Efficacy of acupoint injection of metoclopramide for post-chemotherapy vomiting: A systematic review and meta-analysis.

BACKGROUND: Vomiting is one of the most common adverse events of chemotherapy. The purpose of this study was to systematically review the clinical efficacy of acupoint injection of metoclopramide in the treatment of post-chemotherapy vomiting. METHODS: We searched 4 general English databases and 4 conventional Chinese databases, all with a time frame from database creation to December 2022. The retrieved clinical trials of acupoint injection of metoclopramide for post-chemotherapy vomiting were then subjected to meta-analysis and trial sequential analysis. RESULTS: A total of 12 studies were included, with a total sample size of 965 cases. Meta-analysis showed that acupoint injection of metoclopramide was effective in improving anti-vomiting effective rate [odds ratio = 5.67, 95% confidence interval = (3.80,8.47), P < .00001] compared with intramuscular/intravenous injection, and trial sequential analysis showed that this benefit was conclusive. Subgroup analysis demonstrated that acupoint injection significantly improved the anti-vomiting effective rate at doses of 10 mg qd, 20 mg qd, and 30 mg qd, as well as at durations of 1 day and 5 days. Subgroup analysis also indicated that injection at the Zusanli acupoint significantly increased the anti-vomiting effective rate, while injection at the Neiguan acupoint had an anti-vomiting effective rate comparable to that of the control group. Harbord regression showed no significant publication bias (P = .730). CONCLUSION: Acupoint injection of metoclopramide for post-chemotherapy vomiting is more effective than intramuscular and intravenous injections and is not limited by dose or duration of treatment, which may be the preferred way of administration.

Up-regulation of miR-155 protects against chronic heart failure by inhibiting HIF-1α.

BACKGROUND: Despite a crucial role of miR-155 in human cancers, its function in heart failure (HF) is still under investigation. This study was designed to explore its association with HF. METHODS: The abdominal transverse aortic constriction (TAC) was adopted for establishment of mouse HF models. qRT-PCR and WB were adopted to detect the changes of miR-155, HIF-1α, Cle-caspase-3, BCL2 and Bax levels in myocardial cells and heart tissues. The changes of cardiac function were checked by ultrasound. Additionally, luciferase reporter gene was adopted for interaction analysis of miR-155 with HIF-1α, and in situ end labelling method was used for detecting myocardial apoptosis. RESULTS: MiR-155 in myocardial tissue of HF mice was significantly down regulated. In HF mice injected with agomiR-155, the up-regulation of miR-155 strongly improved cardiac function, and also significantly lowered the protein levels of apoptosis-associated markers, C-caspase-3 and Bax, but up regulated Bcl-2. Additionally, HIF-1α was identified as the direct target of miR-155. As expected, over-expression of HIF-1α greatly reversed the effects of agomiR-155 on cardiac function and the expression of apoptosis-associated markers in heart tissues of HF mice. CONCLUSION: MiR-155 overexpression can suppress myocardial cell apoptosis through HIF-1α, and strongly alleviate the cardiac function damage in HF mice, indicating the potential of miR-155/HIF-1α axis to be a target for the diagnosis and therapy of HF.

Identification of ANXA3 as a biomarker associated with pyroptosis in ischemic stroke.

BACKGROUND: Pyroptosis plays an important role in the pathological process of ischemic stroke (IS). However, the exact mechanism of pyroptosis remains unclear. This paper aims to reveal the key molecular markers associated with pyroptosis in IS. METHODS: We used random forest learning, gene set variation analysis, and Pearson correlation analysis to screen for biomarkers associated with pyroptosis in IS. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were constructed in vitro and in vivo. Cells were transfected with an Annexin A3 silencing (si-ANXA3) plasmid to observe the effects of ANXA3 on OGD/R + lipopolysaccharides (LPS)-induced pyroptosis. qRT‒PCR and western blotting were used to detect the expression of potential biomarkers and pyroptotic pathways. RESULTS: Samples from a total of 170 IS patients and 109 healthy individuals were obtained from 5 gene expression omnibus databases. Thirty important genes were analyzed by random forest learning from the differentially expressed genes. Then, we investigated the relationship between the above genes and the pyroptosis score, obtaining three potential biomarkers (ANXA3, ANKRD22, ADM). ANXA3 and ADM were upregulated in the MCAO/R model, and the fold difference in ANXA3 expression was greater. Pyroptosis-related factors (NLRP3, NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, IL-1ß, and IL-18) were upregulated in the MCAO/R model. Silencing ANXA3 alleviated the expression of pyroptosis-related factors (NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, and IL-18) induced by OGD/R + LPS or MCAO/R. CONCLUSION: This study identified ANXA3 as a possible pyroptosis-related gene marker in IS through bioinformatics and experiments. ANXA3 could inhibit pyroptosis through the NLRC4/AIM2 axis.

