RNA-sequencing for transcriptional profiling of whole blood in early stage and metastatic pancreatic cancer patients.

We investigated the transcriptional profile of whole blood in early and metastatic stages of pancreatic cancer (PaC) patients to identify potential diagnostic factors for early diagnosis. Blood samples from 18 participants (6 healthy individuals, 6 patients in early stage (I/II) PaC, and 6 patients in metastatic PaC) were analyzed by RNA-sequencing. The expression levels of identified genes were subsequently compared with their expression in pancreatic tumor tissues based on TCGA data reported in UALCAN and GEPIA2 databases. Overall, 331 and 724 genes were identified as differentially expressed genes in early and metastatic stages, respectively. Of these, 146 genes were shared by early and metastatic stages. Upregulation of PTCD3 and UBA52 genes and downregulation of A2M and ARID1B genes in PaC patients were observed from early stage to metastasis. TCGA database showed increasing trend in expression levels of these genes from stage I to IV in pancreatic tumor tissue. Finally, we found that low expression of PTCD3, A2M, and ARID1B genes and high expression of UBA52 gene were positively correlated with PaC patients survival. We identified a four-gene set (PTCD3, UBA52, A2M, and ARID1B) expressed in peripheral blood of early stage and metastatic PaC patients that may be useful for PaC early diagnosis.

The association of dietary intake and plasma fatty acid panel in pancreatic cancer patients: Results from Golestan cohort study.

BACKGROUND & AIMS: High mortality rate of pancreatic cancer (PC) as one of the most common cancers worldwide made it a center of attention for recent researches on its pathology, etiology, screening and early diagnosis. In previous researches, association of dietary intake and plasma levels of fatty acids with risk of pancreatic cancer was investigated. In this study we aimed to evaluate the correlation between dietary and plasma fatty acids in case and control groups. METHODS: From 50,045 adults between 40-75 years old participated in Golestan cohort study, fifty incident cases of PC were diagnosed and 150 controls matched by age, sex and residence place were randomly selected. Dietary intakes and plasma levels of fatty acids was evaluated by validated food-frequency questionnaire (FFQ) and Gas Chromatography - Flame Ionization Detector (GC-FID), respectively. Then, Spearman's correlation was used to measure the correlation between dietary and plasma levels of fatty acids in case and control groups. RESULTS: Among all the fatty acids, there was a significant association between plasma and dietary intake of a few fatty acids including trans fatty acids (TFA), polyunsaturated fatty acids (PUFA), 22:6n-3 and 14:0 only in control group. Only total PUFA intake modified plasma level of some fatty acids in case group. There was no difference between association of desaturase enzymes and fatty acids in case and controls. CONCLUSIONS: Since, plasma levels of fatty acids might be influenced by recent diet, we did not find any specific differences between the associations of plasma levels of fatty acids with dietary intake of fats in case and control groups.

Dietary intake of fatty acids and risk of pancreatic cancer: Golestan cohort study.

BACKGROUND: As pancreatic cancer (PC) is a malignancy with poor prognosis, finding strategies for its prevention became a notable priority. Among all the factors influencing the risk of PC, dietary items especially fats are considered as the most modifiable risk factors.This study is designed to assess the associations of dietary intake of fatty acids with the risk of PC incidence. METHODS: A total of 50,045 adults between 40 and 75 years old participated in this cohort study in 2004-2008 and were followed up to the present. Intakes of fatty acids was evaluated by validated food-frequency questionnaire (FFQ). Cox proportional hazards regression model was used to estimate hazard ratio (HR) with 95 % confidence interval of differing levels of dietary intakes of fatty acids for incidence of PC. RESULTS: At the end of follow-up period, 76 cases of PC were identified and 46,904 participants without history of cancer, acute kidney disorders, fibrosis and cirrhosis were included in the study. Dietary total saturated fatty acids (SFAS) was associated with PC risk (HR = 1.05 (1.01-1.09), Ptrend=0.01), whereas dietary total monounsaturated fatty acids (MUFAS) was inversely associated with the risk of PC (HR = 0.92 (0.86-0.99), Ptrend=0.04). Dietary total polyunsaturated fatty acids (PUFAS) did show a protective but not significant association with the risk of PC (HR = 0.91(0.84-1.00), Ptrend=0.05). CONCLUSIONS: The amount of total fat intake is not a risk factor for PC in our study and focusing on the intake of specific fatty acids becomes more striking. Unsaturated fatty acids including PUFAS and especially MUFAS are considered as protective dietary factors in PC prevention. In contrast, total SFAS is positively associated with the increased risk of PC. However, very long chain and odd-chain saturated fatty acids intake may be protective against PC.

