The duration of spinal anaesthesia in elective caesarean section in Trendelenburg and reverse Trendelenburg positions: a randomized clinical trial.

Objective: One of the common methods of anaesthesia for caesarean sections (CSs) involves the use of spinal anaesthesia in mothers. Various positions are utilized in this method. This study aims to compare the evaluation of two positions, Trendelenburg and reverse Trendelenburg, in candidates for CS to assess the duration of anaesthesia and changes in vital signs in women. Methods: This study was a randomized clinical trial in which 60 pregnant mothers who met the inclusion criteria entered the study. These mothers were randomly allocated into two equal groups using block randomization. One group of patients received spinal anaesthesia in the Trendelenburg position, while the other group received it in the Reverse Trendelenburg position. Vital signs (systolic and diastolic blood pressure, heart rate, Apgar score, and SPO2) of participants from both groups were evaluated for 1 h after the induction of anaesthesia. Additionally, sensory level and duration of anaesthesia were measured. Finally, the data from both groups were subjected to statistical analysis using SPSS version 26 software. Results: The mean (SD) age of participating mothers in the Reverse Trendelenburg and Trendelenburg groups was 28.93 (5.82) and 30.97 (4.94), respectively. The two study groups did not significantly differ in baseline characteristics such as age, BMI, which could potentially impact vital sign outcomes or anaesthesia duration, and education (P>0.05). The mean (SD) duration of anaesthesia in the Trendelenburg position was significantly higher than in the Reverse Trendelenburg position [221.57(min) vs. 159.00(min)] (P<0.0001). There was no significant difference between the two positions, Trendelenburg and Reverse Trendelenburg, in terms of sensory level and its extent (P=0.08). The two study groups did not significantly differ in hemodynamic changes measured 13 times, including heart rate, systolic and diastolic blood pressure, and Apgar score (P>0.05). Conclusion: In spinal anaesthesia with the Trendelenburg position compared to the Reverse Trendelenburg position, there is a longer duration of anaesthesia. This is while the two positions did not differ in terms of hemodynamic changes and sensory level.

Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review.

Background: Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans. Objective: In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action. Methods: To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review. Results: RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic ß-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy. Conclusion: RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated.

Comprehensive Analysis of the Expression, Prognosis, and Immune Infiltrates for Chromodomain-Helicase-DNA-Binding Proteins in Breast Tumor.

BACKGROUND: Several recent studies suggest that chromodomain-helicase -DNA-binding domains (CHDs) are linked with cancers. We explored the association between chromodomain-Helicase-DNA-binding domain proteins and breast cancer (BrCa) and introduced potential prognostic markers using various databases. MATERIALS AND METHODS: We analyzed the expression of the CHD family and their prognostic value in BrCa by mining UALCAN, TIMER, and Kaplan-Meier plotter databases. The association of CHD expression and immune infiltrating abundance was studied via the TIMER database. In addition, microRNAs related to the CHD family were identified by using the MirTarBase online database. RESULTS: The present study indicated that compared to normal tissues, BrCa tissues showed increased mRNA levels of CHD3/4/7 but decreased CHD2/5/9 expression. Interestingly, We also found a positive correlation between CHD gene expression and the infiltration of macrophage, neutrophil, and dendritic cells in BrCa, except CHD3/5. The Kaplan-Meier Plotter analysis suggested that high expression levels of CHD1/2/3/4/6/8/9 were significantly related to shorter relapse-free survival (RFS), while higher mRNA expression of CHD1, CHD2, CHD8, and CHD9 was significantly associated with longer overall survival of BrCa patients. The miRNAs of hsa-miR-615-3p and hsa-let-7b-5p were identified as being more correlated with the CHD family. CONCLUSION: The altered expression of some CHD members was significantly related to clinical cancer outcomes, and CHD1/2/8/9 could serve as potential prognostic biomarkers to improve the survival of BrCa patients. However, to evaluate the studied CHD members in detail are needed further investigations including experimental validation.

The implications of exosomes in psoriasis: disease: emerging as new diagnostic markers and therapeutic targets.

