Randomized study of the effects of empagliflozin and topiramate dual therapy on anthropometric and metabolic indices in non-diabetic individuals with overweight/obesity on a calorie-restricted diet.

OBJECTIVES: The objective of this study was to evaluate the effectiveness of the combined use of empagliflozin (EMPA) and topiramate (TPM) versus a placebo in overweight/obese individuals without diabetes on a calorie-restricted diet. METHODS: In this study, 44 non-diabetic and overweight/obese subjects who were on a calorie restricted diet were randomly assigned into 2 groups: (1) Participants received a 10 mg EMPA tablet daily plus TPM tablet (at the 1st week 25 mg once a day and from the second week 25 mg twice a day); (2) Participants received an empagliflozin placebo (daily) plus a topiramate placebo (as mentioned for topiramate tablet in group 1), for 12 weeks. At baseline and weeks 4, 8, 12, weight, height, body mass index (BMI), waist circumference (WC), and body composition were evaluated. Before and after the intervention, blood pressure, C reactive protein, and glucose and lipid profile parameters were measured. RESULTS: The EMPA/TPM group, compared to placebo, had a greater percent change of weight at week 12 (- 8.92 ± 1.80 vs. - 4.93 ± 1.17). The intervention group had a greater percent change of fat mass and fat percent at week 12 (P < 0.05). However, there was no difference in the percent of change in fat-free percent between the two groups at week 12 (P = 0.577). Within-group analysis found a significant reduction in SBP, DBP, FBS, insulin, HOMA-IR, TC, LDL, HDL, TG, and CRP in both groups (P < 0.05). At week 12, no statistically significant difference was observed between the two groups in any of mentioned variables (P > 0.05). CONCLUSION: In non-diabetic overweight/obese individuals, the combination of EMPA/TPM and calorie restriction led to a notable decrease in body weight and was generally well-tolerated. Further research is required to evaluate the potential advantages of utilizing this combination for sustained weight management in the long run. LEVEL I: Randomized clinical trial.

Mediterranean diet enriched with olive oil shows no consistent benefits on cardiometabolic and anthropometric parameters: a systematic review with meta-analysis of randomized controlled trials.

PURPOSE: Cardiovascular disease (CVD) is the primary cause of death worldwide but there is a variation in its burden across some nations that seems to be related to dietary habits. Mediterranean populations have lower rates of morbidity and mortality from CVD. Thus, this systematic review and meta-analysis aimed to assess the impacts of the Mediterranean diet (MedDiet) enriched with olive oil on blood lipids, glycemic indices, blood pressure, and anthropometric indices. METHODS: A comprehensive search of the Web of Science, PubMed (MEDLINE), Scopus, Cochrane Library, Google Scholar, Embase, and CINAHL databases until March 2024 was conducted to identify clinical trials studying the effects of MedDiet enriched with olive oil on the aforementioned parameters. RESULTS: In total, 3303 records were retrieved. A total of 18 clinical trials met the inclusion criteria after records were screened for eligibility. According to the pooled analysis from the random-effects model, the MedDiet enriched with olive oil significantly reduced triglycerides (TG) compared with the control group (WMD = -2.40 mg/dl; 95%CI, -4.533 to -0.262; P = 0.027). Strong heterogeneity was observed. Sensitivity analysis did not change our results and no significant effect of any trial on the overall effect sizes of all variables were found. There was a concern about the reporting bias for some studies which reported some main outcomes. CONCLUSION: MedDiet enriched with olive oil showed no consistent effects on any of the reported markers of cardiovascular health except on TG. SYSTEMATIC REVIEW REGISTRATION: CRD42023424641.

Evaluation of potential alterations related to ADHD in the effective connectivity between the default mode network and cerebellum, hippocampus, thalamus, and primary visual cortex.

