Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the novel global coronavirus (COVID-19) disease outbreak. Its pathogenesis is mostly located in the respiratory tract. However, other organs are also affected. Hence, realizing how such a complex disturbance affects patients after recovery is crucial. Regarding the significance of control of COVID-19-related complications after recovery, the current study was designed to review the cellular and molecular mechanisms linking COVID-19 to significant long-term signs including renal and cardiac complications, cutaneous and neurological manifestations, as well as blood coagulation disorders. This virus can directly influence on the cells through Angiotensin converting enzyme 2 (ACE-2) to induce cytokine storm. Acute release of Interleukin-1 (IL1), IL6 and plasminogen activator inhibitor (PAI-1) have been related to elevating risk of heart failure. Also, inflammatory cytokines like IL-8 and Tumor necrosis factor-α (TNF-α) cause the secretion of von Willebrand factor (VWF) from human endothelial cells and then VWF binds to Neutrophil extracellular traps (NETs) to induce thrombosis. On the other hand, the virus can damage the blood-brain barrier by increasing its permeability and subsequently enters into the central nervous system (CNS) and the systemic circulation. Furthermore, SARS-induced ACE2-deficiency decreases [des-Arg9]bradykinin (desArg9-BK) degradation in kidneys to induce inflammation, thrombotic problems, fibrosis and necrosis. Notably, the angiotensin II-angiotensin II type 1 receptor (ANGII-AT1R) binding causes an increase in aldosterone and mineralocorticoid receptors on the surface of dendritic cells (DC) cells, leading to recalling macrophage and monocyte into inflammatory sites of skin. In conclusions, all the pathways play a key role in the pathogenesis of these disturbances. Nevertheless, more investigations are necessary to determine more pathogenetic mechanisms of the virus.

Cisplatin (CDDP) is a well-known platinum-based drug used in the treatment of various malignancies. However, the widespread side effects that this drug leaves on normal tissues make its use limited. Since cisplatin is mainly eliminated from the kidneys, CDDP-induced nephrotoxicity is the most significant dose-limiting complication attributed to cisplatin, which often leads to dose withdrawal. Considering the high efficiency of cisplatin in chemotherapy, finding renoprotective drug delivery systems for this drug is a necessity. In this regard, we can take advantages of different nanoparticle-based approaches to deliver cisplatin into tumors either using passive targeting or using specific receptors. In an effort to find more effective cisplatin-based nano-drugs with less nephrotoxic effect, the current 2011–2022 review study was conducted to investigate some of the nanotechnology-based methods that have successfully been able to mitigate CDDP-induced nephrotoxicity. Accordingly, although cisplatin can cause renal failures through inducing mitochondria dysfunction, oxidative stress, lipid peroxidation and endoplasmic reticulum stress, some CDDP-based nano-carriers have been able to reverse a wide range of these advert effects. Based on the obtained results, it was found that the use of different metallic and polymeric nanoparticles can help renal cells to strengthen their antioxidant systems and stay alive through reducing CDDP-induced ROS generation, inhibiting apoptosis-related pathways and maintaining the integrity of the mitochondrial membrane. For example, nanocurcumin could inhibit oxidative stress and acting as a ROS scavenger. CONPs could reduce lipid peroxidation and pro-inflammatory cytokines. CDDP-loaded silver nanoparticles (AgNPs) could inhibit mitochondria-mediated apoptosis. In addition, tea polyphenol-functionalized SeNPs (Se@TE) NPs could mitigate the increased level of dephosphorylated AKT, phosphorylated p38 MAPK and phosphorylated c-Jun N-terminal kinase (JNK) induced by cisplatin. Moreover, exosomes mitigated cisplatin-induced renal damage through inhibiting Bcl2 and increasing Bim, Bid, Bax, cleaved caspase-9, and cleaved caspase-3. Hence, nanoparticle-based techniques are promising drug delivery systems for cisplatin so that some of them, such as lipoplatins and nanocurcumins, have even reached phases 1–3 trials.

Today, growing evidence indicates that patients with type 2 diabetes (T2D) are at a higher risk of developing Alzheimer's disease (AD). Indeed, AD as one of the main causes of dementia in people aged more than 65 years can be aggravated by insulin resistance (IR) and other metabolic risk factors related to T2D which are also linked to the function of the brain. Remarkably, a new term called “type 3 diabetes” has been suggested for those people who are diagnosed with AD while also showing the symptoms of IR and T2D. In this regard, the role of genetic and epigenetic changes associated with AD has been confirmed by many studies. On the other hand, it should be noted that the insulin signaling pathway is highly regulated by various mechanisms, including epigenetic factors. Among these, the role of noncoding RNAs (ncRNAs), including microRNAs and long noncoding RNAs has been comprehensively studied with respect to the pathology of AD and the most well‐known underlying mechanisms. Nevertheless, the number of studies exploring the association between ncRNAs and the downstream targets of the insulin signaling pathway in the development of AD has notably increased in recent years. With this in view, the present study aimed to review the interplay between different ncRNAs and the insulin signaling pathway targets in the pathogenesis of AD to find a new approach in the field of combining biomarkers or therapeutic targets for this disease.

Abstracts: Due to the importance of control and prevention of COVID-19-correlated long-term symptoms, the present review article has summarized what has been currently known regarding the molecular and cellular mechanisms linking COVID-19 to important long-term complications including psychological complications, liver and gastrointestinal manifestations, oral signs as well as even diabetes. COVID-19 can directly affect the body cells through their Angiotensin-converting enzyme 2 [ACE-2] to induce inflammatory responses and cytokine storm. The cytokines cause the release of reactive oxygen species [ROS] and subsequently initiate and promote cell injuries. Another way, COVID-19-associated dysbiosis may be involved in GI pathogenesis. In addition, SARS-CoV-2 reduces butyrate-secreting bacteria and leads to the induction of hyperinflammation. Moreover, SARS-CoV-2-mediated endoplasmic reticulum stress induces de novo lipogenesis in hepatocytes, which leads to hepatic steatosis and inhibits autophagy via increasing mTOR. In pancreas tissue, the virus damages beta-cells and impairs insulin secretion. SARS-COV-2 may change the ACE2 activity by modifying ANGII levels in taste buds which leads to gustatory dysfunction. SARS-CoV-2 infection and its resulting stress can lead to severe inflammation that can subsequently alter neurotransmitter signals. This, in turn, negatively affects the structure of neurons and leads to mood and anxiety disorders. In conclusion, all the pathways mentioned earlier can play a crucial role in the disease's pathogenesis and related comorbidities. However, more studies are needed to clarify the underlying mechanism of the pathogenesis of the new coming virus.