As the largest human organ, the skin is continuously exposed to various external and internal triggers that affect body homeostasis. Psoriasis is a persistent inflammatory skin condition that has a major bearing on patients' physiological functioning as well as their mental well-being. It is an autoimmune disorder and has been the focus of extensive research efforts in recent years. Cells secrete exosomes into the environment surrounding them, which comprises a lipid bilayer. The movement of cellular components like microRNAs, mRNAs, DNA, lipids, metabolites, and cell-surface proteins is mediated by exosomes. Exosomes are crucial for inducing communication between cells. There has been extensive study of exosomes, both preclinical and clinical, looking at their potential role in autoimmune diseases. Besides the role that they play in the body's basic processes, exosomes are also considered an increasingly essential part as diagnostic and therapeutic agents. In the following article, we conduct a literature review of current studies related to molecular and structural aspects of exosomes. We emphasis on the function of exosomes in pathogenesis, as well as the possibility of their usage in medicinal applications and as biomarkers.

Screening the critical protein subnetwork to delineate potential mechanisms and protective agents associated with arsenic-induced cutaneous squamous cell carcinoma: A toxicogenomic study.

Recent studies show that complex mechanisms are involved in arsenic-induced malignant transformation of cells. This study aimed to decipher molecular mechanisms associated with arsenic-induced cutaneous squamous cell carcinoma (cSCC) and suggest potential protective factors. RNA-seq-based differentially expressed genes between arsenic-exposed human keratinocytes (HaCaT) and controls were used to construct a protein-protein interaction (PPI) network and discover critical subnetwork-based mechanisms. Protective compounds against arsenic toxicity were determined and their target interactions in the core sub-network were identified by the comparative toxicogenomic database (CTD). The binding affinity between the effective factor and target was calculated by molecular docking. A total of 15 key proteins were screened out as critical arsenic-responsive subnetwork (FN1, IL-1A, CCN2, PECAM1, FGF5, EDN1, FGF1, PXDN, DNAJB9, XBP1, ERN1, PDIA4, DNAJB11, FOS, PDIA6) and 7 effective protective agents were identified (folic acid, quercetin, zinc, acetylcysteine, methionine, catechin, selenium). The GeneMANIA predicted detailed interactions of the subnetwork and revealed terms related to unfolded protein response as the main processes. FN1, IL1A and CCN2, as top significant genes, had good docking affinity with folic acid and quercetin, as selected key compounds. Integration of gene expression and protein-protein interaction related to arsenic exposure in cSCC explored the potential mechanisms and protective agents.

Evaluation of the Cellular Resistance Process in Treated Cells Via Extracorporeal Photopheresis.

Introduction: Extracorporeal photopheresis (ECP) is a therapeutic method applied against some diseases such as cancers. Using 8-methoxypsoralen (8-MOP) and UVA radiation in ECP is associated with achievement in the treatment of patients with leukemic cutaneous T-cell lymphoma (CTCL). Evaluation of cellular resistance versus ECP is the aim of this study. Methods: Data were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed via the GEO2R program. The significant DEGs were assessed via protein-protein interaction (PPI) network analysis by using the STRING database and Cytoscape software. The critical genes were evaluated via gene ontology by using the ClueGO application of Cytoscape software. The identified biological processes were determined and analyzed. Results: Fifty-seven significant DEGs were determined. The main connected component of the PPI network including 32 queried significant DEGs plus 50 first neighbors was constructed. Nineteen histones as critical nodes were assessed via gene ontology, and "nucleosome organization" was pointed out as the crucial biological process. Finally, 15 histones from H2A, H2B, and H3 histone families were identified as the key genes that are involved in the resistance property of the treated cells. Conclusion: In conclusion, 15 members of H2A, H2B, and H3 families (especially H2A family) were considered as the origin of resistance versus ECP treatment. It is concluded that sensitivity to ECP treatment depends on gross molecular events which are involved in the functions of histones.

Comparison of the effect of vaginal misoprostol and evening primrose oil capsule with misoprostol alone on the consequences of abortion in women with intrauterine fetal death: a randomized clinical trial.

