The Pharyngeal Packs for Dental and Otolaryngological Surgery: A Meta-Analysis of High-Quality Randomized Controlled Trials.

Background: Pharyngeal packs are employed to mitigate postoperative nausea and vomiting (PONV) and have become prevalent in dental and otolaryngological surgeries. However, their clinical efficacy continues to be a topic of debate. The objective of the present study was to conduct a quantitative assessment of the impact of pharyngeal packing in dental and otolaryngological surgeries through meta-analysis. Methods: We identified relevant randomized controlled trials (RCTs) through systematic searches of online databases, including PubMed, Embase, and Cochrane Central. Potential eligible studies were evaluated using the Jadad scoring system (range 0-5 points), with only high-quality RCTs (3 points or more) being included. The incidence of PONV, morbidity, and the level of throat pain were aggregated and estimated. Publication bias was evaluated using funnel plot symmetry and the Egger test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was utilized to rate the evidence. Results: Ten high-quality RCTs comprising 1026 participants were ultimately included. Subsequent quantitative pooled estimation unveiled that the utilization of pharyngeal packing did not lead to a significant reduction in the incidence of nausea (P = .272), vomiting (P = .775), overall PONV (P = .118), or throat pain (P = .149). By contrast, the application of pharyngeal packs was found to significantly increase the level of throat pain (P = .003). No obvious publication bias was detected, and the majority of evidence was rated high or moderate. Conclusion: Based on the existing evidence, we conclude that pharyngeal packing lacks clinical benefit and is not advised for dental and otolaryngological surgeries.

Decreased DIO3OS Expression Predicts Poor Prognosis in Hepatocellular Carcinoma and is Associated with Immune Infiltration.

Hepatocellular carcinoma has become one of the most shared cancers in the whole world because of its high morbidity, poor survival rate, and low recovery rate. LncRNA DIO3 opposite strand upstream RNA (DIO3OS) has been reported to be obviously important in several human cancers, while its biological function in hepatocellular carcinoma (HCC) remains unclear. Here, DIO3OS gene expression data and clinical information of HCC patients were extracted from the Cancer Genome Atlas (TCGA) database and the university of California Santa Cruz (UCSC) Xena database. In our study, the Wilcoxon rank sum test was used to compare DIO3OS expression between healthy individuals and HCC patients. It was found that patients with HCC had significantly lower DIO3OS expression than healthy individuals. Furthermore, Kaplan-Meier curves and Cox regression analysis showed that high DIO3OS expression tended to predict better prognosis and higher survival rate in HCC patients. In addition, the gene set enrichment analysis (GSEA) assay was used to annotate the biological function of DIO3OS. It was found that DIO3OS was significantly correlated with immune invasion in HCC. This was also aided by the subsequent ESTIMATE assay. Our study provides a novel biomarker and therapeutic strategy for patients with hepatocellular carcinoma.

Leveraging Nanodrug Delivery System for Simultaneously Targeting Tumor Cells and M2 Tumor-Associated Macrophages for Efficient Colon Cancer Therapy.

Tumor-associated macrophages (TAMs) widely exist in the solid tumors, which participate in the entire course of tumor development and execute momentous impacts. Therefore, manipulating TAMs has been identified as an expecting strategy with immense potential for cancer therapy. Herein, a nanodrug delivery system was leveraged for simultaneously targeting tumor cells and M2-type TAMs for efficient colon cancer therapy. The broad-spectrum anticancer chemotherapeutic drug doxorubicin (DOX) was hitchhiked in a mannose-modified bovine serum albumin (MAN-BSA) carrier. The DOX@MAN-BSA nanodrug delivery system was verified to possess feasible physical performances for unhindered systemic circulation and active targeting on colon tumors. DOX@MAN-BSA nanoparticles could be preferentially swallowed by colon tumor cells and M2 TAMs through mannose receptor-mediated endocytosis. Further in vivo antitumor therapy in CT26 colon tumor-bearing mice has achieved remarkable suppression efficacy with satisfactory biosafety. Leveraging the nanodrug delivery system for simultaneously targeting tumor cells and M2 TAMs has contributed a feasible strategy to collaboratively repress the malignant tumor cells and the collusive M2 TAMs for efficient cancer therapy.

3,4­Dihydroxyacetophenone attenuates oxidative stress­induced damage to HUVECs via regulation of the Nrf2/HO­1 pathway.

