Differential Gene Analysis of Ferroptosis in the Treatment of Allergic Rhinitis with Bu-Zhong-Yi-Qi-Decoction Based on GEO Using Network Pharmacology and Molecular Docking.

Objective: The differential gene analysis of ferroptosis inreating allergic rhinitis with Bu-Zhong-Yi-Qi-Decoction based on GEO using network pharmacology and molecular docking . Method: This study used databases such as TCMSP to search for traditional Chinese herbal medicine's active ingredients and targets in Bu-Zhong-Yi-Qi-Decoction in treating allergic rhinitis. GeneCards, OMIM, TTD, and PharmaGkb were used to obtain disease targets for allergic rhinitis, and R language was used to screen Bu-Zhong-Yi-Qi-Decoction as the main target for treating allergic rhinitis. Retrieve the gene dataset of allergic rhinitis using the GEO database, analyze ferroptosis-related genes, and select the intersection of effective targets of Bu-Zhong-Yi-Qi-Decoction for treating allergic rhinitis and ferroptosis-related genes of allergic rhinitis, draw protein interaction networks using the STRING database, use Cytoscape software to construct the target regulatory network of Bu-Zhong-Yi-Qi-Decoction for treating allergic rhinitis and ferroptosis related genes, and then use the CytoNCA plugin to screen key targets. Using R language, Gene ontology, and the biological pathway enrichment analysis were performed on the predicted targets related to the treatment of allergic rhinitis and ferroptosis with Bu-Zhong-Yi-Qi-Decoction. Selecting key targets and active ingredients for molecular docking to explore the potential mechanism of Bu-Zhong-Yi-Qi-Decoction in treating ferroptosis in allergic rhinitis. Result: After searching the TCMSP database, a total of 182 active ingredients were obtained from 8 traditional Chinese medicines of Bu-Zhong-Yi-Qi-Decoction, such as naringenin, kaempferol, Isorhamnetin, corresponding to 3023 targets and 2025 targets related to allergic rhinitis. There are 30 remarkably enriched Go analyses for biological function of potential target genes of Bu-Zhong-Yi-Qi-Decoction in allergic rhinitis, such as regulation of apoptotic signaling pathway, cellular response to peptide, wound healing, etc. Among them, there are 7 key genes related to the treatment of allergic rhinitis and ferroptosis with Bu-Zhong-Yi-Qi-Decoction, namely TP53, MAPK1, MAPK14, HIF1A, AR, CAV1, GSK3B. Conclusion: The treatment of allergic rhinitis with Bu-Zhong-Yi-Qi-Decoction is a process involving multiple divisions, targets, and pathways. These results indicated that oral Bu-Zhong-Yi-Qi-Decoction may effectively treat allergic rhinitis in clinical practice.

Network meta-analysis of acupuncture for tinnitus.

OBJECTIVE: To provide evidence for medical management of tinnitus based on an assessment of the evidence concerning the effectiveness of acupuncture as a treatment for tinnitus using network meta-analysis (NMA). METHODS: We conducted a systematic literature review by searching 8 national and international databases (inception to February 2023) for randomized controlled trials (RCTs) for tinnitus. Only RCTs that recruited participants aged over 18 and diagnosed with tinnitus, and that evaluated acupuncture or acupuncture in combination with conventional western medical therapy were included. We used response rate and tinnitus handicap inventory (THI) to examine efficacy. We conducted NMA with random effects, and the rate ratio or mean difference with its 95% credible interval was calculated. In addition, we ranked all treatments via their SUCRA and assessed the quality of evidence according to the GRADE criteria. RESULTS: A total of 2575 patients were included in the study. The main findings of the current NMA were that acupoint injection combined with warm acupuncture was the most effective for response rate, followed by warm acupuncture and acupoint injection combined with western medical treatment. Acupuncture combined with western medical treatment was the most effective for THI, followed by electroacupuncture combined with warm acupuncture and acupuncture combined with moxibustion. CONCLUSION: Acupuncture seems to be a better trend treatment for tinnitus. Further rigorous RCT studies that include direct comparisons for different acupuncture-related treatments are encouraged to provide the most promising evidence for patients with tinnitus. PROTOCOL REGISTRATION: CRD42023398745.

The Effective Analysis for Blue Honeysuckle Extract in the Treatment of Hepatocellular Carcinoma.