Critical complications of COVID-19: A descriptive meta-analysis study.

The coronavirus disease 2019 (COVID-19) is a novel coronavirus infection that has rapidly spread worldwide, causing a pandemic. The main objective of this meta-analysis was to evaluate the prevalence of the most common symptoms and complications of COVID-19. All relevant studies on the clinical complications of COVID-19 have been identified by searching two web databases (i.e., PubMed and Scopus). Afterward, the relevant data were extracted from the selected studies, and then analyzed by the STATA (Version 14) random-effects model. The 30 studies selected for our meta-analysis covered 6,389 infected patients. The prevalence rates of the most common symptoms were as follows: fever: 84.30% (95% CI: 77.13-90.37; I2 = 97.74%), cough: 63.01% (95% CI: 57.63-68.23; I2 = 93.73%), dyspnea: 37.16% (95% CI: 27.31-47.57%; I2 = 98.32%), fatigue: 34.22% (95% CI: 26.29-42.62; I2 = 97.29%), and diarrhea: 11.47% (95% CI: 6.96-16.87; I2 = 95.58%). Moreover, the most prevalent complications were found to be acute respiratory distress syndrome (ARDS) with 33.15% (95% CI: 23.35-43.73; I2 = 98.56%), arrhythmia with 16.64% (95% CI: 9.34-25.5; I2 = 92.29%), acute cardiac injury with 15.68% (95% CI: 11.1-20.97; I2 = 92.45%), heart failure with 11.50% (95% CI: 3.45-22.83; I2 = 89.48%), and acute kidney injury (AKI) with 9.87% (95% CI: 6.18-14.25; I2 = 95.64%). In this study, we assessed the prevalence of the main clinical complications of COVID-19, and found that following respiratory complications, cardiac and renal complications are the most common clinical complications of COVID-19.

The Effect of Vitamin D on Serum Asymmetric Dimethylarginine in Patients with Mild to Moderate Ulcerative Colitis.

Purpose: In inflammatory bowel disease increased asymmetric dimethylarginine (ADMA) levels could inhibit nitric oxide (NO) synthase. Vitamin D may increase activity and expression of endothelial NO synthase, which could be done through its possible mechanism of decreasing ADMA levels. The aim of this study is to investigate the possible effect of Vitamin D3 on serum ADMA levels in ulcerative colitis (UC) patients. Methods: Ninety mild to moderate UC patients were randomized. Each patient received one single muscular injection of 300,000 IU (7500 µg) Vitamin D3 (Vitamin D group) or 1 ml normal saline (Placebo group). At baseline and 90 days after the intervention measurements were done. Data were analyzed using independent t-test and analysis of covariance. Baseline correlations were assessed by Pearson and Spearman correlation coefficients. Results: Following data analysis of 86 participants (40 in placebo and 46 in vitamin D group), there was no correlation between baseline ADMA with baseline vitamin D, ESR and hs-CRP at baseline (p = 0.77) and at the end of study (p = 0.82). Serum ADMA levels were not statistically different between two groups. Adjustment for baseline ADMA levels and baseline body mass index (BMI) did not change the results. With subgroup analyses based on gender and vitamin D level no statistical differences in ADMA levels between two groups were found. Conclusions: In this study, we found no significant changes in serum ADMA levels 3 months following a high dose vitamin D administration in mild to moderate UC patients. Further studies in vitamin D deficient patients are needed.

Kaempferol increases apoptosis in human acute promyelocytic leukemia cells and inhibits multidrug resistance genes.

