Jianpi Jiedu decoction reverses 5-fluorouracil resistance in colorectal cancer by suppressing the xCT/GSH/GPX4 axis to induce ferroptosis.

Introduction: Innate and acquired chemoresistance in colorectal cancer (CRC) often results in 5-fluorouracil (5-FU) treatment failure. This study aimed to investigate the potential of Jianpi Jiedu (JPJD) decoction to reverse 5-FU resistance in CRC and clarify its potential mechanism of action. Methods: The CCK-8 assay was employed to assess cell activity. Flow cytometry was employed to assess various parameters including cell apoptosis, cell cycle distribution, P-glycoprotein (P-gp) activity, reactive oxygen species levels, and lipid peroxidation. Metabolomics analysis was conducted to identify differentially expressed metabolites. Western blotting was utilized for protein expression analysis. Results: In this study, we demonstrated that the combined JPJD and 5-FU treatment reversed 5-FU resistance in HCT8/5-FU cells, inducing cell apoptosis, causing G2/M-phase cell cycle arrest, and reducing P-gp protein expression and activity. Metabolomics analysis revealed ferroptosis as a key pathway in the development of 5-FU resistance. Furthermore, the combination treatment reversed drug resistance primarily by impacting ferroptosis and triggering critical ferroptosis events through the suppression of the cystine/glutamate transporter (xCT)/glutathione (GSH)/glutathione peroxidase (GPX4) axis. Conclusion: JPJD decoction primarily suppressed the xCT/GSH/GPX4 axis to trigger ferroptosis, thereby effectively reversing 5-FU resistance in colorectal cancer (CRC).

Mapping the intellectual structure and landscape of colorectal cancer immunotherapy: A bibliometric analysis.

Immunotherapy, particularly immune checkpoint inhibitor (ICIs) therapy, stands as an innovative therapeutic approach currently garnering substantial attention in cancer treatment. It has become a focal point of numerous studies, showcasing significant potential in treating malignancies, including lung cancer and melanoma. The objective of this research is to analyze publications regarding immunotherapy for colorectal cancer (CRC), investigating their attributes and identifying the current areas of interest and cutting-edge advancements. We took into account the publications from 2002 to 2022 included in the Web of Science Core Collection. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel. The quantity of publications associated with this domain has been steadily rising over the years, encompassing 3753 articles and 1498 reviews originating from 573 countries and regions, involving 19,166 institutions, 1011 journals, and 32,301 authors. In this field, China, the United States, and Italy are the main countries that come forward for publishing. The journal with the greatest impact factor is CA-A Cancer Journal for Clinicians. Romain Cohen leads in the number of publications, while Le Dt stands out as the most influential author. The immune microenvironment and immune infiltration are emerging as key hotspots and future research directions in this domain. This research carries out an extensive bibliometric examination of immunotherapy for colorectal cancer, aiding researchers in understanding current focal points, investigating possible avenues for research, and recognizing forthcoming development trends.

Erratum: A Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of LiuWei DiHuang Pill in Treating Type 2 Diabetes Mellitus [Corrigendum].

[This corrects the article DOI: 10.2147/DDDT.S216644.].

A Network Pharmacology-Based Strategy For Predicting Active Ingredients And Potential Targets Of LiuWei DiHuang Pill In Treating Type 2 Diabetes Mellitus.

BACKGROUND: Traditional Chinese medicine (TCM) formulations have proven to be advantageous in clinical treatment and prevention of disease. LiuWei DiHuang Pill (LWDH Pill) is a TCM that was employed to treat type 2 diabetes mellitus (T2DM). However, a holistic network pharmacology approach to understanding the active ingredients and the therapeutic mechanisms underlying T2DM has not been pursued. METHODS: A network pharmacology approach including drug-likeness evaluation, oral bioavailability prediction, virtual docking, and network analysis has been used to predict the active ingredients and potential targets of LWDH Pill in the treatment of type 2 diabetes. RESULTS: The comprehensive network pharmacology approach was successfully to identify 45 active ingredients in LWDH Pill. 45 active ingredients hit by 163 potential targets related to T2DM. Ten of the more highly predictive components (such as :quercetin, Kaempferol, Stigmasterol, beta-sitosterol, Kadsurenone, Diosgenin, hancinone C, Hederagenin, Garcinone B, Isofucosterol) are involved in anti-inflammatory, anti-oxidative stress, and the reduction of beta cell damage. LWDH Pill may play a role in the treatment of T2DM and its complications (atherosclerosis and nephropathy) through the AGE-RAGE signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. CONCLUSION: Based on a systematic network pharmacology approach, our works successfully predict the active ingredients and potential targets of LWDH Pill for application to T2DM and helps to illustrate mechanism of action on a comprehensive level. This study provides identify key genes and pathway associated with the prognosis and pathogenesis of T2DM from new insights, which also demonstrates a feasible method for the research of chemical basis and pharmacology in LWDH Pill.

