Ophiopogonin D: review of pharmacological activity.

Background: Ophiopogon D is an important natural organic compound in Ophiopogon japonicus, which often has significant biological activity. Purpose: The purpose of this review is to systemically summarize and discuss the pharmacological activity and underlying mechanisms of OP-D in recent years. Method: PubMed and Web of Science were searched with the keywords:"Ophiopogon japonicus", "Ophiopogon D" "pharmacology", and "pharmacokinetics". There was no restriction on the publication year, and the last search was conducted on 1 Jan 2024. Results: Emerging evidence suggests that OP-D possess numerous pharmacological activities, including bone protection, cardiovascular protection, immune regulation, anti-cancer, anti-atherosclerosis, anti-inflammatory and anti-NAFLD. Conclusion: OP-D has a potential value in the prevention and treatment of many diseases. We hope that this review will contribute to therapeutic development and future studies of OP-D.

The roles of E2F7 in cancer: Current knowledge and future prospects.

Background: E2F7 is a recently discovered member of the E2F family. Investigating the function and mechanism of E2F7 in the growth of tumors is significant for the clinical diagnosis and therapy of these malignancies. Objective: The purpose of this review is to provide theoretical basis for the diagnosis and treatment of malignant tumors by exploring E2F7. Methods: The relevant information was collected through the PubMed database using keyword searches "E2F7" and "cancer". Results: On the one hand, E2F7 plays an essential role in embryonic development, angiogenesis, and the nervous system. On the other hand, E2F7 is also linked to the occurrence and growth of various malignant tumors. Conclusion: E2F7 has potential as a therapeutic target in future cancer treatments.

Mini-review: research and progress of oxeiptosis in diseases.

Oxeiptosis is a novel cell death pathway that was introduced in 2018. As a form of regulated cell death, it operates independently of caspases and is induced by ROS. Distinguished from other cell death pathways such as apoptosis, necroptosis, pyroptosis, and ferroptosis, oxeiptosis features unique damage causes pivotal genes, and signaling pathways (KEAP1/PGAM5/AIFM1). Emerging studies indicate that oxeiptosis plays a significant role in the progression of various diseases and its regulation could serve as a promising therapeutic target. However, the precise molecular mechanisms underlying oxeiptosis remain to be fully elucidated. In this mini-review, we systematically summarize the latest developments in oxeiptosis-related diseases while detailing the molecular mechanisms and regulatory networks of oxeiptosis. These insights offer a foundation for a deeper understanding of oxeiptosis.

Necrostatin-1: a promising compound for neurological disorders.

Necrostatin-1, a small molecular alkaloid, was identified as an inhibitor of necroptosis in 2005. Investigating the fundamental mechanism of Necrostatin-1 and its role in various diseases is of great significance for scientific and clinical research. Accumulating evidence suggests that Necrostatin-1 plays a crucial role in numerous neurological disorders. This review aims to provide a comprehensive overview of the potential functions of Necrostatin-1 in various neurological disorders, offering valuable insights for future research.

Mechanism of efferocytosis in atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory vascular disease that occurs in the intima of large and medium-sized arteries with the immune system's involvement. It is a common pathological basis for high morbidity and mortality of cardiovascular diseases. Abnormal proliferation of apoptotic cells and necrotic cells leads to AS plaque expansion, necrotic core formation, and rupture. In the early stage of AS, macrophages exert an efferocytosis effect to engulf and degrade apoptotic, dead, damaged, or senescent cells by efferocytosis, thus enabling the regulation of the organism. In the early stage of AS, macrophages rely on this effect to slow down the process of AS. However, in the advanced stage of AS, the efferocytosis of macrophages within the plaque is impaired, which leads to the inability of macrophages to promptly remove the apoptotic cells (ACs) from the organism promptly, causing exacerbation of AS. Moreover, upregulation of CD47 expression in AS plaques also protects ACs from phagocytosis by macrophages, resulting in a large amount of residual ACs in the plaque, further expanding the necrotic core. In this review, we discussed the molecular mechanisms involved in the process of efferocytosis and how efferocytosis is impaired and regulated during AS, hoping to provide new insights for treating AS.

Progress in Research on CNPY2 in Diseases.