Acute promyelocytic leukemia (APL) is one of the most life-threatening hematological malignancies. Defects in the cell growth and apoptotic pathways are responsible for both disease pathogenesis and treatment resistance. Therefore, pro-apoptotic agents are potential candidates for APL treatment. Kaempferol is a flavonoid with antioxidant and anti-tumor properties. This study was designed to investigate the cytotoxic, pro-apoptotic, and differentiation-inducing effects of kaempferol on HL-60 and NB4 leukemia cells. Resazurin assay was used to determine cell viability following treatment with kaempferol (12.5-100 µM) and all-trans retinoic acid (ATRA; 10 µM; used as a positive control). Apoptosis and differentiation were also detected using propidium iodide and NBT staining techniques, respectively. Furthermore, the expression levels of genes involved in apoptosis (PI3 K, AKT, BCL2, BAX, p53, p21, PTEN, CASP3, CASP8, and CASP9), differentiation (PML-RAR and HDAC1), and multi-drug resistance (ABCB1 and ABCC1) were determined using quantitative real-time PCR. The protein expressions of Bax/Bcl2 and casp3 were confirmed using Western blot. The results showed that kaempferol decreased cell viability and increased subG1 population in the tested leukemic cells. This effect was associated with decreased expression of Akt, BCL2, ABCB1, and ABCC1 genes, while the expression of CASP3 and BAX/BCL-2 ratio were significantly increased at both gene and protein levels. Kaempferol promoted apoptosis and inhibited multidrug resistance in a concentration-dependent manner, without any differential effect on leukemic cells. In conclusion, this study suggested that kaempferol may be utilized as an appropriate alternative for ATRA in APL patients.

The possible impact of sortilin in reducing HBsAg expression in chronic hepatitis B.

Hepatitis B virus (HBV) infection is a major global health problem. Chronically infected people are at risk for progressive hepatic fibrosis and consequent cirrhosis. Hepatitis B surface antigen (HBsAg) level in serum is a complementary marker for intrahepatic HBV DNA and covalently closed circular DNA (cccDNA). Sortilin-1 (SORT1) has been reported to be involved in the post-Golgi vesicle trafficking of Apo lipoproteins degradation pathways. This study was designed to evaluate the hepatic and serum expression of HBsAg and its association with hepatic SORT1 gene expression in patients with chronic HBV. Thirty chronic hepatitis B patients with histological examination results were enrolled in this study. Liver biopsies were analyzed for hepatic HBsAg and SORT1 gene expression by immunohistochemistry and quantitative real time PCR (qRT-PCR), respectively. Twenty seven out of 30 (90%) liver biopsies had positive staining for HBsAg and showed a significant inverse association with hepatic SORT1 fold change gene expression (ß = -0.5, P = 0.042). There was significant association between HBV DNA levels and HBsAg expression in hepatocyte or serum titer of HBsAg (r = 0.39, P = 0.029; r = 0.39, P = 0.032 respectively). Serum ALT was also correlated with hepatic activity index (HAI) score (ß = 0.6, P = 0.001). Inverse association between hepatic SORT1 gene expression and hepatic HBsAg expression indicates the possible role of sortilin in HBsAg particle formation.

The Increased Level of Serum p53 in Hepatitis B-Associated Liver Cirrhosis.

BACKGROUND: The ability of tumour suppressor protein p53 (P53) to regulate cell cycle processes can be modulated by hepatitis B virus (HBV). While preliminary evidences indicates the involvement of protein-x of HBV (HBx) in altering p53 DNA binding, no further data have been accumulated for the significance of serum p53 in chronic hepatitis B virus infected patients. METHODS: 72 non-cirrhotic and 19 cirrhotic patients infected by HBV were enrolled for the analysis in this study. Enzyme linked immunosorbent assay (ELISA) was performed to study the concentrations of serum p53 protein. The tertiary structures of HBx and P53 were docked by Z-dock and Hex servers for in-silico protein-protein interaction analysis. RESULTS: There was a significant association between the serum p53 and cirrhosis (OR=1.81 95% CI: 1.017-3.2, P=0.044). Cirrhotic patients had higher level of serum p53 compare with chronic infection of HBV (1.98±1.22 vs. 1.29±0.72 U/ml, P=0.05). No evidence of correlation was seen between the different variables such as age, gender, log viral load, serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) with serum p53. Tertiary model shows that the amino acid residues from Arg110 to Lys132 of the N-terminal of P53 which is critical for ubiquitination, are bonded to a region in N- terminal of HBx amino acid residues from Arg19 to Ser33. CONCLUSION: There is an increase in serum p53 in HBV-related cirrhosis patients. In this case, HBx might be responsible for such higher concentration of p53 through HBx-p53 protein-protein interaction, as is shown by molecular modeling approach.

Insights into Organochlorine Pesticides Exposure in the Development of Cardiovascular Diseases: A Systematic Review.

