Current Signal Transduction Therapy最新文献

{"title":"Deciphering the Role of Various Signaling Pathways in the Pathophysiology of Depression","authors":"Etash Vashisht, Vishal Vats, Ravinder Verma, Jatin Parashar, Vandana Garg, Rohit Dutt, Vineet Mittal, Govind Singh, Deepak Kaushik","doi":"10.2174/0115743624255521230920070219","DOIUrl":"https://doi.org/10.2174/0115743624255521230920070219","url":null,"abstract":"Background: Depression is one of the leading causes of disability around the globe. In the early years of depression, it is hypothesized that neurotransmitters have a major or dominant role in depression pathophysiology. The roles of different parts of the brain and neurotransmitters have emerged at different intervals of time, and various hypotheses beyond monoamines have arisen. In this review, numerous theories that have been proposed in the last 60 years are covered based on the literature. Methodology: This review was prepared with literature and data presented from different databases including PubMed, Frontier in Pharmacology, Elsevier, Journal of Depression and Anxiety, etc. Results: The different hypotheses of depression have been presented in different eras. Each hypothesis of depression tries to explore different aspects of depression, which shifts the pathogenesis of depression approaches towards bio-molecule and genetic roles. Conclusion: The pathophysiology of depression is very complex. None of the hypotheses alone can explain the pathophysiology of depression. All of these hypotheses are interconnected with each other. Through these hypotheses, it can be concluded that neuro-inflammation can be the base of depression and by reducing this factor we can overcome this problem","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135546036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Identification of RET inhibitor: A Computational Study","authors":"A. Verma, P. Wadhwa","doi":"10.2174/1574362418666230817100406","DOIUrl":"https://doi.org/10.2174/1574362418666230817100406","url":null,"abstract":"\u0000\u0000RET (Rearranged during transcription) kinase is one of the key targets for anticancer drug development. Understanding the real mechanism of pharmacological action is aided by the protein-ligand interaction. The purpose of this study is to find the most effective RET inhibitors.\u0000\u0000\u0000\u0000Firstly, through a literature survey, we understood that tetrazole is useful nuclei to provide anticancer activity. Hence, a molecule was drawn containing tetrazole ring using Chemdraw 16.0. This drawn compound was used to determine further ligands employing Zincpharmer. Then, the 3D energy minimized structure of proposed ligands and positive control (selpercatinib and pralsetinib) were drawn using Chem3D. Further, docking was performed for all the ligands with phosphorylated RET kinase (PDB ID – 2IVU) using trial version of Molegro virtual docker 7.0.\u0000\u0000\u0000\u0000Determined ligands were docked with the help of Molegro virtual Docker (MVD) 7.0 employing RET kinase (2ivu) as protein.\u0000\u0000\u0000\u0000Top 10 compounds were selected and their drug-like properties along with their oral bioavailability were also determined. ZINC12180698, ZINC12180696, ZINC09616526, ZINC12180701, ZINC09616182, ZINC09616145, ZINC17052231, ZINC17052262, ZINC12180700, and ZINC09616518 were among the top ten compounds that showed the strongest affinity for the target for RET-mediated cancer in this study.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41780607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation S249C of FGFR3b Promotes Bladder Cancer through Downstream\u0000Signaling Proteins FRS2 and FRS3: A Computational Approach","authors":"A. Ali, Alwisha Lateef, Zuha Waheed, Mishal Waseem, Tahreem Zaheer, Miriam K Gomez, R. Blaheta, Saira Justin","doi":"10.2174/1574362418666230810094626","DOIUrl":"https://doi.org/10.2174/1574362418666230810094626","url":null,"abstract":"\u0000\u0000Bladder cancer is the 9th most prevalent malignancy worldwide. Fibroblast\u0000Growth Factor Receptor 3b (FGFR3b), involved in cell proliferation, differentiation, and migration,\u0000is a mutations hotspot for bladder cancer with the most prevalent aberration being S249C.\u0000\u0000\u0000\u0000Impact of S249C of FGFR3b on bladder tumorigenesis via immediate downstream adapter\u0000proteins, Fibroblast Growth Factor Receptor Substrate (FRS2 and FRS3) is analyzed computationally.\u0000\u0000\u0000\u0000Wildtype FGFR3b monomer was modeled using I-TASSER and Phyre2. Whereas,\u0000S249C mutation was introduced via DynaMut. Wildtype FGFR3b homodimer and mutant heterodimer were structured and docked with downstream proteins using HADDOCK. PDBSum was\u0000used to study the amino acid residues involved in intermolecular and intramolecular interactions.