Canopy FGF signaling regulator 2 (CNPY2) is a novel angiogenic growth factor. In recent years, increasing evidence highlights that CNPY2 has important functions in health and disease. Many new blood vessels need to be formed to meet the nutrient supply in the process of tumor growth. CNPY2 can participate in the development of tumors by promoting angiogenesis. CNPY2 also enhances neurite outgrowth in neurologic diseases and promotes cell proliferation and tissue repair, thereby improving cardiac function in cardiovascular diseases. Regrettably, there are few studies on CNPY2 in various diseases. At the same time, its biological function and molecular mechanism in the process and development of disease are still unclear. This paper reviews the recent studies on CNPY2 in cervical cancer, renal cell carcinoma, prostate cancer, colorectal cancer, lung cancer, gastric cancer, hepatocellular carcinoma, cerebral ischemia-reperfusion injury, spinal cord ischemia-reperfusion injury, Parkinson's disease, ischemic heart disease, myocardial ischemiareperfusion injury, myocardial infarction, heart failure, and non-alcoholic fatty liver disease. The biological function and molecular mechanism of CNPY2 in these diseases have been summarized in this paper. Many drugs that play protective roles in tumors, cardiovascular diseases, non-alcoholic fatty liver disease, and neurologic diseases by targeting CNPY2, have also been summarized in this paper. In addition, the paper also details the biological functions and roles of canopy FGF signaling regulator 1 (CNPY1), canopy FGF signaling regulator 3 (CNPY3), canopy FGF signaling regulator 4 (CNPY4), and canopy FGF signaling regulator 5 (CNPY5). The mechanism and function of CNPY2 should be continued to study in order to accelerate disease prevention in the future.

Legumain: a potential biomarker for atherosclerosis.

Atherosclerosis is a lipid-driven chronic inflammatory disease that poses a serious threat to health. Legumain (LGMN), also known as asparagine endonuclease, is a new type of cysteine proteases that can specifically hydrolyze substrate molecules containing asparagine residues. It has anti-apoptotic effects in mammals and plays an antigen-presenting role in inflammatory response. Several studies have found that LGMN can activate multiple signal pathways to promote cell apoptosis and migration, inflammatory response, and the development of atherosclerosis. Importantly, LGMN exerts pro-atherogenic effects by participating in a variety of pathophysiological mechanisms of atherosclerosis, including vascular remodeling, inflammatory response, plaque stability, and the degradation of extracellular matrix. In the present review, we describe the LGMN distribution, structure, generation, and functional partners. Furthermore, we summarize the relationship between LGMN and atherosclerosis. Based on the relationship between LGMN and atherosclerosis, LGMN may be a potential biomarker for atherosclerosis.

Research and progress of inflammasomes in nonalcoholic fatty liver disease.

With the development of the social economy, unhealthy living habits and eating styles are gradually affecting people's health in recent years. As a chronic liver disease, NAFLD is deeply affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. As a protein complex in clinical research, the inflammasomes play a crucial role in the development of NAFLD, atherosclerosis, and other diseases. This paper reviews the types, composition, characteristics of inflammasomes, and molecular mechanism of the inflammasome in NAFLD. Meanwhile, the paper reviews the drugs and non-drugs that target NLRP3 inflammasome in the treatment of NAFLD in the past decades. we also analyzed and summarized the related experimental models, mechanisms, and results of NAFLD. Although current therapeutic strategies for NAFLD are not effective, we expect that we will be able to find an appropriate treatment to address this problem in the future with further research on inflammasome.

Research and Progress of Probucol in Nonalcoholic Fatty Liver Disease.

With the development of the social economy over the last 30 years, non-alcoholic fatty liver disease (NAFLD) is affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. It is very important to investigate the pathogenesis and treatment of NAFLD for the development of human health. Probucol is an antioxidant with a bis-phenol structure. Although probucol is a clinically used cholesterol-lowering and antiatherosclerosis drug, its mechanism has not been elucidated in detail. This paper reviews the chemical structure, pharmacokinetics and pharmacological research of probucol. Meanwhile, this paper reviews the mechanism of probucol in NAFLD. We also analyzed and summarized the experimental models and clinical trials of probucol in NAFLD. Although current therapeutic strategies for NAFLD are not effective, we hope that through further research on probucol, we will be able to find suitable treatments to solve this problem in the future.