Many human diseases such as cancer, neurological diseases, autism and diabetes are associated with exposure to pesticides, especially organochlorine pesticides. However, pesticide exposure is also associated with cardiovascular disease (CVD) as the leading cause of death worldwide. In this systematic review, results on the link between organochlorine pesticide pollution and CVD were collected from databases (Medline (PubMed), Scopus and Science Direct) in May 2022 from studies published between 2010 and 2022. A total of 24 articles were selected for this systematic review. Sixteen articles were extracted by reviewers using a standardized form that included cross-sectional, cohort, and ecological studies that reported exposure to organochlorine pesticides in association with increased CVD risk. In addition, eight articles covering molecular mechanisms organochlorine pesticides and polychlorinated biphenyls (PCBs) on cardiovascular effects were retrieved for detailed evaluation. Based on the findings of the study, it seems elevated circulating levels of organochlorine pesticides and PCBs increase the risk of coronary heart disease, especially in early life exposure to these pesticides and especially in men. Changes in the regulatory function of peroxisome proliferator-activated γ receptor (PPARγ), reduction of paroxonase activity (PON1), epigenetic changes of histone through induction of reactive oxygen species, vascular endothelial inflammation with miR-expression 126 and miR-31, increased collagen synthesis enzymes in the extracellular matrix and left ventricular hypertrophy (LVH) and fibrosis are mechanisms by which PCBs increase the risk of CVD. According to this systematic review, organochlorine pesticide exposure is associated with increased risk of CVD and CVD mortality through the atherogenic and inflammatory molecular mechanism involving fatty acid and glucose metabolism.

A Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant.

BACKGROUND: The LIPA gene on chromosome 10q23.31 contains 10 exons and encodes lipase A, the lysosomal acid lipase (LAL) containing 399 amino acids. Pathogenic variants in the LIPA result in autosomal recessive Wolman disease and cholesteryl ester storage disease (CESD). Here, we report a novel missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of LIPA in an Iranian family with fatty liver disease identified by whole-exome sequencing and confirmed by Sanger sequencing. METHODS: A 28-year-old woman referred with lean NASH cirrhosis and extremely high cholesterol levels. Fatty liver disease was found in six of her family members using vibration-controlled transient elastography (VCTE). Baseline routine laboratory tests were performed and whole-exome sequencing and confirmation by Sanger sequencing were done. RESULTS: The index case had severe dyslipidemia and cirrhosis despite a body mass index of 21.09 kg/m2 . Six other family members had dyslipidemia and fatty liver or cirrhosis. A homozygous missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of LIPA which caused LAL-D was found to be associated with fatty liver disease and/or cirrhosis. CONCLUSION: A homozygous missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of the LIPA gene which caused LAL-D was found to be associated with dyslipidemia, fatty liver disease and/or cirrhosis in six members of an Iranian family. These results should be confirmed by functional studies and extending the study to at least three families.

Influence of B cells in liver fibrosis associated with hepatitis B virus harboring basal core promoter mutations.

The development of the liver disease in chronic hepatitis B with common viral variants can be determined through the interaction between the virus and the host immune response. B cells constitute half of the intrahepatic lymphocyte population with an impact on fibrosis. A proliferation-inducing ligand (APRIL) has been shown to have a co-stimulatory activity on B cells. For this study HBV DNA was amplified and then sequenced to show the presence of the basal core promoter (BCP) mutations in the serum from 57 patients with chronic hepatitis B. The range of IgD-positive B cells was detected by immunohistochemistry in liver biopsies; and patients serum was assayed for APRIL levels by enzyme immunoassay. Twenty-seven patients (47.4%) harbored the A1762T-G1764A BCP mutations. Coefficients of logistic regression showed that the effect of increasing IgD-positive B cells in rising odds of the liver disease is the same in the patients with BCP mutation A1762T-G1764A and in the patients without mutation, nevertheless the effect of APRIL is not similar in these two groups of patients. Logistic regression in patients with BCP A1762T-G1764A mutations demonstrated that increasing one score of APRIL decreased the odds of fibrosis stage about 8%. These results suggest that in infection with viral variants of hepatitis B virus, the population of IgD-positive B cells may play a decisive role in later stages of the liver disease which is reduced by APRIL in chronic hepatitis patients with BCP mutations.