BACKGROUND: Misoprostol is the choice drug for inducing an abortion with intrauterine fetal death, but it has several side effects that increase with accumulating the dose received. Induction abortion with cheap and non-invasive methods with minimal complications is essential. This study aimed to compare the effect vaginal misoprostol plus vaginal evening primrose oil capsule with vaginal misoprostol alone on the consequences of abortion in pregnant women with intrauterine fetal death at 12-20 weeks of pregnancy. METHODS: This study is a randomized, triple-blind clinical trial with two parallel groups at a ratio of 1:1. We randomized 82 women with indications of termination of pregnancy due to intrauterine fetal death into two groups. The experimental group (n = 42) received 200 mcg of misoprostol tablet with 1000 mg evening primrose oil capsule intravaginal. The control group (n = 40) received 200 mcg of misoprostol tablet with 1000 mg evening primrose oil placebo capsule intravaginal. Both groups received the drugs every 4 h for up to five doses. The primary outcome was the mean induction-to-fetal expulsion interval. Secondary outcomes were the mean dose of misoprostol, the highest pain intensity in the induction-to-fetal expulsion interval, the frequency of participants requiring blood transfusion, curettage, and the frequency of side effects of misoprostol or evening primrose oil. Pain intensity was measured through the Visual Analog Scale. RESULTS: The mean age of the experimental group was 32.30 ± 6.19 years, and the control group was 30.27 ± 7.68 years. The mean gestational age of the experimental group was 15.29 ± 2.26 weeks, and the control group was 15.10 ± 1.89 weeks. The mean induction-to-fetal expulsion interval in the experimental group (3.12 ± 2.17 h) was significantly lower than that in the control group (8.40 ± 4.1 h) (p < 0.001). The mean dose of misoprostol received in the experimental group (271.42 ± 115.39 mcg) was significantly lower than that in the control group (520 ± 201.53 mcg) (p < 0.001). Also, the mean pain intensity in the experimental group (5.02 ± 0.60) was significantly lower than that in the control group (8.65 ± 1.001) (p < 0.001). The two groups were not significantly different in the frequency of blood transfusion requirements, analgesia and drug side effects. The need for curettage in the experimental group (4.8%) was significantly lower than that in the control group (47.5%) (p < 0.001). CONCLUSIONS: Vaginal administration of evening primrose oil with misoprostol reduced duration of time of fetal expulsion, pain intensity, mean dose of misoprostol received, and the need for curettage in participants. Therefore, we suggest this method for induced abortion in women with intrauterine fetal death. TRIAL REGISTRATION: IRCT20181207041873N3. Dated 16/2/2021 prospectively registered https://en.irct.ir/user/trial/53681/view .

Clinicopathological and prognostic value of lncRNA TPT1-AS1 in cancer: A systematic review study and meta-analysis.

INTRODUCTION: Aberrant expression of lncRNAs in cancer cells can impact their key phenotypes. We aimed to summarize available evidence on clinicopathological and prognostic value of lncRNA TPT1-AS1 in cancer. METHODS: A systematic search was performed on Medline and Embase databases using relevant key terms covering lncRNA TPT1-AS1, cancer, and clinical outcomes. The effect size estimates and their 95 % confidence interval (CI) were pooled using random-effects models. Meta- analyses were conducted using STATA 16.0 software. RESULTS: Seventeen articles met our eligibility criteria. Tumor tissue compared to normal tissue showed increased level of lncRNA TPT1-AS1 expression (pooled standardized mean difference (95 % CI): 0.65 (0.52-0.79)). Overexpression of this lncRNA was a significant predictor for poor prognosis (Pooled log-rank test P-value < 0.001); in patients with high-level of lncRNA TPT1-AS1, the risk of death at five years was 1.40 times greater than their counterparts. The pooled Odds ratios for association lncRNA TPT1-AS1 with tumor stage, tumor size, and lymph node metastasis were 1.94 (95 % CI: 0.90-4.19, 8 studies, I2 = 79.6 %), 2.33 (95 % CI: 1.31-4.14, 5 studies, I2 = 40.0 %), and 1.89 (95 % CI: 1.08-3.36, 5 studies, I2 = 61.7 %), respectively. Regarding the identified potential mechanisms, lncRNA TPT1-AS1 plays a role in cancer growth mainly by sponging miRNAs and regulating their downstream targets or controlling the expression of key cell cycle regulators. CONCLUSION: In cancer patients, elevated expression of lncRNA TPT1-AS1 might be associated with a shorter Overall Survival, advanced stages, larger tumor size, and lymph node metastasis.

The Effect of Using Dexamethasone Tablets Vaginally for Improving Cervical Bishop Score in Nulliparous Pregnant Women: A Randomized Clinical Trial.

