Functional analyses of Toxoplasma gondii dihydroorotase reveal a promising anti-parasitic target.

Toxoplasma gondii relies heavily on the de novo pyrimidine biosynthesis pathway for fueling the high uridine-5'-monophosphate (UMP) demand during parasite growth. The third step of de novo pyrimidine biosynthesis is catalyzed by dihydroorotase (DHO), a metalloenzyme that catalyzes the reversible condensation of carbamoyl aspartate to dihydroorotate. Here, functional analyses of TgDHO reveal that tachyzoites lacking DHO are impaired in overall growth due to decreased levels of UMP, and the noticeably growth restriction could be partially rescued after supplementation with uracil or high concentrations of L-dihydroorotate in vitro. When pyrimidine salvage pathway is disrupted, both DHOH35A and DHOD284E mutant strains proliferated much slower than DHO-expressing parasites, suggesting an essential role of both TgDHO His35 and Asp284 residues in parasite growth. Additionally, DHO deletion causes the limitation of bradyzoite growth under the condition of uracil supplementation or uracil deprivation. During the infection in mice, the DHO-deficient parasites are avirulent, despite the generation of smaller tissue cysts. The results reveal that TgDHO contributes to parasite growth both in vitro and in vivo. The significantly differences between TgDHO and mammalian DHO reflect that DHO can be exploited to produce specific inhibitors targeting apicomplexan parasites. Moreover, potential DHO inhibitors exert beneficial effects on enzymatic activity of TgDHO and T. gondii growth in vitro. In conclusion, these data highlight the important role of TgDHO in parasite growth and reveal that it is a promising anti-parasitic target for future control of toxoplasmosis.

Immobilization mechanisms of heavy metals by utilizing natural cow bone waste for municipal solid waste incineration fly ash treatment.

Municipal solid waste incinerator (MSWI) fly ash poses intricate compositional challenges and potential environmental hazards. Effective management of such hazardous waste is imperative to mitigate the release of toxic compounds into the environment. Solidification/stabilization (S/S) processes have emerged as a viable strategy to transform MSWI fly ash from incineration waste into a safer and more environmentally benign material. This study aims to comprehensively investigate the potential of utilizing cow bone waste to stabilize heavy metals, focusing on Pb, within municipal solid waste incineration fly ash. Experimental investigations encompassed cow bone-to-fly ash weight ratios ranging from 0.0 (control group) to 7:3, a settling time of 2 h, and a liquid-to-solid (L/S) ratio of 1.0 mL/g. Cow bone waste exhibited pronounced efficacy, particularly within the short settling time, yielding a remarkable Pb removal efficiency of up to 99% at a cow bone waste dose of merely 2% and an L/S ratio of 1.0 mL/g. Concurrently, other heavy metals such as Cd, Cu, and Zn were effectively stabilized with a cow bone waste dose of 1.5% during the same 2-h settling period. The results underscore the pivotal roles of ash/bone ratio and settling time in augmenting Pb stabilization in MSWI fly ash. The application of cow bone waste is anticipated to offer a cost-effective and environmentally sound approach, aligning with sustainable waste management principles.

Deep learning radiomics of dual-modality ultrasound images for hierarchical diagnosis of unexplained cervical lymphadenopathy.