Climate Crises and Developing Vector-Borne Diseases: A Narrative Review.

Background: Climate change based on temperature, humidity and wind can improve many characteristics of the arthropod carrier life cycle, including survival, arthropod population, pathogen communication, and the spread of infectious agents from vectors. This study aimed to find association between content of disease followed climate change we demonstrate in humans. Methods: All the articles from 2016 to 2021 associated with global climate change and the effect of vector-borne disease were selected form databases including PubMed and the Global Biodiversity information facility database. All the articles selected for this short review were English. Results: Due to the high burden of infectious diseases and the growing evidence of the possible effects of climate change on the incidence of these diseases, these climate changes can potentially be involved with the COVID-19 epidemic. We highlighted the evidence of vector-borne diseases and the possible effects of climate change on these communicable diseases. Conclusion: Climate change, specifically in rising temperature system is one of the world's greatest concerns already affected pathogen-vector and host relation. Lice parasitic, fleas, mites, ticks, and mosquitos are the prime public health importance in the transmission of virus to human hosts.

Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review.

Background: Multiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabolism, generates a variety of neurotoxic as well as neuroprotective compounds, affecting MS pathology and the severity of impairments. Alterations in KP have been described not only in MS, but also in various psychiatric and neurodegenerative diseases. The purpose of this systematic review is to investigate the previously reported dysregulation of KP and differences in its metabolites and enzymes in patients with MS compared to healthy control subjects. Method: Electronic databases of PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science were searched to identify studies measuring concentrations of KP metabolites and enzymes in MS patients and control subjects. The following metabolites and enzymes implicated in the KP were investigated: TRP, kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), hydroxyindoleacetic acid (HIAA), indoleamine 2,3-dioxygenase (IDO), kynurenine aminotransferase (KAT), and their related ratios. Result: Ten studies were included in our systematic review. Our review demonstrates that IDO expression is reduced in the peripheral blood mononuclear cells (PBMCs) of MS patients compared to healthy controls. Also, increased levels of QUIN and QUIN/KYNA in the serum and cerebrospinal fluid (CSF) of MS patients is observed. Differences in levels of other metabolites and enzymes of KP are also reported in some of the reviewed studies, however there are discrepancies among the included reports. Conclusion: The results of this investigation suggest a possible connection between alterations in the levels of KP metabolite or enzymes and MS. QUIN levels in CSF were higher in MS patients than in healthy controls, suggesting that QUIN may be involved in the pathogenesis of MS. The data indicate that differences in the serum/blood or CSF levels of certain KP metabolites and enzymes could potentially be used to differentiate between MS patients and control subjects.

Gut Microbiota Modification via Glucagon-like Peptide-1 with Beneficial Neuroprotective Effects.

BACKGROUND: In recent decades, it has been shown that the association between intestinal bacterial imbalance (dysbiosis) and various diseases such as type 2 diabetes can play a role in the development of Alzheimer's and Parkinson's diseases. In this study, the beneficial effects of intestinal microbiota glucagon-like peptide 1 (GLP-1) in cognitive disorders were investigated. METHODS: PubMed-Medline, Web of Science, and Scopus were searched to identify experimental studies based on the bacterial strains along with GLP-1 1 expression in preventing or reducing cognitive impairment. Of the 233 studies, six were eligible for inclusion, and the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool was used to evaluate the risk of bias in individual studies. RESULTS: The results showed that intestinal expression of GLP-1 1 could reduce the intestinal pathogenic genus such as Enterobacteriaceae and was obviously associated with a greater number of beneficial genera such as Lactobacillus and Akkermansia. Also, the neuroprotective effects of Clostridium butyricum with GLP-1 1 in a mice were approved. Therefore, the modulation of the intestinal microbiota, mediated by an increase in the intestinal GLP-1 1 level, consequently improved cognitive function. CONCLUSION: In this review, we have indicated that the gut microbiota, by stimulating the expression of the intestinal hormones like GLP-1 1, and also with a beneficial effect in inhibiting some involved genes in inflammation, can declined the development of cognitive disorders.

Challenges of cancer immunotherapy and chemotherapy during the COVID-19 pandemic.