[Effects of Fuzhengyangying granules on the bone marrow proliferation and bcl-2 expression in mice with immune mediated aplastic anemia].

OBJECTIVE: To explore the effect of Fuzhengyangying granules (FZYYG) on the expression of the bone marrow proliferation and bcl-2 in mice with immune mediated aplastic anemia. METHODS: Forty BALB/c mice were randomly allocated to 4 groups: a normal control group, a model group, cyclosporine A (CSA) group and FZYYG group. The model group was fed with physical salt, while the CSA and FZYYG group were fed with CSA and FZYYG respectively, and then the changes of peripheral hemoglobin (Hb), platelet, bone marrow nucleus cell (BMNC), bone marrow hematopoiesis tissue volume and bcl-2 expression were examined. RESULTS: The count of Hb, the platelet, BMNC, the bone marrow hematopoiesis tissue volume and the bcl-2 positive rate in the model group were lower than those in the normal group (P<0.05), whereas the count of Hb, the platelet, BMNC, the bone marrow hematopoiesis tissue volume and the bcl-2 positive rate in both CAS and FZYYG groups were significantly higher than those in the model group (P<0.05). CONCLUSION: FZYYG can induce the bcl-2 antigen expression and postpone the haematogenous cells apoptosis, and it is effective for mice with immune mediated aplastic anemia.

Chinese medicine for outcomes in colorectal cancer patients: A retrospective clinical study.

OBJECTIVE: To investigate the effect of Chinese medicine (CM) on survival of patients with stage II and III colorectal cancer (CRC). METHODS: A total of 295 patients who received chemotherapy were assigned to Group 1. The other 171 patients received the same chemotherapy treatment combined with the usage of CM Jianpi Jiedu Formula (, JPJD) for more than 3 months (Group 2). Patients' survival time, relapse and metastasis, and cause of death were observed. Cox proportional hazard regression models were established for the analysis of the effect of independent factors on the survival prognosis of patients with CRC. RESULTS: The survival rate of patients in Group 2 was higher than that of Group 1 (P<0.05). Compared with Group 1, the mean survival time was prolonged by 5.594 months and the median survival time was prolonged by 6 months in Group 2 (P=0.004). Cox regression analysis indicated that CM combined with chemotherapy provided signifificant protective effect, as observed with the improvements in the survival rates of CRC patients (P<0.01). CONCLUSION: CM can improve the survival rate in patients with stage II and III CRC.

[Effect of naoling decoction on the behavior and the mRNA expression of beta-amyloid precursor protein in the hippocampus in rats with Alzheimer's disease].

OBJECTIVE: To observe the effect of naoling decoction (NLD) on the behavior and the mRNA expression of beta-amyloid precursor protein (APP) in the hippocampus in rat model with Alzheimer's disease (AD). METHODS: D-galactose was intra-abdominally injected and AlCl3was hypodermically injected to build the AD models. The behavior of rats was measured by gamma-electric maze and the level of APP mRNA in the model rat hippocampus was observed by RT-PCR. RESULTS: The learning and memory capacity in the NLD group was improved and the APP mRNA expression level was significantly lower in the NLD group compared with the untreated model and the control group (All P < 0.05). CONCLUSION: NLD can lower the expression of APP mRNA to reduce beta-amyloid protein deposition of rat hippocampus, which may be one of the mechanisms of improving the learning and memory capacity of AD model rats.

[Therapeutic effect of fuzheng yangying oral solution on immune-induced aplastic anemia mice].

OBJECTIVE: To observe the effect of fuzheng yangying oral solution on bone marrow proliferation and serum interleukin 2 in immune-induced aplastic anemia mice. METHODS: The immune-induced aplastic anemia mouse models were built up, and then were divided into 4 groups by randomized allocation. The models were fed with physical salts (Group A, n = 10 ), fuzheng yangying oral solution (Group B, n = 10), cyclosporin A (Group C, n = 10), and fuzheng yangying oral solution plus cyclosporin A (Group D, n =10), respectively. Another 10 healthy mice served as controls (Group E). The changes in blood cells, bone marrow karyocyte count, marrow hematopoietic tissue capacity, and serum interleukin 2 level were observed. RESULTS: The blood cells, bone marrow karyocyte count, and marrow hematopoietic tissue capacity in Group A were significantly lower than those of Group E (P < 0. 05) ; those in the 3 treated groups (Group B, C, and D) were significantly higher than those of Group A ( P < 0. 05 ); and Group D was the highest ( P < 0. 05 ). There were no significant difference between Group B and C ( P > 0. 05 ). The level of interleukin 2 in Group A was obviously higher than that of Group E (P < 0. 05 ); The levels of interleukin 2 in the 3 treated group ( Group B, C, and D) were significantly lower than those of Group A ( P < 0. 05 ); and Group D was the lowest ( P < 0. 05). There was no significant difference in the level of interleukin 2 between Group B and C ( P < 0. 05). CONCLUSION: Fuzeng yangying oral solution can impove the bone marrow proliferation and reduce the level of serum interleukin 2 in immune-induced aplastic anemia mice.