Background: Cervix ripening and labor induction are common interventions in obstetrics. For optimal maternal health, labor may be induced under certain situations to improve fetal survival outcomes. Labor induction of an unripe cervix can lead to complications; therefore, several approaches can facilitate the ripening process. Methods: This randomized clinical trial was a triple-blind study that involved 84 pregnant nulliparous women enrolled between October 2019 and June 2021 in the labor ward of Kamali Hospital, Karaj, Iran. The pregnant women in the study underwent labor induction and were randomized into 2 groups: 1 group received vaginal dexamethasone and the other group was given a placebo. Results: There was no significant difference between the groups regarding maternal age, demographic characteristics, and initial Bishop score. The median second Bishop score (6 hours after intervention) was 3.5 in dexamethasone recipients and 3 in placebo recipients (P = 0.48). The median labor latent phase duration was 4 hours in dexamethasone recipients and 5 hours in placebo recipients (P = 0.57). Conclusions: This randomized clinical trial demonstrated that administering dexamethasone tablets vaginally did not significantly improve cervical Bishop scores. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX). ClinicalTrials.gov identifier: NCT05070468.

Cavernous sinus thrombosis in ulcerative colitis recurrent after pregnancy: A case report.

Inflammatory bowel disease and pregnancy are risk factors for increased hyper coagulopathy state. A 35-year-old woman with ulcerative colitis was presented in this study. She had the recurrence of the disease during pregnancy. She suffered cavernous sinus thrombosis simultaneously.

Unveiling diagnostic and therapeutic strategies for cervical cancer: biomarker discovery through proteomics approaches and exploring the role of cervical cancer stem cells.

Cervical cancer (CC) is a major global health problem and leading cause of cancer deaths among women worldwide. Early detection through screening programs has reduced mortality; however, screening compliance remains low. Identifying non-invasive biomarkers through proteomics for diagnosis and monitoring response to treatment could improve patient outcomes. Here we review recent proteomics studies which have uncovered biomarkers and potential drug targets for CC. Additionally, we explore into the role of cervical cancer stem cells and their potential implications in driving CC progression and therapy resistance. Although challenges remain, proteomics has the potential to revolutionize the field of cervical cancer research and improve patient outcomes.

The effect of magnesium sulfate on maternal serum electrolytes and parathyroid hormone in pre-eclampsia.

OBJECTIVE: To evaluate possible interactions of magnesium sulfate-the drug of choice in the management of pre-eclampsia/eclampsia-in response to a few case reports that revealed maternal electrolyte disturbances, especially symptomatic changes, following magnesium sulfate administration in pre-eclampsia. METHODS: Prospectively, women with pre-eclampsia were given 4 g of intravenous magnesium sulfate followed by a 2 g/h infusion up to 24 h after delivery. Sequential blood samples were drawn from each patient and used to measure the serum levels of sodium, potassium, calcium, phosphorus, magnesium, and parathyroid hormone. RESULTS: A total of 30 pregnant women with pre-eclampsia were evaluated. They were aged between 20 and 41 years with median gestational age of 37.6 (interquartile range 35.4-38.9) weeks. Only five patients reached the therapeutic window of magnesium in at least one of our measuring intervals during magnesium sulfate infusion. Plasma magnesium concentrations increased significantly during magnesium sulfate administration and dropped during the next 12 and 24 h after infusion discontinuation (P < 0.05). Fifteen of 30 (50%) patients developed asymptomatic hypocalcemia, mainly at hour 24 of infusion. Negative moderate correlations were detected between the calcium and magnesium concentrations at 12 and 24 hours of infusion (ρ = -0.390, P = 0.044 and ρ = 0.315, P = 0.096, respectively). None of the patients with hypocalcemia reached the therapeutic level of magnesium or experienced parallel hyperphosphatemia. Eleven of 30 (36.6%) patients developed hyperphosphatemia mainly at 2 and 12 h of magnesium sulfate infusion. CONCLUSIONS: Our study implies that magnesium sulfate could cause hypermagnesemia-induced hypocalcemia in women with pre-eclampsia, independent from parathyroid hormone. The negative correlations between calcium and magnesium concentrations could be indicative of dose-dependent associations between serum magnesium level and degree of hypocalcemia in our study.

Systematic Analysis of Protein-Protein and Gene-Environment Interactions to Decipher the Cognitive Mechanisms of Autism Spectrum Disorder.

