Matrix metalloproteinase-9 (MMP-9) plays an important role in the pathophysiology of sepsis. A single-nucleotide polymorphism (SNP) at position -1562 (C/T) in the MMP-9 gene has been associated with differential MMP-9 expression, being higher when the -1562 T allele is present. We evaluated the association of the SNP MMP9 -1562 C/T with severity and mortality in patients with sepsis to establish whether the prognosis of the disease is affected.

Curcuminoids, as the main ingredient of turmeric, are popularly used in food additives and condiments, and are widely accepted to be beneficial for human health for their antioxidant activity. However, curcuminoids are highly susceptible in terms of thermal-induced degradation, and curry is usually boiled, roasted, or fried in the use of food additives and condiments. Thus, it is interesting to explore the effect of cooking on the antioxidant activity of curcuminoids. In the present study, the total antioxidant capacity (T-AOC) of cooked curcuminoids (boiled curcuminoids, roasted curcuminoids, and fried curcuminoids) processed through three heating conditions, and their protective effects against oxidative damage to rat pheochromocytoma (PC12) cells, a well-established neuronal model, were evaluated. It was found that cooking slightly lowered the T-AOC of curcuminoids, with boiled curcuminoids being relatively stronger than roasted curcuminoids, and fried curcuminoids being the weakest form. Both boiled and roasted curcuminoids could significantly improve cell viability, mitigate intracellular accumulation of reactive oxygen species and reduce malondialdehyde activity, reduce caspase-3 and caspase-9 protein expression, and increase superoxide dismutase activity of PC12 cells compared with the control group. In comparison with parent curcuminoids, the protective effects of cooked curcuminoids got relatively lower overall, with boiled curcuminoids being relatively stronger than roasted curcuminoids. In conclusion, the cooked curcuminoids, including boiled and roasted forms, still have antioxidant and neuroprotective activity.

Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the first sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5-11 years) and 10 adults (18-52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at different healthy system levels needs more research. This trial is registered with NCT01284855.

In developing countries, tobacco smoking has its own contribution to the burden of noncommunicable causes of morbidity and mortality. Studies estimated the burden of cigarette smoking among school-going adolescents in different geographical areas of East Africa. However, due to discrepancies found among those different findings, there is no representative data about the burden of smoking in the continent.

Information on anatomy of the Cun position at wrist is lacking; whether the blood vessel taking pulse in Cun is the radial artery or the superficial palmar branch is also clinically controversial. The objective was to investigate the boundaries and contents, and the vascular distribution and their pulse points in Cun. Thirty-two upper extremities of 16 human cadavers were investigated for dissection and observation. The boundaries, contents, and blood vessel distribution in Cun were observed; the location of pulse points in Cun was identified; the length of the superficial palmar branch in wrist pulse (L1), the pulp width of the index finger (L2), and the angle between the radial artery and the superficial palmar branch were measured. The results showed that the Cun was located in the region formed by the bulge of the prominent bone proximal to the palm, the radial flexor tendon, the tubercle of scaphoid, and the abductor longus muscle tendon. In this area, the radial artery could be pulsed part in the medial side of the abductor longus muscle tendon, while the superficial palmar branch lied near the surface and was easy to pulse in the lateral side of the radial flexor tendon and the medial side of the tubercle of scaphoid. The ratio of L1 to L2 was 1.2±0.8, and the angle was 23.3±9.9°. The results suggested that it could not be generalized that the blood vessel taking pulse in Cun was the radial artery or the superficial palmar branch; it might depend on the vascular distribution in Cun, the region of finger positioning, and the patient's pulse condition.

Tofacitinib is an oral small molecule directed against the JAK/STAT pathway, blocking the inflammatory cascade. Oral formulation of tofacitinib has recently been approved for the treatment of patients with moderate-severe ulcerative colitis. Its efficacy and safety have been demonstrated in three phase III clinical trials and confirmed by promising real-life data. The purpose of this review is to summarize the available evidence on the efficacy and safety of tofacitinib and to define its role and position in the treatment algorithms for patients with ulcerative colitis.