Effects of Fengbaisan on the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung tissue of rats with chronic obstructive pulmonary disease.

OBJECTIVE: To observe effects of Fengbaisan (, FBS) on the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in lung tissue of rats with chronic obstructive pulmonary disease (COPD) and to investigate the preventive and therapeutic mechanisms of FBS. METHODS: The COPD rat model was established by cigarette smoke exposure and lipopolysaccharide (LPS) intra-tracheal dripping. The histopathological changes of lung tissue was observed via hematoxylin/eosin staining. The expression of MMP-9 and TIMP-1 in lung tissue was measured by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The typical histopathological changes of COPD were displayed in the model group, Ambroxol Hydrochloride group and FBS group, and the pathological lesions in the FBS group were less than those in the model group. The expression of MMP-9 and TIMP-1 in the model group increased significantly compared with those in the normal group (P<0.05). After treatment for successive 28 days, the expression of MMP-9 and TIMP-1 in the FBS group decreased remarkably as compared with the model group (P<0.05). CONCLUSIONS: FBS can regulate MMP-9/TIMP-1 imbalance to prevent airway and lung parenchyma remodeling process via reducing the expression of MMP-9 and TIMP-1 in the lung tissue of COPD rats, and this may be a possible therapeutic mechanism of FBS on COPD.

Fructus Aurantii induced antidepressant effect via its monoaminergic mechanism and prokinetic action in rat.

Depression could hardly get a satisfactory effect from the currently available antidepressants. To get a more effective treatment, antidepressant effect and monoaminergic mechanism of Fructus Aurantii (FRA) in the rat forced swimming test (FST) and open field test (OFT), and its prokinetics were examined. FST and OFT were respectively used to evaluate the antidepressant effect and locomotor activity of FRA. We observed the effects of monoamine receptor antagonists on FRA-induced antidepressant effect in rat. The effects of FRA on intestinal transit, gastric emptying and in vitro jejunum contractile activity were assessed. FRA decreased significantly the immobility time (32.6±8.5, 30.3±5.2 vs 56.4±9.4, all p<0.01) in FST, dose-dependent increased the locomotor activity (102±17.5, 120±18.5 vs 89±9.8, p<0.05 or 0.01), significantly accelerated gastric emptying (GE: 48.1±6.3, 39.5±5.7 vs 19.5±3.8, p<0.01) and intestinal transit (IT: 67.3±9.1, 64.2±6.3 vs 49.1±8.2, p<0.01) of the semi-liquid meal, compared with vehicle. And FRA (1 µM, 10 µM) significantly increased the mean amplitude (0.24±0.021 and 0.281±0.015) of contraction in jejunum of rat compared with vehicle (0.149±0.011) in vitro. FRA (10 µM) could induce a largest amplitude (0.281±0.015) of contraction in jejunum. The anti-immobility effect of FRA in FST was prevented by pre-treatment of rat with p-chlorophenylalanine methyl ester, WAY100635, ketanserin, haloperidol, SCH233390, sulpiride, yohimbine, but not prazosin. FRA could simultaneously induce prokinetics and antidepressant effect, deserves further to investigate.

[Clinical curative effect of dengzhanhua injection on acute cerebral infarction: a report of 100 cases].

OBJECTIVE: To observe the clinical curative effect of dengzhanhua injection on acute cerebral infarction. METHODS: One hundred cases of acute cerebral infarction were treated with dengzhanhua injection (Group A) and 62 treated with fufangdanshen injection (Group B). The curative effects and the patients' hemorrheology and lipemia before and after the treatment were compared. RESULTS: The total effective rate and evidently effective rate of Group A were significantly higher than those of Group B (92.0% vs. 75.8%, 44.0 vs. 29.0%, P < 0.01). The levels of hemorrheology and lipemia in 72 hyperviscosityemia patients and 76 hyperlipidemia patients in Group A were significantly improved after the treatment. The integral difference of nerve function injury and the obsorbed situation of infarct focus in Group A were significantly higher than those in Group B. Group A had no adverse reaction during the treatment. CONCLUSION: Dengzhanhua injection in the treatment of acute cerebral infarction is safe and effective.