect of SO2 and its derivatives might be related to the expression changes of KATP, BKCa and L-Ca(2+) channel subunits, which may play a role in the pathogenesis of SO2-associated cardiovascular diseases.

Effect of sulfur dioxide on inflammatory and immune regulation in asthmatic rats.

BACKGROUND: Exposure to sulfur dioxide (SO2) increases asthma risk. Inflammatory and immune responses are typical in asthma disease. The exact effect of SO2 on modulation of the inflammatory and immune responses in asthmatic rats remains unclear. OBJECTIVES: Here we sought to investigate the molecular mechanisms underlying the NF-κB inflammatory pathway and the Th1/Th2 imbalance in asthmatic rats exposed to SO2. METHODS: Male Wistar rats were challenged by ovalbumin (OVA) or SO2 alone or together, and then mRNA and protein levels of some inflammatory and immune genes were measured. NF-κB nuclear translocation was analyzed. Bronchoalveolar lavage (BAL), inflammatory cell counts and histopathologic examination were performed. RESULTS: (1) OVA plus SO2 induced abnormal pathological changes and inflammatory responses in lung relative to exposure to OVA alone; (2) showing NF-κB nuclear translocation and activation through up-regulating IKKß mRNA and protein expression and down-regulating IκBα expression in the presence of OVA or OVA plus SO2; (3) OVA plus SO2 significantly raised TNF-α and IL-6 levels in BALF compared with the OVA group; (4) SO2 markedly elevated IL-4 levels and decreased IFN-γ levels in BALF in the asthmatic rats, stimulating IgE generation which was closely related to inhibiting the expression of Foxp3, a specific marker of regulatory T cells. CONCLUSIONS: SO2 affects the airway inflammatory and immune responses of the asthmatic rats and enhances the susceptibility to OVA by aggravating inflammatory responses in lungs, up-regulating pro-inflammatory cytokine expression, and causing the Th1/Th2 imbalance, which might contribute to the increased risk of asthma disease.

The vasorelaxant effect and its mechanisms of sodium bisulfite as a sulfur dioxide donor.

To study the biological role of bisulfite on vascular contractility and its underlying cellular and molecular mechanisms, to explore whether bisulfite can be used as a sulfur dioxide (SO(2)) donor in the biological experiments, the vasorelaxant effects of sodium bisulfite and sodium sulfite on isolated rat thoracic aortic rings were compared; and the signal transduction pathways and the ion channels involved in the vascular effects of bisulfite were investigated. The results show that: (1) Sodium bisulfite relaxed rat thoracic aortic rings in a concentration-dependent manner (from 100 to 4000 µM); however, sodium sulfite at 500 and 1000 µM caused vasoconstriction, and only at higher concentrations (from 2000 to 4000 µM) it caused vasorelaxation in a concentration-dependent manner. (2) The vasorelaxation caused by the bisulfite at low concentrations (≤500 µM) was endothelium-dependent, but at high concentrations (≥1000 µM) it was endothelium-independent. (3) The vasorelaxation by the bisulfite at the low concentrations was partially mediated by the cGMP pathway and the vasorelaxation was related to big-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, but not due to prostaglandin, protein kinase C (PKC) and cAMP pathways. (4) The vasorelaxation by the bisulfite at high concentrations was partially inhibited by tetraethylammonium (TEA) and glibenclamide, suggesting that the vasorelaxation was related to ATP-sensitive K(+) channel (K(ATP)) and L-type calcium-channel. These results led to the conclusion that bisulfite (HSO(3)(-)) might be a vasoactive factor and sodium bisulfite can be used as a SO(2) donor for the study of SO(2) biology.

The vasodilator mechanisms of sodium metabisulfite on precontracted isolated aortic rings in rats: signal transduction pathways and ion channels.

Sodium metabisulfite (SMB) is most commonly used as a food additives, however few study was performed on the vasodilator effect of SMB. In the present paper, the vasodilator effects of SMB and roles of Ca(2+) and K(+) channels as well as the cGMP pathway on isolated rat aortic rings were studied. The results show that: (1) SMB could relax isolated aortic rings precontracted by norepinephrine in a concentration-dependent manner. The maximal endothelium-dependent vasorelaxation was approximately 20% whereas that not depending on the presence of the endothelium was more than 90%. (2) The vasorelaxant effects induced by 50 or 200 µM SMB were partially inhibited by iberiotoxin, NS-2028 or l-NNA. The vasorelaxation of 1000 µM SMB was partially inhibited by nifedipine or glibenclamide. The SMB induced vasorelaxation was partially inhibited by tetraethylammonium. These results led to the conclusions that the vasorelaxation of SMB at low concentrations (<400 µM) was endothelium-dependent and mediated by the cGMP pathway and BK(Ca) channel, but at high concentrations (>500 µM) was endothelium-independent and mediated by K(ATP) channel and L-type Ca(2+) channel. The maximal allowable concentration from China and the acceptable daily intake level from WHO of SMB as a food additive should be revised.

The negative inotropic effects of gaseous sulfur dioxide and its derivatives in the isolated perfused rat heart.