Rhein Inhibited Ferroptosis and EMT to Attenuate Diabetic Nephropathy by Regulating the Rac1/NOX1/ß-Catenin Axis.

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious complications of diabetes. Rhein has been reported to be effective in treating DN. This study aimed to investigate the role and mechanism of rhein in the treatment of DN. METHODS: High glucose-induced (HG) podocyte injury model and streptozocin-induced (STZ) DN mouse model were constructed and intervened with rhein. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. The reactive oxygen species (ROS) level was measured by flow cytometry. The expression of Ras-related C3 botulinum toxin substrate 1 (Rac1), NADPH Oxidase 1 (NOX1), and ß-catenin were measured by quantitative real-time PCR (RT-qPCR). The contents of glutathione peroxidase 4 (GPX4), α-smooth muscle actin (α-SMA), Nephrin, and Podocin were characterized by immunofluorescence (IF) staining. Hematoxylin-eosin (HE) staining and Masson staining were employed to observe the renal morphological changes and tubulointerstitial fibrosis. The contents of α-SMA and Nephrin were detected by immunohistochemistry (IHC) staining. The kits were utilized to analyze various biochemical indicators. RESULTS: Rhein inhibited the HG-induced accumulation of ROS, malondialdehyde (MDA), and Fe2+, and the expression of α-SMA, Transferrin Receptor 1 (TFR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), Vimentin, Snail, and Desmin. Rhein inhibited the expression of Rac1 and its downstream targets NOX1 and ß-catenin. Rac1 silencing (si-Rac1) inhibited the accumulation of MDA and Fe2+ and the expression of Rac1, NOX1, ß-catenin, α-SMA, TFR1, and ACSL4. Rac1 overexpression (oe-Rac1) resulted in the inhibition of superoxide dismutase (SOD), glutathione (GSH), GPX4 synthesis, and down-regulation of Recombinant Solute Carrier Family 7, Member 11 (SLC7A11) and Nephrin expression in HG-treated podocytes. Rac1 Lentivirus (LV-Rac1) injection significantly promoted the accumulation of MDA and Fe2+ and increased the expression of RAC1, NOX1, ß-catenin, TFR1, ACSL4, and α-SMA in DN mice. CONCLUSIONS: Rhein inhibited ferroptosis and epithelial-mesenchymal transition (EMT) to attenuate DN by regulating the Rac1/NOX1/ß-catenin axis.

Upregulation of phosphatidylinositol glycan anchor biosynthesis class C is associated with unfavorable survival prognosis in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumor, and is the second highest cause of cancer-associated mortality, behind lung carcinoma. It is urgent to identify novel genes that can be used to confirm the diagnosis and prognosis of patients with HCC. The present study aimed to investigate the expression pattern of phosphatidylinositol glycan anchor biosynthesis class C (PIGC) in HCC and assess its clinical prognostic significance. Bioinformatics analyses were used to investigate PIGC mRNA expression levels in HCC and adjacent non-cancerous tissue samples. Furthermore, the present study detected the expression levels of PIGC protein in HCC and matched normal tissue samples via immunohistochemistry, and evaluated the prognostic significance of PIGC protein in HCC. The levels of PIGC mRNA and protein were found to be significantly higher in tissue from patients with HCC compared with non-cancerous liver tissue. The survival analysis showed that the expression levels of PIGC mRNA or protein were associated with the survival of patients with HCC. PIGC protein expression was significantly associated with Tumor-Node-Metastasis stage. A negative correlation between PIGC DNA methylation and mRNA expression was observed (Spearman r=-0.453). PIGC is an oncogene that is negatively regulated by DNA methylation, and high levels of PIGC mRNA or protein may predict an unfavorable prognosis in patients with HCC.

