Severe chemical pneumonitis by vanadium pentoxide responded well to aggressive steroid therapy.

The optimal treatment of acute chemical pneumonitis remains controversial. Here we report a healthy man with severe chemical pneumonitis caused by accidental inhalation of vanadium pentoxide. He presented with acute respiratory distress and received aggressive steroid therapy on arrival. Pulmonary symptoms and chest X-ray were improved dramatically the next day. The beneficial effect of steroid therapy for such a critical patient may outweigh the infection risk following inhalation of relative sterile material. We suggest early and aggressive steroid therapy may help shorten the disease course.

New Triterpenoids and Anti-Inflammatory Constituents from Glinus oppositifolius.

Three new triterpenoids-spergulagenin B (1), spergulagenin C (2), and spergulagenin D (3)-were isolated from the aerial part of Glinus oppositifolius, along with 17 known compounds (4-20). The structures of these new compounds were identified by spectroscopic and MS analyses. Compounds 3, 5, 19, and 20 were evaluated for inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells with IC50 values of 17.03, 18.21, 16.30, and 12.64 µM, respectively. Compounds 3, 5, and 20 exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 cells with IC50 values of 18.35 ± 1.34, 17.56 ± 1.41, and 14.27 ± 1.29 µM, respectively.

Two new chromones and a new coumarin from the fruit of Cnidium monnieri (L.) Cusson.

Two new chromones named cnidimol G (1) and cnidimol H (2), one new coumarin, 7-methoxy-8-(3-methoxy-3-methyl-2-oxobutyl)coumarin (3), and twenty known compounds were isolated from MeOH extract of the fruit of Cnidium monnieri (L.) Cusson. The structures of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, HRESIMS, IR and UV. Anti-inflammatory activity of the selected isolated compounds were evaluated. Compounds 1 and 8 exhibited inhibitory activities against nitric oxide production.

Neovasculogenic effect of 11,12-epoxyeicosatrienoic acid involves the Akt/eNOS signaling pathways in human endothelial progenitor cells.

The 11,12-epoxy-eicosatrienoic acid (11,12-EET) is formed from arachidonic acid (AA) by cytochrome P450 2J2 (CYP 2J2) epoxygenase and function as an effector in blood vessels. Human endothelial progenitor cells (hEPCs), a preceding cell source for endothelial cells (ECs), involve in the vascular tissue repairing by postnatal neovasculogenesis. However, the effect of 11, 12-EET on hEPCs and neovasculogenesis is not well known. In the current study, we examined the function of 11, 12-EET in hEPCs-mediated neovasculogenesis by using tubular formation analysis, Western Blotting assay, immunofluorescence staining, flow cytometry analysis and zymogram analysis. The results suggest that 11, 12-EET significantly induces neovasculogenesis through the phosphorylation of phosphoinositide 3-kinase (PI3-K)/Akt, endothelial-nitric oxide synthase (e-NOS) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways. 11, 12-EET up-regulates the expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and nuclear factor kappa B (NF-κB) proteins. Moreover, 11, 12-EET augments the expression of VE-cadherin and CD31 proteins in hEPCs. 11, 12-EET also augmented Rac1/Rho A signaling cascades, cell migration and an up-regulation of matrix metalloproteinase (MMP) -2 and -9 proteins. These results demonstrate that 11, 12-EET exerts a significant function in the neovasculogenesis of hEPCs.

The impact of different temporal resolution rainfall data on biosphere model of long-term safety assessment in groundwater release scenario for radioactive waste disposal in the tropical monsoon zone.

The impact of different temporal resolutions of rainfall data on the Biosphere assessment for radioactive waste disposal in the tropical monsoon region with concentrated rainfall is evaluated in this research. Two scenarios are considered to verify the effect of release location. A simplified surface water budget model is used to generate the surface water flow rates for the biosphere model, which is implemented using three different temporal averaging intervals to consider the uncertainty caused by short-term impact. Kaohsiung in Taiwan is chosen as an example because of its extreme rainfall distribution. The results show that it is improper to use the annual rainfall data for this case, and it is suggested to consider a 20% margin to cover the underestimation of dose if the monthly rainfall data are used. The results of the biosphere models built with different timesteps show that a non-negligible difference occurs for radionuclides with a low Kd value in the river water release scenario and no difference for the well water release scenario.

Chemical constituents and their anti-neuroinflammatory activities from the bark of Taiwan incense cedar, Calocedrus formosana.