People at high risk of morbidity and mortality from coronavirus disease 2019 (COVID-19), including patients dealing with malignancies and patients on immunosuppressive anticancer therapies, need to be followed carefully as the pandemic continues. Challenges in continuing cancer management and patient monitoring are of concern given the importance of timing in cancer therapy. Alternative treatment decisions and priorities are also important considerations. The efficacy and safety of various cancer treatments in patients with COVID-19 are other important considerations. In this systematic review, we summarize the potential risks and benefits of cancer treatments applied to patients with COVID-19 and malignant tumors. Using the PubMed and Scopus databases, we reviewed studies involving cancer therapy and COVID-19 to address the recent discoveries and related challenges of cancer therapy in patients with COVID-19 and cancer.

Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by neuroinflammation, formation of Lewy bodies, and progressive loss of dopaminergic neurons in the substantia nigra of the brain. In this review, we summarize evidence obtained by animal studies demonstrating neuroinflammation as one of the central pathogenetic mechanisms of PD. We also focus on the protein factors that initiate the development of PD and other neurodegenerative diseases. Our targeted literature search identified 40 pre-clinical in vivo and in vitro studies written in English. Nuclear factor kappa B (NF-kB) pathway is demonstrated as a common mechanism engaged by neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), as well as the bacterial lipopolysaccharide (LPS). The α-synuclein protein, which plays a prominent role in PD neuropathology, may also contribute to neuroinflammation by activating mast cells. Meanwhile, 6-OHDA models of PD identify microsomal prostaglandin E synthase-1 (mPGES-1) as one of the contributors to neuroinflammatory processes in this model. Immune responses are used by the central nervous system to fight and remove pathogens; however, hyperactivated and prolonged immune responses can lead to a harmful neuroinflammatory state, which is one of the key mechanisms in the pathogenesis of PD.

The contribution of gut-brain axis to development of neurological symptoms in COVID-19 recovered patients: A hypothesis and review of literature.

The gut microbiota undergoes significant alterations in response to viral infections, particularly the novel SARS-CoV-2. As impaired gut microbiota can trigger numerous neurological disorders, we suggest that the long-term neurological symptoms of COVID-19 may be related to intestinal microbiota disorders in these patients. Thus, we have gathered available information on how the virus can affect the microbiota of gastrointestinal systems, both in the acute and the recovery phase of the disease, and described several mechanisms through which this gut dysbiosis can lead to long-term neurological disorders, such as Guillain-Barre syndrome, chronic fatigue, psychiatric disorders such as depression and anxiety, and even neurodegenerative diseases such as Alzheimer's and Parkinson's disease. These mechanisms may be mediated by inflammatory cytokines, as well as certain chemicals such as gastrointestinal hormones (e.g., CCK), neurotransmitters (e.g., 5-HT), etc. (e.g., short-chain fatty acids), and the autonomic nervous system. In addition to the direct influences of the virus, repurposed medications used for COVID-19 patients can also play a role in gut dysbiosis. In conclusion, although there are many dark spots in our current knowledge of the mechanism of COVID-19-related gut-brain axis disturbance, based on available evidence, we can hypothesize that these two phenomena are more than just a coincidence and highly recommend large-scale epidemiologic studies in the future.

Protein-x of hepatitis B virus in interaction with CCAAT/enhancer-binding protein α (C/EBPα)--an in silico analysis approach.

BACKGROUND: Even though many functions of protein-x from the Hepatitis B virus (HBV) have been revealed, the nature of protein-x is yet unknown. This protein is well-known for its transactivation activity through interaction with several cellular transcription factors, it is also known as an oncogene. In this work, we have presented computational approaches to design a model to show the structure of protein-x and its respective binding sites associated with the CCAAT/enhancer-binding protein α (C/EBPα). C/EBPα belongs to the bZip family of transcription factors, which activates transcription of several genes through its binding sites in liver and fat cells. The C/EBPα has been shown to bind and modulate enhancer I and the enhancer II/core promoter of HBV. In this study using the bioinformatics tools we tried to present a reliable model for the protein-x interaction with C/EBPα. RESULTS: The amino acid sequence of protein-x was extracted from UniProt [UniProt:Q80IU5] and the x-ray crystal structure of the partial CCAAT-enhancer α [PDB:1NWQ] was retrieved from the Protein Data Bank (PDB). Similarity search for protein-x was carried out by psi-blast and bl2seq using NCBI [GenBank: BAC65106.1] and Local Meta-Threading-Server (LOMETS) was used as a threading server for determining the maximum tertiary structure similarities. Advanced MODELLER was implemented to design a comparative model, however, due to the lack of a suitable template, Quark was used for ab initio tertiary structure prediction.The PDB-blast search indicated a maximum of 23% sequence identity and 33% similarity with crystal structure of the porcine reproductive and respiratory syndrome virus leader protease Nsp1α [PDB:3IFU]. This meant that protein-x does not have a suitable template to predict its tertiary structure using comparative modeling tools, therefore we used QUARK as an ab initio 3D prediction approach. Docking results from the ab initio tertiary structure of protein-x and crystal structure of the C/EBPα- DNA region [PDB:1NWQ] illustrated the protein-binding site interactions. Indeed, the N-terminal part of 1NWQ has a high affinity for certain regions in protein-x (e.g. from Ala76 to Ser101 and Thr105 to Glu125). CONCLUSION: In this study, we predicted the structure of protein-x of HBV in interaction with C/EBPα. The docking results showed that protein-x has an interaction synergy with C/EBPα. However, despite previous experimental data, protein-x was found to interact with DNA. This can lead to a better understanding of the function of protein-x and may provide an opportunity to use it as a therapeutic target.