Zingiberene targets the miR-16/cyclin-B1 axis to regulate the growth, migration and invasion of human liver cancer cells.

PURPOSE: Liver cancer or hepatocellular carcinoma (HCC) is considered as one of the most frequent malignancies with significantly high morbidity and mortality across the globe. MicroRNAs (miRs) are regarded as important regulators of liver cancer formation and its development. However, the full biochemical mechanism of their role is still very less understood. The main objective of the current research work was to examine the role of miR-16/cyclin-B1 axis in liver cancer regulation and how this pathway along with liver cancer migration and invasion are targeted by zingiberene molecule. METHODS: Quantitative reverse transcriptase polymerase chain reaction was used to evaluate miR-16 expression in HCC cell lines. Western blotting was performed to evaluate the expression of the miR-16 target genes. Effects on cell migration and invasion were evaluated by in vitro wound healing assay and transwell Matrigel assay, respectively. Effects of zingiberene on HCC cell viability were evaluated by MTT assay. RESULTS: Zingiberene treatment led to downregulation of miR-16 in HepG2 human hepatocellular carcinoma cells, accompanied by induction of G0/G1 cell cycle arrest targeting cyclin B1 as direct target. These effects were also accompanied by inhibition of cell migration and invasion, indicating that miR-16 can have a significant role as liver cancer suppressor after zingiberene treatment. Luciferase reporter assay confirmed that miR-16, which was one of HCC downregulated miRs, directly targeted Cyclin B1 in HCC cells. CONCLUSION: The current study indicates miR-16/cyclin B1 axis might have significant applications as a therapeutic target for patients with liver cancer.

Anticancer effects of Lanostane against human gastric cancer cells involves autophagy, apoptosis and modulation of m-TOR/PI3K/AKT signalling pathway.

PURPOSE: Gastric carcinoma is the fourth leading cause of cancer-related morbidity throughout the globe. There are limited clinical therapies for gastric cancer due to lack of effective drugs and ambiguity in molecular mechanisms. As such there is a pressing need for novel and effective anticancer drugs for gastric cancer. The main aim of the current research work was to investigate the anticancer effects of Lanostane natural product in MKN-45 human gastric cancer cells along with evaluating its effects on cell autophagy, apoptosis, and m-TOR/PI3K/AKT signalling pathway. METHODS: MTT cytotoxicity assay was used to evaluate cell viability of MKN-45 human gastric cancer cells. Apoptosis was evaluated by fluorescence microscopy using Hoechst 33258 and Annexin-V/propidium iodide (PI) assay using flow cytometry. Autophagy was evaluated by transmission electron microscopy (TEM) and western blot method. Effects on m-TOR/PI3K/AKT related protein expression were evaluated by western blot method. RESULTS: Lanostane molecule led to substantial and dose-dependent growth inhibitory effects onMKN-45 human gastric cancer cells. Clonogenic assay showed significant decrease in MKN-45 cell colonies. Hoechst 33258 and annexin V/PI revealed that lanostane induced dominant apoptotic effects in these cells and exhibited dose-dependence. TEM revealed that lanostane induced autophagy in MKN-45 cells by forming autophagosomes and autophagic vacuoles. Lanostane also targeted m-TOR/PI3K/AKT signalling pathway by altering the expression of some key proteins. CONCLUSION: Lanostane displayed strong anticancer effects in MKN-45 human gastric cancer cells by triggering apoptosis and autophagy and targeting m-TOR/PI3K/AKT signalling pathway.

The Combining Effects of Cell-Free Circulating Tumor DNA of Breast Tumor to the Noninvasive Prenatal Testing Results: A Simulating Investigation.