One undescribed C40 terpenoid, calomacroquinoic acid; four undescribed diterpenes, 5α,6α-epoxy-7α-hydroxyferruginol, 15-ethoxysugiol, 7-methoxy-6,7-secoabieta-8,11,13-triene-6,12-diol, and ethyl 7,8-secoabieta-11,14-dioxo-7-ate; two compounds isolated from Nature for the first time, 6ß,7α-dihydroxyferruginol and 12-O-methyltaxochinon; and six known compounds were successfully identified from the bark of Taiwan incense cedar Calocedrus formosana. Structures of all isolates were elucidated by physical data (appearance, ultraviolet, infrared, specific rotation, and X-ray) and spectroscopic data (1D and 2D nuclear magnetic resonance, and high-resolution electron ionization mass spectrometry). The biosynthetic pathway of calomacroquinoic acid is also described in the current study. Nitric oxide production in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells was inhibited by 6,7-dehydroferruginol, 7α,11-dihydroxy-12-methoxy-8,11,13-abietriene, and trans-communic acid. Altogether, the bark of C. formosana possessed several potential natural therapeutics against inflammation-related neuronal diseases.

Tyrosinase Inhibitors Derived from Chemical Constituents of Dianella ensifolia.

Dianella ensifolia is a perennial herb with thickened rhizome and is widely distributed in tropical and subtropical regions of Asia, Australia, and the Pacific islands. This plant has the potential to be used as a source of herbal medicine. This study investigated further phytochemistry and tyrosinase inhibitory effect of some constituents isolated from D. ensifolia. Four new flavans, (2S)-4'-hydroxy-6,7-dimethoxyflavan (1), (2S)-3',4'-dihydroxy-7-methoxy-8-methylflavan (2), (2S)-2'-hydroxy-7-methoxyflavan (3), and (2S,1'S)-4-hydroxy-4-(7-methoxy-8-methylchroman-2-yl)-cyclohex-2-enone (4), together with 67 known compounds, including 10 flavans (5−14), 5 flavanones (15−19), 3 flavone (20−22), 5 chalcones (23−27), 3 chromones (28−30), 15 aromatics (31−45), 7 phenylpropanoids (46−52), one lignan (53), 7 steroids (54−60), one monoterpene (61), one diterpene (62), 4 triterpenes (63−66), a carotenoid (67), 2 alkaloids (68 and 69), and 2 fatty acids (70 and 71) were isolated from D. ensifolia. Their structures were elucidated on the basis of physical and spectroscopic data analyses. Moreover, compounds 1−4, 8, 10−15, 20, 21, and 41 were evaluated for their mushroom tyrosinase inhibitory effect. Compounds 11 and 14 strongly inhibited mushroom tyrosinase activity with IC50 values of 8.6 and 14.5 µM, respectively.

N-3 polyunsaturated fatty acids block the trimethylamine-N-oxide- ACE2- TMPRSS2 cascade to inhibit the infection of human endothelial progenitor cells by SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is a novel coronavirus that infects many types of cells and causes cytokine storms, excessive inflammation, acute respiratory distress to induce failure of respiratory system and other critical organs. In this study, our results showed that trimethylamine-N-oxide (TMAO), a metabolite generated by gut microbiota, acts as a regulatory mediator to enhance the inerleukin-6 (IL-6) cytokine production and the infection of human endothelial progenitor cells (hEPCs) by SARS-CoV-2. Treatment of N-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) could effectively block the entry of SARS-CoV-2 in hEPCs. The anti-infection effects of N-3 PUFAs were associated with the inactivation of NF-κB signaling pathway, a decreased expression of the entry receptor angiotensin-converting enzyme 2 (ACE2) and downstream transmembrane serine protease 2 in hEPCs upon the stimulation of TMAO. Treatment of DHA and EPA further effectively inhibited TMAO-mediated expression of IL-6 protein, probably through an inactivation of MAPK/p38/JNK signaling cascades and a downregulation of microRNA (miR)-221 in hEPCs. In conclusion, N-3 PUFAs such as DHA and EPA could effectively act as preventive agents to block the infection of SARS-CoV-2 and IL-6 cytokine production in hEPCs upon the stimulation of TMAO.

Sengstaken-Blakemore tube in critical upper gastrointestinal bleeding: Implications for aeromedical retrieval.