Epidemiological investigations have revealed that sulfur dioxide (SO(2) ) exposure is linked to cardiovascular diseases. The present study was designed to investigate the negative inotropic effects of gaseous SO(2) and its derivatives in the isolated perfused rat heart and the possible mechanisms involved in their effects. The results showed that both SO(2) and SO(2) derivatives elicited a negative inotropic effect in a dose-dependent manner, and SO(2) produced a higher negative effect than SO(2) derivatives. The mechanism of SO(2) -induced negative inotropic effects at low concentrations was different from that at high concentrations. At low concentrations, the mechanism of SO(2) -induced negative inotropic effects might occur through promoting the activities of protein kinase C (PKC), cycloxygenase, and cGMP, while the mechanism of SO(2) derivatives-induced effects might be related to the opening of ATP-sensitive K(+) (K(ATP) ) channel and the inhibition of Ca(2+) influx via L-type calcium-channel. At high concentrations, the mechanisms of SO(2) and SO(2) derivatives-induced negative inotropic effects were similar, which might be related to the K(ATP) channel and L-type calcium-channel as well as the possible alterations in PKC, cycloxygenase, and cGMP. Further work is needed to determine the relative contribution of each pathway in SO(2) -mediated inotropic effect.

[Progress in sulfur dioxide biology: from toxicology to physiology].

Based on our studies for more than 20 years, we review the recent advances in sulfur dioxide (SO2) biology. Three sections are involved: (1) The studies on SO2 toxicological effects and its underlying mechanisms; (2) The new investigations on SO2 donor and physiological role of SO2 as a new type-gas transmitter; (3) The observations on pathophysiologic roles of SO2.

The inotropic effects of ammonia on isolated perfused rat hearts and the mechanisms involved.

Ammonia (NH(3)) is a common exogenous gas in the atmosphere, as well as an endogenous chemical produced by amino acid catabolism and other pathways in vivo. Physiological and pathophysiological roles of NH(3) in the nervous system have been studied. Recently, endogenous NH(3) has been suggested to be a gas transmitter. However, so far the role of NH(3) in cardiovascular functions has not been reported. The present study was designed to investigate the inotropic effects of NH(3) on isolated perfused rat hearts and the possible mechanisms involved in these effects. The results showed that NH(3) had a positive inotropic effect in a concentration-dependent manner and produced a higher positive effect than NaOH and NH(4)Cl. At low concentrations, the effect of NH(3) on cardiac function was caused by NH(3) molecules; at high concentrations, the effect of NH(3) on hearts may be partly correlated with a change of pH value, but was mainly caused by NH(3) molecules. The mechanisms involved in the NH(3)-induced positive inotropic effect may be related to the ATP-sensitive K(+) (K(ATP)) channel and the nitric oxide (NO)-cyclic GMP (cGMP) signaling pathway. In addition, at a concentration of 1.5 mmol l(-1), NH(3) significantly increased the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary perfusate and decreased the activity of Na(+),K(+)-ATPase and Ca(2+),Mg(2+)-ATPase in the hearts. These results indicate that NH(3) at physiological or low concentrations may play a modulatory role in heart function, but at high concentrations had a damaging effect on isolated rat hearts.

Protective effects of epigallocatechin-3-gallate against lead-induced oxidative damage.

A positive association of lead exposure with clinical cardiovascular outcomes has been identified. Epigallocatechin-3-gallate (EGCG) is one of the active polyphenols in green tea, it has not been reported as an antioxidant against lead toxicity. This study was carried out to investigate whether EGCG could protect the ventricular myocytes of rats against lead-induced oxidative damage. Isolated ventricular myocytes were exposed to lead and/or EGCG, then activities of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) and the levels of hydroxyl radical (OH(·)), hydrogen peroxide (H(2)O(2)), and superoxide anion (O(2) (·-)) were measured. The results showed that lead induced a significant decrease of SOD and CAT activities, while the levels of MDA increased significantly. Increases in intracellular OH(·), O(2) (·-), and H(2)O(2) were found as well. These processes were concentration-dependent and statistically significant different when compared to 2.0 µM lead exposure. The activity of SOD and CAT increased while the levels of MDA and reactive oxygen species (ROS) decreased after treatment with EGCG. While there were progressive benefits with increasing EGCG concentrations, there was no statistical significance at a 30 µg/mL dose when compared with the control. These results will provide more evidence for lead toxicity to tissue, cell, and biological macromolecule.

Sulfur dioxide upregulates the aortic nitric oxide pathway in rats.