It has been reported that oxidative stress plays a prominent role in diabetic macrovascular diseases. 3,4­Dihydroxyacetophenone (3,4­DHAP) has been found to have a variety of biological activities. However, few studies have assessed the antioxidant capacity of 3,4­DHAP and the underlying mechanisms. Thus, the aim of the present study was to explore the effects of 3,4­DHAP on oxidative stress in human umbilical vein endothelial cells (HUVECs). HUVECs were pre­treated with 3,4­DHAP and then exposed to high glucose conditions. Cell viability and cytotoxicity were measured using an MTT assay. Reactive oxygen species (ROS) levels were measured using an inverted fluorescence microscope and a fluorescent enzyme labeling instrument. Protein expression levels of nuclear factor E2­related factor 2 (Nrf2), heme oxygenase­1 (HO­1), microtubule­associated protein 1A/1B­light chain 3 (LC3) and poly ADP­ribose polymerase­1 (PARP­1) were measured using western blotting, and mRNA expression of Nrf2 and HO­1 were measured through reverse transcription­quantitative PCR (RT­qPCR). Nrf2 nuclear translocation was evaluated using immunofluorescence analysis and autophagosomes were observed using transmission electron microscope (TEM). The results of the present study demonstrated that compared with the control group, cell viability of the high glucose group was reduced and cell cytotoxicity of the high glucose group was increased. ROS production in the high glucose group was clearly enhanced. In addition, high glucose upregulated Nrf2 and HO­1 protein and mRNA expression levels. Nuclear translocation of Nrf2 in the high glucose group was also increased. The formation of autophagosomes in the high glucose group was also higher than that in the control group. Furthermore, LC3­II/LC3­I and PARP­1 protein expression levels were increased after treatment with high glucose. However, compared to the high glucose group, 3,4­DHAP (10 µmol/l) significantly enhanced cell viability. 3,4­DHAP markedly decreased the production of ROS, increased Nrf2 and HO­1 protein and mRNA expression levels, and promoted nuclear translocation of Nrf2 in HUVECs. In addition, 3,4­DHAP promoted the formation of autophagosomes, and notably increased the protein expression levels of LC3­II/LC3­I and PARP­1. Moreover, it was determined that compared to the 3,4­DHAP group, treatment with 3,4­DHAP and ML385 enhanced cell viability, and decreased ROS production, Nrf2 and HO­1 protein and mRNA expression levels, nuclear translocation of Nrf2, and LC3­II/LC3­I and PARP­1 protein expression levels. Collectively, the results of the present study showed that 3,4­DHAP protected HUVECs against oxidative stress via regulation of the Nrf2/HO­1 pathway, by increasing autophagy and promoting DNA damage repair.

Potential roles of AMP-activated protein kinase in liver regeneration in mice with acute liver injury.

Liver regeneration post severe liver injury is crucial for the recovery of hepatic structure and function. The energy sensor AMP­activated protein kinase (AMPK) has a crucial role in the regulation of nutrition metabolism in addition to other energy­intensive physiological and pathophysiological processes. Cellular proliferation requires intensive energy and nutrition support, therefore the present study investigated whether AMPK is involved in liver regeneration post carbon tetrachloride (CCl4)­induced acute hepatic injury. The experimental data indicated that phosphorylation level of AMPK increased 48 h post­CCl4 exposure, which was accompanied with upregulation of proliferating cell nuclear antigen (PCNA) and recovery of alanine aminotransferase (ALT) level. Pretreatment with the AMPK inhibitor compound C had no obvious effects on ALT elevation in plasma and histological abnormalities in liver 24 h post CCl4 exposure. However, treatment with compound C 24 h post CCl4 exposure significantly suppressed CCl4­induced AMPK phosphorylation, PCNA expression and ALT recovery. These data suggest that endogenous AMPK was primarily activated at the regeneration stage in mice with CCl4­induced acute liver injury and may function as a positive regulator in liver regeneration.

[Polydatin induces human cervical cancer cell apoptosis via PI3K/AKT/mTOR signaling pathway].