Diagnostic Significance of Serum Fatty Acid Synthase in Patients with Pancreatic Cancer.

BACKGROUND Pancreatic cancer is considered as the most deadly tumor among gastrointestinal cancers because of its poor prognosis. The frequently deregulated pathway in the cancer cell is associated with an increased expression of various genes, including the synthesis of fatty acids. We aimed to evaluate the level of serum fatty acid synthase (FASN) as a diagnostic marker for early diagnosis of pancreatic cancer. METHODS Serum FASN levels were measured by ELISA in 92 patients with pancreatic adenocarcinomas and in 92 healthy controls. Logistic regression analysis was used to identify independent predictors of certain diagnostic categories. RESULTS Serum FASN levels were significantly higher in patients with pancreatic cancer than in healthy controls (1.35 [0.98-2.3] ng/mL vs 1.04 [0.19-1.34] ng/mL, p < 0.001) and in smokers compared to non-smokers (1.41 [0.79-2.52] ng/mL vs 1.07 [0.21-1.74] ng/mL, p < 0.001). FASN levels and smoking were associated with increased risk of PC (1.54 [1.1- 2.14] ng/mL, p = 0.011 and 5.69 [2.68-12.09] ng/mL, p < 0.001, respectively). CONCLUSION Elevated serum FASN levels in patients with pancreatic cancer indicate the need for the production of large numbers of lipids for the survival and proliferation of human cancer cells and the diagnostic value of FASN as a new diagnostic biomarker.

Dehydroepiandrosterone modulates oxidative DNA damage in pancreatic cancer: A case-control study.

BACKGROUND AND AIM: Dehydroepiandrosterone (DHEA) has a protective role against several types of cancer, although its mechanisms of action are still unknown, it may be related to the antioxidant effect of DHEA. We hypothesized that DHEA has a preventive effect on the formation of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) DNA adduct in pancreatic cancer patients. METHODS: Serum DHEAs were quantified by the ELISA method in 50 pancreatic cancer patients with histopathological diagnosis of adenocarcinoma and 50 matched controls. The amount of 8-OHdG was assessed in peripheral blood leukocyte extracted DNA using a 32P-DNA postlabeling technique. RESULTS: Pancreatic cancer patients had lower serum DHEA levels than healthy controls, although it did not differ significantly. Instead, the 8-OHdG DNA adduct was significantly higher in the case than in the control (P = <0.001). Remarkably, the negative correlation between 8-OHdG and DHEA was distinguished between cases (P = 0.025, r = -0.315) but not in controls (P = 0.078, r = -0.250). In the crude and corrected estimate for pancreatic cancer risk, a significant protective effect of DHEA against pancreatic cancer was found with increasing DHEA when 8-OHdG is greater than its median (adjusted OR = 0, 79, 95% confidence intervals [CI]: 0.66-0.94). Similarly, a lower risk of pancreatic cancer was observed in the third tertile of DHEA (adjusted OR = 0.05, 95% CI: 0.004-0.69). CONCLUSIONS: These results indicate that serum DHEA reduces the risk of pancreatic cancer with an anti-DNA damage effect. Hence, the influence of DHEA to prohibit the accumulation of 8-OHdG may be one of its physiological functions.