\u0000\u0000\u0000\u0000Parameters of molecular flexibility and interatomic interactions predicted S249C heterodimer mutation of FGFR3b to be stable. Furthermore, docking with FRS2 protein revealed greater\u0000stability and higher binding affinity for S249C heterodimer mutant compared to wildtype homodimer. However, FRS3 docking showed a negligible decline in binding affinity for the S249C mutation but based on Van der Waal’s energy and insights into the interacting residues, it was revealed\u0000that these interactions might be stronger and for longer duration in comparison to the wildtype homodimer.\u0000\u0000\u0000\u0000S249C heterodimer mutation of FGFR3b is predicted to be stable with a tumorigenic\u0000potential where FRS2 and FRS3 might be among the key players of altered downstream signaling.\u0000Further investigations are required for a detailed picture.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42422047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretation and Classification of Phonocardiogram Using Principal Component Analysis","authors":"Nikita Jatia, Sachin Kumar, K. Veer","doi":"10.2174/1574362418666230803145322","DOIUrl":"https://doi.org/10.2174/1574362418666230803145322","url":null,"abstract":"\u0000\u0000Large datasets are logically common yet frequently difficult to interpret. Principal Component Analysis (PCA) is a technique to reduce the dimensionality of a dataset.\u0000\u0000\u0000\u0000The main objective of this work is to use principal component analysis to interpret and classify phonocardiogram signals.\u0000\u0000\u0000\u0000Finding new factors aids in the reduction of important components of an eigenvalue/eigenvector problem, thus enabling the new factors to be represented by the current dataset and making PCA a flexible data analysis tool. PCA is adaptable to a variety of systems created to update different data types and technology advancements.\u0000\u0000\u0000\u0000Signals acquired from a patient, i.e., bio-signals, are used to investigate the patient's strength. One such bio-signal of central significance is the phonocardiogram (PCG), which addresses the working of the heart. Any change in the PCG signal is a characteristic proportion of heart failure, an arrhythmia condition.\u0000\u0000\u0000\u0000Long-term observation is difficult due to the many complexities, such as the lack of human competence and the high chance of misdiagnosis.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48335790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Docking Analysis of Deltamethrin Pesticide with Mhc I and Mhc Ii Molecules to Establish Immunomodulation Effects","authors":"Anupam Kumar, Bhupender Singh, Deepak Kumar, Anil Verma, Pankaj Wadhwa","doi":"10.2174/1574362418666230908153504","DOIUrl":"https://doi.org/10.2174/1574362418666230908153504","url":null,"abstract":"Background: Deltamethrin is a class II synthetic pyrethroid pesticide extensively used to control pests and vectors in the agriculture sector and health management programme. Due to excessive applications of this pesticide in the environment, it is harming many organisms other than the target organisms. Higher organisms like human beings are also affected by this pesticide because it instigates the impairment of the central nervous system and also distresses the immune system of vertebrates. Methods: In the current research study, MHC I and MHC II molecules of human origin have been targeted to evaluate the interaction with deltamethrin molecules by the AutoDock tool to establish the immunomodulatory effect. MHC I receptor molecule is presented on every nucleated cell, and MHC II receptors are located specifically on cell surfaces of antigen-presenting cells. These receptors play a role in cell-mediated and humoral immune responses. The binding affinity of deltamethrin with MHC receptors can affect the immune response, specifically the acquired immunity of an individual. Results: Findings of the current research study support that deltamethrin causes the suppression of the immune system by interaction with MHC I and MHC II molecules and may cause the organisms to be more prone towards antigen and disease development. Conclusion: The autoDock tool can be utilized to analyse other pesticides’ effects on the immune system and in the drug development process to minimize the toxic effects due to several types of pesticides.","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":"107 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135804970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of DNA Concentration on the HRM performance in detecting Jak2 p.V617F variant in patients with myeloproliferative neoplasms","authors":"Alireza Moradabadi, Atefeh Soltani, A. Shariati, M. Didehdar, A. Anoushirvani, Seidamir Pasha Tabaeian","doi":"10.2174/1574362418666230609112551","DOIUrl":"https://doi.org/10.2174/1574362418666230609112551","url":null,"abstract":"\u0000\u0000Janus kinase 2 (JAK2) is an intracellular signaling protein. JAK2 p. V617F is a common variant in normal karyotype myeloproliferative neoplasms (MPN). High-resolution melting (HRM) analysis is one of the essential methods for detecting the JAK2 p.V617F variant. In this study, we have investigated the effect of DNA concentration on detecting the JAK2 p.V617F variant using the HRM method.