Explore the vast range of titles available.

Background. Breast cancer-related depression (BCRD) seriously inhibits the life quality of patients with breast cancer. The Xiaoyao Kangai Jieyu Formula is known to inhibit the progression of depression. However, the detailed function of the Xiaoyao Kangai Jieyu Formula in BCRD remains unclear. Methods. Network pharmacology was constructed to assess the downstream target of the Xiaoyao Kangai Jieyu Formula in BCRD. In addition, the tail suspension test, sucrose preference test, and forced swimming test were used to test the symptom of depression in mice. Fluoro-Jade B staining was performed to observe the structure of neurons. RT-qPCR and western blot were applied to evaluate mRNA and protein levels. Besides, ELISA was performed to test the inflammatory responses and the immune response-related cytokines. Results. Quercetin was identified as the key component of the Xiaoyao Kangai Jieyu Formula. Quercetin significantly inhibited BCRD-induced neuron pyroptosis via downregulation of PYD and card domain containing (ASC), NLR family pyrin domain containing 3 (NLRP3), and caspase-1, and quercetin could reverse BCRD-caused inhibition of neuron viability. Quercetin significantly attenuated the symptom of BCRD in mice, and it could reverse the contents of 5-hydroxytryptamine (5-HT), dopamine (DA), and neutrophil elastase (NE) in mice. Moreover, quercetin could promote the immune responses in xenograft mice via upregulation of interleukin- (IL-) 2, interferon-γ (IFN-γ), and IL-10. Conclusion. Quercetin, the active ingredient of the Xiaoyao Kangai Jieyu Formula, effectively mitigated the progression of BCRD by inhibiting pyroptosis, promoting immune response, and improving serum metabolism.

Diabetic foot ulcer (DFU) is a break in the skin of the foot caused by diabetes. It is one of the most serious and debilitating complications of diabetes. The previous study suggested that dominant M1 polarization during DFU could be the leading reason behind impaired wound healing. This study concluded that macrophage M1 polarization predominates in DFU skin tissue. iNOS was increased in HG-induced M1-polarized macrophages; conversely, Arg-1 was decreased. Macrophage pellets after HG stimulation can impair endothelial cell (EC) function by inhibiting cell viability, tube formation and cell migration, indicating M1 macrophage-derived small extracellular vesicles (sEVs) -mediated HUVEC dysfunction. sEVs miR-503 was significantly upregulated in response to HG stimulation, but inhibition of miR-503 in HG-stimulated macrophages attenuated M1 macrophage-induced HUVEC dysfunction. ACO1 interacted with miR-503 and mediated the miR-503 package into sEVs. Under HG stimulation, sEVs miR-503 taken in by HUVECs targeted IGF1R in HUVECs and inhibited IGF1R expression. In HUVECs, miR-503 inhibition improved HG-caused HUVEC dysfunction, whereas IGF1R knockdown aggravated HUVEC dysfunction; IGF1R knockdown partially attenuated miR-503 inhibition effects on HUVECs. In the skin wound model in control or STZ-induced diabetic mice, miR-503-inhibited sEVs improved, whereas IGF1R knockdown further hindered wound healing. Therefore, it can be inferred from the results that the M1 macrophage-derived sEVs miR-503 targets IGF1R in HUVECs, inhibits IGF1R expression, leads to HUVEC dysfunction, and impedes wound healing in diabetic patients, while packaging miR-503 as an M1 macrophage-derived sEVs may be mediated by ACO1.

In China and other Asian nations, traditional medicine has long been utilized in the treatment of cardiovascular diseases (CVD). While Chinese authorities have incorporated traditional Chinese medicine (TCM) treatment experiences as a supplementary guide for CVD, its international recognition remains limited due to a scarcity of high-quality and reliable randomized controlled trials (RCTs) evidence. The purpose of this study was to examine the clinical outcomes with TCM for CVD after the recent publication of large trials adding >20,000 individuals to the published data. Here, we systematically reviewed 55 published RCTs (modified Jadad scores > 4) in the past 20 years, involving a total of 36,261 patients. In most studies, TCM has been associated with significant improvements in alternative endpoints such as hypertension, coronary heart disease, stroke and heart failure. A total of 19 trials reported on primary outcomes such as cardiovascular events and death events. During the follow-up period, some Chinese patent medicines can effectively reduce the “hard” endpoints of coronary heart disease, stroke, and heart failure, the overall trend of cardiovascular outcomes is lower. The risk of adverse effects was not significantly increased compared to the control group, suggesting its potential as an alternative approach for primary and secondary prevention of CVD based on the available evidence.

Hypertension generally causes target organ damage (TOD) in the heart, brain, kidney, and blood vessels. This can result in atherosclerosis, plaque formation, cardiovascular and cerebrovascular events, and renal failure. Recent studies have indicated that mitochondrial dysfunction is crucial in hypertensive target organ damage. Consequently, mitochondria-targeted therapies attract increasing attention. Natural compounds are valuable resources for drug discovery and development. Many studies have demonstrated that natural compounds can ameliorate mitochondrial dysfunction in hypertensive target organ damage. This review examines the contribution of mitochondrial dysfunction to the development of target organ damage in hypertension. Moreover, it summarizes therapeutic strategies based on natural compounds that target mitochondrial dysfunction, which may be beneficial for preventing and treating hypertensive target organ damage.

