Nature is a vast source of bioactive molecules and has provided an active and efficient reservoir for drug discovery. Among natural compounds, one of the most promising is Schisandrin B (Sch B), isolated from Schisandra chinensis, which was documented to possess diversified pharmacokinetic propriety, among them antioxidant, anti-inflammation, cardioprotection, and neuroprotection. Due to its large biological properties, Sch B was recorded to be a potent cure for several diseases by targeting several signaling pathways. This review is aimed at emphasizing the recent data on the biological properties of Sch B among the molecular mechanism of this drug on tumoral, cardiac, and neural diseases. The data suggest that the antitumor activities of Sch B were mainly through apoptosis and cell cycle arrest at the diver’s stage. It is reported that Sch B could be used as effective chemotherapy, neuroprotection, and cardioprotection since it possesses a spectrum of biological activities; however, further investigations on the mechanism of its action and preclinical trials are still mandatory to further validate the potential of this natural drug candidate.

The cardiac microenvironment profoundly restricts the efficacy of myocardial regeneration tactics for the treatment of myocardial infarction (MI). A prospective approach for MI therapeutics encompasses the combined strategy of scavenging reactive oxygen species (ROS) to alleviate oxidative stress injury and facilitating macrophage polarization towards the regenerative M2 phenotype. In this investigation, we fabricated a ROS-sensitive hydrogel engineered to deliver our previously engineered IL-1β-VHH for myocardial restoration. In mouse and rat models of myocardial infarction, the therapeutic gel was injected into the pericardial cavity, effectively disseminated over the heart surface, forming an in situ epicardial patch. The IL-1β-VHH released from the hydrogel exhibited penetrative potential into the myocardium. Our results imply that this infarct-targeting gel can adhere to the damaged cardiac tissue and augment the quantity of anti-IL-1β antibodies. Moreover, the anti-IL-1β hydrogel safeguards cardiomyocytes from apoptosis by neutralizing IL-1β and inducing M2-type polarization within the myocardial infarction regions, thereby facilitating therapeutic cardiac repair. Our results emphasize the effectiveness of this synergistic comprehensive treatment modality in the management of MI and showcase its considerable potential for promoting recovery in infarcted hearts.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have an irreplaceable role in the treatment of myocardial infarction (MI), which can be injected into the transplanted area with new cardiomyocytes (Cardiomyocytes, CMs), and improve myocardial function. However, the immaturity of the structure and function of iPSC-CMs is the main bottleneck at present. Since collagen participates in the formation of extracellular matrix (ECM), we synthesized nano colloidal gelatin (Gel) with collagen as the main component, and confirmed that the biomaterial has good biocompatibility and is suitable for cellular in vitro growth. Subsequently, we combined the PI3K/AKT/mTOR pathway inhibitor BEZ-235 with Gel and found that the two combined increased the sarcomere length and action potential amplitude (APA) of iPSC-CMs, and improved the Ca²⁺ processing ability, the maturation of mitochondrial morphological structure and metabolic function. Not only that, Gel can also prolong the retention rate of iPSC-CMs in the myocardium and increase the expression of Cx43 and angiogenesis in the transplanted area of mature iPSC-CMs, which also provides a reliable basis for the subsequent treatment of mature iPSC-CMs.

Mesenchymal stem cell (MSC) transplantation has been explored for the clinical treatment of various diseases. However, the current two-dimensional (2D) culture method lacks a natural spatial microenvironment in vitro. This limitation restricts the stable establishment and adaptive maintenance of MSC stemness. Using natural polymers with biocompatibility for constructing stereoscopic MSC microenvironments may have significant application potential. This study used chitin-based nanoscaffolds to establish a novel MSC three-dimensional (3D) culture. We compared 2D and 3D cultured human umbilical cord-derived MSCs (UCMSCs), including differentiation assays, cell markers, proliferation, and angiogenesis. When UCMSCs are in 3D culture, they can differentiate into bone, cartilage, and fat. In 3D culture condition, cell proliferation is enhanced, accompanied by an elevation in the secretion of paracrine factors, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) by UCMSCs. Additionally, a 3D culture environment promotes angiogenesis and duct formation with HUVECs (Human Umbilical Vein Endothelial Cells), showing greater luminal area, total length, and branching points of tubule formation than a 2D culture. MSCs cultured in a 3D environment exhibit enhanced undifferentiated, as well as higher cell activity, making them a promising candidate for regenerative medicine and therapeutic applications.

Inactivity is a significant risk factor for cardiovascular disease. Exercise may greatly enhance the metabolism and function of the cardiovascular system, lower several risk factors, and prevent the development and treatment of cardiovascular disease while delivering easy, physical, and emotional enjoyment. Exercise regulates the cardiovascular system by reducing oxidative stress and chronic inflammation, regulating cardiovascular insulin sensitivity and the body’s metabolism, promoting stem cell mobilization, strengthening autophagy and myocardial mitochondrial function, and enhancing cardiovascular damage resistance, among other effects. Appropriate exercise intervention has become an essential adjuvant therapy in clinical practice for treating and rehabilitating various cardiovascular diseases. However, the prescription of exercise for preventing and treating cardiovascular diseases, particularly the precise selection of individual exercise techniques and their volume, remains controversial. Using multiomics to explain further the molecular process underlying the positive effects of exercise on cardiovascular health will not only improve our understanding of the effects of exercise on health but also establish a scientific basis and supply new ideas for preventing and treating cardiovascular diseases by activating the endogenous protective mechanisms of the body and suggesting more specific exercise prescriptions for cardiovascular rehabilitation.

Pyroptosis is an inflammatory form of programmed cell death with great potential in cancer immunotherapies. Photodynamic therapy (PDT) represents a promising treatment modality to trigger pyroptosis. However, the hypoxic microenvironment inside the tumors often induces limited therapeutic efficacy. Herein, in this work, the first type of mitochondrial-targeting oxime-ester photogenerator (T-Oximer) was constructed to boost type-I ROS/aryl free radicals which could induce DNA damage by DNA cleaving and facilitate high-efficiency pyroptosis-mediated photoimmunotherapy. Detailed mechanism investigations revealed that T-Oximer could produce aryl free radicals via photolysis reaction and generate type-I ROS (O₂^•− and •OH) based on the type-I electron transfer process. Meanwhile, T-Oximer could accumulate in the mitochondria, boost mitochondrial radicals, and damage mitochondria in hypoxic tumor cells. Of peculiar interest, T-Oixmer could bind with DNA and cleave DNA to induce DNA damage. Combined mitochondrial damage with DNA cleavage, T-Oximer can initiate pyroptosis, activate the ICD effect, and trigger robust systemic antitumor immunity for efficient tumor regression and metastasis suppression. Our finding provides a new strategy for constructing oxygen-independent photogenerator for high-efficiency pyroptosis-mediated anti-hypoxia photoimmunotherapy.