Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy.

Esophageal cancer (ESC) is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract. Although the exact pathogenesis of ESC has not been fully elucidated, excessive oxidative stress is an important characteristic that leads to the development of many cancers. Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs, which alters the growth and proliferation of ESCs and promotes their metastasis. Natural compounds, including alkaloids, terpenes, polyphenols, and xanthine compounds, can inhibit reactive oxygen species production in ESCs. These compounds reduce oxidative stress levels and subsequently inhibit the occurrence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10, superoxide dismutase, the NF-+ACY-kappa+ADs-B/MAPK pathway, and the mammalian Nrf2/ARE target pathway. Thus, targeting tumor oxidative stress has become a key focus in anti-ESC therapy. This review discusses the potential of Natural products (NPs) for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment. The findings of this review provide a reference for drug development targeting ESCs. Nonetheless, further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Natural products for gastric carcinoma prevention and treatment: Focus on their antioxidant stress actions in the Correa's cascade.

BACKGROUND: Correa's cascade is a pathological process beginning from gastritis to gastric precancerous lesions, and finally to gastric carcinoma (GC). While the pathogenesis of GC remains unclear, oxidative stress plays a prominent role throughout the entire Correa's cascade process. Studies have shown that some natural products (NPs) could halt and even reverse the development of the Correa's cascade by targeting oxidative stress. METHODS: To review the effects and mechanism by which NPs inhibit the Correa's cascade through targeting oxidative stress, data were collected from PubMed, Embase, Web of Science, ScienceDirect, and China National Knowledge Infrastructure databases from initial establishment to April 2023. NPs were classified and summarized by their mechanisms of action. RESULTS: NPs, such as terpenoid, polyphenols and alkaloids, exert multistep antioxidant stress effects on the Correa's cascade. These effects include preventing gastric mucosal inflammation (stage 1), reversing gastric precancerous lesions (stage 2), and inhibiting gastric carcinoma (stage 3). NPs can directly impact the conversion of gastritis to GC by targeting oxidative stress and modulating signaling pathways involving IL-8, Nrf2, TNF-α, NF-κB, and ROS/MAPK. Among which polyphenols have been studied more and are of high research value. CONCLUSIONS: NPs display a beneficial multi-step action on the Correa's cascade, and have potential value for clinical application in the prevention and treatment of gastric cancer by regulating the level of oxidative stress.

Berberine: An inspiring resource for the treatment of colorectal diseases.

Colorectal cancer is a prevalent malignant tumor with a complex and diverse pathogenesis. In recent years, natural products have shown promising application prospects as sources of anticancer drugs. BBR, a class of benzoquinoline alkaloids extracted from various plants, is widely used in disease treatments owing to its pharmacological activities, including antibacterial, anti-inflammatory, antioxidant, anticancer, and anti-angiogenesis properties. Research has demonstrated that BBR exerts an anti-Salmonella and -Escherichia coli infection effect, attenuating inflammatory reactions by inhibiting harmful bacteria. During the stage of colorectal precancerous lesions, BBR inhibits the activity of cell cyclin by regulating the PI3K/AKT, MAPK, and Wnt signaling pathways, thereby decelerating the cell cycle progression of polyp or adenoma cells. Moreover, the inhibitory effect of BBR on colorectal cancer primarily occurs through the regulation of the cancer cell cycle, anti-angiogenesis, gut microbiota, and antioxidant pathways. The specific involved pathways include the MPK/ERK, NF-kB, and EGFR signaling pathways, encompassing the regulation of Bcl-2 family proteins, vascular endothelial growth factor, and superoxide dismutase. This study reviews and summarizes, for the first time, the specific mechanisms of action of BBR in the carcinogenesis process of colorectal cancer, providing novel insights for its clinical application in intestinal diseases.

Targeting lipid metabolism with natural products: A novel strategy for gastrointestinal cancer therapy.

Gastrointestinal cancer (GIC), including gastric cancer and colorectal cancer, is a common malignant tumor originating from gastrointestinal epithelial cells. Although the pathogenesis of GIC remains unclear, aberrant lipid metabolism has emerged as a hallmark of cancer. Several enzymes, proteins, and transcription factors are involved in lipid metabolism reprogramming in GIC, and their abnormal expression can promote lipid synthesis and accumulation of lipid droplets through numerous mechanisms, thereby affecting the growth, proliferation, and metastasis of GIC cells. Studies show that some natural compounds, including flavonoids, alkaloids, and saponins, can inhibit the de novo synthesis of lipids in GIC, reduce the level of lipid accumulation, and subsequently, inhibit the occurrence and development of GIC by regulating Sterol regulatory element-binding protein 1 (SREBP-1), adenosine monophosphate-activated protein kinase (AMPK), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), phosphatidylinositol-3-kinase/Akt and the mammalian target of rapamycin PI3K/Akt/mTOR, amongst other targets and pathways. Therefore, targeting tumor lipid metabolism is the focus of anti-gastrointestinal tumor therapy. Although most natural products require further high-quality studies to firmly establish their clinical efficacy, we review the potential of natural products in the treatment of GIC and summarize the application prospect of lipid metabolism as a new target for the treatment of GIC, hoping to provide a reference for drug development for gastrointestinal tumors.

Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique.

Background: Canmei formula (CMF) is a traditional Chinese medicine compound with definite effect on the prevention and treatment of colorectal adenoma (CRA). CMF can prevent the transformation of intestinal inflammation to cancer. This study explored the mechanism of action of CMF in anti-CRA using multi-omics techniques. Method: The mice were randomly divided into four groups: blank group (Control), high-fat diet (HFD) + AOM/DSS colorectal adenoma model (ADH) groups, Canmei formula treatment group (ADH-CMF) and sulfasalazine treatment group (Sul). Except for the blank group, ADH model was established in the other three groups by intraperitoneal injection with AOM reagent, and then mice were given 2.5% DSS in free drinking water and high-fat diet. The mice in the blank group and ADH groups were intragastrically perfused with normal saline, and the mice in the other two groups were treated with corresponding drugs for 20 weeks. During this period, the changes of physical signs of mice in each group were observed. The differentially expressed genes and proteins in the Control group, ADH group and ADH-CMF group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. After the combined analysis and verification, the key targets were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, the changes of intestinal flora in mice of the three groups were examined. Results: A total of 2,548 differential genes were obtained by transcriptomics analysis, and 45 differential proteins were obtained by proteomics analysis. The results of proteomics data and experimental verification showed that CMF mainly affected the Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) target. GO analysis showed that the targets of CMF were involved in the biological processes such as cellular process, metabolic process and biological regulation. KEGG analysis showed that those genes were involved in oxidative phosphorylation, cell senescence, and metabolic pathways. Studies have shown that LHPP overexpression impeded colorectal cancer cell growth and proliferation in vitro, and was associated with a change in PI3K/AKT activity. The results of 16S DNA high-throughput sequencing showed that CMF could effectively regulate the abundance of Bifidobacterium, Candidatus_Saccharimonas and Erysipelatoclostridium in the intestinal flora at the genus level. Conclusion: CMF regulates LHPP via the PI3K/AKT signaling pathway. CMF affects the abundance of specific intestinal flora and can regulate the disorder of intestinal flora to achieve the role of prevention and treatment of CRA.

Bioinformatics Analysis to Screen Key Targets of Curcumin against Colorectal Cancer and the Correlation with Tumor-Infiltrating Immune Cells.

PURPOSE: Curcumin is a potential drug for the treatment of colorectal cancer (CRC). Its mechanism of action has not been elucidated. This study aims to investigate the mechanism of action of curcumin in the treatment of CRC via bioinformatics methods such as network pharmacology and molecular docking. METHODS: The targets of curcumin and CRC were obtained from the public databases. The component-targets network of curcumin in the treatment of CRC was constructed by Cytoscape v3.7.2. Through protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), important targets and signaling pathways related to CRC treatment were identified. Finally, the results were verified by molecular docking, and the correlation between the key targets and tumor-infiltrating immune cells (TICs) was analyzed. RESULTS: A total of 30 potential targets of curcumin for CRC treatment were collected. The GO function enrichment analysis showed 140 items, and the KEGG pathway enrichment analysis showed 61 signaling pathways related to the regulation of protein kinase activity, negative regulation of apoptosis process, cancer signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results showed that curcumin could be combined with AKT1, EGFR, and STAT3 more stably, and AKT1 has the strongest binding to curcumin. Bioinformatics analysis discovered that the expression of core targets AKT1, EGFR, and STAT3 in CRC was related to TICs. CONCLUSION: This study explored the targets and pathways of curcumin in the treatment of CRC. The core targets are AKT1, EGFR, and STAT3. The study indicated that curcumin has preventive and treatment effects on CRC through multitarget and multipathway, which laid the foundation for follow-up research.

The Instant and Sustained Effect of Electroacupuncture in Postgraduate Students with Depression: An fMRI Study.

