Negative gallbladder stones: Diagnostic advantages of dual-energy CT and analysis of a unique case.

BACKGROUND: Gallbladder stones are a common digestive system disease, but their diagnosis can be limited in some cases, especially in identifying "negative" stones, which may be difficult to recognize with traditional CT scans. OBJECTIVE: This study aims to explore the advantages of dual-energy CT in diagnosing negative gallbladder stones through a unique case of gallbladder stones. METHODS AND RESULTS: A case of a 31-year-old female is described, who was diagnosed with gallbladder stones during a physical examination two years ago and occasionally experienced pain in the upper right abdomen. Dual-energy CT scanning revealed a mixed-density stone, approximately 2 cm in diameter, in the neck of the gallbladder, consisting of a calcified shell (positive stone) and a homogenous density nucleus (negative stone). Verified by dual-energy CT, single-energy images and spectral curves can very intuitively identify negative stones, demonstrating significantly superior performance compared to traditional CT. CONCLUSION: Dual-energy CT, through single-energy images and spectral curves, intuitively identifies negative gallbladder stones, showcasing significant advantages compared to traditional CT, and offers a valuable approach to enhancing the diagnostic accuracy of gallbladder stones.

The global state of research in stem cells therapy for spinal cord injury (2003-2022): a visualized analysis.

Objective: Our study aimed to visualize the global status and frontiers in stem cell therapy for spinal cord injury by using bibliometric methodology. Methods: Publication citation information related to stem cell therapy for spinal cord injury (SCI) studies between 2003 and 2022 was retrieved from the Web of Science Core Collection database. For the visualized study, VOS viewer software and Graph Pad Prism 9.5 were used to perform bibliometric analysis of included data and publication number statistics in stem cell therapy for the SCI domain. Results: A total of 6,686 publications were retrieved. The USA and China made the highest contributions to global research with the highest number of citations and link strength. The journal Experimental Neurology ranks as the top journal, combining the publication amount and bibliometrics results. The University of Toronto, based in Canada, was the first-ranking institution. The directions of the current study could be divided into five clusters. The research of Transplantation and Regenerative Medicine and Neurosciences Mechanism Research may be the emerging frontiers in this domain. Conclusion: In summary, stem cell therapy for spinal cord injuries is poised for more valuable advances.

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis.

Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis is usually present upon initial diagnosis, and metastasis is the primary factor affecting the poor prognosis of patients with OS. Current research shows that the ability to regulate the cellular microenvironment is essential for preventing the distant metastasis of OS, and anoxic microenvironments are important features of solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels and stability increase. Increased HIF-1α promotes tumor vascular remodeling, epithelial-mesenchymal transformation (EMT), and OS cells invasiveness; this leads to distant metastasis of OS cells. HIF-1α plays an essential role in the mechanisms of OS metastasis. In order to develop precise prognostic indicators and potential therapeutic targets for OS treatment, this review examines the molecular mechanisms of HIF-1α in the distant metastasis of OS cells; the signal transduction pathways mediated by HIF-1α are also discussed.

Liquid concrete as a gastrointestinal tract foreign body.

Gastrointestinal foreign bodies present a common clinical challenge. We present an unusual case of a 58-year-old construction worker who ingested liquid concrete that risked solidifying in his stomach. Gastroscopy revealed only partial solidification and pyloric obstruction, which were successfully resolved through endoscopic fragmentation and mechanical removal. To protect the gastric mucosa during elimination, liquid paraffin and a cellulose-based formula were administered. Complete gastrointestinal evacuation was achieved within 3 days, with no complications observed. This case emphasises the urgency of the early removal of concrete.

Traumatic intestinal ischemic necrosis.

A 71-year-old male patient presented to our emergency department with a 1-day history of abdominal pain after an accidental fall. Laboratory test results were as follows: a white blood cell count of 2.32 × 109/L, blood lactate of 3.0 mmol/L, pH 7.30, calcitonin precursor level of 71.09 ng/ml, and creatinine of 115 umol/L. The abdominal CT revealed: portal vein gas accumulation (PVGA) accompanied by a fluid-air level; pneumatosis cystoides intestinalis (PCI) manifested as multiple gas collections within the wall of the lower small intestine. Based on lowered blood pH and elevated lactate levels, there was a high suspicion of small intestinal ischemic necrosis. Subsequent emergency laparotomy and pathological examination confirmed necrosis of the small intestine.

