Pachymic Acid Inhibits Growth and Metastatic Potential in Liver Cancer HepG2 and Huh7 Cells.

Pachymic acid (PA), exacted from Polyporaceae, has been known for its biological activities including diuretic, dormitive, anti-oxidant, anti-aging, anti-inflammatory and anticancer properties in several types of diseases. Recently, studies have demonstrated that PA could suppress cell growth and induce cell apoptosis in different kinds of cancer cells. But the underlying mechanisms remain poorly elucidated. In the current study, we investigated the effect of pachymic acid on liver cancer cells and its underlying mechanisms. Our results evidenced that pachymic acid effectively inhibited the cell growth and metastatic potential in HepG2 and Huh7 cells. Mechanistically, we revealed that pachymic acid triggered cell apoptosis by increasing caspase 3 and caspase 9 cleavage, upregulating Bax and cytochrome c expression, while reducing the expression of Bcl2. Besides, pachymic acid could markedly inhibit the cell invasion and migration and cell metastatic potential by mediating epithelial-to-mesenchymal transition (EMT) markers and metastasis-associated genes in HepG2 and Huh7 cells. In addition, we demonstrated that FAK-Src-Jun N-terminal kinase (JNK)-matrix metalloproteinase 2 (MMP2) axis was involved in PA-inhibited liver cell EMT. Together, these results contribute to our deeper understanding of the anti-cancer effects of pachymic acid on liver cancer cells. This study also provided compelling evidence that PA might be a potential therapeutic agent for liver cancer treatment.

Axially torsional Meckel's diverticulum accompanied by small bowel volvulus: a case report.

Small bowel volvulus secondary to Meckel's diverticulum is rare, and a delayed diagnosis results in disastrous outcomes. Computed tomography is conducive to early differential diagnosis. In particular, a blind-ending pouch structure on CT always indicates Meckel's diverticulum. Diverticulectomy with or without adjacent partial small intestinal resection is the standard treatment for symptomatic Meckel's diverticulum. However, the therapy for asymptomatic Meckel's diverticulum is controversial. Here, we report the case of a 20-year-old man who suffered intestinal obstruction secondary to small bowel volvulus caused by an axially torsional, gangrenous, and giant Meckel's diverticulum. Diverticulectomy with partial intestinal resection was performed.

Internal hernia caused by the appendix adhering to the right ovary: a case report.

Internal hernias are a rare condition and sometimes life-threatening, and they need an emergency exploratory laparotomy. Appendicectomy for chronic appendicitis is controversial. Without timely treatment, chronic appendicitis may develop into a ruptured appendix and an infection that spreads to other parts of the body, and other serious complications. Here we report the case of 48-year-old female who had intestinal ischemia secondary to internal hernia caused by the appendix adhering to the right ovary. Her medical history indicated a chronic, right lower abdominal pain for three years.

Identification of key miRNA-gene pairs in gastric cancer through integrated analysis of mRNA and miRNA microarray.

Nowadays, the current bioinformatic methods have been increasingly applied in the field of oncological research. In this study, we expect a better understanding of the molecular mechanism of gastric cancer from the bioinformatic methods. By systematically addressing the differential expression of microRNAs (miRNAs) and mRNAs between gastric cancer specimens and normal gastric specimens with the application of bioinformatics tools, A total of 206 DEGs and 38 DEMs were identified. The Gene Ontology (GO) analysis of Annotation, Visualization and Integrated Discovery (DAVID) database revealed that the differentially expressed genes (DEGs) were significantly enriched in biological process, molecular function and cellular component, while Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed DEGs were significantly enriched in 8 signal pathways. The miRNA-gene regulatory network was constructed based on 385 miRNA-gene (DEM-DEG) pairs, consisting of 35 miRNAs and 107 target genes. In the regulatory network, the top 5 up-regulated genes were Transmembrane Protease, Serine 11B (TMPRSS11B), regulator of G protein signaling 1 (RGS1), cysteine rich angiogenic inducer 61 (CYR61), inhibin subunit beta A (INHBA), syntrophin gamma 1 (SNTG1), and the top 5 down-regulated genes were tumor necrosis factor receptor superfamily, member 19 (TNFRSF19), pleckstrin homology domain containing B2 (PLEKHB2), Tax1 binding protein 3 (TAX1BP3), presenilin enhancer, gamma-secretase subunit (PSENEN), NME/NM23 nucleoside diphosphate kinase 3 (NME3). Based on the gastric cancer patient database from Kaplan-Meier Plotter tools, we found that 8 of 10 genes with most significant changes in the miRNA-gene regulatory network possessed a prognostic value for survival time of gastric cancer patients. Patients with higher level of RGS1, PLEKHB2, TAX1BP3 and PSENEN in gastric cancer had a longer survival time compared with the patients with lower level of these genes. On the contrary, patients with higher level of INHBA, SNTG1, TNFRSF19 and NME3 were found associated with a shorter survival time. In conclusion, our findings provided several potential targets regarding gastric cancer, which may result in a new strategy to treat gastric cancer from a system rather than a single-gene perspective.