BACKGROUND: Accurate diagnosis of unexplained cervical lymphadenopathy (CLA) using medical images heavily relies on the experience of radiologists, which is even worse for CLA patients in underdeveloped countries and regions, because of lack of expertise and reliable medical history. This study aimed to develop a deep learning (DL) radiomics model based on B-mode and color Doppler ultrasound images for assisting radiologists to improve their diagnoses of the etiology of unexplained CLA. METHODS: Patients with unexplained CLA who received ultrasound examinations from three hospitals located in underdeveloped areas of China were retrospectively enrolled. They were all pathologically confirmed with reactive hyperplasia, tuberculous lymphadenitis, lymphoma, or metastatic carcinoma. By mimicking the diagnosis logic of radiologists, three DL sub-models were developed to achieve the primary diagnosis of benign and malignant, the secondary diagnosis of reactive hyperplasia and tuberculous lymphadenitis in benign candidates, and of lymphoma and metastatic carcinoma in malignant candidates, respectively. Then, a CLA hierarchical diagnostic model (CLA-HDM) integrating all sub-models was proposed to classify the specific etiology of each unexplained CLA. The assistant effectiveness of CLA-HDM was assessed by comparing six radiologists between without and with using the DL-based classification and heatmap guidance. RESULTS: A total of 763 patients with unexplained CLA were enrolled and were split into the training cohort (n=395), internal testing cohort (n=171), and external testing cohorts 1 (n=105) and 2 (n=92). The CLA-HDM for diagnosing four common etiologies of unexplained CLA achieved AUCs of 0.873 (95% CI: 0.838-0.908), 0.837 (95% CI: 0.789-0.889), and 0.840 (95% CI: 0.789-0.898) in the three testing cohorts, respectively, which was systematically more accurate than all the participating radiologists. With its assistance, the accuracy, sensitivity, and specificity of six radiologists with different levels of experience were generally improved, reducing the false-negative rate of 2.2-10% and the false-positive rate of 0.7-3.1%. CONCLUSIONS: Multi-cohort testing demonstrated our DL model integrating dual-modality ultrasound images achieved accurate diagnosis of unexplained CLA. With its assistance, the gap between radiologists with different levels of experience was narrowed, which is potentially of great significance for benefiting CLA patients in underdeveloped countries and regions worldwide.

Study of Corrosion Kinetic Measurement and Morphology Observation of Superheater Tube 12Cr1MoV Alloy in Simulated MSWI Flue Gas Containing Varied HCl or SO2 Concentrations.

Severe corrosion to superheater tubes at high temperatures was gained virtually by gaseous corrosion media, such as HCl and SO2, in the municipal solid waste incineration flue gas. To clarify the effect of varying concentrations of HCl and SO2 in the oxidizing atmosphere on the corrosion of 12Cr1MoV, a commercial alloy used in superheaters, two series of corrosion tests under simulated flue gas were performed. Both the corrosion kinetics and corrosion morphology were measured in this work. The results of the present study demonstrated that the addition of HCl was more corrosive than that of SO2 under an oxidizing atmosphere. The increased HCl concentration had an accelerating effect on the corrosion rate, but the relation between the two was not linear. In contrast, SO2 exhibited a negligible or even inhibitory effect on corrosion. Both series of test results consistently proved that the temperature had a significant influence on the corrosion of 12Cr1MoV alloy, in particular at 580 °C.

Radix Tetrastigma Extracts Enhance the Chemosensitivity in Triple-Negative Breast Cancer Via Inhibiting PI3K/Akt/mTOR-Mediated Autophagy.

OBJECTIVE: Drug resistance in tumors is one of the major factors that leads to chemotherapy failure. This study aims to investigate the effect of Radix Tetrastigma extracts (RTEs) on Taxol-induced autophagy and the chemosensitivity against drug resistance in triple-negative breast cancer (TNBC). METHODS: Taxol-resistant MDA-MB-468 (MDA-MB-468/Taxol) cells were induced and treated with RTEs and/or Taxol. Mice were subcutaneously inoculated with MDA-MB- 468/Taxol cells to establish xenograft models. The associated protein levels were measured by western blotting. Flow cytometry, CCK-8 and EdU assay were performed to detect cell apoptosis, viability, and proliferation, respectively. RESULTS: In MDA-MB-468/Taxol cells, RTEs & Taxol treatment increased cell apoptosis, reduced cell viability and proliferation, up-regulated anti-autophagy marker LC3I/LC3II ratio, and enhanced mTOR level. With RTEs & Taxol treatment, mTOR silencing downregulated LC3I/LC3II ratio, increased cell viability and proliferation, and reduced cell apoptosis, while mTOR overexpression showed the opposite results. PI3K inhibitor reduced AKT and mTOR levels, and the effects on cell activities were similar to the results of mTOR silencing. After RTEs & Taxol injection, xenograft tumor was smaller, and AKT, mTOR, LC3I/LC3II ratio and apoptotic marker cleaved caspase-3 were increased. CONCLUSION: RTEs enhanced the chemosensitivity of resistant TNBC cells to Taxol through inhibiting PI3K/Akt/mTOR-mediated autophagy. MICRO: RTEs exerted anti-tumor effects in various cancers, and this study determined its role in TNBC. Taxol-resistant MDA-MB-468 cells were induced and xenograft models were established. We found that RTEs inhibited autophagy of MDA-MB-468/Taxol cells and reduced tumor growth. Inhibition of PI3K/Akt/mTOR pathway promoted autophagy of MDA-MB-468/Taxol cells. We may provide a new potential strategy for TNBC treatment.