Prevalence, risk factors, and mortality of COPD in young people in the USA: results from a population-based retrospective cohort.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been considered a disease of the elderly, but it could also occur in young people aged 20-50 years. However, the characteristics and prognosis of COPD in such young people remain unclear. METHODS: Our retrospective cohort study was based on the National Health and Nutrition Examination Survey (NHANES). Participants who 20-50 years old at baseline and completed the pulmonary function test were enrolled in our study cohort. These participants were followed up to 31 December 2019. The sample weight and Taylor Linearization Procedures were adapted to make representative estimations of prevalence and baseline characteristics. The weighted logistic regression model was used to assess the risk factors. The propensity score method and Cox proportional hazard models were applied to calculate the risk of mortality. RESULTS: The weighted prevalence of COPD in young people in the USA was 1.64% and it increased with age, with a higher prevalence in males than females (2.59% vs 0.72%, p<0.001). The proportion of Global Initiative for COPD 1-2 was 96.7%. Males (OR=4.56, 95% CI: 2.74 to 7.61), non-Hispanic black (OR=2.77; 95% CI: 1.14 to 6.75), non-Hispanic white (OR=4.93; 95% CI: 2.16 to 11.28) and smoking (current smoking, OR=2.36; 95% CI: 1.40 to 3.98; ever smoking, OR=1.92; 95% CI: 1.05 to 3.51; passive smoking, OR=2.12; 95% CI: 1.41 to 3.20) were shown to be independent risk factors for COPD in young people. Compared with those matched by sex, age and race, the young people with COPD had a higher risk of all-cause death (HR=3.314, p<0.001). CONCLUSION: COPD in young people has a low prevalence in the USA and its independent risk factors included male, race (non-Hispanic black and non-Hispanic white) and smoking. Young COPD has a higher risk of all-cause mortality than the matched non-COPD.

A glycometabolic gene signature associating with immune infiltration and chemosensitivity and predicting the prognosis of patients with osteosarcoma.

Background: Accumulating evidence has suggested that glycometabolism plays an important role in the pathogenesis of tumorigenesis. However, few studies have investigated the prognostic values of glycometabolic genes in patients with osteosarcoma (OS). This study aimed to recognize and establish a glycometabolic gene signature to forecast the prognosis, and provide therapeutic options for patients with OS. Methods: Univariate and multivariate Cox regression, LASSO Cox regression, overall survival analysis, receiver operating characteristic curve, and nomogram were adopted to develop the glycometabolic gene signature, and further evaluate the prognostic values of this signature. Functional analyses including Gene Ontology (GO), kyoto encyclopedia of genes and genomes analyses (KEGG), gene set enrichment analysis, single-sample gene set enrichment analysis (ssGSEA), and competing endogenous RNA (ceRNA) network, were used to explore the molecular mechanisms of OS and the correlation between immune infiltration and gene signature. Moreover, these prognostic genes were further validated by immunohistochemical staining. Results: A total of four genes including PRKACB, SEPHS2, GPX7, and PFKFB3 were identified for constructing a glycometabolic gene signature which had a favorable performance in predicting the prognosis of patients with OS. Univariate and multivariate Cox regression analyses revealed that the risk score was an independent prognostic factor. Functional analyses indicated that multiple immune associated biological processes and pathways were enriched in the low-risk group, while 26 immunocytes were down-regulated in the high-risk group. The patients in high-risk group showed elevated sensitivity to doxorubicin. Furthermore, these prognostic genes could directly or indirectly interact with other 50 genes. A ceRNA regulatory network based on these prognostic genes was also constructed. The results of immunohistochemical staining showed that SEPHS2, GPX7, and PFKFB3 were differentially expressed between OS tissues and adjacent normal tissues. Conclusion: The preset study constructed and validated a novel glycometabolic gene signature which could predict the prognosis of patients with OS, identify the degree of immune infiltration in tumor microenvironment, and provide guidance for the selection of chemotherapeutic drugs. These findings may shed new light on the investigation of molecular mechanisms and comprehensive treatments for OS.

Ternary complexes of cyclodextrins with alkali earth cations and amino acids in gas phase investigated by mass spectrometry.