STK25: a viable therapeutic target for cancer treatments?

Serine/threonine protein kinase 25 (STK25) is a critical regulator of ectopic lipid storage, glucose and insulin homeostasis, fibrosis, and meta-inflammation. More and more studies have revealed a strong correlation between STK25 and human diseases. On the one hand, STK25 can affect glucose and fatty acid metabolism in normal cells or tumors. On the other hand, STK25 participates in autophagy, cell polarity, cell apoptosis, and cell migration by activating various signaling pathways. This article reviews the composition and function of STK25, the energy metabolism and potential drugs that may target STK25, and the research progress of STK25 in the occurrence and development of tumors, to provide a reference for the clinical treatment of tumors.

Salusins: advance in cardiovascular disease research.

Salusins are discovered in 2003 and divided into salusin-α and salusin-ß, which are bioactive peptides with hemodynamic and mitotic activity and mainly distributed in plasma, urine, endocrine glands and kidneys. A large number of studies have shown that salusins can regulate lipid metabolism, inflammatory response and vascular proliferation. Despite the profound and diverse physiological properties of salusins, the exact mechanism of their cardiovascular effects remains to be determined. The potential mechanisms of action of salusins in cardiovascular-related diseases such as atherosclerosis, hypertension, heart failure, myocardial infarction and myocarditis, and their use as biomarkers of cardiovascular disease are discussed. This review aims to provide a new strategy for the diagnosis and prevention of clinical cardiovascular diseases.

Monocular Depth Estimation with Self-Supervised Learning for Vineyard Unmanned Agricultural Vehicle.

To find an economical solution to infer the depth of the surrounding environment of unmanned agricultural vehicles (UAV), a lightweight depth estimation model called MonoDA based on a convolutional neural network is proposed. A series of sequential frames from monocular videos are used to train the model. The model is composed of two subnetworks-the depth estimation subnetwork and the pose estimation subnetwork. The former is a modified version of U-Net that reduces the number of bridges, while the latter takes EfficientNet-B0 as its backbone network to extract the features of sequential frames and predict the pose transformation relations between the frames. The self-supervised strategy is adopted during the training, which means the depth information labels of frames are not needed. Instead, the adjacent frames in the image sequence and the reprojection relation of the pose are used to train the model. Subnetworks' outputs (depth map and pose relation) are used to reconstruct the input frame, then a self-supervised loss between the reconstructed input and the original input is calculated. Finally, the loss is employed to update the parameters of the two subnetworks through the backward pass. Several experiments are conducted to evaluate the model's performance, and the results show that MonoDA has competitive accuracy over the KITTI raw dataset as well as our vineyard dataset. Besides, our method also possessed the advantage of non-sensitivity to color. On the computing platform of our UAV's environment perceptual system NVIDIA JETSON TX2, the model could run at 18.92 FPS. To sum up, our approach provides an economical solution for depth estimation by using monocular cameras, which achieves a good trade-off between accuracy and speed and can be used as a novel auxiliary depth detection paradigm for UAVs.

The adsorption mechanism of Zn2+ by triclinic birnessite and the mechanism.

In this paper, the reaction mechanism for the adsorption of Zn2+ by synthetic triclinic Na-birnessite was studied by reacting synthetic triclinic Na-birnessite with Zn2+ in solution, thereby providing a theoretical basis for the purification of heavy metal ions in acid soil and water by triclinic birnessite. The adsorption effect of Zn2+ on Na-birnessite enhances with an increase in either reaction time or Na-birnessite dosage, as well as decrease of pH. Na-birnessite can effectively adsorb Zn2+ in acidic solutions without any secondary pollution, and the stronger the acidity, the better the treatment effect. In acidic conditions, H+ in solution exchanges with Na+ in the interlayer of triclinic Na-birnessite, then a small part of Zn2+ in solution exchanges with the Mn2+ produced during the triclinic-to-hexagonal phase transformation, and most of the Zn2+ forms a complex with OH- on the octahedral layer, which loses protons due to the consumption of H+ ions. Finally, Zn2+ adsorbs above and below octahedral vacancies in hexagonal birnessite in either an octahedral or tetrahedral coordination.