The Curcumin Analog EF24 Inhibits Proliferation and Invasion of Triple-Negative Breast Cancer Cells by Targeting the Long Noncoding RNA HCG11/Sp1 Axis.

EF24, a curcumin analog, exerts a potent antitumor effect on various cancers. However, whether EF24 retards the progression of triple-negative breast cancer (TNBC) remains unclear. In this study, we explored the role of EF24 in TNBC and clarified the underlying mechanism. In a mouse model of TNBC xenograft, EF24 administration reduced the tumor volume, suppressed cell proliferation, promoted cell apoptosis, and downregulated long noncoding RNA human leukocyte antigen complex group 11 (HCG11) expression. In TNBC cell lines, EF24 administration reduced cell viability, suppressed cell invasion, and downregulated HCG11 expression. HCG11 overexpression reenhanced the proliferation and invasion of TNBC cell lines suppressed by EF24. The following mechanism research revealed that HCG11 overexpression elevated Sp1 transcription factor (Sp1) expression by reducing its ubiquitination, thereby enhanced Sp1-mediated cell survival and invasion in the TNBC cell line. Finally, the in vivo study showed that HCG11-overexpressed TNBC xenografts exhibited lower responsiveness in response to EF24 treatment. In conclusion, EF24 treatment reduced HCG11 expression, resulting in the degradation of Sp1 expression, thereby inhibiting the proliferation and invasion of TNBC cells.

Inhibition of DNA­PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC.

Lung cancer has the highest incidence and mortality rates among the malignant tumor types worldwide. Platinum­based chemotherapy is the main treatment for advanced non­small­cell lung cancer (NSCLC), and epidermal growth factor receptor­tyrosine kinase inhibitors (EGFR­TKIs) have greatly improved the survival of patients with EGFR­sensitive mutations. However, there is no standard therapy for treating patients who are EGFR­TKI resistant. Combining EGFR­TKIs and platinum­based chemotherapy is the most popular strategy in the clinical practice. However, the synergistic mechanism between EGFR­TKIs and platinum remains unknown. Therefore, the aim of the present study was to determine the synergistic mechanism of gefitinib (an EGFR­TKI) and cisplatin (a main platinum­based drug). MTT assay, apoptosis analysis, tumorsphere formation and an orthotropic xenograft mouse model were used to examine the combination effects of gefitinib and cisplatin on NSCLC. Co­immunoprecipitation and immunofluorescence were used to identify the underlying mechanism. It was found that gefitinib could selectively inhibit EGFR from entering the nucleus, decrease DNA­PK activity and enhance the cytotoxicity of cisplatin on NSCLC. Collectively, the results suggested that inhibition of DNA­dependent protein kinase by gefitinib may be due to the synergistic mechanism between gefitinib and cisplatin. Thus, the present study provides a novel insight into potential biomarkers for the selection of combination therapy of gefitinib and cisplatin.

Bioinformatics analysis of prognosis-related long non-coding RNAs in invasive breast carcinoma.