Hyperactivity in children with attention-deficit/hyperactivity disorder (ADHD) leads to restlessness and impulse-control impairments. Nevertheless, the relation between ADHD symptoms and brain regions interactions remains unclear. We focused on dynamic causal modeling to study the effective connectivity in a fully connected network comprised of four regions of the default mode network (DMN) (linked to response control behaviors) and four other regions with previously-reported structural alterations due to ADHD. Then, via the parametric empirical Bayes analysis, the most significant connections, with the highest correlation to the covariates ADHD/control, age, and sex were extracted. Our results demonstrated a positive correlation between ADHD and effective connectivity between the right cerebellum and three DMN nodes (intrinsically inhibitory connections). Therefore, an increase in the effective connectivity leads to more inhibition imposition from the right cerebellum to DMN that reduces this network activation. The lower DMN activity makes leaving the resting-state easier, which may be involved in the restlessness symptom. Furthermore, our results indicated a negative correlation between age and these connections. We showed that the difference between the average of effective connectivities of ADHD and control groups in the age-range of 7-11 years disappeared after 14 years-old. Therefore, aging tends to alleviate ADHD-specific symptoms.

Green-synthesized copper oxide nanoparticles induce apoptosis and up-regulate HOTAIR and HOTTIP in pancreatic cancer cells.

Aim: Cu2O nanoparticles were synthesized using an extract from S. latifolium algae (SLCu2O NPs). Their effect on PANC-1 cells and the expression of two drug resistance-related lncRNAs were evaluated in comparison with Arsenic trioxide.Materials & methods: SLCu2O NPs were characterized using XRD, SEM, and TEM microscopies. The effects of SLCu2O NPs on cell cytotoxicity, cell cycle, and apoptosis, and expression of two drug resistance-related lncRNAs were examined using MTT assay, flow cytometry, and real-time PCR, respectively.Results: SLCu2O NPs demonstrated anti-cancer properties against PANC-1 cells comparable to Arsenic trioxide, and the expression of lncRNAs increased upon treatment with them.Conclusion: SLCu2O NPs demonstrate anti-cancer properties against PANC-1 cells; however, using gene silencing strategies along with SLCu2O NPs is suggested.

[Box: see text].

Correction to "A Comprehensive Review of Biological Roles and Interactions of Cullin-5 Protein".

[This corrects the article DOI: 10.1021/acsomega.1c06890.].

Diagnostic Accuracy of the Desmopressin Stimulation Test in the Comprehensive Assessment of ACTH-Dependent Cushing's Syndrome: A Comparative Analysis with BIPSS and TSS.

BACKGROUND: Cushing's syndrome (CS) poses diagnostic challenges, particularly in distinguishing pituitary-dependent Cushing's syndrome, Cushing's disease (CD), from the ectopic ACTH syndrome (EAS). This study evaluated the diagnostic value of the desmopressin stimulation test (DST) in patients with ACTH-dependent CS in helping this discrimination. METHODS: Twenty-three ACTH-dependent CS patients underwent sequential DST, bilateral inferior petrosal sinus sampling (BIPSS), and transsphenoidal surgery (TSS). Two definitions of a positive DST results were applied. Diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios. To avoid bias from predetermined criteria, we generated univariate receiver-operating characteristic (ROC) curves, plotting sensitivity against 1-specificity at various percentage cortisol and ACTH response levels. RESULTS: Against BIPSS, DST demonstrated robust sensitivity (Definition 1: 90.0%, Definition 2: 76.2%) and overall accuracy (Definition 1: 87.0%, Definition 2: 73.9%). PPV was high (Definition 1: 95.0%, Definition 2: 94.1%), but NPV indicated potential false negatives. Compared to TSS, DST showed good sensitivity (Definition 1: 90.9-77.3%) and PPV (100.0%) but limited NPV (16.7%). The likelihood ratios emphasized the diagnostic value of the test. Notably, against TSS, DST showed perfect discriminatory power (AUC 1.000 for percent ACTH, 0.983 for percent cortisol). CONCLUSION: The desmopressin test shows promise in accurately identifying the underlying cause of ACTH-dependent CS, potentially reducing the reliance on invasive procedures and providing a practical solution for managing complex cases. Further research with larger cohorts is required to validate the utility of the DST in routine clinical practice.

The association between dietary inflammatory index with some cardio-metabolic risk indices among the patients with type 2 diabetes from Hoveyzeh cohort study: a cross-sectional study.

