Exposure to low ambient temperature imposes great challenge to human health. Epidemiological evidence has noted significantly elevated emergency admission and mortality rate in cold climate in many regions, in particular, adverse events in cardiovascular system. Cold stress is becoming one of the important risk factors for cardiovascular death. Through recent advance in echocardiography and myocardial histological techniques, both clinical and experimental experiments have unveiled that cold stress triggers a variety of pathological and pathophysiological injuries, including ventricular wall thickening, cardiac hypertrophy, elevated blood pressure, decreased cardiac function, and myocardial interstitial fibrosis. In order to examine the potential mechanism of action behind cold stress-induced cardiovascular anomalies, ample biochemical and molecular biological experiments have been conducted to denote a role for mitochondrial injury, intracellular Ca²⁺ dysregulation, generation of reactive oxygen species (ROS) and other superoxide, altered gene and protein profiles for apoptosis and autophagy, and increased adrenergic receptor sensitivity in cold stress-induced cardiovascular anomalies. These findings suggest that cold stress may damage the myocardium through mitochondrial injury, apoptosis, autophagy, metabolism, oxidative stress, and neuroendocrine pathways. Although the precise nature remains elusive for cold stress-induced cardiovascular dysfunction, endothelin (ET-_A) receptor, endoplasmic reticulum (ER) stress, transient receptor potential vanilloid, mitochondrial-related protein including NRFs and UCP-2, ROS, Nrf2-Keap1 signaling pathway, Bcl-2/Bax, and lipoprotein lipase (LPL) signaling may all play a pivotal role. For myocardial injury evoked by cold stress, more comprehensive and in-depth mechanisms are warranted to better define the potential therapeutic options for cold stress-associated cardiovascular diseases.

Vaccines administered orally enable the stimulation of both the mucous membrane and system immune responses. However, tumor vaccines, whose effective elements are antigen protein molecules or gene-encoding antigens, are hardly accustomed to the harsh gastrointestinal environment. Here, we explored an oral nanoecapsulated tumor vaccine complex to evaluate the anti-tumor effect. Tomato lectin (TL) was modified on the surface of a nanoemulsion (NE) composed of MAGE1-HSP70/SEA (MHS). C57BL/6 mice were immunized with NE (-), NE (MHS) and TL-NE (MHS) via po. or sc. administration. Additionally, the cellular immunocompetence was detected by the enzyme-linked immunospot assay and lactate dehydrogenase release assay. Serum antibody titers were analyzed using the enzyme-linked immuno sorbent assay. Next, the therapeutic and tumor challenge assays were performed. The TL-NE (MHS) particles were 20 ± 5 nm in diameter and could resist pepsin and trypsin digestion. The cellular immune responses elicited by TL-NE (MHS) perioral were stronger than those by TL-NE (MHS)-sc. (p < 0.05) when targeted to B16-MAGE1 tumor cells. The levels of MAGE-1 antibody induced by TL-NE (MHS) via the oral route was higher than control group (p < 0.05). The percentage of CD4+ and CD8+ T cells in TL-NE (MHS)-po. group was more than other groups (p < 0.05). Furthermore, oral TL-NE (M)HScould delay tumor growth and defer tumor occurrence and tumor recurrence after resection in mice challenged with B16-MAGE-1 tumor cells. The study suggested that the oral TL-NE (MHS) vaccine delivery system is feasible to improve the vaccine protection effect and may have broad application in cancer therapy.

During the process of aging, the retina exhibits chronic oxidative stress (OS) damage. Our preliminary experiment showed that acetaldehyde dehydrogenase 2 (ALDH2) could alleviate retinal damage caused by OS. This study aimed to explore whether ALDH2 could inhibit mice retinal cell apoptosis and enhance the function of unfolded protein response in endoplasmic reticulum (UPRER) through reducing OS in aging process. Retinal function and structure in vivo and in vitro were examined in aged ALDH2+ overexpression mice and ALDH2 agonist Alda1-treated aged mice. Levels of ALDH2, endoplasmic reticulum stress (ERS), apoptosis and inflammatory cytokines were evaluated. Higher expression of ALDH2 was observed at the outer nuclear layer (ONL) and the inner nuclear layer (INL) in aged ALDH2+ overexpression and aged Alda1-treated mice. Moreover, aged ALDH2+ overexpression mice and aged Alda1-treated mice exhibited better retinal function and structure. Increased expression of glucose-regulated protein 78 (GRP78) and ERS-related protein phosphorylated eukaryotic initiation factor 2 (peIF2α) and decreased expression of apoptosis-related protein, including C/EBP homologous protein (CHOP), caspase12 and caspase9, and retinal inflammatory cytokines were detected in the retina of aged ALDH2+ overexpression mice and aged Alda1-treated mice. The expression of ALDH2 in the retina was decreased in aging process. ALDH2 could reduce retinal oxidative stress and apoptosis, strengthen UPRER during the aging process to improve retinal function and structure.

Regular moderate-intensity exercise elicits benefit cardiovascular health outcomes. However, exhaustive exercise (EE) triggers arrhythmia, heart failure, and sudden cardiac death. Therefore, a better understanding of unfavorable heart sequelae of EE is important. Various mechanisms have been postulated for EE-induced cardiac injury, among which mitochondrial dysfunction is considered the cardinal machinery for pathogenesis of various diseases. Mitochondrial quality control (MQC) is critical for clearance of long-lived or damaged mitochondria, regulation of energy metabolism and cell apoptosis, maintenance of cardiac homeostasis and alleviation of EE-induced injury. In this review, we will focus on MQC mechanisms and propose mitochondrial pathophysiological targets for the management of EE-induced myocardial injury. A thorough understanding of how MQC system functions in the maintenance of mitochondrial homeostasis will provide a feasible rationale for developing potential therapeutic interventions for EE-induced injury.