Breast cancer is one of the most common types of cancer among women worldwide and needs more sensitive prognostic biomarkers to improve its treatment. In the present study, differentially expressed long non-coding RNAs (lncRNAs) in invasive breast carcinoma from The Cancer Genome Atlas and cBioPortal database were investigated, identifying 292 differentially expressed lncRNAs in 1,100 cases. By analyzing the overall survival rate, 10 lncRNAs were significantly correlated with poor prognosis. To explore the underlying molecular mechanisms of the 10 prognosis-related lncRNAs, bioinformatic methods were used to predict the potential target miRNAs, mRNAs and proteins, and to construct a lncRNA-miRNA-mRNA regulatory network and lncRNA-protein interaction network. Finally, the functions of the target genes and proteins were insvestigated using Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The results showed that these 10 lncRNAs could be novel prognostic markers for invasive breast carcinoma and the present study aimed to provide novel insight into the diagnosis and treatment of breast cancer.

Punicalagin inhibits the viability, migration, invasion, and EMT by regulating GOLPH3 in breast cancer cells.

Breast cancer (BC) is one of the most common malignancies worldwide. Punicalagin (PN), which is a type of polyphenol, has been reported to act as a tumor suppressor. This study aimed to investigate the effects of PN on cellular process in BC and its molecular mechanism. The effects of various doses of PN on cell viability, migration, and invasion capacities of MCF-7 and MDA-MB-231 cells were detected by CCK-8, wound-healing, and Transwell assays. Golgi phosphoprotein 3 (GOLPH3) was then transfected into the cells with or without PN treatment, and GPLPH3 expression level was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, and expressions of epithelial-mesenchymal transition (EMT)-related protein matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-Cadherin, and N-Cadherin were measured by Western blot. High dose of PN treatment (50 µM or higher) significantly inhibited viability, migration, and invasion of MCF-7 and MDA-MB-231 cells, while overexpressed GOLPH3 promoted cell viability, migration, and invasion, and partially reversed the effects of PN treatment on the BC cells. PN inhibited the expressions of GOLPH3, MMP-2, MMP-9, and N-Cadherin, and promoted E-Cadherin expression, while overexpression of GOLPH3 partly reversed above effects attributing to PN. Thus, PN suppresses cell viability and metastasis via regulating GOLPH3 in BC, which provides a possible therapeutic direction to the treatment of BC.

Development of an inflammation imaging tracer, 111In-DOTA-DAPTA, targeting chemokine receptor CCR5 and preliminary evaluation in an ApoE-/- atherosclerosis mouse model.

BACKGROUND: Chemokine receptor 5 (CCR5) plays an important role in atherosclerosis. Our objective was to develop a SPECT tracer targeting CCR5 for imaging plaque inflammation by radiolabeling D-Ala-peptide T-amide (DAPTA), a CCR5 antagonist, with 111In. METHODS: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated DAPTA (DOTA-DAPTA) was labeled with 111In. Cell uptake studies were conducted in U87-CD4-CCR5 and U87-MG cells. Biodistribution was determined in C57BL/6 mice. Autoradiography, en face and Oil Red O (ORO) imaging studies were performed in ApoE-/- mice. RESULTS: DOTA-DAPTA was radiolabeled with 111In with high radiochemical purity (> 98%) and specific activity (70 MBq·nmol). 111In-DOTA-DAPTA exhibited fast blood and renal clearance and high spleen uptake. The U87-CD4-CCR5 cells had significantly higher uptake in comparison to the U87-MG cells. The cell uptake was reduced by three times with DAPTA, indicating the receptor specificity of the uptake. Autoradiographic images showed significantly higher lesion uptake of 111In-DOTA-DAPTA in ApoE-/- mice than that in C57BL/6 mice. The tracer uptake in 4 month old ApoE-/- high fat diet (HFD) mice with blocking agent was twofold lower than the same mice without the blocking agent, demonstrating the specificity of the tracer for the CCR5 receptor. CONCLUSION: 111In-DOTA-DAPTA, specifically targeting chemokine receptor CCR5, is a potential SPECT agent for imaging inflammation in atherosclerosis.

