Anticancer potential of active alkaloids and synthetic analogs derived from marine invertebrates.

In recent years, the number of cancers has soared, becoming one of the leading causes of human death. At the same time, marine anticancer substances have been the focus of marine drug research. Marine alkaloids derived from marine invertebrates like sponges are an important class of secondary metabolites, which have good bioactivities of blocking the cancer cell cycle, inducing autophagy and apoptosis of cancer cells, inhibiting cancer cell invasion and proliferation. They show potential as anticancer drug candidates. Therefore, in this review, we focus on the detailed introduction of bioactive alkaloids and their synthetic analogs from marine invertebrates, such as 4-chloro fascapysin and other 41 kinds of marine alkaloids or marine alkaloid synthetic analogs. They have significant anticancer activities on breast cancer, cervical cancer, colorectal cancer, prostate cancer, lung cancer, liver cancer, and so on. It provides new candidate compounds for anticancer drug research and provides a reference basis for marine drug resources research.

Plant-derived flavonoids are a potential source of drugs for the treatment of liver fibrosis.

Liver fibrosis is a dynamic pathological process that can be triggered by any chronic liver injury. If left unaddressed, it will inevitably progress to the severe outcomes of liver cirrhosis or even hepatocellular carcinoma. In the past few years, the prevalence and fatality of hepatic fibrosis have been steadily rising on a global scale. As a result of its intricate pathogenesis, the quest for pharmacological interventions targeting liver fibrosis has remained a formidable challenge. Currently, no pharmaceuticals are exhibiting substantial clinical efficacy in the management of hepatic fibrosis. Hence, it is of utmost importance to expedite the development of novel therapeutics for the treatment of this condition. Various research studies have revealed the ability of different natural flavonoid compounds to alleviate or reverse hepatic fibrosis through a range of mechanisms, which are related to the regulation of liver inflammation, oxidative stress, synthesis and secretion of fibrosis-related factors, hepatic stellate cells activation, and proliferation, and extracellular matrix synthesis and degradation by these compounds. This review summarizes the progress of research on different sources of natural flavonoids with inhibitory effects on liver fibrosis over the last decades. The anti-fibrotic effects of natural flavonoids have been increasingly studied, making them a potential source of drugs for the treatment of liver fibrosis due to their good efficacy and biosafety.

Gastrodin: a comprehensive pharmacological review.

Tianma is the dried tuber of Gastrodia elata Blume (G. elata), which is frequently utilized in clinical practice as a traditional Chinese medicine. Gastrodin (GAS) is the main active ingredient of Tianma, which has good pharmacological activity. Therefore, for the first time, this review focused on the extraction, synthesis, pharmacological effects, and derivatives of GAS and to investigate additional development options for GAS. The use of microorganisms to create GAS is a promising method. GAS has good efficacy in the treatment of neurological diseases, cardiovascular diseases, endocrine diseases, and liver diseases. GAS has significant anti-inflammatory, antioxidant, neuroprotective, vascular protective, blood sugar lowering, lipid-regulating, analgesic, anticancer, and antiviral effects. The mechanism involves various signaling pathways such as Nrf2, NF-κB, PI3K/AKT, and AMPK. In addition, the derivatives of GAS and biomaterials synthesized by GAS and PU suggested a broader application of GAS. The research on GAS is thoroughly summarized in this paper, which has useful applications for tackling a variety of disorders and exhibits good development value.

Toxic warhead-armed antibody for targeted treatment of glioblastoma.

Glioblastoma is a fatal intracranial tumor with a poor prognosis, exhibiting uninterrupted malignant progression, widespread invasion throughout the brain leading to the destruction of normal brain tissue and inevitable death. Monoclonal antibodies alone or conjugated with cytotoxic payloads to treat patients with different solid tumors showed effective. This treatment strategy is being explored for patients with glioblastoma (GBM) to obtain meaningful clinical responses and offer new drug options for the treatment of this devastating disease. In this review, we summarize clinical data (from pubmed.gov database and clinicaltrial.gov database) on the efficacy and toxicity of naked antibodies and antibody-drug conjugates (ADCs) against multiple targets on GBM, elucidate the mechanisms that ADCs act at the site of GBM lesions. Finally, we discuss the potential strategies for ADC therapies currently used to treat GBM patients.

Hypericin as a promising natural bioactive naphthodianthrone: A review of its pharmacology, pharmacokinetics, toxicity, and safety.