The nonmotor symptom spectrum of Parkinson's disease (PD) includes progressive cognitive decline mainly in late stages of the disease. The aim of this study was to map the patterns of altered structural connectivity of patients with PD with different cognitive profiles ranging from cognitively unimpaired to PD-associated dementia.

The aim of this study was to investigate the contributions of FAM84B in prostate tumorigenesis and progression.

Efficacy of second-line systemic chemotherapy in recurrent gastric cancer with peritoneal metastasis (RGCPM) is limited. We assessed the feasibility, safety and possible efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with RGCPM after ⩾1 line of palliative intravenous chemotherapy.

Leucyl-tRNA synthetase (LRS) is an aminoacyl-tRNA synthetase catalyzing ligation of leucine to its cognate tRNA and is involved in the activation of mTORC1 by sensing cytoplasmic leucine. In this study, the usefulness of LRS as a therapeutic target of non-small cell lung cancer (NSCLC) and the anticancer effect of the LRS inhibitor, BC-LI-0186, was evaluated.

Available studies demonstrate that receptor-type tyrosine-protein phosphatase zeta (PTPRZ1) is expressed in different tumor tissues, and functions in cell proliferation, cell adhesion and migration, epithelial-to-mesenchymal transition, cancer stem cells and treatment resistance by interacting with or binding to several molecules. These included pleiotrophin (PTN), midkine, interleukin-34, β-catenin, VEGF, NF-κB, HIF-2, PSD-95, MAGI-3, contactin and ErbB4. PTPRZ1 was involved in survival signaling and could predict the prognosis of several tumors. This review discusses: the current knowledge about PTPRZ1, its expression, co-receptors, ligands, functions, signaling pathway, prognostic values and therapeutic agents that target PTPRZ1.

Chemoresistance remains an obstacle to the successful treatment of ovarian carcinoma. CUE domain-containing 2 (CUEDC2) plays critical roles in tumor genesis and overexpresses in many solid cancers, including ovarian serous carcinoma. In previous study, we found that overexpression of CUEDC2 might be a promising biomarker to evaluate the progression and to predict likely relapse of serous ovarian carcinoma. In present study, we found that higher expression of CUEDC2 was associated with higher resistance to cisplatin. The overall survival (OS) and disease-free survival time (DFS) of patients with cisplatin resistant was shorter than that of those with cisplatin sensitive, respectively, and the cisplatin sensitivity was independent predictor of a shorter OS time and DFS time. Knockdown of CUEDC2 by small interfering RNA enhanced the cisplatin sensitivity of serous ovarian carcinoma cells in SKOV3 cell lines. Furthermore, the phosphorylation of p38 MAPK were obviously increased after CUEDC2 knockdown, while p38 MAPK signaling contributes to cell growth and cell apoptosis. Our data suggest that CUEDC2 takes part in cisplatin-based chemotherapy resistance by regulating p38 MAPK signaling. And CUEDC2 is a promising biomarker and therapeutic target of cisplatin resistance in ovarian serous carcinoma.

Purpose: Circular RNAs (circRNAs) as prognostic biomarkers have spurred considerable interest in several types of tumors. In the present study, we aimed to elucidate the clinicopathological and prognostic values of circRNAs in human cancer. Methods: We systematically searched PubMed Central (PMC), PubMed, Web of Science, EMBASE, Scopus, CBM and the Cochrane Library databases up to Nov 29, 2018. Eligible studies reporting on the association between circRNAs expression and clinicopathological and prognostic outcomes in cancer were incorporated. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess clinicopathological parameters, and hazard ratios (HRs) and 95% CIs to estimate overall survival (OS). Results: Thirty-two studies involving 4529 patients were incorporated into our meta-analysis. Pooled results showed that high expression of oncogenic circRNAs was significantly associated with poor clinicopathological characteristics (tumor size: OR=1.29, 95%Cl: 1.10-1.51; TNM stage: OR=1.62, 95%Cl: 1.41-1.87; differentiation grade: OR=1.41, 95%Cl: 1.11-1.78; lymph node metastasis: OR=1.69; 95%Cl: 1.34-2.13; distant metastasis: OR=2.75; 95%Cl: 1.92-3.95) and a poor prognosis (OS: HR=2.75; 95%Cl: 2.34-3.15). Furthermore, we found that high expression of tumor-suppressor circRNAs was correlated with improved clinical characteristics (tumor size: OR=0.72; 95%Cl: 0.56-0.92; TNM stage: OR=0.77, 95%Cl: 0.68-0.88) and longer survival times (OS: HR=0.49; 95%Cl: 0.42-0.56). Subgroup analyses based on cancer types and circRNA types were also performed. Conclusion: Our study indicates that circRNAs may serve as important biomarkers for clinicopathologic features and prognosis in human cancer.