OBJECTION: This study was a primary study to evaluate the instant and sustained effect of electroacupuncture (EA) at GV20 (Baihui) in postgraduate students with mild depression by using a special flexible head coil. METHODS: A total of 20 postgraduate students with mild depression underwent EA stimulation at GV20 and 3 phases of resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Phase I: Preparation (before needle insertion); Phase II: during EA; Phase III: 15 minutes after needle removal. The Rs-fMRI data were processed using DPABI and SPSS 25. RESULTS: 1) ReHo values showed significantly differences in the right posterior cingulate cortex, right calcarine gyrus, right angular gyrus, right precuneus, right cuneus, and bilateral postcentral gyri among Phase I, Phase II and Phase III; 2) Relative to the Phase I, increased brain activity in the Phase II was observed in the bilateral postcentral gyri, right calcarine gyrus, right cuneus. Compared with the Phase II, decreased brain activity in the Phase III was observed in the right precuneus, right posterior cingulate cortex, right angular gyrus. Relative to the Phase I, Significantly increased brain activity in the Phase III was observed in the right calcarine gyrus, right cuneus, and bilateral postcentral gyri. While decreased ReHo values were found in the right posterior cingulate cortex, right angular gyrus, right precuneus; and 3) Correlation analysis showed that the ReHo values of multiple brain regions in Phase I and Phase III were significantly correlated with the VAS and HRSD-17 scores. CONCLUSION: This study focuses on the instant and sustained effect in postgraduate students with depression. Our study showed that instant effect produced by EA stimulation at GV20 firstly induced changes in somatosensory and visual area, and then, sustained effect (Phase III) have a higher intensity and more extensive than instant effects. Meanwhile, we provide a visualization way to study the instant effects of head acupoints by using a flexible head coil.

Warm acupuncture therapy for Primary sciatica: A protocol of systematic review and meta-analysis.

INTRODUCTION: This meta-analysis aims to assess the effectiveness and safety of warm acupuncture therapy for treating Primary sciatica. METHODS: The following 9 databases will be search from their inception to December 6, 2020: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese Biomedical Literature Database (CBM), the Chinese Medical Current Content (CMCC), the Wan-Fang Database and the China National Knowledge Infrastructure (CNKI). Randomized controlled trials (RCTs) of warm acupuncture for treating Primary sciatica, Chinese or Japanese without restriction of publication status will be included. Two researchers will independently undertake study selection, extraction of data and assessment of study quality. Meta-analysis will be conducted after screening of studies. Data will be analyzed using risk ratio for dichotomous data, and standardized mean difference or weighted mean difference for continuous data. DISSEMINATION: This meta-analysis will be disseminated electronically through a peer-reviewed publication or conference presentations. CONCLUSION: This study will provide evidence to judge whether warm acupuncture. TRIAL REGISTRATION NUMBER: INPLASY2020120109.

Effect of acupoint application of / 中国针灸

OBJECTIVE@#To compare the effect between acupoint application of @*METHODS@#A total of 62 KOA patients with knee swelling after knee arthroscopy were randomly divided into an observation group and a control group, 31 cases in each group. In the control group, cold compress was adopted after surgery, 3 times a day. On the basis of the treatment as the control group, acupoint application of @*RESULTS@#The VAS scores 3, 5 and 7 days into treatment were lower than those before treatment in the two groups (@*CONCLUSION@#Acupoint application of

New meroterpenoid compounds from the culture of mushroom Panus lecomtei.

Two new meroterpenoid compounds (1 and 2) together with five known meroterpenoid derivatives (3-7) were isolated from solid culture of mushroom Panus lecomtei. The structures of new compounds were confirmed by the analysis of NMR and HR-ESI-MS spectroscopic data. The biosynthetic pathway of 1-7 was postulated. All isolated compounds were evaluated for antibacterial activities against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa and Bacillus Calmette-Guérin. Compound 3 exhibited weak antibacterial activity against Bacillus Calmette-Guérin with the inhibition rate of 83.6% at 100 µmol·L-1. Other compounds showed no antibacterial activities against all tested pathogens at 100 µmol·L-1.

P2X7 receptor: A potential therapeutic target for autoimmune diseases.

P2X7 receptor (P2X7R), a distinct ligand-gated ion channel, is a member of purinergic type 2 receptor family with ubiquitous expression in human body. Previous studies have revealed a pivotal role of P2X7R in innate and adaptive immunity. Once activated, it will meditate some vital cascaded responses including the assembly of nucleotide-binding domain (NOD) like receptor protein 3 (NLRP3) inflammasome, non-classical secretion of IL-1ß, modulation of cytokine-independent pathways in inflammation such as P2X7R- transglutaminase-2 (TG2) and P2X7R-cathepsin pathway, activation and regulation of T cells, etc. In fact, above responses have been identified to be involved in the development of autoimmunity, specifically, the NLRP3 inflammasome could promote inflammation in massive autoimmune diseases and TG2, as well as cathepsin may contribute to joint destruction and degeneration in inflammatory arthritis. Recently, numerous evidences further suggested the significance of P2X7R in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), etc. In this review, we will succinctly discuss the biological characteristics and summarize the recent progress of the involvement of P2X7R in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.