Microtubule affinity regulating kinase 4: A promising target in the pathogenesis of atherosclerosis.

Microtubule affinity regulating kinase 4 (MARK4), an important member of the serine/threonine kinase family, regulates the phosphorylation of microtubule-associated proteins and thus modulates microtubule dynamics. In human atherosclerotic lesions, the expression of MARK4 is significantly increased. Recently, accumulating evidence suggests that MARK4 exerts a proatherogenic effect via regulation of lipid metabolism (cholesterol, fatty acid, and triglyceride), inflammation, cell cycle progression and proliferation, insulin signaling, and glucose homeostasis, white adipocyte browning, and oxidative stress. In this review, we summarize the latest findings regarding the role of MARK4 in the pathogenesis of atherosclerosis to provide a rationale for future investigation and therapeutic intervention.

Nesfatin-1 in lipid metabolism and lipid-related diseases.

Nesfatin-1, an anorexic neuropeptide discovered in 2006, is widely distributed in the central nervous system and peripheral tissues. It has been shown to be involved in the regulation of food intake and lipid metabolism, inhibiting fat accumulation, accelerating lipid decomposition, and in general, inhibiting the development of lipid-related diseases, such as obesity and metabolic syndrome. Potential mechanisms of Nesfatin-1 action in lipid metabolism and lipid-related diseases will be discussed as well as its role as a biomarker in cardiovascular disease. This review expected to provide a new strategy for the diagnosis and prevention of clinically related diseases.

Role of Gut Microbiota in Neuroendocrine Regulation of Carbohydrate and Lipid Metabolism via the Microbiota-Gut-Brain-Liver Axis.

Gut microbiota play an important role in maintaining intestinal health and are involved in the metabolism of carbohydrates, lipids, and amino acids. Recent studies have shown that the central nervous system (CNS) and enteric nervous system (ENS) can interact with gut microbiota to regulate nutrient metabolism. The vagal nerve system communicates between the CNS and ENS to control gastrointestinal tract functions and feeding behavior. Vagal afferent neurons also express receptors for gut peptides that are secreted from enteroendocrine cells (EECs), such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and 5-hydroxytryptamine (5-HT; serotonin). Gut microbiota can regulate levels of these gut peptides to influence the vagal afferent pathway and thus regulate intestinal metabolism via the microbiota-gut-brain axis. In addition, bile acids, short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and Immunoglobulin A (IgA) can also exert metabolic control through the microbiota-gut-liver axis. This review is mainly focused on the role of gut microbiota in neuroendocrine regulation of nutrient metabolism via the microbiota-gut-brain-liver axis.

Anti-Inflammatory and Immune Regulatory Actions of Naja naja atra Venom.

Naja naja atra venom (NNAV) is composed of various proteins, peptides, and enzymes with different biological and pharmacological functions. A number of previous studies have reported that NNAV exerts potent analgesic effects on various animal models of pain. The clinical studies using whole venom or active components have confirmed that NNAV is an effective and safe medicine for treatment of chronic pain. Furthermore, recent studies have demonstrated that NNAV has anti-inflammatory and immune regulatory actions in vitro and in vivo. In this review article, we summarize recent studies of NNAV and its components on inflammation and immunity. The main new findings in NNAV research show that it may enhance innate and humoral immune responses while suppressing T lymphocytes-mediated cellular immunity, thus suggesting that NNAV and its active components may have therapeutic values in the treatment of inflammatory and autoimmune diseases.

Cobrotoxin extracted from Naja atra venom relieves arthritis symptoms through anti-inflammation and immunosuppression effects in rat arthritis model.