BACKGROUND: The dietary inflammatory index (DII) serves as a tool to assess the inflammatory impact of an individual's diet. This study aimed to investigate the association between DII and some cardio-metabolic risk indices among patients with T2DM. METHODS: Data from the Hoveyzeh Cohort Study, encompassing 2045 adults with T2DM, were analyzed. DII scores were calculated based on food frequency questionnaires. Anthropometric measurements and biochemical tests were performed to assess cardio-metabolic risk factors. RESULTS: Higher DII scores were positively associated with elevated triglyceride levels, triglyceride-glucose (TyG) index, lipid accumulation product (LAP), anthropometric indices including a body shape index (ABSI), body roundness index (BRI), body mass index (BMI), hip, waist circumferences (WC), and waist-to-height ratio (all Ptrend < 0.05). Notably, no significant association was observed between DII and fasting blood sugar (FBS) levels (Ptrend > 0.05). Additionally, dietary intake analysis revealed a negative correlation between DII scores and intake of fiber, fruits, vegetables, legumes, fish, seafood, dairy products, magnesium, and vitamins A, C, D, and E (all Ptrend < 0.05). Conversely, higher DII scores were associated with increased consumption of red meat, processed meat, refined cereals, potatoes, and soft drinks (all Ptrend < 0.05). CONCLUSION: This study underscores the critical link between dietary inflammation, assessed by the DII score, and a multitude of cardio-metabolic risk factors in patients with T2DM. Notably, while the study did not find a significant association between DII and fasting blood sugar levels, it identified robust associations with novel anthropometric and biochemical indices indicative of cardio-metabolic risk. These findings highlight the potential of dietary interventions as a cornerstone strategy for managing T2DM and mitigating its associated complications.

Obesity and thyroid cancer: unraveling the connection through a systematic review and meta-analysis of cohort studies.

Background: The relationship between adiposity indicators and thyroid cancer (TC) risk has garnered increasing attention due to the rising prevalence of obesity and its potential impact on cancer incidence. We conducted a comprehensive meta-analysis to investigate this association across various effect measures. Method: Until July 2022, a comprehensive search of databases was conducted to identify cohort studies that assessed the association between adiposity and the development of TC. Meta-analysis was performed using random effects models. Subgroup analyses were conducted to explore heterogeneity. Publication bias was assessed using Begg's tests. Results: A systematic literature search identified 27 eligible studies reporting odds ratios (OR), relative risks (RR), or hazard ratios (HR) as effect measures. Pooling the studies irrespective of the effect measure, a significant positive association between adiposity indicators and TC risk was observed, yielding an effect estimate of 1.16 (95% CI 1.12-1.21). The combined effect estimate for OR/RR studies was 1.10 (95%CI 1.04-1.17), while HR studies yielded an effect estimate of 1.20 (95%CI 1.13-1.26). Subgroup analyses revealed associations across different age groups, obesity indices, and regions, with some variations based on effect measure. Meta-regression identified follow-up duration as a confounding factor only in HR studies. Conclusion: The synthesis of 27 studies with diverse designs and populations underscores a robust positive association between adiposity and TC risk, providing compelling evidence for the potential role of increased adiposity in TC development. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01425-3.

Corrigendum: The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: focus on the role of oxidative stress.

[This corrects the article DOI: 10.3389/fphar.2022.1015835.].

Association of vitamin D levels with anthropometric and adiposity indicators across all age groups: a systematic review of epidemiologic studies.

Objectives: It has not been established whether vitamin D deficiency is associated with anthropometric state; therefore, this systematic review examined the relationship between serum vitamin D levels with anthropometrics and adiposity across different ages. Methods: Studies that examined vitamin D deficiency with adiposity measures in different age groups were searched in the PubMed, Scopus, Embase, and Google Scholar databases until November 2023. Two investigators independently reviewed titles and abstracts, examined full-text articles, extracted data, and rated the quality in accordance with the Newcastle-Ottawa criteria. Results: Seventy-two studies, with a total of 59,430 subjects, were included. Of these studies, 27 cross-sectional studies and one longitudinal study (with 25,615 participants) evaluated the possible link between 25(OH)D serum concentrations and anthropometric/adiposity indices in the pediatric population. Forty-two cross-sectional studies and two cohort investigations (with 33,815 participants) investigated the relationship between serum 25(OH)D levels and adiposity measures in adults and/or the elderly population. There is evidence supporting links between vitamin D deficiency and obesity, and revealed an inverse association between vitamin D and adiposity indicators, specifically in female subjects. However, the effects of several confounding factors should also be considered. Conclusion: Most published studies, most of which were cross-sectional, reported a negative association between vitamin D and female adiposity indicators. Therefore, serum vitamin D levels should be monitored in overweight/obese individuals.

