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Malignant tumor is a major killer that seriously endangers human health. At present, the methods of treating tumors include surgical resection, chemotherapy, radiotherapy and immunotherapy. However, the survival rate of patients is still very low due to the complicated mechanism of tumor occurrence and development and high recurrence rate. Individualized treatment will be the main direction of tumor treatment in the future. Because only by understanding the molecular mechanism of tumor development and differentially expressed genes can we carry out accurate treatment and improve the therapeutic effect. MicroRNA (miRNA) is a kind of small non coding RNA, which regulates gene expression at mRNA level and plays a key role in tumor regulation. Ferroptosis is a kind of programmed death caused by iron dependent lipid peroxidation, which is different from apoptosis, necrosis and other cell death modes. Now it has been found that ferroptosis plays an important role in the occurrence and development of tumors and drug resistance. More and more studies have found that miRNAs can regulate tumor development and drug resistance through ferroptosis. Therefore, in this review, the mechanism of ferroptosis is briefly outlined, and the relationship between miRNAs and ferroptosis in tumors is reviewed.

Stroke is a fatal neurological disease, which seriously threatens human health and life. Ischemic stroke (IS) is the most common type of stroke in clinic. Its pathogenesis is very complex, mainly caused by nerve damage caused by brain blood supply disorder. Previous studies have confirmed that natural products play important roles in improving neurological disorders. Furthermore, our previous results also suggested that Shenxiong Tongmai granule, a clinically used herbal medicines’ prescription, has a good ameliorating effect on IS. In the present study, we found that Monomethyl lithospermate (MOL), a constituent of Shenxiong Tongmai granule, significantly improved the neurological damage in middle cerebral artery occlusion (MCAO) rats. MOL can significantly improve the neurological deficit score of MCAO rats, and improve the damage of hippocampal neurons caused by ischemia-reperfusion (IR). At the same time, we also found that MOL could reduce the level of oxidative stress in the brain tissues of MCAO rats. Furthermore, the oxygen and glucose deprivation/Reoxygenation (OGD/R)-induced SHSY-5Y cell model was established in vitro to investigate the pharmacological activity and molecular mechanisms of MOL in improving the nerve injury of IS rats. The results showed that MOL could increase the cell viability of SHSY-5Y cells, inhibit the mitochondrial membrane potential (MMOP) collapse and suppress apoptosis. In addition, MOL also ameliorated the elevated oxidative stress level caused by OGR/R treatment in SHSY-5Y cells. Further mechanistic studies showed that MOL could activate the PI3K/AKT pathway via promoting the phosphorylation of PI3K and AKT in MCAO rats and OGR/R-induced SHSY-5Y cells, which could be partially blocked by addition of PI3K/AKT pathway inhibitor of LY294002. Taken together, our current study suggested that MOL exerts a protective effect against neural damage caused by IS in vivo and in vitro by activating the PI3K/AKT pathway.

The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis is an iron-mediated form of cell death caused by the accumulation of lipid peroxides. The intracellular imbalance between oxidant and antioxidant due to the abnormal expression of multiple redox active enzymes will promote the produce of reactive oxygen species (ROS). So far, a few pathways and regulators have been discovered to regulate ferroptosis. In particular, the cystine/glutamate antiporter (System Xc−), glutathione peroxidase 4 (GPX4) and glutathione (GSH) (System Xc−/GSH/GPX4 axis) plays a key role in preventing lipid peroxidation-mediated ferroptosis, because of which could be inhibited by blocking System Xc−/GSH/GPX4 axis. This review aims to present the current understanding of the mechanism of ferroptosis based on the System Xc−/GSH/GPX4 axis in the treatment of drug-resistant solid tumors.

