Significance: This review discusses the coronavirus disease 2019 (COVID-19) pathophysiology in the context of diabetes and intracellular reactions by COVID-19, including mitochondrial oxidative stress storms, mitochondrial ROS storms, and long COVID.Recent advances: The long COVID is suffered in ~10% of the COVID-19 patients. Even the virus does not exist, the patients suffer the long COVID for even over a year, This disease could be a mitochondria dysregulation disease.Critical issues: Patients who recover from COVID-19 can develop new or persistent symptoms of multi-organ complications lasting weeks or months, called long COVID. The underlying mechanisms involved in the long COVID is still unclear. Once the symptoms of long COVID persist, they cause significant damage, leading to numerous, persistent symptoms.Future directions: A comprehensive map of the stages and pathogenetic mechanisms related to long COVID and effective drugs to treat and prevent it are required, which will aid the development of future long COVID treatments and symptom relief.

Questions about which reactive oxygen species (ROS) or reactive nitrogen species (RNS) can escape from the mitochondria and activate signals must be addressed. In this study, two parameters, the calculated dipole moment (debye, D) and permeability coefficient (Pm) (cm s⁻¹), are listed for hydrogen peroxide (H₂O₂), hydroxyl radical (•OH), superoxide (O₂^•−), hydroperoxyl radical (HO₂•), nitric oxide (•NO), nitrogen dioxide (•NO₂), peroxynitrite (ONOO⁻), and peroxynitrous acid (ONOOH) in comparison to those for water (H₂O). O₂^•− is generated from the mitochondrial electron transport chain (ETC), and several other ROS and RNS can be generated subsequently. The candidates which pass through the mitochondrial membrane include ROS with a small number of dipoles, i.e., H₂O₂, HO₂•, ONOOH, •OH, and •NO. The results show that the dipole moment of •NO₂ is 0.35 D, indicating permeability; however, •NO₂ can be eliminated quickly. The dipole moments of •OH (1.67 D) and ONOOH (1.77 D) indicate that they might be permeable. This study also suggests that the mitochondria play a central role in protecting against further oxidative stress in cells. The amounts, the long half-life, the diffusion distance, the Pm, the one-electron reduction potential, the pK_a, and the rate constants for the reaction with ascorbate and glutathione are listed for various ROS/RNS, •OH, singlet oxygen (¹O₂), H₂O₂, O₂^•−, HO₂•, •NO, •NO₂, ONOO⁻, and ONOOH, and compared with those for H₂O and oxygen (O₂). Molecules with negative electrical charges cannot directly diffuse through the phospholipid bilayer of the mitochondrial membranes. Short-lived molecules, such as •OH, would be difficult to contribute to intracellular signaling. Finally, HO₂• and ONOOH were selected as candidates for the ROS/RNS that pass through the mitochondrial membrane.

Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders. This study investigated the ethanolic extract of Garcinia atroviridis fruits for its phenolic and flavonoid contents, antioxidant activity, and impact on melanogenesis pathways using qRT-PCR and Western blot analysis. Utilizing network pharmacology, molecular docking, and dynamics simulations, researchers explored G. atroviridis fruit extract’s active compounds, targets, and pharmacological effects on hyperpigmentation. G. atroviridis fruit extract exhibited antioxidant properties, scavenging DPPH^• and ABTS^•+ radicals radicals and chelating copper. It inhibited cellular tyrosinase activity and melanin content in stimulated B16F10 cells, downregulating TYR, TRP-1, phosphorylated CREB, CREB, and MITF proteins along with transcription levels of MITF, TYR, and TRP-2. LC-MS analysis identified thirty-three metabolites, with seventeen compounds selected for further investigation. Network pharmacology revealed 41 hyperpigmentation-associated genes and identified significant GO terms and KEGG pathways, including cancer-related pathways. Kaempferol-3-O-α-L-rhamnoside exhibited high binding affinity against MAPK3/ERK1, potentially regulating melanogenesis by inhibiting tyrosinase activity. Stable ligand–protein interactions in molecular dynamics simulations supported these findings. Overall, this study suggests that the ethanolic extract of G. atroviridis fruits possesses significant antioxidant, tyrosinase inhibitory, and anti-melanogenic properties mediated through key molecular targets and pathways.

This study examined the efficacy of curcumin (Cur) against lead (Pb)-induced oxidative damage, inflammation, and cholinergic dysfunction. Institute for Cancer Research (ICR) mice received Pb (II) acetate in drinking water (1%) with or without Cur via oral gavage. Blood and brain tissues were collected for investigation. Pb increased the inflammatory markers and oxidative parameters, which were ameliorated by Cur administration. Cur treatment also improved memory loss, learning deficit, and cholinergic dysfunction via elevating acetylcholinesterase (AChE) enzymatic activity and protein expression. In silico molecular docking supported the results; Cur had a potent binding affinity for AChE receptors, tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), phosphorylations of IκB kinase (IKK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38). According to the chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile, Cur could serve as a potential candidate for Pb detoxication substance via exerting antioxidant activity. Taken together, our results suggest that Cur is a natural compound that could be used for the treatment of neurodegenerative disorders via suppressing lead-induced neurotoxicity.

It has been known that reactive oxygen species (ROS) are generated from the mitochondrial electron transport chain (ETC). Majima et al. proved that mitochondrial ROS (mtROS) caused apoptosis for the first time in 1998 (Majima et al. J Biol Chem, 1998). It is speculated that mtROS can move out of the mitochondria and initiate cellular signals in the nucleus. This paper aims to prove this phenomenon by assessing the change in the amount of manganese superoxide dismutase (MnSOD) by MnSOD transfection. Two cell lines of the same genetic background, of which generation of mtROS are different, i.e., the mtROS are more produced in RGK1, than in that of RGM1, were compared to analyze the cellular signals. The results of immunocytochemistry staining showed increase of Nrf2, Keap1, HO-1 and 2, MnSOD, GCL, GST, NQO1, GATA1, GATA3, GATA4, and GATA5 in RGK1 compared to those in RGM1. Transfection of human MnSOD in RGK1 cells showed a decrease of those signal proteins, suggesting mtROS play a role in cellular signals in nucleus.

Atherosclerosis is a persistent inflammatory disorder influenced by oxidative stress and lipid imbalances, and it continues to be a major contributor to cardiovascular diseases. Rich in catechins and flavonoids, green tea pressurized hot water extract (GPHWE) demonstrated potent antioxidant activity through DPPH, ABTS, hydroxyl, and nitric oxide scavenging assays. In vitro, GPHWE protected RAW264.7 macrophages from oxidized LDL (Ox-LDL)-induced cytotoxicity and apoptosis by mitigating oxidative stress and enhancing cell survival. Animal studies using mice fed a high-fat diet (HFD) revealed notable improvements in lipid profiles, including decreases in total cholesterol, LDL, the atherosclerosis index (AI), the coronary risk index (CRI), and triglycerides, as well as lower levels of malondialdehyde (MDA), an indicator of oxidative stress. These results were comparable to those achieved with Simvastatin. Molecular docking studies indicated strong binding affinities of catechins to essential targets such as LOX-1, HMG-CoA reductase, caspase-3, and Nrf2, implying that the mechanisms of GPHWE involve antioxidant properties, regulation of lipids, and stabilization of plaques. The catechins of GPHWE, including epigallocatechin gallate (EGCG), epicatechin gallate (ECG), and epigallocatechin (EGC), were tentatively identified through qualitative analysis performed by UHPLC-QTOF-MS. This comprehensive approach positions GPHWE as a promising natural remedy for preventing atherosclerosis and reducing cardiovascular risk.