[Effects of purified humic acid on the growth and nitrogen metabolism of cucumber seedlings under nitrogen stress.] / çº¯åŒ–è æ¤é ¸å¯¹æ°®èƒè¿«ä¸‹é»„ç“œå¹¼è‹—ç”Ÿé•¿å’Œæ°®ä»£è°¢çš„å½±å“.

To investigate the effects of purified humic acid (PHA) on the growth and nitrogen metabolism of cucumber under different levels of nitrogen stress and to explore the mechanism of PHA's alleviation on abiotic stress, we examined the effects of PHA on 'Xintaimici' cucumber growth and nitrogen metabolism under low nitrogen (1.0 mmol·L-1 NO3-) stress and high nitrogen (101 mmol·L-1 NO3-) stress in hydroponics compared with normal level (11 mmol·L-1 NO3-). The results showed that the growth of cucumber seedlings was inhibited under nitrogen stress treatments. Plant height, stem diameter, leaf area and dry matter accumulation under nitrogen stress were lower than that at normal nitrogen level. Dry matter accumulation under the normal nitrogen level and low nitrogen stress were significantly increased by PHA, but there was no significant difference under high nitrogen stress. The absorption of NO3- in cucumber seedlings was affected by PHA, showing increased nitrate content in cucumber seedlings under low nitrogen stress and decreased under high nitrogen stress. PHA significantly decreased ammonium content in roots and leaves under low and high nitrogen stress. Compared with normal level of nitrogen (CK), NR, GS, GOGAT, GDH activity in roots and leaves and NiR activity in roots significantly decreased under low and high nitrogen stress. PHA increased the activities of NR, NiR, GS, GOGAT, and GDH to different extents. PHA increased amino acid and soluble protein content in cucumber seedling roots and leaves. In summary, PHA addition alleviated the inhibitory effect of nitrogen stress on the growth of cucumber seedlings.

[Effects of sodium nitroprusside on growth and physiological characteristics of tomato seedlings under iron deficiency and NO3- stress]. / ç¡æ™®é’ å¯¹ç¼ºé“å’Œç¡é ¸ç›èƒè¿«ä¸‹ç•ªèŒ„å¹¼è‹—ç”Ÿé•¿åŠç”Ÿç†ç‰¹æ€§çš„å½±å“.

The solution culture method was used to study the effects of sodium nitroprusside (SNP) on plant growth, nutrient uptake and antioxidant enzyme activities of tomato seedlings under iron deficiency and NO3- stress. The results indicated that after 7 d of treatment, iron deficiency inhibited the tomato seedling growth, decreased chlorophyll (a and b) and carotenoid contents, and led to obvious chlorosis; iron deficiency also reduced the activity of SOD, POD and CAT, resulting in significant accumulation of MDA contents and higher electrolytic leakage; proline and soluble sugar contents were not significantly changed; contents of N, P, K, Ca, Mg and Fe in both leaves and roots of tomato seedlings were decreased under iron deficiency in varying degrees. The combined stress of NO3- stress and iron deficiency promoted the inhibition of plant growth, decreased chlorophyll (a and b), carotenoid contents and the activities of SOD, POD and CAT; electrolytic leakage MDA, proline and soluble sugar contents of N, P, Mg, Fe in both leaves and roots of tomato seedlings were much lower, but the contents of K and Ca were significantly increased. Compared to the treatment without SNP, adding 0.1 mmol·L-1 SNP could alleviate the growth inhibition of stressed tomato seedlings. Adding 0.1 mmol·L-1 SF (sodium ferrocyanide) also showed alleviating or promoting effect on some above indexes including the activity of SOD, POD and CAT to some degree, but the other physiological indexes were not significantly changed because iron was contained in SF.

Interferon-α reduces the gefitinib sensitivity of human non-small cell lung cancer.