Cell division cycle associated 5 (CDCA5) is an important element for the interaction between cohesin and chromatin in interphase. It is abnormally expressed in many types of cancer and works as an indicator of poor prognosis, but little is known about its activity in hepatocellular carcinoma (HCC). In the present study, we found that the expression of CDCA5 was upregulated in HCC tissues compared to paracancerous tissues and had a negative correlation with patient survival. Cell proliferation and tumorigenesis were inhibited and cell apoptosis was induced with the knockdown of CDCA5, suggesting an oncogenic role of CDCA5 in liver cancer. Luciferase reporter assay and chromatin immunoprecipitation showed that CDCA5 was transcribed by E2F1. Furthermore, we confirmed that CDCA5 interrupted cell behavior via the AKT pathway. These findings demonstrated that CDCA5 plays an important role in HCC progression.

Genome-wide association studies (GWASs) have consistently identified chromosome 3q28 as a lung cancer susceptibility region. To further characterize the potential genetic mechanism of the variants in this region, we conducted a fine-mapping study on chromosome 3q28 region. We performed a target resequencing in 200 lung cancer cases and 300 controls in the screening and followed by validation in multi-ethnic lung cancer GWASs with 12,843 cases and 12,639 controls. For our identified novel variants, we conducted expression quantitative trait loci (eQTL) analysis to reveal the potential target genes. Two susceptibility variants were identified (rs4396880: G>A, OR = 0.35, 95%CI: 0.20-0.62, P = 3.01×10-4; and rs3856776: C>T, OR = 2.05, 95%CI: 1.32-3.18, P = 1.49×10-3) and further supported in Asian population (rs4396880: OR = 0.88, P = 7.43×10-6; and rs3856776: OR =1.17, P = 1.64×10-4). The eQTL analysis showed the A allele of rs4396880 was significantly associated with higher mRNA expression of TP63 (P = 1.70×10-4) in lung tissues, while rs3856776 showed significant association with the expression of LEPREL1-AS1 (P = 6.90×10-3), which was the antisense RNA of LEPREL1 and could suppress the translation of LEPREL1. Notably, LEPREL1 was aberrantly downregulated (P = 2.54×10-18) in lung tumor tissues based on TCGA database. In conclusion, this is the first fine-mapping analysis of 3q28 region in Han Chinese, and we found two variants associated with lung cancer susceptibility in Asian population. What's more, rs3856776 was newly identified and might modulate lung cancer susceptibility by suppressing the function of LEPREL1.