To further determine how BHE affected the growth of HCC cells, the proportion of each cell cycle phase was explored in HCC cells by flow cytometry. Blue honeysuckle (Lonicera caerulea L.) is a species of bush that grows in eastern Russia. Blue honeysuckle extract (BHE) is rich in bioactive phytochemicals which can inhibit the proliferation of tumor cells. The mechanism underlying the anticancer activity of BHE in primary liver cancer is poorly understood. The purpose of this study was to evaluate the growth inhibition mechanism of bioactive substances from blue honeysuckle on hepatocellular carcinoma (HCC) cells and to explore its protein and gene targets. The compounds in BHE were determined by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Cell counting kit-8 (CCK8) assay was used to evaluate the effects of BHE on HCC cell proliferation, and flow cytometry assay (FCA) was used to determine how BHE arrested the proportion of each cell cycle phase in HCC cells. Western blot (WB) was performed to determine the expression of cell cycle-related proteins in HCC cells treated with different concentrations of BHE. The xenograft tumor animal models were established by HCC cell implantation. The results showed that cyanidin-3-o-glucoside and cyanidin-3-o-sophoroside which are the main biologically active components were detected in BHE. BHE is highly effective in inhibiting the proliferation of HCC cells by arresting the HCC cell cycle in the G2/M phase. BHE also downregulated the expression of conventional or classical dendritic cells-2 (cDC2) and cyclin B1 by promoting the expression of myelin transcription factor 1 (MyT1) in HCC cells. The weight and volume of xenografts were significantly decreased in the BHE treated groups when compared to the control group. BHE increased the expression of MyT1 in xenograft tissues. These findings showed that blue honeysuckle extract inhibits proliferation in vivo and in vitro by downregulating the expression of cDC2 and cyclin B1 and upregulating the expression of MyT1 in HCC cells.

Hydroxyphenyl Butanone Induces Cell Cycle Arrest through Inhibition of GSK3ß in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is among the top three gastrointestinal malignancy in morbidity and mortality. The abnormal activation of Wnt/ß-catenin pathway is considered to be a key factor in the occurrence and development of CRC. Novel inhibitor discovery against key factor in WNT pathway is important for CRC treatment and prevention. METHODS: Cell proliferation was detected after hydroxyphenyl butanone treatment in human colorectal cancer HCT116, LOVO, and normal colonic epithelial NCM460 cells. Colony formation, cell invasion ability, and cell cycle were detected with and without GSK-3ß knockdown. RESULTS: Hydroxyphenyl butanone induces cycle arresting on G1-S phase of colorectal cancer cell line through GSK3ß in Wnt/ß-catenin pathway and inhibits malignant biological manifestations of cell proliferation, colony formation, and invasion. The inhibition in the high concentration group is stronger than that in the low concentration group, and the antitumor effect is different for different tumor cells. Under the same concentration of natural hydroxyphenyl butanone, the inhibition on normal colonic epithelial cells is significantly lower than that on tumor cells. The natural hydroxyphenyl butanone with medium and low concentration could promote the proliferation of normal colonic epithelial cells. CONCLUSION: This study illustrated natural hydroxyphenyl butanone as new inhibitor of GSK3ß and revealed the mechanisms underlying the inhibitory effects in colorectal cancer.

The neuroprotective effects of isoflurane preconditioning in a murine transient global cerebral ischemia-reperfusion model: the role of the Notch signaling pathway.

Inhalational anesthetic preconditioning can induce neuroprotective effects, and the notch signaling pathway plays an important role in neural progenitor cell differentiation and the inflammatory response after central nervous system injury. This study evaluated whether the neuroprotective effect of isoflurane preconditioning is mediated by the activation of the notch signaling pathway. Mice were divided into two groups consisting of those that did or did not receive preconditioning with isoflurane. The expression levels of notch-1, notch intracellular domain (NICD), and hairy and enhancer of split (HES-1) were measured in mice subjected to transient global cerebral ischemia-reperfusion injury. The notch signaling inhibitor DAPT and conditional notch-RBP-J knockout mice were used to investigate the mechanisms of isoflurane preconditioning-induced neuroprotection. Immunohistochemical staining, real-time polymerase chain reaction assays, and Western blotting were performed. Isoflurane preconditioning induced neuroprotection against global cerebral ischemia. Preconditioning up-regulated the expression of notch-1, HES-1, and NICD after ischemic-reperfusion. However, these molecules were down-regulated at 72 h after ischemic-reperfusion. The inhibition of notch signaling activity by DAPT significantly attenuated the isoflurane preconditioning-induced neuroprotection, and similar results were obtained using notch knockout mice. Our results demonstrate that the neuroprotective effects of isoflurane preconditioning are mediated by the pre-activation of the notch signaling pathway.

