Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new ...susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 × 10(-13)), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 × 10(-10)) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 × 10(-9)). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.
BACKGROUND: A lipid emulsion composed of soybean oil (long-chain triglycerides, LCT), medium-chain triglycerides (MCT) and n-3 poly-unsaturated fatty acids (PUFAs) was evaluated for immune-modulation ...efficacy, safety, and tolerance in patients undergoing major surgery for gastric and colorectal cancer. METHODS: In a prospective, randomized, double-blind study, 99 patients with gastric and colorectal cancer receiving elective surgery were recruited and randomly assigned to either the study group, receiving the n-3 PUFAs enriched intravenous fat emulsion (IVFE), or the control group, receiving a lipid emulsion comprised of soybean oil and MCTs (0.8 – 1.5 g · kg⁻¹ · day⁻¹) as part of total parenteral nutrition (TPN) regimen from surgery (day -1) up to post-operative day 7. Safety and efficacy parameters were assessed on day -1 and post-operative visits on day 1, 3, and 7. Adverse events were documented daily and compared between the groups. RESULTS: Pro-inflammatory markers, laboratory parameters, and adverse events did not differ prominently between the 2 groups, with the exception of net changes (day 7 minus day -1) of free fatty acids (FFAs), triglyceride, and high-density lipoprotein (HDL). Net decrease of FFAs was remarkably higher in the study group, while the net increase of triglyceride and decrease of HDL was significantly lower. CONCLUSIONS: The n-3 PUFA-enriched IVFE showed improvements in lipid metabolism. In respect of efficacy, safety and tolerance both IVFE were comparable. In patients with severe stress, there is an inflammation-attenuating effect of n-3 PUFAs. Further, adequately powered clinical trials will be necessary to address this question in postsurgical GI cancer patients. TRIAL REGISTRATION: US ClinicalTrials.gov NCT00798447 .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The prognosis of metastatic colorectal cancer (mCRC) depends on the metastatic site and systemic therapy regimen. Peritoneal metastases are associated with a relatively unfavorable prognosis among ...patients with mCRC. In this article, we present the treatment outcomes of patients with peritoneal carcinomatosis (PC)-only, liver metastasis (LiM)-only, and lung metastasis (LuM)-only CRC.
Overall, 206 mCRC patients with single-site metastasis and who had received treatment from January 2014 to December 2018 were recruited. Among 206 patients with mCRC, 15 had PC-only mCRC, 145 had LiM-only mCRC, and 46 had LuM-only mCRC. They attended regular follow-ups until November 2020, and the median follow-up period was 24.7 months (5.1-41.3 months). Patients' characteristics, including clinical data, gene mutation profiles, and clinical outcomes, were evaluated. All patients with PC-only CRC were treated with first-line bevacizumab and FOLFIRI, and the irinotecan dose escalation depended on
polymorphism.
Of the 206 patients, no statistical difference was observed between the PC-only, LiM-only, and LuM-only groups in terms of age, primary tumor location,
mutation status,
mutation status, and epidermal growth factor receptor overexpression (all
> 0.05). Patients with PC-only CRC had a median progression-free survival (mPFS) of 18.0 months and a median overall survival (mOS) of 24.6 months. Patients with LiM-only or LuM-only CRC had mPFS of 18.2 and 26.6 months and mOS of 25.0 and 44.5 months, respectively. No significant differences regarding PFS and OS (both
> 0.05) between the three groups of patients with mCRC were observed.
Our study revealed that in patients with PC-only mCRC treatment of first-line bevacizumab and FOLFIRI through irinotecan dose escalation according to
polymorphism could confer such patients with comparable outcomes to that of patients with LiM-only and LuM-only mCRC.
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•Our meta-analysis confirmed the positive correlation between DED and DEP.•The genetic architecture similarity between DED-DEP was 0.19 in TW biobank and 0.109 in UK ...biobank.•Transcriptome study underlined immune activation at the transaction of DED-DEP concurrence.•Bi-direction DED-to-DEP and DEP-to-DED disease Causation was detected by IVW-MR analysis.•Disease causation inference remains valid after COJO selected LD-free IVSNPs for MR experiments.
The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined.
To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study GWAS and Mendelian randomization MR) to elucidate the association, common pathways and causality between DED and DEP.
A meta-analysis comprising 26 case−control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP.
Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (rG = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein−protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained.
With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.
Ultraviolet A light (UV-A, 320–400 nm), which is unblockable by sunscreen, requires careful detection for disease avoidance. In this study, we propose a novel photosensing device capable of detecting ...UV-A. Cancer-causing UV light can be simultaneously monitored with tiny rapid response sensors for a high carrier transition speed. In our research, a multifunctional ZnO/ZnS nanomaterial hybrid-sprinkled carbon nanotube (CNT) was created for the purpose of fabricating a multipurpose, semiconductorbased application. For our research, ZnO nanorods (NRs) were grown by using a facile hydrothermal method on SiO2 substrate, then vulcanized to form ZnO/ZnS coreshell nanorods, which were sprinkled with carbon nanotubes (CNTs). Results indicate that SiO2/ZnO/ZnS/CNT structures exhibited a stronger conducting current with and without light than those samples without CNTs. Multiple material characterizations of the nanostructures, including of atomic force microscopy (AFM) surface morphology evaluation, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) indicate that CNTs could be successfully spread on top of the ZnO/ZnS coreshell structures. Furthermore, chemical binding properties, material crystallinity, and optical properties were examined by X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), and photoluminescence (PL). Owing to their compact size, simple fabrication, and low cost, ZnO/ZnS coreshell NRs/CNT/SiO2-based nanocomposites are promising for future industrial optoelectronic applications.