Alzheimer’s disease (AD), the most common type of senile dementia, includes the complex pathogenesis of abnormal deposition of amyloid beta-protein (Aβ), phosphorylated tau (p-tau) and neuroimmune inflammatory. The neurodegenerative process of AD triggers microglial activation, and the overactivation of microglia produces a large number of neuroimmune inflammatory factors. Microglia dysfunction can lead to disturbances in iron metabolism and enhance iron-induced neuronal degeneration in AD, while elevated iron levels in brain areas affect microglia phenotype and function. In this manuscript, we firstly discuss the role of microglia in AD and then introduce the role of microglia in the immune-inflammatory pathology of AD. Their role in AD iron homeostasis is emphasized. Recent studies on microglia and ferroptosis in AD are also reviewed. It will help readers better understand the role of microglia in iron metabolism in AD, and provides a basis for better regulation of iron metabolism disorders in AD and the discovery of new potential therapeutic targets for AD.

Inflammation is a protective response of the body to an irritant. When an inflammatory response occurs, immune cells are recruited to the injury, eliminating the irritation. The excessive inflammatory response can cause harm to the organism. Inflammation has been found to contribute to cervical cancer if there is a problem with the regulation of inflammatory response. Cervical cancer is one of the most common malignant tumors globally, and the incidence tends to be younger. The harm of cervical cancer cannot be ignored. The standard treatments for cervical cancer include surgery, radiotherapy and chemotherapy. However, the prognosis for this treatment is poor, so it is urgent to find a safer and more effective treatment. Natural products are considered excellent candidates for the treatment of cervical cancer. In this review, we first describe the mechanisms by which inflammation induces cervical cancer. Subsequently, we highlight natural products that can treat cervical cancer through inflammatory pathways. We also introduce natural products for the treatment of cervical cancer in clinical trials. Finally, methods to improve the anticancer properties of natural products were added, and the development status of natural products was discussed.

In human sperm, a fraction of its chromatin retains nucleosomes that are positioned on specific sequences containing genes and regulatory units essential for embryonic development. This nucleosome positioning (NP) feature provides an inherited epigenetic mark for sperm. However, it is not known whether there is a structural constraint for these nucleosomes and, if so, how they are localized in a three-dimensional (3D) context of the sperm nucleus. In this study, we examine the 3D organization of sperm chromatin and specifically determine its 3D localization of nucleosomes using structured illumination microscopy. A fraction of the sperm chromatin form nucleosome domains (NDs), visible as microscopic puncta ranging from 40 μm to 700 μm in diameter, and these NDs are precisely localized in the post acrosome region (PAR), outside the sperm's core chromatin. Further, NDs exist mainly in sperm from fertile men in a pilot survey with a small sample size. Together, this study uncovers a new spatially-restricted sub-nuclear structure containing NDs that are consistent with NPs of the sperm, which might represent a novel mark for healthy sperm in human.

Extraction of elements of mobile forms is one of the important techniques in deep-penetrating geochemistry for finding concealed orebodies. However, the single extraction agent cannot be applied to all elements and all coverage areas. Moreover, the effective information of mobile forms is easily obscured because the extraction time, pH and extraction temperature have important effects on the extraction results. Determination of the mobile forms of multi-metal elements (W, Mo, Cu, Pb, Zn) in extractant using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) has been established. The optimum conditions include solid-liquid mixing ratio of 1:10, extraction time of 24 h, pH of 7.0, and an extraction temperature of 25℃. The determination limit of the proposed method is 0.006-0.021 μg/g and the relative standard deviation (RSD) is 1.91%-6.56%. This method has been applied to Xiyuku concealed porphyry Mo-W ore deposit in the Luanchuan ore concentrated district. The prospecting anomaly in mobile forms of W and Mo is consistent with the projection position of concealed orebodies in the ground surface.