Background: Breast cancer-related depression (BCRD) is strongly associated with BC and increases recurrence and mortality. This study investigated the role of kaempferol in the pathogenesis of BCRD and its underlying mechanism. Methods: 4T1 mouse BC cells were treated with corticosterone (Cort) in vitro to develop a neuronal injury model, and a BCRD mouse model was established by injecting 4T1 cells and Cort. The effects of kaempferol on 4T1 cells and BCRD models were measured by behavioral tests, Cell Counting Kit-8 assay, wound healing assay, colony formation assay, Western blot analysis, quantitative real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay, and immunofluorescence. BCRD cells were transfected with the cyclo-oxygenase-2 (COX-2) overexpression plasmid to study the role of the COX-2/prostaglandin E2 (PGE2) axis in the anti-BCRD activity of kaempferol. The connection between kaempferol and COX-2 was analyzed by molecular docking. Results: Kaempferol reduced the viability, migration, and clones of 4T1 cells and inhibited BC growth and depression-like behavior in mice. Kaempferol alleviated inflammation in BCRD, decreased interleukin 1 beta (IL-1β) and IL-6 levels, and increased transforming growth factor beta 1 (TGF-β1) and IL-10 levels. In addition, kaempferol elevated the levels of serotonin, dopamine, and norepinephrine and the amount of 5-Bromo-2′-deoxyuridine/neuronal nuclei-positive cells. Kaempferol downregulated COX-2 and PGE2, and kaempferol could dock with the protein structure of COX-2. Overexpression of COX-2 reduced BCRD viability, upregulated IL-1β and IL-6 levels, and downregulated TGF-β1 and IL-10 expression. Overexpression of COX-2 reversed the protective effects of kaempferol. Conclusion: Kaempferol exerted anti-BCRD effects, at least in part by inhibiting the COX-2/PGE2 pathway, which regulates neuroinflammation, neurotransmitter imbalance, and defective neurogenesis. Therefore, kaempferol may be a promising candidate active ingredient for treating BCRD.

Depression, a leading cause of disability worldwide, is characterized by dysfunction of immature neurons, resulting in dysregulated calcium homeostasis and impaired structural plasticity. Jujuboside A (JuA), a biologically active compound derived from , has demonstrated anti-anxiety and anti-insomnia properties. Recent studies suggest that JuA may be a promising antidepressant, but its underlying mechanisms remain unclear. Sprague-Dawley rats were subjected to chronic unpredictable mild stress (CUMS) to induce a depression model. JuA (12.5 mg/kg, 25 mg/kg, 50 mg/kg) was administered orally for 4 weeks. Emotional and cognitive function were assessed. Monoamine neurotransmitter levels were measured using enzyme-linked immunosorbent assay (ELISA). The number of immature neurons and calcium homeostasis were evaluated by immunofluorescence. Western blotting and immunofluorescence were employed to detect the expression of Sonic hedgehog (Shh) signaling proteins. Additionally, lentiviral vector expressing Shh shRNA (LV-Shh-RNAi) were infused intracerebrally to investigate the role of Shh in JuA's antidepressant effects. JuA significantly ameliorated depressive-like behavior and cognitive dysfunction in CUMS rats, increased monoamine neurotransmitter levels in serum and hippocampal tissue, reduced the number of BrdU/DCX (bromodeoxyuridine/doublecortin)-positive immature neurons, and attenuated calcium ion (Ca ) concentration and Ca /calmodulin-dependent protein kinase II (CaMKII) levels in immature neurons. JuA also markedly elevated synaptic density and prominence complexity, upregulated Shh, Gli family zinc finger 1 and 2 (Gli1/2), synaptophysin (Syn) and postsynaptic density protein-95 (PSD-95) expression in the ventral dentate gyrus (vDG). However, knockdown of Shh in the vDG counteracted JuA's therapeutic effects. These findings collectively suggest that JuA improves depressive-like behavior in CUMS rats by modulating calcium homeostasis and synaptic structural plasticity in immature neurons through the Shh signaling pathway.