Noncovalent ternary complexes between cyclodextrins (CDs), small molecules and alkali earth cations drew growing attention due to their potential application in many chemical and pharmaceutical fields. To date, the main factors affect the formation mechanism of noncovalent ternary complexes in gas phase have not been fully investigated. In this study, ternary complexes of CDs, divalent metal cations and amino acids (AAs) were investigated by electrospray ionization mass spectrometry (ESI-MS), demonstrating the formation of 1:1:1 stoichiometric noncovalent ternary complex of [CD + cation(II)+AA]2+ in gas phase. The results revealed that only +2 valence cations can form stable ternary complexes in ESI-MS. The ratio of peak intensities for [ß-CD + Mg(II)+AA]2+ to those for [ß-CD + Mg(II)]2+ hydrophobicity of AAs was also determined to discuss the effect of hydrophobicity of AAs. Exceptions exist for Pro, Gly, and Val indicated that other factors such as side-chain structure and rigidity of AAs can also influence the binding strength for ternary complexes. Collision induced dissociations (CID) were performed to further confirm the formation of the ß-CD ternary complexes, revealing the binding strength of [CD + Mg(II)+Phe]2+ decreased in the order of γ-CD, ß-CD, and α-CD. Although Leu and Ile are isomers, the ESI-MS demonstrated the peak intensity for ternary complexe of [ß-CD + Mg(II)+Ile]2+ exhibited stronger than that of [ß-CD + Mg(II)+Leu]2+, DFT theoretical calculations were conducted to explain the phenomenon. The calculation indicated when Mg2+ existing, the conformations of the two ternary complexes could be affected due to the electrostatic force. In the complexes, the Leu and Ile turn a way round, inserting to the cavity with their carboxylic acid side into the large rim side of ß-CD and interacting with Mg2+. This work not only clearly explained the factors influencing the formation of [CD + cation(II)+AA]2+ in gas phase, but it also provides an insight in designing ternary complexes for areas such as drug design and chiral discrimination.

Early evaluation of liver metastasis using spectral CT to predict outcome in patients with colorectal cancer treated with FOLFOXIRI and bevacizumab.

PURPOSE: Early evaluation of the efficacy of first-line chemotherapy combined with bevacizumab in patients with colorectal cancer liver metastasis (CRLM) remains challenging. This study used 2-month post-chemotherapy spectral computed tomography (CT) to predict the overall survival (OS) and response of CRLM patients with bevacizumab-containing therapy. METHOD: This retrospective analysis was performed in 104 patients with pathologically confirmed CRLM between April 2017 and October 2021. Patients were treated with 5-fluorouracil, leucovorin, oxaliplatin or irinotecan with bevacizumab. Portal venous phase spectral CT was performed on the target liver lesion within 2 months of commencing chemotherapy to demonstrate the iodine concentration (IoD) of the target liver lesion. The patients were classified as responders (R +) or non-responders (R -) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at 6 months. Multivariate analysis was performed to determine the relationships of the spectral CT parameters, tumor markers, morphology of target lesions with OS and response. The differences in portal venous phase spectral CT parameters between the R + and R - groups were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the predictive power of spectral CT parameters. RESULTS: Of the 104 patients (mean age ± standard deviation: 57.73 years ± 12.56; 60 men) evaluated, 28 (26.9%) were classified as R + . Cox multivariate analysis identified the iodine concentration (hazard ratio [HR]: 1.238; 95% confidence interval [95% CI]: 1.089-1.408; P < 0.001), baseline tumor longest diameter (BLD) (HR: 1.022; 95% CI: 1.005-1.038, P = 0.010), higher baseline CEA (HR: 1.670; 95% CI: 1.016-2.745, P = 0.043), K-RAS mutation (HR: 2.027; 95% CI: 1.192-3.449; P = 0.009), and metachronous liver metastasis (HR: 1.877; 95% CI: 1.179-2.988; P = 0.008) as independent risk factors for patient OS. Logistic multivariate analysis identified the IoD (Odds Ratio [OR]: 2.243; 95% CI: 1.405-4.098; P = 0.002) and clinical N stage of the primary tumor (OR: 4.998; 95% CI: 1.210-25.345; P = 0.035) as independent predictor of R + . Using IoD cutoff values of 4.75 (100ug/cm3) the area under the ROC curve was 0.916, sensitivity and specificity were 80.3% and 96.4%, respectively. CONCLUSIONS: Spectral CT IoD can predict the OS and response of patients with CRLM after 2 months of treatment with bevacizumab-containing therapy.