Effects of prey of different nutrient quality on elemental nutrient budgets in Noctiluca scintillans.

Noctiluca scintillans (Noctiluca) is a cosmopolitan red tide forming heterotrophic dinoflagellate. In this study, we investigated its ingestion, elemental growth yield and excretion when supplied with different quality food (nutrient-balanced, N-limited and P-limited). Total cellular elemental ratios of Noctiluca were nearly homeostatic, but the ratio of its intracellular NH4+ and PO43- was weakly regulated. Noctiluca thus seems able to differentially allocate N and P to organic and inorganic pools to maintain overall homeostasis, and it regulated its internal N more strongly and efficiently than P. The latter was substantiated by its comparatively stable C:N ratio and compensatory feeding on N-limited prey. Using both starvation experiments and mass balance models, it was found that excretion of C, N, and P by Noctiluca is highly affected by prey nutritional quality. However, based on modeling results, nutrients seem efficiently retained in actively feeding Noctiluca for reproduction rather than directly released as was shown experimentally in starved cells. Moreover, actively feeding Noctiluca tend to retain P and preferentially release N, highlighting its susceptible to P-limitation. Recycling of N and P by Noctiluca may supply substantial nutrients for phytoplankton growth, especially following bloom senescence.

Anti-prostate cancer effect of roemerine: An experimental study / 中华男科学杂志

Objective@#To investigate the anti-prostate cancer (PCa) effect of roemerine in vitro and in vivo in the mouse model of PCa.@*METHODS@#We detected the effects of roemerine on the proliferation, apoptosis and migration of PCa cells DU145, LNCaP, PC-3 and 22RV1, screened out the sensitive cell line and constructed a tumor-bearing model in mice for verification of the antitumor efficacy of roemerine in vivo.@*RESULTS@#Roemerine inhibited the proliferation and migration of the DU145, LNCaP, PC-3 and 22RV1 cells and induced their apoptosis in different degrees, particularly those of the LNCaP cells. The average tumor weight was less in the roemerine intervention group (［1.99±0.95］ g) than in the control (［2.95±1.04］ g), the least in the high-dose roemerine (30 mg/kg) plus paclitaxel intervention group (［0.90±0.16］ g). The mean heart, liver, and kidney indexes were markedly lower in the roemerine (0.58±0.06, 6.20±0.42 and 1.49±0.33) than in the paclitaxel group (0.66±0.04, 6.99±0.72 and 1.95±0.34), while the mean spleen and thymus indexes were remarkably higher in the former (0.54±0.11 and 0.06±0.01) than in the latter (0.41±0.09 and 0.05±0.01). Pathological staining showed a lower degree of malignancy and metastasis in both the roemerine and the roemerine + paclitaxel intervention group than in the control, as well as a lower degree of visceral injury in the roemerine and roemerine + paclitaxel groups than in the paclitaxel group.@*CONCLUSIONS@#Roemerine has some anti-PCa effect and alleviates adverse reactions in paclitaxel combination administration.

Simultaneous determination of alizarin and rubimaillin in Rubia cordifolia by ultrasound-assisted ionic liquid-reversed phase liquid chromatography.

Four kinds of ionic liquids were adopted to analyze the content of rubimaillin and alizarin in Rubia cordifolia roots with ultrasonic-assisted extraction coupled with HPLC. The chromatographic column, Purospher star RP-C18 (4.6 mm x 250 mm, 5 microm), was used. Methanol and 0.4% acetic acid-water as mobile phase with flow rate at 0.85 mL min(-1), gradient elution, detection wavelength at 250 nm, chromatographic column temperature was controlled at room temperature. The result showed that rubimaillin and alizarin had the highest extraction yield when the [ HMIM] PF6methanol solution concentration of 0.6 mol x L(-1) as extraction solvent and the conditions were solid-liquid ratio of 1:80 (g x mL(-1)). Under the optimal extraction conditions, the content of alizarin from 0.01 to 0.04 microg showed a good linearity (r = 0.9999), the average recovery was 97.12%, the content of rubimaillin from 0.41 to 1.35 microg showed a good linearity (r = 0.9999), the average recovery was 98.10%. This experiment adopted environmentally friendly reagent as extraction solvent, the extraction efficiency was improved, and the environmental pollution caused by organic solvent was avoided, the harm of human body aslo was reduced. This method was simple and reliable, its repeatability was also very good, which had an important significance in the study of traditional Chinese medicine active ingredient extraction methods.