Lipid storage droplet protein 5 reduces sodium palmitate­induced lipotoxicity in human normal liver cells by regulating lipid metabolism­related factors.

Lipid storage droplet protein 5 (LSDP5) is specifically expressed in tissues with high oxidative metabolism such as liver and heart. The present study aimed to explored the role of LSDP5 in sodium palmitate­induced lipotoxicity in LO2 normal human liver cells. LO2 cells were treated with various concentrations of sodium palmitate (25, 50, 75, 100, 125 and 150 µmol/l) for 12, 24 and 48 h, and cell viability was determined by Cell Counting Kit­8. Subsequently, LO2 cells were exposed to 100 µmol/l sodium palmitate for 48 h to induce lipotoxicity (Model). Lipotoxicity Model LO2 cells were also transfected with pCMV5­LSDP5 overexpression vector, and reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) and apoptotic rates were measured. The contents of non­esterified fatty acid (NEFA), malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. The expression levels of LSDP5, and apoptosis­, mitochondrial­, lipid metabolism­related factors were detected using reverse transcription­quantitative polymerase chain reaction and western blot assays. The results indicated that sodium palmitate exposure inhibited cell viability and induced lipotoxicity in LO2 cells. LSDP5 overexpression decreased ROS and apoptotic rates, and reduced NEFA and MDA content. LSDP5 transfection rescued the loss of MMP and elevated SOD content in lipotoxicity Model LO2 cells. In addition, LSDP5 upregulated the expression levels of B­cell lymphoma­2, acetyl­CoA carboxylase1/2 and fatty acid synthase (Fas), whereas the expression levels of activated­caspase­3, Bcl­2­associated X protein, cytochrome c, cytochrome c oxidase subunits IV, carnitine palmitoyltransferase 1a and peroxisome proliferator­activated receptors α levels were downregulated. LSDP5 may produce a protective effect on sodium palmitate­induced lipotoxicity in LO2 cells by regulating lipid metabolism­related factors.

Spontaneous rupture of a splenic artery aneurysm with splenic epithelioid hemangioendothelioma: a case report.

Spontaneous rupture of a splenic artery aneurysm with splenic epithelioid hemangioendothelioma is a rare condition. Splenic artery aneurysm can be complicated by rupture resulting in hypovolemic shock, which can be fatal if not treat properly. We report a case of a 50-year-old man who presented with sudden onset of left upper quadrant pain and shock. This patient underwent splenectomy with distal pancreatectomy. His pathological diagnosis showed splenic epithelioid hemangioendothelioma.

MicroRNA-21 inhibits lipopolysaccharide-induced acute lung injury by targeting nuclear factor-κB.

Acute lung injury (ALI) is a frequent, but severe complication following sepsis in patients with critical illness. The present study aimed to investigate the potential role of microRNA-21 (miR-21) in the regulation of inflammation in the ALI induced by lipopolysaccharide (LPS) in vitro and in vivo. The levels of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß and IL-10, and the level of miR-21 expression were measured in the lungs of LPS-induced ALI rats and NR8383 alveolar macrophages (AMs). To confirm the regulatory effect of miR-21 in the inflammatory reactions of ALI, NR8383 cells were transfected with a mimic of miR-21 or an anti-miR-21 inhibitor, and the subsequent changes of the miR-21 level and the levels of inflammatory cytokines were detected. The underlying molecular mechanism was also investigated. LPS-induced ALI in rats resulted in significant overexpression of pro-inflammatory cytokines, TNF-α, IL-6 and IL-1ß, and miR-21, but reduced the expression of the anti-inflammatory cytokine IL-10. LPS treatment also led to a higher expression level of miR-21 and increased secretion of pro-inflammatory cytokines in NR8383 cells in a time-dependent manner. Manipulation with the miR-21 mimic significantly suppressed the LPS-mediated induction of TNF-α, IL-6 and IL-1ß in NR8383 cells, while that induction was upregulated when miR-21 expression was silenced via transfection with the anti-miR-21 inhibitor. Further mechanism experiments revealed that miR-21 regulates LPS-induced inflammation responses via the Toll-like receptor 4 and nuclear factor-κB (Nf-κB) signaling pathway. miR-21 negatively regulates inflammatory responses in LPS-induced ALI by targeting the NF-κB signaling pathway, providing further insight into the molecular mechanism of ALI progression.

Migration of metal clips into the duodenum after laparoscopic cholecystectomy: A report of two cases.