The Combination of Chrysin and Cisplatin Induces Apoptosis in HepG2 through Down-regulation of cFLIP and Activity of Caspase.

AIM: The study aims to investigate the combined effects of chrysin and cisplatin on hepatoma(HepG2) cell lines in vivo and in vitro. OBJECTIVE: Studies have suggested that chrysin can enhance the sensitivity of tumor cells to apoptosis. Drug resistance in tumor cells reduced the effectiveness of chemotherapy drugs such as cisplatin. We investigated whether the combination of chrysin and cisplatin can induce more apoptosis than chrysin alone and cisplatin alone. METHODS: HepG2 cells were pretreated with chrysin for 2 h, followed by the addition of cisplatin for another 24 h. The morphologic changes were observed under inverted microscope and the cell viability was measured using the MTT test. The protein and cleavage of caspase-3,8,9, PARP, and cFLIP were determined by Western blotting. RESULTS: The cell viability of the HepG2 cell can be reduced by the combination of chrysin pretreatment for 2 h and cisplatin addition for 24 h; Caspase-3,8,9 and PARP were cleaved after 12 h treatment with chrysin and cisplatin; Pancaspase inhibitor, Z-VAD-fmk, could reverse the apoptosis induced by chrysin and cisplatin in HepG2 cells; cFLIP was down-regulated by the combination of chrysin and cisplatin, and could be reversed by Z-VAD-fmk; the xenografted HepG2 cells formed a tumor in one week; At the end of the experiment, there were significant differences in relative tumor volume (RTV) and relative tumor proliferation rate between the combined group and the control group, the chrysin group and the cisplatin group; Western blotting showed that the levels of PARP, cFLIP, and caspase-3 proteins in isolated tumor tissues also decreased under the combined action of chrysin and cisplatin. CONCLUSION: The combination of chrysin and cisplatin induces apoptosis of hepatic tumor in vivo and in vitro. It downregulates cFLIP and then activates caspase-8, which triggers caspase-mediated apoptosis of HepG2 cell.

N6-methyladenosine Modification-Related Long Non-Coding RNAs are Potential Biomarkers for Predicting the Prognosis of Patients With Osteosarcoma.

Background: The role of N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) in osteosarcoma (OS) has not been fully studied yet. We aimed to identify m6A-related lncRNAs that could act as prognostic biomarkers for OS. Methods: Pearson correlation was performed to identify m6A-related lncRNAs. Univariate and multivariate Cox regression analyses were performed to construct the risk model and assess whether the risk score was an independent prognostic factor for patients with OS. Gene Set Enrichment Analysis (GSEA) was performed to analyze the functions of genes in high-risk and low-risk groups. StarBase and Cytoscape were used to construct a competing endogenous RNA (ceRNA) network based on m6A-related prognostic lncRNA signature. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the function of genes involved in the ceRNA network. Results: We extracted 122 common lncRNAs from TCGA and Gene Expression Omnibus (GEO) databases. Pearson correlation results revealed 59 significant m6A-related lncRNAs in The Cancer Genome Atlas (TCGA) database, from which 2 were screened to construct a risk signature in TCGA dataset, which was then validated in the GEO dataset. A corresponding risk score was calculated and shown to be an independent prognostic factor for patients with OS. Enrichment analysis indicated that cell proliferation-related biological processes were more common in the high-risk group, while immune-related biological processes were more common in the low-risk group. Moreover, we established a nomogram that had a good ability to predict the overall survival of patients with OS. Additionally, a ceRNA network based on small nucleolar RNA host gene 7 (SNHG7) and small nucleolar RNA host gene 12 (SNHG12) was constructed, with genes that were enriched in hepatocellular carcinoma, gastric cancer, and non-small-cell lung cancer pathways. Conclusion: Our study revealed the prognostic role of m6A-related lncRNAs in OS and identified SNHG7 and SNHG12 as potential biomarkers for predicting the prognosis of patients with OS. These findings have enriched our understanding of the role of m6A modification in the dysregulation of lncRNAs in OS.

CircRASSF2 promotes IGF1R and osteosarcoma metastasis via sponging miR-6838-5p.