Mimecan, a Hormone Abundantly Expressed in Adipose Tissue, Reduced Food Intake Independently of Leptin Signaling.

Adipokines such as leptin play important roles in the regulation of energy metabolism, particularly in the control of appetite. Here, we describe a hormone, mimecan, which is abundantly expressed in adipose tissue. Mimecan was observed to inhibit food intake and reduce body weight in mice. Intraperitoneal injection of a mimecan-maltose binding protein (-MBP) complex inhibited food intake in C57BL/6J mice, which was attenuated by pretreatment with polyclonal antibody against mimecan. Notably, mimecan-MBP also induced anorexia in A(y)/a and db/db mice. Furthermore, the expression of interleukin (IL)-1ß and IL-6 was up-regulated in the hypothalamus by mimecan-MBP, as well as in N9 microglia cells by recombinant mouse mimecan. Taken together, the results suggest that mimecan is a satiety hormone in adipose tissue, and that mimecan inhibits food intake independently of leptin signaling by inducing IL-1ß and IL-6 expression in the hypothalamus.

Protective effect of astragaloside on focal cerebral ischemia/reperfusion injury in rats.

This study was to observe the neurological protective effects of astragalosides (AST) on focal cerebral ischemia-reperfusion (I/R) injury in rats and to explore its possible mechanism. Male SD rats received right middle cerebral artery occlusion for 120 min and AST (40 mg/kg) was orally administered. The rats were decapitated 1, 3, 7, and 14 days after reperfusion. The neurological deficit score, infarct volume and water content of brain were measured; the activity of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and nitric oxide synthase (NOS), and the content of malondialdehyde (MDA), lactate (LD) and nitric oxide (NO) of brain tissue were detected too. The expression of inducible nitric synthase (iNOS), nerve growth factor (NGF) and tropomyosin receptor kinase A (TrkA) mRNA were measured by RT-PCR or real-time PCR. AST could significantly reduce the neurological deficit score; infract volume and water content, increase SOD and LDH activities, decrease NOS activity and MDA, LD and NO content. AST treatment could down-regulate expression of iNOS mRNA, while, NGF and TrkA mRNA were up-regulated. Our data suggest that AST have the protective effects on focal cerebral ischemia in rats at the different reperfusion time points, the mechanism may be related to the antioxidation, regulated the expressions of iNOS, NGF and TrkA mRNA.

[Protective effect of astragalosides on anoxia/reoxygenation injury of hippocampal neuron].

OBJECTIVE: To study the effect of astragalosides (AST) on the anoxia/reoxygenation (A/R) injured neuron in rat. METHODS: Primary cultured rat's hippocampal neurons were made into A/R model cells. The cell viability was detected by MTT assay and lactate dehydrogenase releasing methods; the activity of superoxide dismutase (SOD), and contents of malondialdehyde (MDA) and nitride oxide (NO) in culture supernate were detected; the apoptosis rate of hippocampal neurons after A/R was measured by flow cytometry with double-staining of Hoechst33258 and AnnexinV-PI; and intracellular calcium ion [Ca2+]i was observed with a cofocal laser-scanning microscope and determined by fluorescent probe Fluo-3/AM. RESULTS: AST enhanced the cell viability of neurons after A/R injury, increased SOD activity and decreased the MDA and NO contents in supernate, reduced the A/R-induced apoptosis and decreased the calcium overload in neurons. CONCLUSION: AST has the protective effects on A/R injured neurons, the mechanism is possibly related with its anti-oxidation and calcium overload reducing actions.

[Effect of opening point method of ziwu liuzhu on myocardial ischemia in the patient of stroke].

OBJECTIVE: To observe effect of opening point method of ziwu liuzhu on myocardial ischemia in the patient of stroke. METHODS: Thirty cases of stroke with myocardial ischemia were treated with opening acupoint according to time of the combination of reinforcing mother point and reducing son point of the heart channel in nazi method of ziwu liuzhu, and 30 cases in the control group were treated with acupuncture at Guangming (GB 37). Changes of electrocardiogram before and after treatment were recorded. RESULTS: ST-T segment raised significantly 30 min after treatment with ziwu liuzhu needling method as compared with the control group (P < 0.05), the treatment group being better than the control group. CONCLUSION: Excessive and deficient changes of the qi and blood in the meridians and collaterals are correlated with time rhythm, and ziwu liuzhu needling method can increase clinical therapeutic effect.