\u0000\u0000\u0000\u0000Genomic DNA was extracted from human blood and diluted ten times in distilled water from 1 to 0.03; afterward, HRM was conducted for each dilution (triplicate). Using SPSS v.20.0 software, the mean Tm of each dilution was calculated and compared.\u0000\u0000\u0000\u0000The HRM results revealed the JAK2 wild type and variant to have Tms of 81/64°C and 80/76°C, respectively. At the endpoint of the pre-amplification, the dilutions had different emissions. The statistical analysis revealed no statistically significant differences in Tm between samples with varying DNA concentrations (P value > 0.05).\u0000\u0000\u0000\u0000There have been no significant differences obtained in the analysis of JAK2 p.V617F point variant in different DNA dilutions, implying that the HRM analysis has no relation to DNA concentration.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49187858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review On Inhibitory Action of Tyrosine Kinase Inhibitors (TKI) by Curbing the ATP-Tyrosine Kinase Interactions","authors":"Vanktesh Kumar, Navjot Kaur","doi":"10.2174/1574362418666230404133417","DOIUrl":"https://doi.org/10.2174/1574362418666230404133417","url":null,"abstract":"\u0000\u0000According to the latest data, the cancer prevalence fraction has surged to the highest number. This is why cancer has become a prominent disease that must be seen as a serious issue. Inhibitory action and ideas become prominent and necessary because of the rising death incidence daily. The simplifying idea of inhibition of cancer is targeting the complex that forms between the tyrosine kinase and ATP, which ultimately provides a clear way. Tyrosine kinase is a proteinaceous enzyme responsible for various cellular events like cell development, growth, and division. But these functions are performed by the activated tyrosine kinase, and the activation occurs by phosphorylation using ATP. The transfer of the phosphate group from ATP to tyrosine is known as phosphorylation. The basic idea is to enhance the competitive inhibition of the ATP-Tyrosine complex is a promising target for treating cancer. Various molecules have a substantial effect on the above-said target. This review summarizes molecules currently in any drug development or clinical trial with the same effect. This review covers most inhibitory molecules from different categories, which either directly or indirectly inhibit the Tyrosin kinase-ATP complex by incorporating.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43696476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust Computational Model for Diagnosis of Mitogenic Activated Protein Kinase Leading to Neurodegenerative Diseases","authors":"A. Salau, Shruti Jain","doi":"10.2174/1574362418666230321152206","DOIUrl":"https://doi.org/10.2174/1574362418666230321152206","url":null,"abstract":"\u0000\u0000Computational modeling is used to develop solutions by formulating and modeling real-world problems. This research article presents an innovative approach to using a computational model, as well as an evaluation of software interfaces for usability\u0000\u0000\u0000\u0000In this work, a machine learning technique is used to classify different mitogenic activated protein kinases (MAPK), namely extracellular signal-regulated kinase (ERK), c-Jun amino (N)-terminal kinases (JNK), and mitogenic kinase (MK2) proteins. A deficiency of ERK and JNK leads to neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease (AD), and prion diseases, while the deficiency of MK2 leads to atherosclerosis. In this study, images from a heat map were normalized, scaled, smoothed, and sharpened. Different feature extraction methods have been used for various attributes, while principal component analysis was used as a feature selection technique. These features were extracted with machine learning algorithms to produce promising results for clinical applications.