BACKGROUND: Osteosarcoma (OS) often occurs in children and adolescents and is highly malignant. Analyzing the pathogenesis of OS has great significance for prognosis and the discovery of new treatment strategies. METHODS: The effects and mechanism of circular RNA (circRNA) on OS were analyzed, as was the correlation between circRASSF2 and insulin-like growth factor 1 receptor (IGF1R) in data from The Cancer Genome Atlas (TCGA). The expression levels of microRNA (miR)-6838-5p and circRASSF2 in OS cells and osteoblasts were detected. The dual luciferase report was used to verify the targeting relationship. OS cells overexpressing circRASSF2, miR-6838-5p and/or IGF1R were constructed. The expression level of IGF1R and the biological behavior of the cells were detected. Eighty-two pairs of OS tissue and adjacent normal tissue samples were collected, and the levels of circRASSF2, miR-6838-5p, and IGF1R mRNA were detected by reverse transcription-quantitative PCR (RT-qPCR). RESULTS: Compared with osteoblasts, OS cells showed lower expression of miR-6838-5p and higher expression of circRASSF2. The dual luciferase report confirmed that miR-6838-5p targeted IGF1R. Overexpression of IGF1R significantly blocked the anticancer effects of miR-6838-5p. The dual luciferase report verified that circRASSF2 targeted miR-6838-5p, and promoted the expression of IGF1R. Overexpression of circRASSF2 not only promoted the malignant biological behavior of OS cells, but also blocked the anticancer effects of miR-6838-5p. In OS tissue, circRASSF2 and IGF1R were upregulated, and the two were positively correlated. MiR-6838-5p was downregulated, which negatively correlated with both circRASSF2 and IGF1R. High levels of circRASSF2 were associated with higher stage and metastasis of OS. CONCLUSIONS: In conclusion, the promoting effects of IGF1R on OS are targeted by miR-6838-5p. CircRASSF2 restored the expression of IGF1R by sponging miR-6838-5p, thereby promoting the progression of OS.

Distinction of chiral penicillamine using metal-ion coupled cyclodextrin complex as chiral selector by trapped ion mobility-mass spectrometry and a structure investigation of the complexes.

Penicillamine (Pen) is a common chiral drug that is obtained from penicillin. Between the two enantiomers of Pen, only D-Pen can be used to treat cystinuria and rheumatoid arthritis while L-Pen is toxic. Therefore, it requires great efforts for the research of the rigorous analysis and distinction of the two enantiomers. The non-covalent combination of chiral molecules and chiral selectors (CSs) has been proved as a unique strategy for chiral distinction by ion mobility spectrometry in coupling with -mss spectrometry (IM-MS). Here, we developed a simple method to distinguish D, L-Pen by using special CSs for IM-MS separation. The CSs utilized here include cyclodextrins (CD) and linear chain oligosaccharides plus metal ions. We found that non-covalent complexes [Pen+ß-CD + Li]+ could be easily formed by electrospray ionization of the mixture of the solution, and the chirality of Pen could be effectively recognized by measuring their mobilities due to the different collision cross collision sections of [D-Pen+ß-CD + Li]+ and [L-Pen+ß-CD + Li]+. A detailed analysis of [Pen+ß-CD + Li]+ was then conducted by the optical rotation measurements and NMR experiments to reveal their structural differences. Furthermore, DFT calculation showed the differences of molecular conformation between the complexes. The results provide a new powerful method for fast analysis and recognition of chirality of Pen compounds by IM-MS.

The role of positive nerve root sedimentation sign in the treatment of patients undergoing lumbar disc herniation.

BACKGROUND: To investigate the efficacy of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of patients who were diagnosed with lumbar disc herniation (LDH) with positive nerve root sedimentation sign (NRSS). METHODS: A total of 86 patients who underwent LDH were recruited and divided into NRSS-positive group (n = 49) and NRSS-negative group (n = 37). The visual analog scale (VAS), Japanese Orthopaedic Association (JOA), and Oswestry disability index (ODI) were used to evaluate the low back pain and functional recovery and were compared between the two groups. RESULTS: There were no significant differences in the demographic parameters between the two groups. The average area of the dural sac compression in the NRSS-positive group was significantly higher than that in the NRSS-negative group. Patients with a positive NRSS showed a better low back pain relief than those with a negative NRSS at 1 week and 1 month after surgery. The JOA and ODI in the NRSS-positive group were better than those in the NRSS-negative group at 3 months and 6 months postoperatively. The apparent efficiency of JOA and the excellent and good rate of ODI in the negative group was lower than that in the positive group at 6 months after surgery. CONCLUSIONS: Patients undergoing LDH with a positive NRSS showed better pain relief and functional recovery than those with a negative NRSS. The present study suggested that NRSS might be a valuable sign and associated with better clinical outcomes in patients undergoing LDH with the treatment of PTED.