Autism spectrum disorder (ASD), a heterogeneous neurodevelopmental disorder resulting from both genetic and environmental risk factors, is manifested by deficits in cognitive function. Elucidating the cognitive disorder-relevant biological mechanisms may open up promising therapeutic approaches. In this work, we mined ASD cognitive phenotype proteins to construct and analyze protein-protein and gene-environment interaction networks. Incorporating the protein-protein interaction (PPI), human cognition proteins, and connections of autism-cognition proteins enabled us to generate an autism-cognition network (ACN). With the topological analysis of ACN, important proteins, highly clustered modules, and 3-node motifs were identified. Moreover, the impact of environmental exposures in cognitive impairment was investigated through chemicals that target the cognition-related proteins. Functional enrichment analysis of the ACN-associated modules and chemical targets revealed biological processes involved in the cognitive deficits of ASD. Among the 17 identified hub-bottlenecks in the ACN, PSD-95 was recognized as an important protein through analyzing the module and motif interactions. PSD-95 and its interacting partners constructed a cognitive-specific module. This hub-bottleneck interacted with the 89 cognition-related 3-node motifs. The identification of gene-environment interactions indicated that most of the cognitive-related proteins interact with bisphenol A (BPA) and valproic acid (VPA). Moreover, we detected significant expression changes of 56 cognitive-specific genes using four ASD microarray datasets in the GEO database, including GSE28521, GSE26415, GSE18123 and GSE29691. Our outcomes suggest future endeavors for dissecting the PSD-95 function in ASD and evaluating the various environmental conditions to discover possible mechanisms of the different levels of cognitive impairment.

Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets.

Deciphering the molecular downstream consequences of severe acute respiratory syndrome coronavirus (SARS-CoV)- 2 infection is important for a greater understanding of the disease and treatment planning. Furthermore, greater understanding of the underlying mechanisms of diagnostic and therapeutic strategies can help in the development of vaccines and drugs against COVID-19. At present, the molecular mechanisms of SARS-CoV-2 in the host cells are not sufficiently comprehended. Some of the mechanisms are proposed considering the existing similarities between SARS-CoV-2 and the other members of the ß-CoVs, and others are explained based on studies advanced in the structure and function of SARS-CoV-2. In this review, we endeavored to map the possible mechanisms of the host response following SARS-CoV-2 infection and surveyed current research conducted by in vitro, in vivo and human observations, as well as existing suggestions. We addressed the specific signaling events that can cause cytokine storm and demonstrated three forms of cell death signaling following virus infection, including apoptosis, pyroptosis, and necroptosis. Given the elicited signaling pathways, we introduced possible pathway-based therapeutic targets; ADAM17 was especially highlighted as one of the most important elements of several signaling pathways involved in the immunopathogenesis of COVID-19. We also provided the possible drug candidates against these targets. Moreover, the cytokine-cytokine receptor interaction pathway was found as one of the important cross-talk pathways through a pathway-pathway interaction analysis for SARS-CoV-2 infection.

Ruled out of preeclampsia-like syndrome due to COVID-19: A case study.

Coronavirus disease (COVID-19) is an infectious disease. In this study, we report a 28-year-old pregnant woman who had a postpartum seizure with a background of HELLP syndrome and a proven COVID-19 infection. Her child survived, and at 12-week postpartum, all maternal COVID-19-related symptoms vanished, and she was cured.

A pregnant woman with a history of SLE with PPROM and severe thrombocytopenia: A case study.

This study discusses the management of a pregnant woman with PPROM and a history of lupus. She was found to be severely thrombocytopenic which was unresponsive to prednisolone. During cesarean section, placental abruption was found and postpartum hemorrhage ensued.

A systematic review of microRNA expression studies with exposure to bisphenol A.

Bisphenol A (BPA), as a common industrial component, is generally consumed in the synthesis of polymeric materials. To gain a deeper understanding of the detrimental effects of BPA, BPA-induced microRNA (miRNA) alterations were investigated. A systematic search was performed in the PubMed, SCOPUS and Web of Science databases to evoke relevant published data up to August 10, 2019. We identified altered miRNAs that have been repeated in at least three studies. Moreover, miRNA homology analysis between human and nonhuman species was performed to determine the toxicity signatures of BPA in human exposure. In addition, to reflect the effects of environmental exposure levels of BPA, the study designs were categorized into two groups, including low and high doses according to the previous definitions. In total, 28 studies encountered our criteria and 17 miRNAs were identified that were differentially expressed in at least three independent studies. Upregulating miR-146a and downregulating miR-192, miR-134, miR-27b and miR-324 were found in three studies. MiR-122 and miR-29a were upregulated in four studies after BPA exposure, and miR-21 was upregulated in six studies. The results indicate that BPA at low-level exposures can also alter miRNA expression in response to toxicity. Finally, the miRNA-related pathways showed that BPA seriously can affect human health through various cell signaling pathways, which were predictable and consistent with existing studies. Overall, our findings suggest that further studies should be conducted to examine the role of miRNA level changes in human BPA exposure.

Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine.

AIM: The present study aimed to identify human protein-host protein interactions of SARS-CoV-2 infection in the small intestine to discern the potential mechanisms and gain insights into the associated biomarkers and treatment strategies. BACKGROUND: Deciphering the tissue and organ interactions of the SARS-CoV-2 infection can be important to discern the potential underlying mechanisms. In the present study, we investigated the human protein-host protein interactions in the small intestine. METHODS: Public databases and published works were used to collect data related to small intestine tissue and SARS-CoV-2 infection. We constructed a human protein-protein interaction (PPI) network and showed interactions of host proteins in the small intestine. Associated modules, biological processes, functional pathways, regulatory transcription factors, disease ontology categories, and possible drug candidates for therapeutic targets were identified. RESULTS: Thirteen primary protein neighbors were found for the SARS-CoV-2 receptor ACE2. ACE2 and its four partners were observed in a highly clustered module; moreover, 8 host proteins belonged to this module. The protein digestion and absorption as a significant pathway was highlighted with enriched genes of ACE2, MEP1A, MEP1B, DPP4, and XPNPEP2. The HNF4A, HNF1A, and HNF1B transcription factors were found to be regulating the expression of ACE2. A significant association with 12 diseases was deciphered and 116 drug-target interactions were identified. CONCLUSION: The protein-host protein interactome revealed the important elements and interactions for SARS-CoV-2 infection in the small intestine, which can be useful in clarifying the mechanisms of gastrointestinal symptoms and inflammation. The results suggest that antiviral targeting of these interactions may improve the condition of COVID-19 patients.

Systems toxicology assessment revealed the impact of graphene-based materials on cell cycle regulators.

Understanding the cellular and molecular toxicity of graphene and its derivatives is essential for their biomedical applications. Herein, gene expression profile of graphene-exposed cells was retrieved from the Gene expression omnibus database. Differentially expressed genes and their functional roles were then investigated through the pathway, protein-protein interaction (PPI) network, and module analysis. High degree (hub) and high betweenness centrality (bottleneck) nodes were subsequently identified. The functional analysis of central genes indicated that these graphene-gene interactions could be of great value for further investigation. Accordingly, we also followed the expression of five hub-bottleneck genes in graphene-treated murine peritoneal macrophages and human breast cancer cell line by real-time PCR. The five hub-bottleneck genes related to graphene cytotoxicity; CDK1, CCNB1, PLK1, TOP2A, and CCNA2 were identified through network analysis, which were highly correlated with regulation of cell cycle processes. The module analysis indicated the cell cycle pathway to be the predominant one. Gene expression evaluation showed downregulation of these genes in the macrophages and cancer cells treated with graphene. These results provided some new intuitions concerning the graphene-cell interactions and unveiled targeting critical cell cycle regulators. The present study indicated some toxic effects of graphene-based materials through systems toxicology assessment. Integrating gene expression and PPI network may help explaining biological responses of graphene and lead to beneficial impacts in nanomedicine.

FDA Approved Drugs Repurposing of Toll-Like Receptor4 (TLR4) Candidate for Neuropathy.

Accumulating evidence indicates that toll-like receptor 4 (TLR4) plays a critical role in promoting adaptive immune responses and are definitively involved in the expansion and maintenance of the neuropathic pain. Though the application of docking in virtual-screening in silico methods to drug discovery has some challenge, it allows directed and meaningful design of drugs for a target protein; which can lead to low costing approaches with shortcuts; resulting in evolution and discovery of promising new drugs. Nevertheless, in parallel with virtual screening methods, attendant developments in cell culture and in-vivo studies must be achieved. In the present paper, we aimed to discover new drugs that have the ability to bind and inhibit TLR4 functions. So, after using the Pathway studio to investigate the biological pathways and protein interaction maps between TLR4 and neuropathy, we reported the application of the affinity-based approach of different pharmaceuticals; these agents contained all of the approved drugs; which could bind to Toll-like receptor 4 in blind high-throughput in silico screening. Our results demonstrated that among the primary list of 1945 retrieved compounds, 39 approved compounds could be the right candidate to perform a biological test in different in-vivo and in-vitro conditions and as a lead for further neurophysiological and neuropathological studies and treatment of neuropathic pain.