Methamphetamine (Meth) is one of the most frequently abused drugs worldwide. Recent studies have indicated that antibodies with high affinity for Meth reduce its pharmacological effects. The purpose ...of this study was to develop a technique for virus-based passive immunization against Meth effects. We generated a recombinant adeno-associated virus serotype-8 vector (AAV-MethAb) carrying the gene for a Meth-specific monoclonal antibody (MethAb). Infection of 293 cells with AAV-MethAb resulted in the expression and secretion of antibodies which bind to Meth. The viral vector was then examined in adult ICR mice. Systemic administration of AAV-MethAb resulted in long-term expression of MethAb in the serum for up to 29 weeks. Serum collected from the animals receiving AAV-MethAb retained a high specificity for (+)-Meth. Animals were challenged with Meth five weeks after viral injection. Meth levels in the brain and serum were reduced while Meth-induced locomotor activity was significantly attenuated. In conclusion, AAV-MethAb administration effectively depletes Meth from brain and serum while reducing the behavioral response to Meth, and thus is a potential therapeutic approach for Meth abuse.
Background: Evidence suggests that major depressive disorder is related to neuroaxonal injury and that neuroflament light chain (NfL) is a biomarker of neuroaxonal injury. In addition, ...proinflammatory cytokines have been reported to be associated with major depression and neuroaxonal injury. Methods: Forty patients with major depression and 40 age- and sex-matched healthy control participants were enrolled for the measurement of NfL and proinflammatory cytokines and assessment of executive function. General linear models were used to examine the association between NfL levels, proinflammatory cytokine levels, and executive function. Results: Patients with major depressive disorder exhibited significantly higher NfL levels (P = .007) than the control participants. NfL levels were positively related to log-transformed levels of tumor necrosis factor-alpha (P = .004). Higher levels of NfL (P = .002) and tumor necrosis factor-alpha (P = .013) were associated with greater deficits in executive function. Discussion: NfL was a novel biomarker for major depressive disorder and related executive dysfunction. Further studies are necessary to elucidate the role of NfL in the pathophysiology of major depression and related cognitive impairment. Keywords: Cognitive function, major depressive disorder, neuroflament light chain, proinflammatory cytokines
A novel dengue vaccine candidate comprised of a consensus dengue virus envelope protein domain III (cED III) was developed to fight against dengue virus infection. The amino acid sequence of this ...novel cED III was obtained by alignment of amino acid sequences from different isolates of the four serotypes of dengue viruses. A proof-of-concept study demonstrated that BALB/c mice immunized with the recombinant cED III developed neutralizing antibodies against all serotypes of dengue virus. Moreover, formulation of recombinant cED III with aluminum phosphate could induce long-lasting antibody responses and anamnestic neutralizing antibody responses following challenge with dengue virus at week 28 after priming. These results demonstrate the possibility of developing a single tetravalent vaccine against dengue viral infections.
With the recent development of molecular markers, strategies for identifying patients with colorectal cancer (CRC) having a high risk of postoperative early relapse (within 1 y) and relapse have been ...improved. We previously constructed a multigene biochip with 19 candidate genes. The objective of the present study was to optimize a multigene biochip for detecting the risk of postoperative early relapse and relapse in patients with CRC.
We included 357 patients with stage I-III CRC who underwent curative resection at a single institution between June 2010 and May 2015. During each follow-up, a postoperative surveillance strategy including the National Comprehensive Cancer Network recommendations and a multigene biochip was used. A statistical algorithm was developed to select candidate biomarkers for an optimal combination.
After a 30.9-mo median follow-up, 67 patients (18.8%) had postoperative relapse, of whom 25 (7.0%) relapsed within 1 y after operation and accounted for 37.3% of all relapsed patients. Of the 19 circulating biomarkers, ELAVL4, PTTG1, BIRC5, PDE6D, CHRNB1, MMP13, and PSG2, which presented significant predictive validity, were selected for combination. The expression of the seven-biomarker biochip resulted in area under the receiver operating characteristic curve values of 0.854 (95% confidence interval: 0.756-0.952) for early relapse and 0.884 (95% confidence interval: 0.830-0.939) for relapse. Moreover, the sensitivity, specificity, and predictive accuracy levels were 84.0%, 83.1%, and 83.2% for early relapse and 76.1%, 91.0%, and 88.2% for relapse (P = 0.415, 0.006, and 0.054, respectively). The median lead times before the detection of postoperative early relapse and relapse were 3.8 and 10.4 mo, respectively.
From 19 circulating biomarkers, we optimized seven contemporary circulating biomarkers. The prediction model used for the early and accurate identification of Taiwanese patients with CRC having a high risk of postoperative early relapse and relapse seems to be feasible and comparable.
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