The genus Erycibe belongs to the Convolvulaceae family that contains approximately 70 species mainly distributed from tropical and subtropical Asia to north of Australia. Several Erycibe species are traditionally used in folk medicine for the treatment of various ailments, including rheumatic arthralgia, primary glaucoma, hepatopathies, and infectious and malignant diseases. This review aims to summarize comprehensive and updated information on traditional medicinal uses, phytochemistry, pharmacology, and toxicology of Erycibe species to provide a reference for the further research and application of the Erycibe genus. The scientific and extensive literatures between 1975 and 2020 were systematically gathered from scientific databases such as SciFinder Scholar, Science Direct, Web of Science, PubMed, Google Scholar, Scopus, Springer Link and China National Knowledge Infrastructure (CNKI), as well as Chinese herbal classic books, PhD and MSc theses, and several official websites. Erycibe species have been used for the treatment of various rheumatoid diseases, glaucoma, a variety of hepatic diseases, infectious diseases and various malignancies in the traditional and local medicine. Since the 1970s, 153 compounds, including coumarins, quinic acid derivatives, flavonoids, alkaloids, lignans, and others have been isolated from five species of the Erycibe genus. Pharmacological studies have shown that these extracts and compounds from the Erycibe genus have extensive activities consistent with the traditional and local applications, such as anti-glaucoma, anti-arthritic, hepatoprotective and anti-cancer activities, as well as anti-inflammatory, anti-respiratory syncytial virus (RSV), and neuroprotective properties. Although there are extensive data on the genus Erycibe , certain specific gaps still exist. For herbal preparations containing Erycibe species, clinical toxicological investigation is required for the safety of these herbal preparation therapies, as well as further investigations on pharmacokinetics and bioavailability for guideline for clinical application. Furthermore, more detailed pharmacological, toxicological and clinical researches are needed to assess the alternatives to Erycibe species. Systematic and comprehensive pre-clinical studies are similarly required to estimate the possibility of extracts and compounds from the genus Erycibe with bioactivity developing into new drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

One new isoflavone, 6'-dihydroxy-2-methyl-2'-methoxyl-3'-acetylisoflavone ( 1 ) and six known compounds ( 2 - 7 ) were isolated from the processed root barks of Paeonia suffruticosa . The structures of these compounds were elucidated using UV, IR, NMR, and HR-ESI-MS data. Compound 1 represents the first example of naturally occurring 2-substituted isoflavone. Compounds 2 - 7 were isolated from the processed root barks of P. suffruticosa for the first time. In addition, all of the compounds were screened for their procoagulant activity. As a result, compounds 4 , 6 , and 7 showed significantly in vitro procoagulant activity.

Isoliensinine (ISO), a natural compound, is a bibenzyl isoquinoline alkaloid monomer in lotus seed, which has strong antioxidant and free radical scavenging activities. The oxidative toxicity caused by glutamic acid overdose is one of the important mechanisms of nerve cell injury, and the oxidative toxicity caused by glutamic acid is related to ferroptosis. This study aims to establish a glutamate-induced injury model of mouse hippocampal neurons HT-22 cells, and investigate the protective effect of ISO on the neurotoxicity of glutamate-induced HT-22 cells. The results showed that ISO inhibited glutamate-induced ferroptosis of neuronal cells through nuclear factor E2-related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) signaling pathway. Pretreatment of HT-22 cells with ISO significantly reduced glutamate-induced cell death. Ferroptosis inhibitors have the same effect. ISO inhibited the decrease of mitochondrial membrane potential detection and the increase of iron content induced by glutamate, the increase of malondialdehyde and reactive oxygen species in cytoplasm and lipid, and protected the activities of GPx and superoxide dismutase enzymes. In addition, WB showed that glutamic acid could induce the upregulated expression of long-chain esteryl coA synthase 4 (ACSL4) protein and the downregulated expression of SLC7A11 and GPX4 protein in HT-22 cells, while ISO could prevent the abnormal expression of these proteins induced by glutamic acid. The nuclear translocation of Nrf2 in HT-22 cells was increased, and the expression of downstream heme oxygenase-1 protein was upregulated. In summary, ISO protects HT-22 cells from glutamate-induced ferroptosis through a novel mechanism of the Nrf2/GPX4 signaling pathway., (© 2024 Wiley Periodicals LLC.)