Sulfur dioxide (SO(2)) is a common gaseous pollutant. It is also, however, endogenously generated from sulfur-containing amino acids. Recent studies have demonstrated that rat blood pressure can be lowered by SO(2)-exposure in vivo and that vasodilation caused by SO(2) at low concentrations (<450 microM) is endothelium-dependent in rat aorta. However, effects of SO(2) on nitric oxide synthase (NOS) and nitric oxide (NO) production have not been previously studied in rat aorta. The objective of the present study is to assess the effects of acute (10 min) and prolonged (2h) stimulation with different concentrations of SO(2) on NO/cGMP pathway in isolated rat aorta. The results show that: (1) the acute and prolonged pretreatments with SO(2) produced an inhibition of vasoconstrictions induced by norepinephrine. (2) SO(2) potentiated activity of endothelial nitric oxide synthase (eNOS), but not of induced NOS (iNOS). (3) SO(2) could increase expression of eNOS gene on the transcription and translation levels in rat aorta. (4) SO(2) enhanced NO formation in aortic tissue. (5) The level of cGMP in rat aorta was increased by SO(2) and no change of cAMP. These findings led to the conclusion: there were acute and prolonged effects of SO(2) on the NO/cGMP signalling pathway; and SO(2) could upregulate the eNOS-NO-cGMP pathway and at least partly by which the SO(2) might cause vasodilation and inhibition to vasoconstriction.

Epigallocatechin-3-gallate protects Na+ channels in rat ventricular myocytes against sulfite.

Sulfite (bisulfite/sulfite) can affect voltage-gated sodium (Na(+)) channels (VGSC) in a concentration-dependent manner in isolated rat ventricular myocytes. In this study, the effect of epigallocatechin-3-gallate (EGCG) on VGSC in isolated ventricular myocytes was studied. Ventricular myocytes were exposed to 10 microM bisulfite/sulfite for 10 min, and EGCG was then administered in different concentrations (10, 30, 50 microg ml(-1)). Decreased activity of superoxide dismutase, catalase (CAT) and glutathione peroxidase (GPx) was observed after bisulfite/sulfite exposure, with significant increase in Na(+) currents (I (Na)) and alterations in half-activation voltage and half-inactivation voltage. Intracellular reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)), hydroxyl (OH(.)), and superoxide anion (O (2) (.-) ) were increased. After EGCG treatment, activity of the aforementioned enzymes increased while the ROS level decreased. The effects progressed with increasing amounts of EGCG, up to a level similar to blank control at the dose of 50 microg ml(-1) EGCG, EGCG also reduced the I (Na) and reversed the alterations in half-activation voltage and half-inactivation voltage. In conclusion, EGCG could protect Na(+) channels in rat ventricular myocytes against the oxidative damage induced by sulfite as a scavenger of the ROS.

Expression of oncogenes and tumor suppressor genes in lungs of rats exposed to sulfur dioxide and benzo(a)pyrene.

Concurrent exposure to SO(2) and benzo(a)pyrene (B(a)P) resulted in an increased incidence of lung tumors in rodents compared to exposure to B(a)P alone. A synergistic effect on the expression of c-fos and c-jun between SO(2) and B(a)P was observed in lungs after SO(2) and B(a)P exposure. However, tumorigenesis occurs by multiple events that may involve the activation of more than one oncogene, as well as the functional loss of the tumor suppressor gene. In order to further investigate the interactions between SO(2) and B(a)P, male Wistar rats were exposed via intratracheal instillation of B(a)P (3 mg) or SO(2) (56 mg/m(3)) inhalation, alone or together. The mRNA and protein levels of oncogenes (c-myc and H-ras) and tumor suppressor genes (p53, p16, and Rb) were analyzed in lungs by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. The results showed that all treatments increased mRNA and protein expression levels of c-myc, H-ras, and p53, and reduced expression levels of p16 and Rb. In general, the combination of SO(2) and B(a)P was more effective in influencing these expression levels than either agent alone, except for H-ras expression. These findings indicate that multiple cell cycle regulatory proteins play key roles in the toxicity of SO(2) and B(a)P. It might involve the activation of c-fos, c-jun, c-myc, and p53. And the p16-Rb pathway might also participate in the progress. Elucidating the expression patterns of those factors after SO(2) and B(a)P exposure may be critical to understanding the mechanisms of SO(2) cocarcinogenesis and helpful for therapeutic intervention.

Expression of caspase and apoptotic signal pathway induced by sulfur dioxide.

Sulfur dioxide (SO(2)) is a common air pollutant that is released in low concentrations into the atmosphere and in higher concentrations in some work places. In the present study, male Wistar rats were housed in exposure chambers and treated with 14.00 +/- 1.01, 28.00 +/- 1.77, and 56.00 +/- 3.44 mg/m(3) SO(2) for 7 days (6 hr/day), while control rats were exposed to filtered air under the same conditions. The mRNA and protein levels of caspase-3, caspase-8, and caspase-9 were analyzed using a real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay and an immunohistochemistry method. Activities of caspases were detected using colorimetric and fluorescent assays. Chromatin degradation and cell morphological changes were investigated by TUNEL assay and H&E staining in livers and lungs, respectively. The results showed that mRNA levels, protein levels and activities of caspase-3, caspase-8, and caspase-9 were increased in a dose-dependent manner in livers and lungs of rats after SO(2) inhalation. In addition, livers were infiltrated with lymphocytes, congestion and inflammation occurred in lungs, and eosinophil cells and apoptotic cells increased in both livers and lungs after SO(2) inhalation. These results suggest that SO(2) exposure increases the expression and activity of both initiator and and effector caspases, and may induce apoptosis in liver and lung of rats through both death receptor and mitochondrial pathways.