Investigating the effect of combined use of selenium and Myo-inositol supplements on thyroid function and autoimmune characteristics in thyroid disorders: a systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically review the effect of selenium and inositol combination on thyroid function, autoimmune characteristics in thyroid diseases. RESEARCH DESIGN AND METHODS: To identify eligible studies, a systematic search was conducted in the PubMed/MEDLINE, Science-Direct, CINHAL, EMBASE, SCOPUS, Psychinfo, Cochrane, ProQuest, and Web of Science were searched using the main concepts, and all English-written articles that were published between 2007 and 2022 and had an available full text were examined. RESULTS: The data analysis of this research revealed that after the simultaneous use of selenium and inositol supplements, the level of Triiodothyronine(T3) increased by 0.105 in patients with thyroid disorders although this increase was not significant (P-value: 0.228). The level of Thyroxine (T4) significantly increased by 0.06 (P-value: 0.04). Anti-Thyroid Peroxidase Antibody (TPOAb) titer decreased by 119.36%, which was not significant (P-value: 0.070). Finally, the level of Thyroid-stimulating hormone (TSH) decreased by 1.45%, which was a significant change (P-value: 0.001). CONCLUSION: It was observed that simultaneous use of selenium and inositol supplements did not change the T3 and TPOAb titer levels; however, it leads to a decrease in TSH and increase in T4 levels. Further studies are required due to the limited number of studies.

Harnessing the Power of CAR-NK Cells: A Promising Off-the-Shelf Therapeutic Strategy for CD38-Positive Malignancies.

Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia. Objective: We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies. Methods: A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated. Results: Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner. Conclusion: The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.

A narrative review on the role of hesperidin on metabolic parameters, liver enzymes, and inflammatory markers in nonalcoholic fatty liver disease.

Insulin resistance, oxidative stress, hyperlipidemia, and inflammation play main roles in the development of nonalcoholic fatty liver disease (NAFLD). Some studies have reported that hesperidin can reduce hyperglycemia and hyperlipidemia by inhibiting inflammatory pathways. In the current study, our purpose was to evaluate whether it can influence the primary parameters in NAFLD and improve the treatment effectiveness for future trials. Various studies have found that hesperidin involves multiple signaling pathways such as cell proliferation, lipid and glucose metabolism, insulin resistance, oxidative stress, and inflammation, which can potentially affect NAFLD development and prognosis. Recent findings indicate that hesperidin also regulates key enzymes and may affect the severity of liver fibrosis. Hesperidin inhibits reactive oxygen species production that potentially interferes with the activation of transcription factors like nuclear factor-κB. Appropriate adherence to hesperidin may be a promising approach to modulate inflammatory pathways, metabolic indices, hepatic steatosis, and liver injury.

Impact of omega-3 fatty acids supplementation on the gene expression of peroxisome proliferator activated receptors-γ, α and fibroblast growth factor-21 serum levels in patients with various presentation of metabolic conditions: a GRADE assessed systematic review and dose-response meta-analysis of clinical trials.

There is some debate about the effects of omega-3 fatty acids on the regulation of adipose tissue related genes. This systematic review and meta-analysis aimed to evaluate the effects of omega-3 fatty acids supplementation on the gene expression of peroxisome proliferator activated receptors (PPAR-α and PPAR-γ) and serum fibroblast growth factor-21 (FGF-21) levels in adults with different presentation of metabolic conditions. To identify eligible studies, a systematic search was conducted in the Cochrane Library of clinical trials, Medline, Scopus, ISI Web of Science, and Google Scholar up to April 2022. Eligibility criteria included a clinical trial design, omega-3 fatty acids supplementation in adults, and reporting of at least one of the study outcomes. Effect sizes were synthesized using either fixed or random methods based on the level of heterogeneity. Fifteen studies met the inclusion criteria. Omega-3 fatty acids supplementation significantly increased the PPAR-γ (10 studies) and PPAR-α (2 studies) gene expression compared to the control group (WMD: 0.24; 95% CI: 0.12, 0.35; p < 0.001 and 0.09; 95% CI: 0.04, 0.13; p < 0.001, respectively). Serum FGF-21 (8 studies) levels exhibited no significant change following omega-3 fatty acids supplementation (p = 0.542). However, a dose-response relationship emerged between the dose of omega-3 fatty acids and both PPAR-γ gene expression and serum FGF-21 levels. Overall, this study suggests that omega-3 fatty acids supplementation may have positive effects on the regulation of adipose tissue related genes in patients with various presentation of metabolic condition. Further research is needed to validate these findings and ascertain the effectiveness of this supplementation approach in this population. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, CRD42022338344.