Migration of metal clips into the duodenum after laparoscopic cholecystectomy is rare. We herein present two cases of migration of metal clips into the duodenum in patients who developed upper quadrant discomfort and a poor appetite after laparoscopic cholecystectomy. Gastroscopy revealed metal clips in the duodenum. In one patient, the clip dropped from the duodenum after 2 months; the other patient went to another institution to undergo duodenotomy. The mechanism underlying migration of a metal clip into the duodenum remains unclear but might be related to chronic inflammation and duodenal peristalsis. In conclusion, clinicians must remember that metal clips can migrate after laparoscopic cholecystectomy and later cause complications.

Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.

The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents.

Gallbladder carcinoma incidentally encountered during laparoscopic cholecystectomy: how to deal with it.

Gallbladder cancer (GBC), characterised by rapid progression and a poor prognosis with a high mortality rate, is a complex disease to treat. Incidental gallbladder carcinoma (IGBC) is defined as carcinoma of the gallbladder suspected for the first time during cholecystectomy or accidentally found on histological examination of the gallbladder. With the increasingly widespread acceptance of laparoscopic cholecystectomy (LC) and difficulties in diagnosing GBC preoperatively, the number of cases of IGBC during and after LC has increased. However, management of IGBC is a difficult issue in the absence of established guidelines. Problems associated with IGBC related to LC are the decisions of whether, when and how to perform additional surgery. Controversy remains regarding the effectiveness of additional resection in different stages of GBC. This review gives an overview of IGBC related to LC, and further discusses the preoperative, intraoperative and postoperative diagnosis and management of IGBC during LC.

Bilateral massive ovarian luteinized follicular cysts of a twin pregnancy.

We report a case of rare bilateral massive ovarian luteinized follicular cysts in a twin pregnancy. A 28-year-old, gravida 1, para 0, abortus 0 woman was incidentally found to have bilateral massive ovarian cysts (left side, 12 × 10 × 8 cm; right side, 15 × 10 × 6 cm) during the cesarean delivery of a twin pregnancy at 36 weeks of gestation. After 1,950-g and 2,350-g female babies were delivered in good condition, the patient received bilateral oophorectomy. Subsequent histopathology led to the diagnosis of giant bilateral ovarian luteinized follicular cysts.

Use of complementary and alternative medicine by cancer patients at Zhejiang University Teaching Hospital Zhuji Hospital, China.

Complementary and alternative medicine (CAM) is garnering increasing interest and acceptance among the general population throughout the world. The use of CAM by cancer patients is very common in China. The referenced English literature has no rural community-based study from China on this subject. This study was conducted to define the prevalence, pattern of use, and reasons for using CAM by cancer patients at Zhejiang University Teaching Hospital Zhuji Hospital (ZUTH-ZJH), China. Face-to-face interviews using a structured questionnaire were used to determine the use of CAM by cancer patients. All consenting cancer patients were interviewed as they presented at the Department of Surgical Oncology of ZUTH-ZJH, from September 2009 to February 2010. One hundred and twenty one patients were interviewed; 64 (52.9%) were males and 57 (47.1%) were females. One hundred and thirteen patients (93.4%) have used CAM at some time during their current cancer illness, fifty two (46.0%) are female and sixty one (54.0%) are male patients; 8 (6.6%) patients have not used any form of CAM. Chinese medicine (73.5.0%) was the most commonly reported CAM modality. Over 71.7% of those who used CAM were satisfied, only 28.3% were disappointed. Twenty eight users (24.8%) did not see any benefit from the CAM, but eighty one patients (71.7%) could describe some specific benefits. Only one patient will use orthodox medicine instead of CAM in the future, almost all patients will continue to use CAM in the future. CAM use is very common among cancer patients in local area of China. Most users obtain the expected benefits, and adverse events are uncommon. It is imperative that oncologists should explore the use of CAM with their cancer patients and work towards an integrated model of health-care provision. This knowledge will enable oncologists to better counsel the patients.

[Regulation of immune suppressive cytokines by TLR4 activation in colon cancer cells].

OBJECTIVE: To investigate the regulation of Toll-like receptors (TLRs) on immune suppressive cytokines in situ colon cancer cells. METHODS: The mRNA and protein expression spectrum of TLRs in HT-29 cells were determined by RT-PCR and Western blot respectively. The cytokines and chemokines levels of supernant of HT-29 stimulated by lipoplysaccharide(LPS) were detected with ELISA. RESULTS: TLR1-9 were expressed in HT-29 cells on mRNA level. After LPS stimulation, TLR4 mRNA and protein expressions were up-regulated in HT-29 cells, and TGF-beta, VEGF, IL-8, CCL20 and IL-6 levels increased significantly(all P<0.01). Except IL-6, up-regulation of the other cytokines was not suppressed by NF-kappa B inhibitor. CONCLUSION: TLRs expressed on colon cancer cells may elevate the immune suppressive cytokines and chemokines, which promote the immune escape of cancer cells.