Objectives: Dihydroisotanshinone I (DT) is a kind of diterpenoid compound extracted from the dried roots of Salvia miltiorrhiza Bunge, and exhibits multiple biological activities including anti-tumor activity. Cisplatin is one of the first-line drugs for the treatment of lung adenocarcinoma (LAUD), but the drug resistance and toxicity limit its efficacy. DT is known to induce apoptosis and ferroptosis, but it is unclear whether DT can inhibit the cisplatin-resistant LAUD cells and reverse the drug resistance in LAUD. Therefore, our study intends to establish the cisplatin-resistant human LAUD cells (A549/DDP), and figure out the influence and related mechanisms of DT reversing cisplatin resistance in A549/DDP cells, so as to provide a theoretical basis for the DT as a new natural candidate for the treatment of LAUD., Methods: The establishment of A549/DDP was the continuous stimulation by exposing A549 to gradient concentrations of Cisplatin. The cell viability of A549 and A549/DDP was detected by CCK-8 kit, and the IC50 value was calculated. The morphological changes of A549 and A549/DDP cells were observed by an inverted microscope. The contents of malondialdehyde (MDA) and glutathione (GSH) in A549/DDP cells after drug treatment were detected by related kits. The levels of Fe2+, cytosolic reactive oxygen species (ROS), and lipid reactive oxygen species (lipid ROS) were detected by a fluorescence microplate reader or fluorescence cell imager according to the related fluorescent probe kit instructions. Western blot was used to detect the expressions of PI3K, phospho-PI3K, AKT, phospho-AKT, MDM2, p53, GPX4, and SLC7A11 in A549/DDP after different drug treatments., Key Findings: Our study demonstrated that the inhibitory effect of DT on A549 and A549/DDP cells was time-dependent and concentration-dependent, and DT and DDP had a synergistic effect on inhibiting the proliferation of A549/DDP cells. Furthermore, DT mainly induced ferroptosis in A549/DDP cells and synergized with cisplatin to promote ferroptosis in A549/DDP cells. The result of KEGG pathway analysis, molecular docking and western blot showed that DT could enhance the cisplatin sensitivity of A549/DDP by inhibiting PI3K/MDM2/P53 signaling pathway., Conclusions: Consequently, we concluded that DT promotes ferroptosis in cisplatin-resistant LAUD A549/DDP cells. Additionally, DT reverses cisplatin resistance by promoting ferroptosis via PI3K/MDM2/P53 pathway in A549/DDP cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

One new flavonostilbene glycoside, polygonflavanol C ( 1 ), two new dimeric stilbene glycosides, multiflorumiside M and multiflorumiside N ( 2 - 3 ), one new diphenyl ethanol glycoside, ( R )-2,3,5,4'-tetrahydroxy-diphenylethanol 2- O - β -D-glucopyranoside ( 4 ), and one new deoxybenzoin glycoside, 2,4,3',5'-tetrahydroxy-6-methyl-deoxybenzoin 2- O - β -D-glucopyranoside ( 5 ), together with six known ones ( 6 - 11 ), were isolated from the roots of Polygonum multiflorum . Their structures were elucidated by the comprehensive spectroscopic analyses. In addition, compounds 1 and 7 showed significantly in vitro anti-inflammatory activity.

Objective: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions., Materials and Methods: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC 0-t and AUC 0-∞ ) and the maximal plasma concentration (C max ). Safety was assessed mainly from the occurrence of adverse events (AEs)., Results: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC 0-t were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC 0-∞ were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for C max were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and C max ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs)., Conclusion: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.

Polygonflavanol B(1), a new flavonostilbene glycoside, was isolated from the roots of Polygonum multiforum(Polygonaceae) by various column chromatography methods including macroporous resin HP-20, silica gel, Sephadex LH-20, and preparative HPLC. The structure with absolute configuration of the new compound was identified by its physicochemical properties, spectroscopic data, ECD calculation, and chemical method.