Hyperbaric oxygen preconditioning protects cortical neurons against oxygen-glucose deprivation injury: role of peroxisome proliferator-activated receptor-gamma.

Ischemic stroke is one of the leading causes of mortality and disability worldwide. Our previous studies have shown that hyperbaric oxygen (HBO) preconditioning can afford significant neuroprotection against cerebral ischemia-reperfusion (I/R) injury in rats. However, it is still unknown whether HBO preconditioning can directly protect primary cultured cortical neurons against oxygen-glucose deprivation (OGD). Peroxisome proliferator-activated receptor-gamma (PPAR γ) plays a central role in the regulation of apoptosis, oxidative stress and inflammation as well as affords significant neuroprotection against cerebral I/R injury. 15-deoxy-∆(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an endogenous ligand with a high affinity for PPAR γ. Recently, some studies demonstrate that activation of PPAR γ mediates lipopolysaccharide and anesthetic preconditioning. In the present study, we firstly found that OGD exposure caused the significant damage of cultured cortical neurons evaluated by cell viability, lactate dehydrogenase (LDH) release and caspase-3 activity, which were significantly ameliorated by HBO preconditioning. Furthermore, HBO preconditioning significantly increased the levels of PPAR γ mRNA and protein, PPAR γ DNA binding activity, 15d-PGJ(2) and antioxidant enzymatic activities in primary cultured cortical neurons with OGD exposure. Moreover, PPAR γ antagonist GW9662 dose-dependently abolished the protection of HBO preconditioning in OGD-exposed neurons. GW9662 blocked the increase of PPAR γ DNA binding activity and antioxidant enzymatic activities, but did not influence the 15d-PGJ(2) level in OGD-exposed neurons with HBO preconditioning. However, the cyclooxygenase (COX)-2 inhibitor NS-398 blocked the production of 15d-PGJ(2) in OGD-exposed neurons with HBO preconditioning. In addition, 15d-PGJ(2) preconditioning could also protect cultured neurons against OGD injury. These results demonstrate that HBO preconditioning has directly beneficial effects on ODG-exposed cortical neurons by the activation of PPAR γ subsequent to the production of 15d-PGJ(2), which in turn increases the downstream antioxidant enzymatic activities.

Autophagy activation is involved in neuroprotection induced by hyperbaric oxygen preconditioning against focal cerebral ischemia in rats.

Our previous studies have demonstrated that hyperbaric oxygen (HBO) preconditioning induces tolerance to focal cerebral ischemia. The present study aimed to investigate whether autophagy is involved in the neuroprotection elicited by HBO preconditioning in a rat model of transient focal cerebral ischemia. Twenty-four hours after the completion of HBO preconditioning (2.5 atm absolute in 100% oxygen for 60 min per day for 5 consecutive days), male Sprague-Dawley rats were subjected to focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 120 min. The neurobehavioral score and infarct volume were used to evaluate cerebral ischemic injury. An intracerebroventricular injection of the autophagy inhibitor 3-methyladenine (3-MA) or the autophagy inducer rapamycin was administered before HBO preconditioning or MCAO. We found that after reperfusion the protein expression of LC3-II and Beclin 1 and the formation of autophagosomes were increased by HBO preconditioning or ischemia, but the increase following HBO preconditioning was higher than the increase following ischemia. 3-MA suppressed the increases in LC3-II and Beclin 1 induced by HBO preconditioning and attenuated the neuroprotection of HBO preconditioning against cerebral ischemia. Furthermore, 3-MA treatment before MCAO aggravated subsequent cerebral ischemic injury. In contrast, pretreatment with rapamycin up-regulated LC3-II and Beclin 1 after reperfusion and mimicked the neuroprotective effect of HBO preconditioning. These results indicate that HBO preconditioning elevates autophagic activity, which elicits a neuroprotective effect against ischemic injury in the brain, and suggest a novel mechanism of HBO preconditioning-induced tolerance against transient focal cerebral ischemia.