AIM OF THE STUDY: Many studies have shown that interferon-α (IFN-α) enhances the antiproliferative effect of gefitinib in some solid tumours. We aimed to determine the effect of combining IFN-α with gefitinib in human non-small cell lung cancer (NSCLC) cell lines (A549, H1299, HCC827) with different EGFR and K-Ras gene statuses. MATERIAL AND METHODS: An MTT assay was used to assess cell proliferation. Apoptosis was detected by an Annexin V/propidium iodide assay using flow cytometry, and western blotting was used to determine the expression of epidermal growth factor receptor/phosphorylated epidermal growth factor receptor (EGFR/p-EGFR) and signal transducers and activators of transcription 3/phosphorylated signal transducers and activators of transcription 3 (STAT3/p-STAT3). RESULTS: There was an additive interaction when gefitinib was combined with IFN-α in all cell lines; however, there was antagonism when gefitinib followed IFN-α pretreatment in three cell lines. Notably, IFN-α pretreatment significantly reduced the gefitinib sensitivity of HCC827 cells. Surprisingly, while IFN-α inhibited STAT3 phosphorylation in cell lines, gefitinib could do so. CONCLUSIONS: The results might confirm the hypothesis that IFN-α induces gefitinib sensitivity of NSCLC, and IFN-α inhibits phosphorylation of STAT3, which may be dependent on EGFR signal activation playing a role in the reduction of gefitinib sensitivity after IFN-α treatment in NSCLC cell lines.

Positive association between CD44 gene rs13347 C>T polymorphism and risk of cancer in Asians: a systemic review and meta-analysis.

BACKGROUND: Cluster of differentiation 44 (CD44) is an important surface marker of cancer stem cells in a variety of tumors. A number of previous studies have been conducted to investigate the association between CD44 gene rs13347 C>T polymorphism and cancer risk in humans; nevertheless, the results remain controversial. We therefore performed this meta-analysis to confirm the role of this polymorphism in susceptibility to human cancer. MATERIALS AND METHODS: The studies published up to December 2015 were searched in PubMed, Web of Science, and China National Knowledge Infrastructure databases. Twelve eligible case-control studies were identified, involving a total of 6,982 cases and 7,430 controls. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated using a fixed or random-effect model to estimate the strength of the association. RESULTS: The results of the overall analyses indicated that CD44 gene rs13347 polymorphism was significantly associated with cancer risk in Asians (CT vs CC: OR =1.35, 95% CI =1.12-1.62; TT vs CC: OR =1.99, 95% CI =1.52-2.60; TT + CT vs CC: OR =1.41, 95% CI =1.16-1.71; and TT vs CC + CT: OR =1.74, 95% CI =1.41-2.14), especially in Chinese population (CT vs CC: OR =1.42, 95% CI =1.16-1.75; TT vs CC: OR =2.13, 95% CI =1.58-2.86; TT + CT vs CC: OR =1.50, 95% CI =1.21-1.87; and TT vs CC + CT: OR =1.80, 95% CI =1.43-2.26). In stratified analyses by cancer types, there was evidence for an association between this polymorphism and nasopharyngeal cancer and breast cancer, respectively. CONCLUSION: The results of this meta-analysis suggest that the CD44 gene rs13347 C>T polymorphism is associated with elevated risk of human cancer in Asians, especially in Chinese population. Further well-designed studies on a larger population covering other ethnicities should be carried out to validate our results.

[Effects of purified humic acid on growth and nutrient absorption of cucumber (Cucumis sativus)seedlings under low nitrogen stress.] / çº¯åŒ–è æ¤é ¸å¯¹ä½Žæ°®èƒè¿«ä¸‹é»„ç“œå¹¼è‹—ç”Ÿé•¿åŠå »åˆ†å¸æ”¶çš„å½±å“.