Sengstaken-Blakemore tubes (SBTs) are rarely used in Australia, because of improved access to endoscopy and interventional radiology, as well as overall lower rate of variceal haemorrhage from improvements in primary prophylaxis. SBT's use is associated with significant rate of serious complications, such as oesophageal perforation, mucosal necrosis, aspiration pneumonia and respiratory compromise secondary to external compression of the trachea. As such, SBT is currently only recommended for use in life-threatening variceal haemorrhage, where endoscopic, embolization and pharmacologic therapy have been unsuccessful or are unavailable. No data exist for its use in Australasia but one area that it could be indicated is for hemodynamically unstable patients in remote setting, where long transfer times often means delayed access to endoscopy. We present a case of SBT insertion in retrieval medicine and discuss placement in the management of an unstable upper gastrointestinal bleed, complicating factors such as lack of radiology to confirm balloon position, the impact of flight altitude on balloon pressures, the maintenance of traction in flight and logistics of long flight times across the state of Queensland. This is the first case report of SBT use in the Australian aeromedical environment. It is also the first one where SBT has been used for duodenal bleeding, although the source of bleeding was unknown prior to insertion.

Evaluation of a Multidisciplinary Integrated Treatment Approach Versus Standard Model of Care for Functional Gastrointestinal Disorders (FGIDS): A Matched Cohort Study.

BACKGROUND: Functional gastrointestinal disorders (FGID) are linked to a variety of potential causes, and treatments include reassurance, life-style (including diet), psychological, or pharmacologic interventions. AIMS: To assess whether a multidisciplinary integrated treatment approach delivered in a dedicated integrated care clinic (ICC) was superior to the standard model of care in relation to the gastrointestinal symptom burden. METHODS: A matched cohort of 52 consecutive patients with severe manifestation of FGID were matched with 104 control patients based upon diagnosis, gender, age, and symptom severity. Patients in the ICC received structured assessment and 12-weeks integrated treatment sessions provided as required by gastroenterologist and allied health team. Control patients received standard medical care at the same tertiary center with access to allied health services as required but no standardized interprofessional team approach. Primary outcome was reduction in gastrointestinal symptom burden as measured by the Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS). Secondary outcome was reduction in anxiety and depressive symptoms as measured by the Hospital Anxiety and Depression Scale (HADS). RESULTS: Mixed models estimated the within ICC change in SAGIS total as -9.7 (95% CI -13.6, -5.8; p < 0.0001), compared with -1.7 (95% CI -4.0, 0.6; p = 0.15) for controls. The difference between groups reached statistical significance, -7.6 (95% CI -11.4, -3.8; p < 0.0001). Total HADS scores in ICC patients were 3.4 points lower post-intervention and reached statistical significance (p = 0.001). CONCLUSION: This matched cohort study demonstrates superior short-term outcomes of FGID patients in a structured multidisciplinary care setting as compared to standard care.

Chapter Open for the Excited-State Intramolecular Thiol Proton Transfer in the Room-Temperature Solution.

We report here, for the first time, the experimental observation on the excited-state intramolecular proton transfer (ESIPT) reaction of the thiol proton in room-temperature solution. This phenomenon is demonstrated by a derivative of 3-thiolflavone (3TF), namely, 2-(4-(diethylamino)phenyl)-3-mercapto-4H-chromen-4-one (3NTF), which possesses an -S-H···O═ intramolecular H-bond (denoted by the dashed line) and has an S1 absorption at 383 nm. Upon photoexcitation, 3NTF exhibits a distinctly red emission maximized at 710 nm in cyclohexane with an anomalously large Stokes shift of 12 230 cm-1. Upon methylation on the thiol group, 3MeNTF, lacking the thiol proton, exhibits a normal Stokes-shifted emission at 472 nm. These, in combination with the computational approaches, lead to the conclusion of thiol-type ESIPT unambiguously. Further time-resolved study renders an unresolvable (<180 fs) ESIPT rate for 3NTF, followed by a tautomer emission lifetime of 120 ps. In sharp contrast to 3NTF, both 3TF and 3-mercapto-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (3FTF) are non-emissive. Detailed computational approaches indicate that all studied thiols undergo thermally favorable ESIPT. However, once forming the proton-transferred tautomer, the lone-pair electrons on the sulfur atom brings non-negligible nπ* contribution to the S1' state (prime indicates the proton-transferred tautomer), for which the relaxation is dominated by the non-radiative deactivation. For 3NTF, the extension of π-electron delocalization by the diethylamino electron-donating group endows the S1' state primarily in the ππ* configuration, exhibiting the prominent tautomer emission. The results open a new chapter in the field of ESIPT, covering the non-canonical sulfur intramolecular H-bond and its associated ESIPT at ambient temperature.