To observe the effect of polydatin on proliferation and apoptosis of cervical cancer HeLa cells and explore its possible mechanism. The growth inhibitory effect was detected with MTT assay. After HeLa cells were treated with different concentrations (50, 100, 150 µmol•L⁻¹) of polydatin, MTT assay was used to detect the inhibitory effect of polydatin on proliferation of HeLa cells; Acridine orange/ethidium bromide staining was used for morphological changes in apoptotic HeLa cells； Annexin/propidium iodide staining was applied to detect HeLa cell apoptotic rate. In addition, flow cytometry was employed to analyze apoptosis and cell cycle distribution； RT-PCR and Western blot assay were used to detect PI3K, AKT, mTOR, and P70S6K mRNA and protein expression levels. The results showed that polydatin significantly inhibited HeLa cells proliferation in a dose-dependent manner. Polydatin can cause S phase arrest for HeLa cells, promote cell apoptosis and decrease the mRNA and protein expression levels of PI3K, AKT, mTOR and P70S6K. It indicated that polydatin could inhibit proliferation and induce apoptosis of cervical cancer HeLa cells, and the mechanism may be associated with inhibiting the PI3K/AKT/mTOR signaling pathway and suppressing downstream gene expression.

Catalpol ameliorates diabetic atherosclerosis in diabetic rabbits.

Catalpol, isolated from the roots of Rehmanniaglutinosa, Chinese foxglove, is an iridoid glycoside with antioxidant, anti-inflammatory and anti-hyperglycemic agent. The present study was to investigate the effects of catalpol on diabetic atherosclerosis in alloxan-induced diabetic rabbits. Diabetes was induced in rabbits by a hyperlipidemic diet and intravenous injection of alloxan (100 mg/kg). Rabbits were treated for 12 weeks. The fasting blood glucose, insulin, homeostasis model of insulin resistance, total cholesterol and triglyceride were measured. The thoracic aorta was excised for histology. The plasma and vascular changes including some markers of oxidative stress, inflammatory cytokines and fibrosis factors were examined. Plasma levels of fasting blood glucose, insulin and homeostasis model of insulin resistance were significantly decreased in catalpol group. Catalpol treatment ameliorated diabetic atherosclerosis in diabetic rabbits as demonstrated by significantly inhibited neointimal hyperplasia and macrophages recruitment. Catalpol treatment also enhanced the activities of superoxide dismutase, glutathione peroxidase, and increased the plasma levels of total antioxidant status, meanwhile reduced the levels of malondialdehyde, protein carbonyl groups and advanced glycation end product. Furthermore, catalpol also reduced circulating levels of tumor necrosis factor-α, monocyte chemotactic protein-1 and vascular cell adhesion molecule-1. Catalpol also decreased transforming growth factor-ß1 and collagen IV mRNA and protein expressions in the vessels. Catalpol exerts an ameliorative effect on atherosclerotic lesion in alloxan-induced diabetic rabbits. The possible mechanisms may be related to inhibition of oxidative stress inflammatory response and anti-fibrosis and reduced aggregation of extracellular matrix.

Cytoproliferative and Cytoprotective Effects of Striatisporolide A Isolated from Rhizomes of Athyrium multidentatum (Doell.) Ching on Human Umbilical Vein Endothelial Cells.

OBJECTIVES: The aim of this study was to investigate the proliferative and protective effects of striatisporolide A (SA) obtained from the rhizomes of Athyrium multidentatum (Doell.) Ching on human umbilical vein endothelial cells (HUVECs). METHODS: Cell viability was measured by the MTT method. Cell apoptosis was determined by flow cytometry. Intracellular ROS was measured by the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. RESULTS: The viability rate in cells treated with 100 µM SA alone was increased to 128.72% ± 0.19% and showed a significant difference compared with the control group (p < 0.05). Meanwhile, SA augmented the cell viabilities in H2O2-treated HUVECs, and the cell viability was enhanced to 56.94% ± 0.13% (p < 0.01) when pre-incubated with 50 µM SA. The cell apoptosis rates were reduced to 2.17% ± 0.20% (p < 0.05) and 3.1% ± 0.34% (p < 0.01), respectively, after treatment with SA alone or SA/H2O2. SA inhibited the overproduction of reactive oxygen species (ROS) in HUVECs induced by H2O2 and the fluorescent intensity was abated to 9.47 ± 0.61 after pre-incubated with 100 µM SA. CONCLUSIONS: The biological activities of SA were explored for the first time. Our results stated that SA exhibited significant cytoproliferative and minor cytoprotective effects on HUVECs. We presume that the mechanisms of the proliferation and protection actions of SA involve interference with the generation of ROS and the cell apoptosis. These findings provide a new perspective on the biological potential of butenolides.