Taking 'Xintaimici' and 'Jinyou 1' as experimental cucumber cultivars, this paper studied the effects of watering purified humic acid (PHA) at different levels (0, 50, 100, 150, 200 mg·L-1) on growth and nutrient absorption of cucumber seedlings under low nitrogen stress (1 mmol·L-1 NO3-) in sand culture pots. The results showed that, under low N condition, PHA could significantly increase the total root length, root surface area, root tip number and root volume of cucumber seedlings, and promote plant height, stem diameter and leaf area. Proline and soluble sugar contents in cucumber leaves were significantly increased by PHA. The absorption of N, P, K, Ca, Mg, Fe in cucumber seedlings was promoted. According to the response of the two cucumber cultivars to PHA under low N stress, some traits of two cultivars showed different sensitivity to PHA level. The comprehensive analysis of the above results inferred that the PHA level from 100 mg·L-1 to 150 mg·L-1 could significantly enhance the growth and nutrient absorption of cucumber seedlings.

Laparoscopic surgery contributes more to nutritional and immunologic recovery than fast-track care in colorectal cancer.

BACKGROUND: Many clinical trials had repeatedly shown that fast-track perioperative care and laparoscopic surgery are both preferred in the treatment of colorectal cancer. But few studies were designed to explore the diverse biochemical impacts of the two counterparts on human immunologic and nutritional status. METHODS: Ninety-two cases of colorectal cancer patients meeting the inclusion criteria were randomized to four groups: laparoscopy with fast-track treatment (LAFT); open surgery with fast-track treatment (OSFT); laparoscopy with conventional treatment (LAC); open surgery with conventional treatment (OSC). Peripheral blood tests including nutritional factors (albumin, prealbumin, and transferrin), humoral immunologic factors (IgG, IgM, and IgA), and cellular immunologic factors (T and NK cells) were evaluated. Blood samples were collected preoperatively (baseline) and 12 and 96 h after surgery (indicated as POH12 and POH96, respectively). RESULTS: Albumin, transferrin, prealbumin, and IgG levels were the highest in the LAFT group for both POH12 and POH96 time intervals. Repeated measures (two-way ANOVA) indicated that the difference of albumin, transferrin, and IgG level were attributed to surgery type (P < 0.05) and not perioperative treatment (P > 0.05). Only in the laparoscopy-included groups, the relative albumin and IgG levels of POH96 were obviously higher than that of POH12. CONCLUSION: Laparoscopic surgery accelerated postoperative nutrition and immune levels rising again while fast-track treatment retarded the drop of postoperative nutrition and immune levels. Laparoscopic surgery might play a more important role than fast-track treatment in the earlier postoperative recovery of nutritional and immunologic status. Combined laparoscopic surgery with fast-track treatment provided best postoperative recovery of nutrition and immune status. These results should be further compared with the clinical outcomes of our FTMDT trial (clinicaltrials.gov: NCT01080547).

Association between interleukin-4 gene intron 3 VNTR polymorphism and cancer risk.

BACKGROUND: Interleukin-4(IL-4) is a critical inflammatory cytokine and has been involved in pathogenesis of cancer. To date, several studies have investigated the association between IL-4 intron 3 variable number of tandem repeats (VNTR) polymorphism and cancer risk in humans; however, the results remain controversial. We performed this meta-analysis to find a more conclusive association between this polymorphism and cancer risk. METHODS: Eight eligible case-control studies were identified through searching electronic databases, including 1583 cases and 1638 controls. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS: The results of overall analyses indicated that the variant RP2 allele was associated with a decreased cancer risk compared with the RP1 allele (RP2/RP2 vs. RP1/RP1, OR = 0.64, 95% CI = 0.44-0.94; RP2/RP2 vs. RP1/RP1 + RP1/RP2, OR = 0.75, 95% CI = 0.60-0.92; RP2 vs. RP1, OR = 0.72, 95% CI = 0.56-0.92). In subgroup analyses stratified by ethnicity, there was evidence in the Asian population for an association between this polymorphism and cancer risk (RP2/RP2 vs. RP1/RP1 + RP1/RP2, OR = 0.79, 95% CI = 0.63-0.99; RP2 vs. RP1, OR = 0.77, 95% CI = 0.61-0.97). CONCLUSIONS: IL-4 intron 3 VNTR polymorphism could influence the risk of human cancer. Due to the limitations of this meta-analysis, further well-designed and functional researches should be performed to validate our results.