ETHNOPHARMACOLOGICAL RELEVANCE: The Naja atra (Chinese cobra), primarily distributing in the low or medium altitude areas of southern China and Taiwan, was considered as a medicine in traditional Chinese medicine and used to treat pain, inflammation and arthritis. AIM OF THE STUDY: To study the anti-inflammatory and anti-arthritic activities of cobrotoxin (CTX), an active component of the venom from Naja atra. MATERIALS AND METHODS: Adjuvant-induced arthritis (AA) rats were used as the animal model of rheumatoid arthritis. The anti-arthritic effects of CTX were evaluated through the arthritis score, paw edema and histopathology changes of joints. The anti-inflammation effects were assayed by the level of IL-6, TNF-α, IL-1ß and the number of inflammatory cells in peripheral blood, as well as the proliferation of fibroblast-like synoviocytes (FLS). The immune level was valued by the proliferation of T cells and the level of CD4 and CD8. RESULTS: CTX alleviated the disease development of AA rats according to the ameliorating arthritis score, paw edema and histopathology character. At the meanwhile, CTX decreased the levels of IL-6, TNF-α, IL-1ß and the numbers of inflammatory cells in peripheral blood. CTX also suppressed the abnormal increasing of CD4+ T cells/ CD8+ T cells ratio, and could significantly inhibit T cell proliferation. Consistent with its effects on inhibiting granuloma's formation, CTX inhibited the proliferation of the cultured FLSs. Further studies on inflammatory signaling in FLSs revealed that CTX could inhibit the NF-κB signaling pathway. CONCLUSIONS: CTX has beneficial effects on rheumatoid arthritis by its immune regulation effects and anti-inflammation effects. The inhibition of NF-κB pathway partly contributes to the anti-inflammatory properties of CTX.

Cobrotoxin from Naja naja atra Venom Ameliorates Adriamycin Nephropathy in Rats.

Chronic kidney disease (CKD) becomes a global health problem with high morbidity and mortality. Adriamycin- (ADR-) induced rodent chronic nephropathy is a classic experimental model of human minimal lesion nephrotic syndrome. The present study investigated the effect of cobrotoxin (CTX) on ADR-induced nephropathy. Rats were given 6 mg/kg ADR once through the tail vein to replicate ADR nephropathy model. CTX was administered to rats daily by placing a fast dissolving CTX membrane strip under the tongue starting from 5 days prior to ADR administration until the end of experiment. The results showed that CTX ameliorated the symptoms of ADR nephropathy syndrome with reduced body weight loss, proteinuria, hypoalbuminemia, dyslipidemia, serum electrolyte imbalance, oxidative stress, renal function abnormities, and kidney pathological lesions. Anti-inflammatory cytokine IL-10 expression was elevated after CTX administration in ADR nephropathy model. CTX inhibited the phosphorylation of IκB-α and NF-κB p65 nuclear translocation. Meanwhile, CTX upregulated the protein level of podocyte-specific nephrin and downregulated the level of fibrosis-related TGF-ß. These findings suggest that CTX may be a potential drug for chronic kidney diseases.

Neurotoxin from Naja naja atra venom inhibits skin allograft rejection in rats.

BACKGROUND: Recent studies reported that Naja naja atra venom (NNAV) regulated immune function and had a therapeutic effect on adjunctive arthritis and nephropathy. We hypothesized that NNAV and its active component, neurotoxin (NTX), might inhibit skin allograft rejection. METHODS: Skin allografts were used to induce immune rejection in rats. In addition, mixed lymphocyte culture (MLC) was used to mimic immune rejection reaction in vitro. Both NNAV and NTX were orally given starting from 5days prior to skin allograft surgery. RESULTS: The results showed that oral administration of NNAV or NTX prolonged the survival of skin allografts and inhibited inflammatory response. The production of Th1 cytokines (IFN-γ, IL-2) was also suppressed. NTX inhibited T-cell proliferation and CD4(+) T cell division induced by skin allografts. NTX also showed immunosuppressive activity in mixed lymphocyte culture. Atropine alone inhibited Con A-induced proliferation of T cells and potentiated NTX' s inhibitory effects on T cells, while pilocarpine only slightly enhanced Con A-induced T cell proliferation and partially reversed the inhibitory effect of NTX. On the other hand, neither nicotine nor mecamylamine had an influence on NTX's inhibitory effects on Con A-induced T cell proliferation in vitro. NTX inhibited T cell proliferation by arresting the cell cycle at the G0/G1 phase. CONCLUSIONS: The present study revealed that NNAV and NTX suppressed skin allograft rejection by inhibiting T cell-mediated immune responses. These findings suggest both NNAV and NTX as potential immunosuppressants for preventing the immune response to skin allografts.