Amelioration by catalpol of atherosclerotic lesions in hypercholesterolemic rabbits.

The aim of the present study was to evaluate the effects of catalpol administration on atherosclerosis. Atherogenesis was induced by a high-cholesterol chow in male New Zealand White rabbits that were randomly assigned to receive atorvastatin (5 mg/kg/day), catalpol (5 mg/kg/day), or vehicle by oral gavage for 12 weeks. The rabbits were sacrificed after 12 weeks, and the thoracic aorta and serum were collected for further pathological and molecular biological analysis. Catalpol administration resulted in significantly attenuated atherosclerotic lesions. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol were remarkably reduced, and high-density lipid cholesterol was elevated in the catalpol-treated group. Catalpol reduced the levels of tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule-1, and soluble intercellular adhesion molecule-1 in the serum, as well as vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-α protein, inducible nitric oxide synthase, matrix metalloproteinases-9, and nuclear factor-κB protein65 in the aortic arch. In addition, catalpol treatment reduced the lipid peroxidation levels, while elevating antioxidant capacity. Catolpol pretreatment inhibited the nuclear translocation and DNA binding activity of nuclear factor-κB protein in oxygenized low-density lipoprotein-stimulated EA.hy926 cells. Furthermore, catolpol pretreatment activated nuclear factor erythroid 2-related factor 2 and upregulated the expression of its downstream antioxidant enzyme heme oxygenase. In summary, catalpol attenuated atherosclerotic lesions by the inhibition of inflammatory cytokines and oxidative stress status in a rabbit atherosclerotic model and enhanced the antioxidant capacity in oxygenized low-density lipoprotein-stimulated EA.hy926 cells. These results suggest that catalpol may be used to prevent and attenuate atherosclerosis.

Effects of 3,4-dihydroxyacetophenone on the hypercholesterolemia-induced atherosclerotic rabbits.

3,4-Dihydroxyacetophenone (3,4-DHAP) is one herbal extract from bald Mao-dong-qing leaves. We reported that 3,4-DHAP had anti-inflammatory function by decreasing tumor necrosis factor-α (TNF-α) secretion in macrophages. The aim of the study was to examine the effects of 3,4-DHAP on plasma and liver lipids, plasma alanine aminotranferase (ALT) and TNF-α level, vascular cell adhesion molecule-1 (VCAM-1) expression, plaque vulnerability and vascular inflammation in hypercholesterolemia-induced atherosclerotic rabbits. Male New Zealand white rabbits were randomized into negative control, positive control, 3,4-DHAP and simvastatin groups. From weeks 2 to 12, the rabbits were treated with 3,4-DHAP or simvastatin. At weeks 12, all the animals were sacrificed. Plasma lipids and ALT were measured using the enzymatic endpoint method. Plasma TNF-α was measured using enzyme-linked immuno sorbent assay (ELISA). Liver lipids concentrations were estimated using commercial kits. The expression of VCAM-1 was measured using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Histological analysis was used to evaluate the pathologic changes of rabbit aortas. The results showed that 3,4-DHAP markedly lowered plasma and liver lipids, lowered plasma ALT and TNF-α levels compared with the positive control group. VCAM-1 mRNA and protein were markedly inhibited by 3,4-DHAP. Decreased aortic plaque instability was evident in 3,4-DHAP-treated rabbits, as demonstrated by a thickened elastic layer, increased vascular smooth muscle cells (VSMCs) accumulation in the plaques, less neointima hyperplasia and macrophages recruitment. 3,4-DHAP may attenuate the progression of atherosclerotic lesions and stabilize plaques by lowering plasma lipids, the number of macrophages and the expression of VCAM-1, while increasing the number of VSMCs in the atherosclerotic plaques.

Inflammation pro-resolving potential of 3,4-dihydroxyacetophenone through 15-deoxy-delta12,14-prostaglandin J2 in murine macrophages.