Association between the interleukin-17A -197G>A (rs2275913) polymorphism and risk of digestive cancer.

Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13- 1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.

Combined degenerative and regenerative remodeling responses of the mandibular condyle to experimentally induced disordered occlusion.

INTRODUCTION: The purposes of this research were to investigate the long-term responses of mandibular condylar cartilage to experimentally induced disordered occlusion and to evaluate changes in the expression of the SDF-1/CXCR4 axis. METHODS: Experimentally induced disordered occlusions were created in 8-week-old female Sprague-Dawley rats by orthodontic methods. After 24 weeks, remodeling of the mandibular condylar cartilage was assessed by hematoxylin and eosin staining. Protein and mRNA expression of SDF-1, CXCR4, MMP9, IL6, OPG, and RANKL were investigated by means of immunohistochemical staining and real-time polymerase chain reaction. RESULTS: Obvious cartilage degenerative remodeling responses were observed; they appeared as uneven distributions of cellular disposition, loss of cartilage surface integrity, and cell-free areas. Regenerative responses presenting as thickening of the whole and the calcified cartilage layers in the experimental group were also observed. Compared with the age-matched controls, the protein and mRNA levels of SDF-1, CXCR4, MMP9, IL6, and OPG, but not RANKL, were increased in the experimental group (all, P <0.05). In addition, the mRNA level of RANKL/OPG showed a decreasing trend in the experimental group compared with the age-matched controls (P = 0.052). CONCLUSIONS: This study demonstrated that long-term experimentally induced disordered occlusion leads to a combined response in degeneration and regeneration of mandibular cartilage, accompanied by active interaction of the SDF-1/CXCR4 axis and local upregulation of MMP9, IL6, and OPG.

No significant association between p53 codon 72 Arg/Pro polymorphism and risk of oral cancer.

The genetic polymorphism of p53 codon 72 Arg/Pro has been implicated in oral cancer risk, but the results of previous studies remain controversial and ambiguous. To estimate the effect of the p53 codon 72 Arg/Pro polymorphism on the risk of oral cancer, a meta-analysis was performed. Based on a comprehensive search in PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases, we identified all available publications assessing the association between p53 codon 72 Arg/Pro polymorphism and oral cancer risk. The pooled odds ratio (OR) with its corresponding 95 % confidence interval (CI) was calculated to assess the association. Subgroup analyses by ethnicity and study quality were performed to further identify the correlation. Totally, 17 studies with 2,975 cases and 3,413 controls were included into this meta-analysis. There was no statistically significant association between the p53 codon 72 Arg/Pro polymorphism and oral cancer risk in all genetic contrast models (OR(Pro allele vs. Arg allele) = 1.05, 95 % CI 0.94-1.18, P(OR) = 0.379; OR(Pro/Pro vs. Arg/Arg) = 1.11, 95 % CI 0.89-1.40, P(OR) = 0.356; OR(Pro/Arg vs. Arg/Arg) = 1.10, 95 % CI 0.93-1.30, P(OR) = 0.256; OR(Pro/Arg + Pro/Pro vs. Arg/Arg) = 1.10, 95 % CI 0.93-1.31, P(OR) = 0.263; and OR(Pro/Pro vs. Arg/Arg + Pro/Arg) = 1.03, 95 % CI 0.90-1.18, P(OR) = 0.647). In the subgroup analysis of high-quality studies, we failed to find the susceptibility of p53 codon 72 Arg/Pro polymorphism to oral cancer. Moreover, the results were similar among Asians, Caucasians, and mixed populations when stratifying by ethnicity. Sensitivity analysis further confirmed the stability of the results. The present meta-analysis of currently available data shows no association between the p53 codon 72 Arg/Pro polymorphism and oral cancer risk.