The Association of MMP9 Promoter Rs3918242 Genotype With Gastric Cancer.

BACKGROUND/AIM: Matrix metalloproteinase 9 (MMP9) is highly expressed in gastric cancer but the role of MMP9 is unclear. This study aimed at revealing the association of MMP9 promoter rs3918242 genotypes with gastric cancer risk. MATERIALS AND METHODS: MMP9 rs3918242 genotypes of 121 patients with gastric cancer and 363 healthy individuals were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using serum samples. RESULTS: MMP9 rs3918242 TT genotype carriers had an elevated gastric cancer risk compared to wild-type CC carriers (odds ratio=3.92, 95% confidence interval=1.28-11.99; p=0.0103). Patients with CT/TT genotypes were at higher risk of metastasis (p=0.0178) than those with CC. No correlation was found between MMP9 rs3918242 genotype and gastric cancer risk with smoking or alcohol behavior, nor Helicobacter pylori infection. No correlation was observed for MMP9 rs3918242 genotypic distributions with age, gender, or body mass index. CONCLUSION: Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.

Adlay hull extracts attenuate ß-amyloid-induced neurotoxicity and oxidative stress in PC12 cells through antioxidative, anti-inflammatory, and antiapoptotic activities.

Alzheimer's disease (AD) is characterized by accumulation of ß-amyloid (Aß) in senile plaques, contributing to oxidative stress, mitochondrial diseases, and synaptic atrophy, consequently leading to the deterioration of brain function. Adlay (Coix lacryma-jobi L.) is an annual botanical. Here, a 95% ethanol extract of adlay hull (AHEE) was partitioned by ethyl acetate (AHEAE), n-butanol (AHBUE), and water (AHWE), and the effects of these extracts on lipopolysaccharide (LPS)-induced RAW264.7 cells and Aß-induced PC12 cells, as experimental models of neurotoxicity, were evaluated. The expression of anti-inflammatory and antiapoptosis-related proteins was investigated and AHEE, AHEAE, and AHWE were found to exert anti-inflammatory effects. AHWE exhibited antiapoptotic effects and inhibited inducible nitric oxide synthase expression and nitric oxide production. We investigated the protective effects of AHWE against Aß-induced neurotoxicity in dPC12 cells and explored the underlying mechanism. Pretreatment with AHWE significantly attenuated cell death and Aß-mediated increase in B cell lymphoma (Bcl)-2/Bax ratio. AHWE significantly inhibited Aß and enhanced protein kinase B (Akt) level in dPC12 cells, suggesting that its protective effect against Aß-induced apoptosis in dPC12 cells was mediated through upregulation of the phosphoinositide 3-kinases (PI3K)/Akt signaling pathway. These extracts and its bioactive compound K36-21 may be potentially useful to treat neurodegenerative disorders.

Epigallocatechin-3-Gallate-Loaded Liposomes Favor Anti-Inflammation of Microglia Cells and Promote Neuroprotection.

Microglia-mediated neuroinflammation is recognized to mainly contribute to the progression of neurodegenerative diseases. Epigallocatechin-3-gallate (EGCG), known as a natural antioxidant in green tea, can inhibit microglia-mediated inflammation and protect neurons but has disadvantages such as high instability and low bioavailability. We developed an EGCG liposomal formulation to improve its bioavailability and evaluated the neuroprotective activity in in vitro and in vivo neuroinflammation models. EGCG-loaded liposomes have been prepared from phosphatidylcholine (PC) or phosphatidylserine (PS) coated with or without vitamin E (VE) by hydration and membrane extrusion method. The anti-inflammatory effect has been evaluated against lipopolysaccharide (LPS)-induced BV-2 microglial cells activation and the inflammation in the substantia nigra of Sprague Dawley rats. In the cellular inflammation model, murine BV-2 microglial cells changed their morphology from normal spheroid to activated spindle shape after 24 h of induction of LPS. In the in vitro free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, EGCG scavenged 80% of DPPH within 3 min. EGCG-loaded liposomes could be phagocytized by BV-2 cells after 1 h of cell culture from cell uptake experiments. EGCG-loaded liposomes improved the production of BV-2 microglia-derived nitric oxide and TNF-α following LPS. In the in vivo Parkinsonian syndrome rat model, simultaneous intra-nigral injection of EGCG-loaded liposomes attenuated LPS-induced pro-inflammatory cytokines and restored motor impairment. We demonstrated that EGCG-loaded liposomes exert a neuroprotective effect by modulating microglia activation. EGCG extracted from green tea and loaded liposomes could be a valuable candidate for disease-modifying therapy for Parkinson's disease (PD).

Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells.

Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received considerable attention in the prevention of metastatic tumors. Several clinical studies suggested that natural forms or analogues of fat-soluble vitamins such as vitamin A and vitamin D can work as anti-cancer agents to inhibit the development of cancer. In this study, our results demonstrated that co-treatment of 13-cis retinoic acid (13-cis RA) and 1,25-dihydroxyvitamin D3 (1,25-VD3) significantly inhibited TNF-α mediated cell invasion in PDAC in vitro. Cotreatment of 13-cis RA and 1,25-VD3 also inhibited TNF-α mediated expression of matrix metalloproteinase-9 (MMP-9) protein through blocking c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB) signaling pathways. Our results demonstrated that treatment of TNF-α lead to a decreased expression of tissue inhibitor of metalloproteinase- 3 (TIMP-3) protein and an induction of MMP-9 protein and cell invasion through an upregulation of microRNA-221 (miR-221) in human PDAC cells. Moreover, treatment of SP600125 (a specific inhibitor of JNK pathway) or cotreatment of 13-cis RA and 1,25-VD3 significantly induced a decreased expression of miR-221 and an increased expression of TIMP-3 protein. These results suggest that 13-cis RA and 1,25-VD3 significantly suppress TNF-α mediated cell invasion and therefore potentially act as preventive agents against PDAC.

The Effects of Bi-Anodal tDCS Over the Prefrontal Cortex Regions With Extracephalic Reference Placement on Insight Levels and Cardio-Respiratory and Autonomic Functions in Schizophrenia Patients and Exploratory Biomarker Analyses for Treatment Response.

BACKGROUND: We previously showed the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over the prefrontal cortex (PFC) regions with extracephalic reference placement in improving negative symptoms in schizophrenia. In this ancillary investigation, the effects of this intervention on insight levels, other clinical outcomes, and cardio-respiratory and autonomic functions were examined and the potential of biomarkers for treatment response was explored. METHODS: Schizophrenia patients were randomly allocated to receive 10 sessions of bi-anodal tDCS over the PFC regions with extracephalic reference placement (2 mA, 20 minutes, twice daily for 5 weeks) or sham stimulation. We examined, in 60 patients at baseline, immediately after stimulation and at follow-up visits, the insight levels, other clinical outcomes, blood pressure, respiratory rate, heart rate, and heart rate variability. RESULTS: Insight levels as assessed by the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia awareness of the disease, positive and negative symptoms dimensions, and beliefs about medication compliance as assessed by Medication Adherence Rating Scale were significantly enhanced by active stimulation relative to sham. No effects were observed on cognitive insight, other clinical outcomes, or cardio-respiratory and autonomic functions. Heart rate variability indices as biomarkers were not associated with the clinical response to the intervention. CONCLUSIONS: Our results provide evidence for bi-anodal tDCS over the PFC regions with extracephalic reference placement in heightening the levels of insight into the disease and symptoms, as well as beliefs about medication compliance in schizophrenia, without impacting other clinical outcomes and cardio-respiratory/autonomic functions.

Huang Lian Jie Du Tang attenuates paraquat-induced mitophagy in human SH-SY5Y cells: A traditional decoction with a novel therapeutic potential in treating Parkinson's disease.

Huang Lian Jie Du Tang (HLJDT) is a traditional Chinese medical decoction for heat-fire clearing and detoxication. Theoretically, the cause of Parkinson's disease (PD) has been attributed to the dysregulations of internal wind, phlegm, fire, and stasis. Thus, HLJDT has been used to treat PD. However, the molecular mechanism is unknown. Besides, paraquat (PQ) as an herbicide has been known to impair midbrain dopaminergic neurons, resemblance to the pathology of PD. Thus, the molecular mechanism of HLJDT in treating PD and PQ-induced in vitro PD model was investigated in this study. Primarily, the dose-response of PQ (0.1∼1 mM)-induced neurotoxicity for 24 h was performed in the human neuroblastoma SH-SY5Y cells. The LD50 of PQ is around 0.3 mM and was applied throughout the following experiments. The neutral red assay was used to estimate cell viability. Co-transfection of the mitochondrial marker and proapoptotic factor genes were applied to measure the release of mitochondrial proapoptotic factors during PQ intoxication and HLJDT protection. The fluorescent dyes were used to detect mitochondrial membrane potential and free radical formation. Western blot and dot-blot analysis and immunocytochemistry were used to estimate the level of proteins related to apoptosis and mitophagy. PINK1 gene silencing was used to determine the significance of mitophagy during PQ intoxication. In this study, HLJDT attenuated PQ-induced apoptosis in SH-SY5Y cells. HLJDT reversed PQ-induced decreased mitochondrial membrane potential and suppressed PQ-induced increased cytosolic and mitochondrial free radical formations and mitochondrial proapoptotic factor releases. Furthermore, HLJDT mitigated PQ-induced increases in full-length PINK1, phosphorylations of Parkin and ubiquitin, mitochondrial translocation of phosphorylated Parkin, and mitophagy. PINK1 gene silencing attenuated PQ-induced neurotoxicity. Therefore, HLJDT attenuated PQ-induced cell death by regulating mitophagy.

Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion / 华西口腔医学杂志

OBJECTIVES@#To investigate the expression of cyclophilin A (CyPA) in oral squamous cell carcinoma (OSCC) and explore the effect of downregulating the expression of CyPA gene on the proliferation and invasion of SCC-25 cells.@*METHODS@#A total of 77 cases of patients with OSCC were selected. The expression levels of CyPA proteins in OSCC and adjacent normal tissues were evaluated. SCC-25 cells were cultured and divided into the CyPA interference sequence group, negative control group, and blank group. The expression levels of CyPA mRNA and protein in cells were detected by using real-time fluorescent quantitative polymerase chain reaction and Western blot, respectively. Cell proliferation was detected by using methyl thiazolyl tetrazolium and plate colony formation assays. Cell invasion was detected by using Transwell assay.@*RESULTS@#The positive expression rate of CyPA protein in OSCC tissues was 76.62%, which was higher than that in adjacent tissues (@*CONCLUSIONS@#The CyPA protein is highly expressed in OSCC tissues, and the downregulation of CyPA gene expression in SCC-25 cells can reduce cell proliferation and inhibit cell invasion.

Docosahexaenoic acid inhibits the proliferation of Kras/TP53 double mutant pancreatic ductal adenocarcinoma cells through modulation of glutathione level and suppression of nucleotide synthesis.

The treatment of cancer cells obtained by blocking cellular metabolism has received a lot of attention recently. Previous studies have demonstrated that Kras mutation-mediated abnormal glucose metabolism would lead to an aberrant cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Previous literature has suggested that consumption of fish oil is associated with lower risk of pancreatic cancer. In this study, we investigated the anti-cancer effects of docosahexaenoic acid (DHA) in human PDAC cells in vitro and in vivo. Omega-3 polyunsaturated fatty acids (PUFAs) such as DHA and eicosapentaenoic acid (EPA) significantly inhibited the proliferation of human PDAC cells. The actions of DHA were evaluated through an induction of cell cycle arrest at G1 phase and noticed a decreased expression of cyclin A, cyclin E and cyclin B proteins in HPAF-II cells. Moreover, it was found that co-treatment of DHA and gemcitabine (GEM) effectively induced oxidative stress and cell death in HPAF-II cells. Interestingly, DHA leads to an increased oxidative glutathione /reduced glutathione (GSSG/GSH) ratio and induced cell apoptosis in HPAF-II cells. The findings in the study showed that supplementation of GSH or N-Acetyl Cysteine (NAC) could reverse DHA-mediated cell death in HPAF-II cells. Additionally, DHA significantly increased cellular level of cysteine, cellular NADP/NADPH ratio and the expression of cystathionase (CTH) and SLCA11/xCT antiporter proteins in HPAF-II cells. The action of DHA was, in part, associated with the inactivation of STAT3 cascade in HPAF-II cells. Treatment with xCT inhibitors, such as erastin or sulfasalazine (SSZ), inhibited the cell survival ability in DHA-treated HPAF-II cells. DHA also inhibited nucleotide synthesis in HPAF-II cells. It was demonstrated in a mouse-xenograft model that consumption of fish oil significantly inhibited the growth of pancreatic adenocarcinoma and decreased cellular nucleotide level in tumor tissues. Furthermore, fish oil consumption induced an increment of GSSG/GSH ratio, an upregulation of xCT and CTH proteins in tumor tissues. In conclusion, DHA significantly inhibited survival of PDAC cells both in vitro and in vivo through its recently identified novel mode of action, including an increment in the ratio of GSSG/GSH and NADP/NADPH respectively, and promoting reduction in the levels of nucleotide synthesis.