3,4-dihydroxyacetophenone (DHAP), an active component isolated from leaves of Tumaodongqing (Ilex Pubescens Hook. Et Arn. Var glaber Chang), is initially used to treat cardiovascular diseases. Previously, we found it had anti-inflammatory effect on macrophages by reducing the production of TNF-alpha in vitro. To further determine whether DHAP could influence inflammatory resolution, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)), an arachidonic acid metabolite and also crucial pro-resolving mediator in inflammation, was chosen as the research target. It showed that 10(-5) M DHAP resulted in obvious increase of 15dPGJ(2) in LPS-activated macrophages. Further, inflammation related cytokines and cell apoptosis were also studied. We found DHAP could markedly inhibit LPS-stimulated production of TNF-alpha. However, it could not change the level of IL-10 obviously. At the same time, LPS-triggered apoptosis of macrophage was enhanced by DHAP significantly. After different kinds of cyclooxygenase (COX) inhibitors were administrated, it showed that the effects of DHAP on TNF-alpha and apoptosis were COX-2 dependent. While, inhibition of both COX-1 and COX-2 with indomethacin and administration of 15dPGJ(2) simultaneous reserved the effect of DHAP to inhibit TNF-alpha and enhance apoptosis in LPS-activated macrophages at least partly. The level of COX-2 mRNA and protein were also detected. It was showed that DHAP could increase the expression of COX-2 at both mRNA and protein levels in LPS-activated macrophages. Our results suggest that DHAP could accelerate resolution phase of acute inflammation though enhance the production of 15dPGJ(2), which was also proved to mediate the function of DHAP to inhibit TNF-alpha and enhance apoptosis in vitro. These results are potentially valuable for future use of DHAP.

Dual effect of 3,4-dihydroxyacetophenone on LPS-induced apoptosis in RAW264.7 cells by modulating the production of TNF-alpha.

To explore the pharmacological effect of 3,4-dihydroxyacetophenone (DHAP) on the apoptosis of RAW264.7 macrophage cells and the mechanism, RAW264.7 macrophage cells were treated with 100 or 500 mg/L lipopolysaccharide (LPS), with or without 10(-5) mol/L DHAP for 24 h. Trypan blue dye exclusion assay was used to assess cell viability. Cell apoptosis was morphological studied and flow cytometric assay was used. Tumor necrosis factor-alpha (TNF-alpha) level was measured by ELISA methods. IkappaB protein was determined by Western blotting. Our results showed that in 100 mg/L LPS-stimulated macrophages, DHAP enhanced the cell apoptosis while in 500 mg/L LPS-stimulated macrophages, DHAP significantly inhibited the cell apoptosis. In both groups, DHAP increased the level of IkappaB but decreased the level of TNF-alpha. It is concluded that DHAP has dual effect on the apoptosis of RAW 264.7 cells treated with different concentrations of LPS. This effect may be due to the inhibition of activation of NF-kappaB and autocrine production of TNFalpha. Our study suggests that DHAP may have anti-inflammatory effect on LPS-activated macrophages.

Expression of cyclooxygenase-2 mRNA and identification of its splice variant in human myometrium obtained from women in labor.

In order to investigate the expression of cyclooxygenase-2 (COX-2) in human lower segments of myometrium obtained from women in labor and those not in labor and identify the splicing variant of COX-2, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of COX-2. The primers were designed and synthesized according to the sequence of rat COX-2 splice variant which was discovered firstly by us. Then the splicing variant of COX-2 in human myometrium from woman in labor was identified, cloned into vector and sequenced. The results showed that the expression of COX-2 mRNA was lower in human myometrium obtained from women who were not in labor than that in labor women and a new band of COX-2 was obtained in myometrium from labor woman. The fragment included an unspliced intron, which pitched between exons 7 and 8. It was suggested that COX-2 gene was not only expressed highly in human myometrium from woman in labor, but also produced splicing variant by alternative splicing.

[Expression of cyclooxygenase-2 mRNA and identification of its spliceriant in human myometrium obtained from women in labor].

OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2) in human lower segments of myometrium obtained from women in labor and those not in labor and identify the splice variant of COX-2. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for investigating the expression of COX-2. According to the sequence of rat COX-2 splice variant, the primers were designed and synthesized, then the splice variant of COX-2 in human myometrium from woman in labor was identified, cloned into vector and sequenced. RESULTS: The results showed that (1) The Expression of COX-2 mRNA was lower in human myometrium obtained from women who were not in labor than those in labor. (2) A new band of COX-2 was obtained in myometrium from a woman in labor. The fragment includes an unspliced intron, which locates between exons 7 and 8. CONCLUSION: COX-2 gene is not only expressed highly in human myometrium from women in labor, but also produced splicing variant by alternative splicing.