Prevalence of overweight and obesity among Iranian population: a systematic review and meta-analysis.

BACKGROUND: Obesity is a major risk factor for chronic diseases. Politicians and practitioners should be aware of the dramatic increase in obesity and its subsequent complications to prevent associated health risks. This systematic review aimed to provide better insight into the prevalence of overweight and obesity in the Iranian population. METHOD: An evaluation was conducted on all published observational studies from both national (SID, Irandoc, Iranmedex) and international (Web of Knowledge, PubMed, Scopus) sources, which reported the prevalence of overweight/obesity among normal population samples, between January 2012 and December 2021. RESULT: A total of 152 eligible studies were included in this meta-analysis. Of the 152 selected studies, 74 reported the prevalence of overweight/obesity in patients aged ≤ 18 years, and 61 studies in adults. In the rest of the articles (17 studies), the results were reported for a combination of these age groups. The prevalence of overweight and obesity in Iran was estimated at 20.1 (95% CI 17.92-22.30) and 13.44 (95% CI 11.76-15.22), respectively. This percentage (95% CI) was 11.71 (10.98-12.46) for overweight and 8.08 (7.02-9.22) for obesity in those aged ≤ 18 years, and 35.26 (32.61-37.99) for overweight and 21.38 (19.61-23.20) for obesity in those aged > 18 years. The overall prevalence of overweight and obesity in the entire population was 35.09% (95% CI 31.31-38.98). CONCLUSION: As obesity is on the rise in Iran, we should seek both weight loss strategies and ways to control comorbidities associated with high BMI.

The association of dietary phytochemical index and nonalcoholic fatty liver disease.

Consumption of phytochemical-rich foods relates to the prevention of chronic diseases. In this study we assessed the dietary phytochemical index (PI) in metabolic parameters, liver enzymes, and severity of fibrosis among nonalcoholic fatty liver disease patients. This cross-sectional study was conducted on 210 patients with NAFLD. Fibrosis-4 index (FLB4), nonalcoholic fatty liver disease fibrosis score (NFS), FBS, lipids profile, AST, ALT, ALP, and GGT were measured. PI was calculated through the information obtained from a validated semi-quantitative food frequency. Multiple regression models were used to estimate mean difference changes in the evaluated variables associated with various dietary PI. Participants' mean ± SD of age and BMI were 39.23 ± 10.52 and 24.40 ± 2.64, respectively. We found that DPI is inversely associated with serum TG, TC, and LDL-C and directly associated with serum HDL-C and a higher score in DPI is associated with lower scores in NFS and FIB-4. Multivariate linear regression showed that there is an inverse association between DPI and AST, ALT, ALP, GGT, NFS, and FIB-4. Higher dietary PI could impact on reduction of NAFLD progression and improvement of metabolic parameters.

Association between thyroid function and obesity phenotypes in healthy euthyroid individuals: an investigation based on Tehran Thyroid Study.

AIMS: We investigated whether thyroid function could be associated with obesity phenotypes amongst euthyroid individuals. MATERIALS AND METHODS: A cross-sectional analysis was conducted among healthy, euthyroid subjects. The study participants were chosen from the Tehran Thyroid Study (TTS). We analyzed 2988 euthyroid adults and classified them into four obesity phenotype groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). The statistical differences between thyroid hormones between various obesity phenotypes according to age and sex was compared using analysis of covariance (ANCOVA). RESULTS: It was found that MHNW participants had higher levels of FT4 when compared with metabolically healthy or unhealthy obese subjects (P < 0.001), even after adjustment for the confounding variables. No difference was observed in the levels of TSH (P = 0.260) among obesity phenotypes. In the subgroup analysis according to the age, a significant difference was observed in the level of FT4 only in subjects with age < 55 years (P = 0.001). However, analyzing men and women separately did not show a significant difference in the FT4 level among obesity phenotypes (P > 0.05). CONCLUSION: "Metabolically abnormality" was independently related to low normal FT4 levels in overweight/obese euthyroid individuals. There is a need for further research to understand how low FT4 levels are linked to metabolically unhealthy states in euthyroid individuals.