Purpose: TIAM2 (T-cell lymphoma invasion and metastasis 2), a RAC1 guanine nucleotide exchange factor, plays crucial roles in human cancer cells. Its homolog, TIAM1, has been reported to promote the migration and invasion of cancer cells through regulating the functions of cancer associated fibroblasts (CAFs). However, the functions of TIAM2 in CAFs have not been investigated. In this study, we explored how fibroblast TIAM2 influences the migration and invasion of lung cancer cells. Methods: We cultured primary lung CAFs and adjacent normal lung fibroblasts (NFs) from 12 non-small cell lung cancer (NSCLC) patients. RT-PCR and western blot were used to compare TIAM2 levels between CAFs and NFs. Two co-culture systems were designed, in which cancer cells were directly co-cultured with fibroblasts and indirectly co-cultured with conditional medium (CM) from fibroblasts. Subsequently, the wound healing and transwell tests were conducted to assess the migration and invasion ability of fibroblasts and co-cultured cancer cells. Finally, cytokine antibody arrays were used to screen differentially secreted cytokines in the CM. Results: The expression levels of TIAM2 were significantly higher in CAFs than NFs, and TIAM2-silenced fibroblasts showed decreased migration and invasion ability. In the direct co-culture system, the migration and invasion of cancer cells were retarded when co-culturing with TIAM2-silenced fibroblasts, and the expression levels of EMT-related genes also changed in cancer cells. Decreased migration and invasion of cancer cells were also observed when culturing with the CM from TIAM2-silenced fibroblasts. In addition, the cytokine antibody arrays revealed that Osteoprotegerin (OPG) was significantly decreased in the CM of TIAM2-silenced fibroblasts. This result suggested that OPG might be one of the main cytokines contributing to the migration and invasion of cancer cells in co-culture systems. Conclusion: Our results suggest that fibroblast TIAM2 promotes the invasion and migration of lung cancer cell, and OPG might be one of the main cytokines contributing to this pro-cancer process.

Background: This study was initially designed to examine whether oxaliplatin-based regimen was superior to cisplatin-based regimen in tumour remission as first-line chemotherapy for advanced gastric cancer (GC). Methods: Literature in EMBASE, PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was searched. Only phase II or III randomized controlled trials (RCTs) comparing the effectiveness and safety between oxaliplatin-based and cisplatin-based regimens as first-line treatment for advanced GC were selected. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. The primary endpoints were complete remission rate (CRR), partial remission rate (PRR), objective response rate (ORR), and disease control rate (DCR). The second endpoint was the toxicity response. Results: 2,140 patients from six phase II or III RCTs were included. Compared to cisplatin-based therapy, subjects who received oxaliplatin-based treatment had significantly higher PRR (OR: 1.25, 95%CI: 1.05-1.48, P=0.01, I2=0%), ORR (OR: 1.21, 95%CI: 1.02-1.44, P=0.03, I2=0%) and DCR (OR: 1.76, 95%CI: 1.31-2.38, P=0.0002, I2=25%), but not CRR (OR: 0.70, 95%CI: 0.37-1.31, P=0.27, I2=0%). In addition, oxaliplatin-based therapy significantly decreased all grades of leukopenia, neutropenia, anemia, febrile neutropenia, nausea, stomatitis, creatinine elevation and thromboembolism, as well as grades 3-4 of leukopenia, neutropenia, anemia and febrile neutropenia than cisplatin-based regimen. However, oxaliplatin-based treatment strikingly increased the risk of thrombocytopenia, sensory neuropathy, diarrhea, fatigue and liver dysfunction. Conclusions: Oxaliplatin-based regimen is superior to cisplatin-based regimen in tumour remission as first-line chemotherapy for advanced GC, and is associated with less toxicity and better tolerability.