Background Insulin secretion deficiency and increased insulin resistance are key pathological pathways that lead to pre-diabetes. Without intervention, pre-diabetes can easily develop into type 2 diabetes mellitus. However, no specific medicine is available for treating pre-diabetes except for intervention through lifestyle changes. Huangjing Qianshi decoction (HJQST) is a qi-replenishing and yin-nourishing Chinese medicinal compound. However, the mode and mechanism of action of HJQST in improving pre-diabetes remain unclear. Here, we studied the effect of HJQST on pre-diabetes. Methods BKS-db mice were induced to develop pre-diabetes and treated with HJQST and metformin (MET). After treatment for 51 days, hematoxylin-eosin and oil red O staining were used to analyze the pathological damage and lipid droplet formation in the pancreatic, liver and skeletal muscle of pre-diabetic mice. Serum levels of free fat acid (FFA), glycated hemoglobin A1c (HbA1c), fasting insulin (INS), reactive oxygen species (ROS), and tumor necrosis factor-α (TNF-α) were analyzed. Levels of glucose transporter 4 (GLUT-4), INS, nuclear receptor subfamily 3 group c member 2 (NR3C2), phosphorylated-signal transducer and activator of transcription 1 (p-STAT1), peroxisome proliferator activated receptor co-activator 1 α (PGC-1α), and protein inhibitor of activated STAT1 (PIAS1) protein were analyzed by immunohistochemistry and western blot. Results The body weight, fasting blood glucose (FBS) levels, and serum levels of HbA1c, FFA, ROS, and TNF-α were significantly decreased, whereas the insulin level was significantly increased in pre-diabetic BKS-db mice after HJQST treatment. Additionally, HJQST treatment improved pancreatic and liver damage and the lipid droplet formation in liver and skeletal muscle. Furthermore, the increased NR3C2 and p-STAT1 protein levels and decreased GLUT-4, INS, PIAS1, and PGC-1a protein levels in pre-diabetic mice were reversed by HJQST treatment. Conclusion HJQST treatment could reverse high FBS level and aberrant lipid metabolism, oxidative stress, and inflammation in pre-diabetes, all of which are related to the NR3C2/PIAS1/STAT1/PGC-1α signal axis.

Breast cancer is one of the most common cancer with high risk in females all over the world. It is usually complicated with depression, which can further accelerate the development and progression of breast tumors. We aim to identify a new drug and identify its functional mechanism in the regulation of hippocampal microglia (MG) in breast cancer complicated with depression (BCCD). The activation model of MG was established by treatments from corticosterone (CORT) or lipopolysaccharides (LPS). The inhibitory effects of resatorvid on MG were investigated by CCK-8, ROS, immunofluorescence, TUNEL, scratch test, ELISA, RT-qPCR and Western blot. BCCD animal model was established using 4T1 inflammatory breast cancer cells and CORT treatment in vitro. Open field experiment (OFE), tail suspension test (TST), ELISA, RT-qPCR and Western blot experiments were utilized to examine the effects of resatorvid on the animal model in vivo. The cell viability and migration ability of the BCCD model group were suppressed. The expressions of inflammatory factors, ROS, and the apoptotic rate of the BCCD model group were up-regulated, in contrast to the control group. The expressions related to the TLR4/NF-κB/NLRP3 signaling in the BCCD model group were also elevated. Resatorvid reversed the above changes, which showed good therapeutic effects in depression-related behavioral changes, tumor treatment, and blood-brain barrier function. In summary, resatorvid inhibited the activation of hippocampal MG in BCCD by regulating TLR4/NF-κB/NLRP3 signaling pathway.

Vaccines are one of the most important means to prevent and control the epidemic of infectious diseases. Commercial vaccines not only include corresponding antigens, but also need vaccine adjuvants. Immune adjuvants play an increasingly important role in the research, development and manufacture of vaccines. Adjuvants combined with antigens can improve the stability, safety and immune efficiency of vaccines. Some substances that can enhance the immune response have been found in nature(mainly plants) and used as adjuvants in vaccines to improve the immune effect of vaccines. These plant-derived immune adjuvants often have the advantages of low toxicity, high stability, low price, etc., providing more possibilities for vaccine development. We summarized and analyzed the advantages, application research, particulate delivery systems, existing problems and future research focus of botanical adjuvant. It is hoped to provide new ideas for the research and development of immune adjuvants in the future.

Background. Mitochondria play an important role in breast cancer (BRCA). We aimed to build a prognostic model based on mitochondria-related genes. Method. Univariate Cox regression analysis, random forest, and the LASSO method were performed in sequence on pretreated TCGA BRCA datasets to screen out genes from a Gene Set Enrichment Analysis, Gene Ontology: biological process gene set to build a prognosis risk score model. Survival analyses and ROC curves were performed to verify the model by using the GSE103091 dataset. The BRCA datasets were equally divided into high- and low-risk score groups. Comparisons between clinical features and immune infiltration related to different risk scores and gene mutation analysis and drug sensitivity prediction were performed for different groups. Result. Four genes, MRPL36, FEZ1, BMF, and AFG1L, were screened to construct our risk score model in which the higher the risk score, the poorer the prognosis. Univariate and multivariate analyses showed that the risk score was significantly associated with age, M stage, and N stage. The gene mutation probability in the high-risk score group was significantly higher than that in the low-risk score group. Patients with higher risk scores were more likely to die. Drug sensitivity prediction in different groups indicated that PF-562271 and AS601245 might be new inhibitors of BRCA. Conclusion. We developed a new workable risk score model based on mitochondria-related genes for BRCA prognosis and identified new targets and drugs for BRCA research.