Hypericin can be derived from St. John's wort, which is widely spread around the world. As a natural product, it has been put into clinical practice such as wound healing and depression for a long time. In this article, we review the pharmacology, pharmacokinetics, and safety of hypericin, aiming to introduce the research advances and provide a full evaluation of it. Turns out hypericin, as a natural photosensitizer, exhibits an excellent capacity for anticancer, neuroprotection, and elimination of microorganisms, especially when activated by light, potent anticancer and antimicrobial effects are obtained after photodynamic therapy. The mechanisms of its therapeutic effects involve the induction of cell death, inhibition of cell cycle progression, inhibition of the reuptake of amines, and inhibition of virus replication. The pharmacokinetics properties indicate that hypericin has poor water solubility and bioavailability. The distribution and excretion are fast, and it is metabolized in bile. The toxicity of hypericin is rarely reported and the conventional use of it rarely causes adverse effects except for photosensitization. Therefore, we may conclude that hypericin can be used safely and effectively against a variety of diseases. We hope to provide researchers with detailed guidance and enlighten the development of it.

Therapeutic Efficacy of Human Mesenchymal Stem Cells With Different Delivery Route and Dosages in Rat Models of Spinal Cord Injury.

Recent studies have shown that the use of mesenchymal stem/stromal cells (MSCs) may be a promising strategy for treating spinal cord injury (SCI). This study aimed to explore the effectiveness of human umbilical cord-derived MSCs (hUC-MSCs) with different administration routes and dosages on SCI rats. Following T10-spinal cord contusion in Sprague-Dawley rats (N = 60), three different dosages of hUC-MSCs were intrathecally injected into rats (SCI-ITH) after 24 h. Intravenous injection of hUC-MSCs (SCI-i.v.) and methylprednisolone reagent (SCI-PC) were used as positive controls (N = 10/group). A SCI control group without treatment and a sham operation group were injected with Multiple Electrolyte Injection solution. The locomotor function was assessed by Basso Beattie Bresnahan (BBB) rating score, magnetic resonance imaging (MRI), histopathology, and immunofluorescence. ELISA was conducted to further analyze the nerve injury and inflammation in the rat SCI model. Following SCI, BBB scores were significantly lower in the SCI groups compared with the sham operation group, but all the treated groups showed the recovery of hind-limb motor function, and rats receiving the high-dose intrathecal injection of hUC-MSCs (SCI-ITH-H) showed improved outcomes compared with rats in hUC-MSCs i.v. and positive control groups. Magnetic resonance imaging revealed significant edema and spinal cord lesion in the SCI groups, and significant recovery was observed in the medium and high-dose hUC-MSCs ITH groups. Histopathological staining showed that the necrotic area in spinal cord tissue was significantly reduced in the hUC-MSCs ITH-H group, and the immunofluorescence staining confirmed the neuroprotection effect of hUC-MSCs infused on SCI rats. The increase of inflammatory cytokines was repressed in hUC-MSCs ITH-H group. Our results confirmed that hUC-MSC administered via intrathecal injection has dose-dependent neuroprotection effect in SCI rats.

Knockdown of circAPLP2 Inhibits Progression of Colorectal Cancer by Regulating miR-485-5p/FOXK1 Axis.

Background: Circular RNAs (circRNAs) have recently been reported to play essential roles in the progression of various cancers, including colorectal cancer (CRC). However, the roles of circRNA amyloid precursor-like protein 2 (circAPLP2) in CRC and its underlying mechanism have not been investigated. Materials and Methods: The expression levels of circAPLP2, microRNA-485-5p (miR-485-5p), and forkhead-box K1 (FOXK1) were determined by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide assay, flow cytometry, and transwell assay, respectively. Western blot assay was performed to measure the protein levels of proliferating cell nuclear antigen, Bcl-2, Bax, vimentin, E-cadherin, fibronectin, and FOXK1. The interaction between miR-485-5p and circAPLP2 or FOXK1 was predicted by starBase and verified by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the functions of circAPLP2 in vivo. The lactate production was measured using lactate assay kit. Results: circAPLP2 expression was enhanced in CRC tissues and cells. circAPLP2 knockdown or miR-485-5p overexpression suppressed cell proliferation, migration, and invasion, whereas it promoted apoptosis in CRC cells, which was reversed by upregulating FOXK1. Moreover, miR-485-5p could directly bind to circAPLP2 and its downregulation reversed the suppressive effect of circAPLP2 knockdown on progression of CRC cells. In addition, FOXK1 was a downstream target of miR-485-5p. Furthermore, circAPLP2 modulated FOXK1 expression by sponging miR-485-5p in CRC cells. Besides, interference of circAPLP2 suppressed tumor growth in vivo and inhibited glycolysis in vitro by upregulating miR-485-5p and downregulating FOXK1. Conclusions: circAPLP2 knockdown inhibited CRC progression through regulating miR-485-5p/FOXK1 axis, providing a novel avenue for treatment of CRC.