Differential expression of sputum and serum autoantibodies in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease. Autoimmune processes have been hypothesized to contribute to disease progression; however, the presence of autoantibodies in the serum has been variable. Given that COPD is a lung disease, we sought to investigate whether autoantibodies in sputum supernatant would better define pulmonary autoimmune processes. Matched sputum and serum samples were obtained from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study and at the Guangzhou Institute of Respiratory Health (GIRH). Samples were collected from patients with varying severity of COPD, asymptomatic smokers, and healthy control subjects. IgG and IgM autoantibodies were detected in sputum and serum of all subjects in both cohorts using a broad-spectrum autoantigen array. No differences were observed in sputum autoantibodies between COPD and asymptomatic smokers in either cohort. In contrast, 16% of detectable sputum IgG autoantibodies were decreased in subjects with COPD compared to healthy controls in the ADEPT cohort. Compared to asymptomatic smokers, approximately 13% of detectable serum IgG and 40% of detectable serum IgM autoantibodies were differentially expressed in GIRH COPD subjects. Of the differentially expressed specificities, anti-nuclear autoantibodies were predominately decreased. A weak correlation between increased serum IgM anti-tissue autoantibodies and a measure of airspace enlargement was observed. The differential expression of specificities varied between the cohorts. In closing, using a comprehensive autoantibody array, we demonstrate that autoantibodies are present in subjects with COPD, asymptomatic smokers, and healthy controls. Cohorts displayed high levels of heterogeneity, precluding the utilization of autoantibodies for diagnostic purposes.

Application of 3D printed osteotomy guide plate-assisted total knee arthroplasty in treatment of valgus knee deformity.

INTRODUCTION: To analyze the application of 3D printed osteotomy guide plate-assisted total knee arthroplasty (TKA) for valgus knee deformity. METHODS: The clinical data of 20 patients with valgus knee deformity admitted to our hospital from April 2012 to April 2017 were collected and analyzed. According to the treatment method, these patients were divided into two groups: 3D printed osteotomy guide plate-assisted TKA (combined treatment group, n = 10) and TKA (treatment group, n = 10). The operation time, intraoperative bleeding volume, postoperative mean femorotibial angle (MFTA), and Knee Society Score (KSS) of the two groups were statistically analyzed. RESULTS: Compared with the treatment group, the operation time was significantly shorter (P < 0.05), the intraoperative blood loss and postoperative MFTA were significantly decreased (P < 0.05), and the clinical and functional scores were significantly increased (P < 0.05) in the combined treatment group. CONCLUSION: 3D printed osteotomy guide plate-assisted TKA for valgus knee deformity is more effective than TKA alone.

Combination of quercetin and cisplatin enhances apoptosis in OSCC cells by downregulating xIAP through the NF-κB pathway.

While cisplatin is a first-line chemotherapeutic drug commonly used to treat patients with oral squamous cell carcinoma (OSCC), the cisplatin-resistance poses a major challenge for its clinical application. Recent studies have shown that quercetin, a natural flavonoid found in various plants and foods possesses an anti-cancer effect. The following study examined the combined effect of quercetin and cisplatin on OSCC apoptosis in vitro and in vivo (using a mice tumor model). We found that quercetin promotes cisplatin-induced apoptosis in human OSCC (cell lines Tca-8113 and SCC-15) by down-regulating NF-κB. Pretreatment of cancer cells with quercetin inhibited the phosphorylation Akt and IKKß, and led to the suppression of NF-κB and anti-apoptotic protein xIAP. In addition, we observed that the pretreatment of cancer cells with quercetin improves extrinsic and intrinsic apoptosis by activating caspase-8 and caspase-9, respectively. Our in vivo data also indicated that the combination of quercetin and cisplatin may inhibit the xenograft growth in mice. To sum up, our results provide a new evidence for the application of quercetin and cisplatin in OSCC therapy.