Background: Exosomes are extracellular microvesicles that are released by most cells and widely distributed in various body fluids. Malignant cells secrete large amounts of exosomes containing various molecular constituents reflecting the originating tumor. We investigated the difference in microRNA (miRNA) expression in serum exosomes from the patients with benign, borderline and malignant ovarian masses to assess the diagnostic relevance of serum exosomal miRNAs as biomarkers for preoperative diagnosis of ovarian carcinoma. Methods: A total of 68 cases of ovarian masses were enrolled, comprising benign ovarian cysts (benign; n=10), borderline ovarian tumors (BOT, n=10), high-grade serous ovarian carcinomas (HGSOC, n=39) and non-HGSOCs (n=9). Exosomal RNA was extracted from the serum, and expression levels of seven miRNAs (miRNA-21, -93, -141, -145, -200a, -200b and -200c), which were reportedly dysregulated in serous ovarian cancer in previous studies, were quantified by real-time PCR, and compared between the four groups. Results: MiR-93, -145, and -200c, showed significantly higher expression in serum exosomes of the cancer group (HGSOC and non-HGSOC) than of the non-cancer group (benign and BOT; all p<0.05). The remaining three miRs (miR-141, -200a, and -200b) were expressed at extremely low levels, and not appropriate as serological biomarkers. To test discrimination of cancer from non-cancer, the area under the receiver operating characteristic curves determined for cancer antigen 125 (CA125), miR-145, miR-200c, miR-21, and miR-93 were 0.801 (p<0.001), 0.910 (p<0.001), 0.802 (p<0.001), 0.585 (p=0.303), and 0.755 (p=0.002), respectively. MiR-145 showed superior sensitivity (91.6%), and miR-200c showed superior specificity (90.0%), compared with CA125. Conclusion: Expression of exosomal miR-93, miR-145 and miR-200c was significantly elevated in the serum of ovarian cancer patients. Serum exosomal miR-145 in particular appeared to be the most promising biomarker for preoperative diagnosis of ovarian cancer.

Osteosarcoma (OS) is the most common primary bone malignancy, predominately affecting children and adolescents. Due to the introduction of chemotherapy, the 5-year survival rate of OS patients has dramatically improved to 60-70%. Unfortunately, OS patients with recurrence or metastatic disease have less than a 20% chance of long-term survival, despite aggressive therapies. In this study, we aimed to identify gene expression patterns associated with metastasis and recurrence in order to identify potential biomarkers with prognostic power. We found that high expression of polyglutamine tract-binding protein 1 (PQBP1) and low expression of phosphoenolpyruvate carboxykinase 2 (PCK2) were related to a high probability of recurrence and metastasis in OS patients and also predicted shorter recurrence-free survival (RFS) and metastasis-free survival (MFS) after adjustment for other clinical variables. Prediction models based on the combination of PQBP1 and PCK2 expression had good and robust predictive power for recurrence and metastasis. A PQBP1 and PCK2-centered protein interaction network was built, and the hypothetical regulatory path between them was identified and termed the PQBP1-SF3A2-UBA52-PCK2 axis. Gene enrichment analysis indicated that aberrations of metabolism might play an important role in recurrence and metastasis in OS patients. Accordingly, PQBP1 and PCK2 are crucial for recurrence and metastasis in OS, and these findings provide a molecular basis for the exploitation of diagnostic and therapeutic strategies for overcoming recurrence and metastasis in OS.

Pancreatic cancer is a highly malignant disease that is associated with poor prognosis. One hallmark of pancreatic cancer is excessive desmoplasia, characterized by fibrous or connective tissue growth and altered tumor stroma. Pancreatic stellate cells (PSCs) comprise a mesenchymal cell type that contributes to pancreas fibrosis and cancer progression. PSME3 is a regulatory subunit of the proteasome that is expressed in various cancers such as breast, ovarian, and pancreatic. Notably, PSME3 modulates lactate secretion in pancreatic cancer, suggesting a potential function in regulating pancreas fibrosis. However, the role of PSME3 in pancreatic cancer cell (PCC)-PSC interactions remains unclear. The current study, for the first time, explored the mechanism involved in PSME3-mediated PCC-PSC interactions. IHC showed that PSME3 is highly expressed in PCCs, and this was found to correlate with tumor differentiation. RNA interference (RNAi) indicated that PSME3 is involved in PCC apoptosis. PCR array and cell co-culture experiments suggested that conditioned culture medium (CM) from PSME3-knockdown PCCs could suppress PSC proliferation by down-regulating TGFB1 secretion. Transcription factor (TF) activation assays showed that PSME3 regulates TGFB1 production by inhibiting activation protein-1 (AP-1). Together, these data demonstrate that PSME3 interacts with AP-1 to regulate TGFB1 secretion in PCCs and promote PSC proliferation. Our results indicate a novel PSME3-regulated association between PSCs and PCCs and provide a promising therapeutic strategy for this malignancy.