Massively parallel sequencing of circulating fetal DNA in the plasma of pregnant women is a common method for noninvasive prenatal testing (NIPT) of fetal trisomy 13, 18, and 21. However, circulating DNA is not restricted to pregnant women, with increased levels of plasma DNA also frequently detected in the plasma of cancer patients. Among pregnant women whose NIPT results were inconsistent with the fetal karyotype, a small number of patients have subsequently been diagnosed with a previously undetected malignancy. However, the extent to which circulating tumor DNA (ctDNA) affects the results of NIPT is still unclear. We examined serum from 50 nonpregnant women with breast tumors by NIPT. These samples were then added to serum containing trisomy 13, 18, and 21 fetal DNA to figure out the extent to which maternal tumors can interrupt NIPT results in pregnant women with breast tumors. Concentrations of cell-free DNA (cfDNA) were higher in both pregnant women and breast tumor patients, relative to nonpregnant healthy controls. Among the 50 samples evaluated, 3 produced false positive NIPT results for trisomy 13, 18, or 21, indicating that genomic copy number variations (CNVs) had occurred. Simulation testing also showed that ctDNA can increase the standard deviation of the associated z-scores, which lower absolute z-scores by decreasing the proportion of circulating fetal DNA relative to total DNA. Of the 50 samples tested, 9 fell within the equivocal range and 8 produced false negative results for trisomy 13, 18, or 21. Data presented here show for the first time that ctDNA is able to affect NIPT results in two ways. First, ctDNA can lead to false positive results due to the detection of genomic CNVs in tumor DNA. Alternatively, ctDNA can increase the likelihood of a false negative by decreasing the proportion of circulating fetal DNA in serum.

[Moxa salt packets at Zhongwan (CV 12) for cisplatin chemotherapy-induced gastrointestinal reac- tions: a clinical study].

OBJECTIVE: To compare the efficacy between moxa salt packets at acupoints combined with tropisetron hydrochloride and single use of tropisetron hydrochloride for cisplatin chemotherapy-induced gastrointestinal reaction. METHODS: Sixty patients with malignant tumor who met inclusive criteria and received chemotherapy for the first time were recruited and randomly divided into an observation group and a control group, 30 cases in each one. Between the first days and fifth day into the chemotherapy, the patients in the control group were treated with daily intravenous injection of tropisetron hydrochloride (5 mg), while patients in the observation group, based on the treatment of control group, were treated with moxa salt packets at Zhongwan (CV 12). The nausea and vomiting between the first days and fifth day into the chemotherapy were compared in the two groups, and the occurrence rates of adverse reactions within the first week into chemotherapy were recorded. RESULTS: Between the second day and fifth day into the chemotherapy, the effective rate for nausea in the observation group was higher than that in the control group (all P < 0.05); between the third day and fifth day into the chemotherapy, the effective rate for vomiting in the observation group was higher than that in the control group (all P < 0.05); one week into the chemotherapy, the occurrence rate of constipation in the observation group was lower than that in the control group (P < 0.05). CONCLUSION: The moxa salt packets combined with tropisetron hydrochloride can effectively reduce the cisplatin chemotherapy-induced nausea and vomiting as well as the occurrence rate of delayed-type vomiting, and improve the constipation, which is superior to single use of tropisetron hydrochloride.

The expression of CXCL13 and its relation to unfavorable clinical characteristics in young breast cancer.

BACKGROUND: Young breast cancer occupies a higher and higher proportion of breast cancer, especially in Asia, and is associated with a more unfavorable prognosis compared with the disease arising in older women. However, the poor prognosis of young breast cancer cannot be fully explained by the clinical and molecular factors. METHODS: This study investigated 1125 Chinese breast cancer patients diagnosed from 2009 to 2013. A data mining of gene expression profiles was performed for the young and older breast cancer patients, identifying significantly differentially expressed genes. Quantitative RT-PCR, Western blotting and immunohistochemistry assay were carried out for the clinical sample validations. RESULTS: The investigation firstly displayed that young patients (≤45 years) accounted for 47.6 % (535/1125) of breast cancer, and clinically associated with some unfavorable factors related to poor prognosis, such as invasive pathological type, high tumor grade, lymph node positive, ER negative and triple-negative subtype. Subsequently, 553 significantly differentially expressed genes were identified by the data mining. Of them, a set of genes related to immune function were observed to be up-regulated in young patients with breast cancer. Impressively, the CXCL13 (C-X-C motif chemokine 13) expression level showed the most significant difference (FC = 2.64, P = 8.2 × 10(-4)). Furthermore, the validations with clinical samples and correlation analysis demonstrated that CXCL13 was indeed highly expressed in young breast cancer and closely associated with some prognostic factors including lymph node positive and ER negative. CONCLUSION: This is the first to indicate the clinical relevance of CXCL13 to young breast cancer and represents a potential therapeutic target for young breast cancer.