Aim: To investigate midkine (MK) and syndecan-3 protein expression in pancreatic cancer by immunohistochemistry, and to analyze their correlation with clinicopathological features, perineural invasion, and prognosis., Methods: Pancreatic cancer tissues (including adequately sized tumor tissue samples and tissue samples taken from areas less than 2.0 cm around the tumor) were taken from 42 patients who were undergoing a partial duodenopancreatectomy. MK and syndecan-3 proteins were detected by immunohistochemistry using a standardized streptavidin-peroxidase method, and analyzed for their correlation with clinicopathological features, perineural invasion, and prognosis. Associations of neural invasion with aggressive characteristics of pancreatic cancer and the presence of perineural invasion were assessed by two independent observers blinded to the patient status., Results: MK and syndecan-3 were found in 26 (61.9%) and 24 (57.1%) specimens, respectively. MK and syndecan-3 expression was associated with perineural invasion (P = 0.018 and 0.031, respectively). High MK expression was closely associated with advanced tumor, node and metastasis stage (P = 0.008), lymph node metastasis (P = 0.042), and decreased postoperative survival at 3 years (51.0% vs 21.8%, P = 0.001). Syndecan-3 levels were correlated with tumor size (P = 0.028). Patients who were syndecan-3 negative had a higher cumulative survival rate than those who were positive, but the difference was not significant (44.0% vs 23.0%, P > 0.05)., Conclusion: MK and syndecan-3 are frequently expressed in pancreatic cancer and associated with perineural invasion. High expression of MK and syndecan-3 may contribute to the highly perineural invasion and poor prognosis of human pancreatic cancer.

Objective: To observe the effective mechanism of electroacupuncture for chronic fatigue syndrome (CFS)., Methods: The dynamic detection of chronobiology was used to test the event-related potentials in 20 healthy subjects and 20 CFS patients. P3a and P3b latencies at 4 equidistant time points (8:00, 14:00, 20:00, 2:00) within 24 hours were collected and analyzed., Results: (1) Latency of P3a in CFS group was obviously prolonged at 14:00 compared to health group with statistical significance (P < 0.05), latency of P3b was decreased at 14:00 after electroacupuncture treatment with statistical significance compared to that of pre-treatment (P < 0.01). (2) There were obviously circadian rhythm in latency of P3a and P3b in health group (P < 0.05), which were not seen in CFS group (P > 0.05); the circadian rhythm latency of P3b restored after treatment (P < 0.05). (3) The latency acrophase of P3a and P3b pre-treatment obviously shifted backward compared to that of healthy subjects (P < 0.05), shifted forward after electroacupuncture treatment (P < 0.05)., Conclusion: The event-related potential circadian rhythms are lost in CFS patients. Electroacupuncture at Shenshu (BL 23) and Zusanli (ST 36) can regulate the circadian rhythm of P3a and P3b latency and improve the cognition of the patients in daytime.

Background & Objective: The drug-resistance and metastasis in early stages of human malignant ovarian neoplasm have significant effect on chemotherapy of human ovarian carcinoma. The objective of this study was to explore the impact of arsenic trioxide(As2O3) on proliferation and metastasis of drug-resistant human epithelial ovarian carcinoma cell line 3AO/cDDP, in order to treat human ovarian carcinoma thoroughly., Methods: The growing inhibiting rates of drug-resistant human ovarian carcinoma cell line 3AO/cDDP by various concentrations of As2O3 in different time course were studied by methyl thiazolyl tetrazolium (MTT) method; Apoptosis percentage, cell cycle phase distribution and expressions of Fas, N-myc, nm23H1 and MTA1 gene were estimated by flow cytometry (FCM); 3AO/cDDP cells apoptosis phenotype was observed by transmissional electron microscopy., Results: 3AO/cDDP cell growing inhibiting rates by As2O3 were significantly different in dose-dependent and time-dependent manners(P < 0.05); Within a certain concentration range, 3AO/cDDP apoptosis inducing rates by As2O3 were dose- and time-dependent, and the most appropriate concentration was 3.0 mumol/L. Lower concentrations of As2O3 perturbed cell progressing through S/G2 phase, while higher concentrations selectively induced S phase cells apoptosis; As2O3 up-regulated Fas and nm23H1 gene expressions, but down-regulated N-myc and MTA1 gene expressions. Morphological observation indicated that As2O3 inducing 3AO/cDDP death characterized by apoptotic phenotype., Conclusion: As2O3 could influence the capacity of growth and proliferation of drug-resistant human ovarian carcinoma cell line and its mechanism could be positively and negatively related with Fas, nm23H1 gene and N-Myc, MTA1 gene expressions.