Increased inflammatory cytokines and oxidative stress enhanced antibody production in breast and prostate cancer patients with COVID-19 related depression.

Cancer management is highly dependent on the immune status of the patient. During the COVID-19 pandemic, a large number of people suffered from anxiety and depression, especially cancer patients. The effect of depression on breast cancer (BC) and prostate cancer (PC) patients, during the pandemic has been analyzed in this study. Levels of proinflammatory cytokines (IFN-γ, TNF-α, and IL-6) and oxidative stress markers malondialdehyde (MDA) and carbonyl content (CC) were estimated in patients' serum samples. Serum antibodies against in vitro hydroxyl radical (•OH) modified pDNA (•OH-pDNA-Abs) were estimated using direct binding and inhibition ELISA. Cancer patients showed increased levels of proinflammatory cytokines (IFN-γ, TNF-α, and IL-6) and oxidative stress markers (MDA and CC levels), which were further significantly enhanced in cancer patients with depression compared to normal healthy (NH) individuals. Increased levels of •OH-pDNA-Abs were detected in breast cancer (0.506 ± 0.063) and prostate cancer (0.441 ± 0.066) patients compared to NH subjects. Serum antibodies were found to be significantly elevated in BC patients with depression (BCD) (0.698 ± 0.078) and prostate cancer patients with depression (PCD) (0.636 ± 0.058). Inhibition ELISA also exhibited significantly high percent inhibition in BCD (68.8% ± 7.8%) and PCD (62.9% ± 8.3%) subjects compared to BC (48.9% ± 8.1%), and PC (43.4% ± 7.5%) subjects. Cancer is characterized by enhanced oxidative stress and increased inflammation, which may be exaggerated with COVID-19 related depression. High oxidative stress and compromised antioxidant homeostasis exerts alterations in DNA, leading to formation of neo-antigens, subsequently leading to the generation of antibodies. COVID-19 pandemic related depression needs to be addressed globally for improved cancer patient care and cancer disease management.

Increased Levels of Autoantibodies against ROS-Modified Proteins in Depressed Individuals with Decrease in Antibodies against SARS-CoV-2 Antigen (S1-RBD).

Coronavirus 2019 (COVID-19) disease management is highly dependent on the immune status of the infected individual. An increase in the incidence of depression has been observed during the ongoing COVID-19 pandemic. Autoantibodies against in vitro reactive oxygen species (ROS) modified BSA and Lys as well as antibodies against receptor binding domain subunit S1 (S1-RBD) (S1-RBD-Abs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were estimated using direct binding and competition ELISA. Serum samples were also tested for fasting blood glucose (FBG), malondialdehyde (MDA), carbonyl content (CC), interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Significant structural changes were observed in ROS modified BSA and Lys. Female depressed subjects who were also smokers (F-D-S) showed the highest levels of oxidative stress (MDA and CC levels). Similarly, increased levels of autoantibodies against ROS modified proteins were detected in F-D-S subjects, in males who were depressed and in smokers (M-D-S) compared to the other subjects from the rest of the groups. However, contrary to this observation, levels of S1-RBD-Abs were found to be lowest in the F-D-S and M-D-S groups. During the pandemic, large numbers of individuals have experienced depression, which may induce excessive oxidative stress, causing modifications in circulatory proteins. Thus, the formation of neo-antigens is induced, which lead to the generation of autoantibodies. The concomitant effect of increased autoantibodies with elevated levels of IFN-γ and TNF-α possibly tilt the immune balance toward autoantibody generation rather than the formation of S1-RBD-Abs. Thus, it is important to identify individuals who are at risk of depression to determine immune status and facilitate the better management of COVID-19.

Pharmacological Profile of Nigella sativa Seeds in Combating COVID-19 through In-Vitro and Molecular Docking Studies

COVID-19 infection is associated with elevated oxidative stress, systemic hyper-inflammatory responses, endothelial dysfunction, and red blood cell membrane deformability. Nigella sativa extract is widely used in alternative and complementary medicine systems in a large population, due to its highly therapeutic, economic, natural, and safe nature. The aim of this study was to evaluate the effect of N. sativa extract on oxidative stress, hemolysis, proteolysis, and glycation through in vitro studies, as well as to find out its anti-viral potential against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using in silico studies. N. sativa seed extract (at 600 µg/mL) displayed 67.33% scavenging activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test, and 70.28% hydrogen peroxide reducing activity. N. sativa exhibited anti-proteolytic activity by decreasing heat-induced denaturation of bovine serum albumin (BSA) and egg albumin by 63.14% and 57.95%, respectively, and exhibited anti-proteinase potential of 66.28% at 600 μg/mL. In addition, heat-induced hemolysis and hypersalinity-induced hemolysis were inhibited by 57.86% and 61.7%, respectively, by the N. sativa seeds. N. sativa also inhibited browning intensity by 56.38%, and percent aggregation index by 51.38%, amyloid structure by 48.28%, and AGE-specific fluorescence by 52.18%, thereby protecting the native structure of BSA from glycation. The binding interactions between bioactive molecules of N. sativa seed with SARS-CoV-2 spike glycoprotein were proven by using in silico molecular docking tools. The functional amino acids involved in the interactions are Asp467, Thr108, Thr114, Ile468, Asn234, Gln155, Glu465, Arg466, Gly232, and Ile233, indicating the inhibiting property of N. sativa on SARS-CoV-2. Finally, we may infer that phytoconstituents of N. sativa seeds have the potential to protect against the spike protein of SARS-CoV-2. Studies on N. sativa seeds might act as a path to develop a potent alternative therapy against viral infections, especially COVID-19 infection, in the future. However, the limitations linked with the use of natural products are also needed to be considered in this regard.