Does one-anastomosis gastric bypass provide better outcomes than sleeve gastrectomy in patients with BMI greater than 50? A systematic review and meta-analysis.

In patients with BMI greater than 50, sleeve gastrectomy (SG) may not be adequate to treat obesity. To determine whether one-anastomosis gastric bypass (OAGB) can provide better outcomes compared with SG in patients with BMI greater than 50, a systematic review and meta-analysis was conducted, including a total of nine retrospective studies with a total of 2332 participants. There was a significant difference in the percentage of excess weight loss [weighted mean difference (WMD): 8.52; 95% CI: 5.81-11.22; P<0.001) and percentage of total weight loss (WMD: 6.65; 95% CI: 5.05-8.24; P<0.001). No significant differences were seen in operative time (WMD: 1.91; 95% CI: -11.24 to 15.07; P=0.77) and length of stay in hospital (WMD: -0.41; 95% CI: -1.18 to 0.37; P=0.30) between the two groups. There were no significant differences between OAGB with SG in Clavien-Dindo grades I-III [odds ratio (OR): 1.56; 95% CI: 0.80-3.05], or grade IV complications (OR: 0.72; 95% CI: 0.18-2.94). The meta-analysis on remission of type 2 diabetes indicated a comparable effect between SG and OAGB (OR: 0.77; 95% CI: 0.28-2.16). The OAGB group had a significantly higher rate of remission of hypertension compared with the SG group (OR: 1.63; 95% CI: 1.06-2.50). The findings of this meta-analysis suggest that the OAGB accomplished a higher percentage of total weight loss and percentage of excess weight loss at short-term and mid-term follow-up but, there was no major difference between the OAGB and SG operations in terms of perioperative outcomes, complications, and diabetes remission.

Hub genes and pathways in gastric cancer: A comparison between studies that used normal tissues adjacent to the tumour and studies that used healthy tissues as calibrator.

Several bioinformatics studies have been performed on high-throughput expression data to determine the cellular pathways and hub genes affected by Gastric cancer (GC). However, these studies differ in using a healthy tissue or normal tissue adjacent to the tumour (NAT) as calibrator tissues. This study was designed to find how using healthy or NAT tissues as calibrator tissues could affect pathway enrichment data and hub genes in GC. Two gene expression datasets with NAT tissues (GSE79973 and GSE118916) and one dataset with healthy tissues (GSE54129) were downloaded and processed by the limma package to screen the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis were performed by the Enrichr online tool. Protein-protein interaction network construction, module analysis, and hub genes selection were performed by Cytoscape software, Molecular Complex Detection plugin, and cytoHubba plugin, respectively. The gene expression profiling interactive analysis web server was used to analyse RNA sequencing expression data from The Cancer Genome Atlas Program. The Kaplan-Meier plotter was used to perform survival analysis. Our results showed that some KEGG and GO pathways were shared between studies with NAT and the study with healthy tissues. However, some terms, especially inflammation-related terms, were missed when NAT tissues were used as calibrator tissues. Also, only FN1 and COL1A1 are common hub genes between DEGs of the studies with NAT and healthy tissues. Since hub genes are usually extracted and suggested as candidate targets for GC diagnosis, prognosis, or treatment, selecting healthy or NAT tissues may affect the hub genes selection.

Receptor tyrosine kinase inhibitors in cancer.

Targeted therapy is a new cancer treatment approach, involving drugs that particularly target specific proteins in cancer cells, such as receptor tyrosine kinases (RTKs) which are involved in promoting growth and proliferation, Therefore inhibiting these proteins could impede cancer progression. An understanding of RTKs and the relevant signaling cascades, has enabled the development of many targeted drug therapies employing RTK inhibitors (RTKIs) some of which have entered clinical application. Here we discuss RTK structures, activation mechanisms and functions. Moreover, we cover the potential effects of combination drug therapy (including chemotherapy or immunotherapy agents with one RTKI or multiple RTKIs) especially for drug resistant cancers.