\u0000\u0000\u0000\u0000The results show that ANN achieves 97.09%, 96.82%, and 96.01% accuracy for JNK, ERK, and MK2 proteins, respectively, whereas CNN achieves 97.60%, 97.36%, and 96.81% accuracy for the same proteins. When CNN is used, the best results are obtained for JNK protein, with a training accuracy of 97.06% and a testing accuracy of 97.6%.\u0000\u0000\u0000\u0000The proposed computational model is validated using a convolution neural network (CNN). The effect of the hidden layer on different activation functions has been then observed using ANN and CNN. The proposed model may assist in the detection of various MAPK proteins, yielding promising results for clinical diagnostic applications.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49096522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of probiotics and resveratrol to target drug resistance in breast cancer: an in vitro and in vivo study","authors":"Wamidh H. Talib, Faten Farhan","doi":"10.2174/1574362418666230228122251","DOIUrl":"https://doi.org/10.2174/1574362418666230228122251","url":null,"abstract":"\u0000\u0000To evaluate new anticancer combination to target drug resistance in breast cancer\u0000\u0000\u0000\u0000Probiotics have significant activity in the immune system by the activation of multiple immune mechanisms. Resveratrol is a non-flavonoid polyphenol. It has various pharmacological effects, including anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenesis.\u0000\u0000\u0000\u0000The present study investigates the potential immunomodulatory and antitumor activity of the combination treatment of probiotics and resveratrol in sensitive and cisplatin resistant breast cancer.\u0000\u0000\u0000\u0000In the in vivo part, tumor-bearing mice received one of the following treatments: 2.5*108 CFU/ml probiotics, 50mg/kg resveratrol, the combination of probiotics and resveratrol, vehicle, or cisplatin. Balb/C mice were inoculated with sensitive EMT6/P & cisplatin resistance EMT6/CPR cancer cell lines and in vivo antitumor activity was evaluated. The antiproliferative activity of the probiotics, resveratrol, and their combination treatments was assessed using MTT assay to evaluate lymphocyte proliferation activity. LDH colorimetric assay was conducted to measure the effectiveness of the treatments on Natural killer cells activity. Nitro blue tetrazolium assay and neutral red method have been used to evaluate macrophage function.\u0000\u0000\u0000\u0000The combination treatment showed enhancement effect in splenic lymphocytes proliferation, macrophage function, phagocytosis, and pinocytosis in both cell lines. It was shown that a significant reduction in tumor size and weight in EMT6/P and EMT6/CPR bearing mice occurred.\u0000\u0000\u0000\u0000The combination treatment of probiotics and resveratrol had a valuable activity against sensitive and cisplatin resistant breast cancer cells and may act as a stimulator of the immune system. Therefore, the combination of probiotics and resveratrol deserves further analysis to be used in cancer prevention and treatment.\u0000\u0000\u0000\u0000Further studies are needed to fully understand the mechanisms of action of this combination\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42035921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Evolution of Bilirubin Physiology and Analysis","authors":"Kabita Kumari, Shravan Kumar Pahuja, Sanjeev Kumar","doi":"10.2174/1574362418666230216152920","DOIUrl":"https://doi.org/10.2174/1574362418666230216152920","url":null,"abstract":"\u0000\u0000Bilirubin is a yellow tetrapyrrole molecule found in the gastrointestinal system, and it is produced when hemoglobin (Hb) is degraded. For treating various liver disorders like jaundice, serum bilirubin in the body is a testing marker. Jaundice develops when the serum bilirubin level is more significant than 2.0 to 2.5 mg/dl. Examining different forms of bilirubin, i.e., conjugated (direct) bilirubin, unconjugated (indirect) bilirubin, and total bilirubin, helps the physician identify the cause and metabolic disorder of jaundice. Inconsistent bilirubin production and removal results in lasting neurologic consequences (kernicterus). In this paper, we have presented a brief introduction to jaundice, the physiological mechanism of bilirubin, its types and causes, clinical approaches toward patients having jaundice, i.e., the conventional method being practiced in clinical laboratories, and various non-invasive systems in the point-of-care settings along with their advantages and disadvantages. Information on bilirubin production and elimination with tracking of bilirubin levels may help to guide the proper clinical management of jaundice. The primary focus is on the progression of established methodologies and techniques to newer ones capable of measuring bilirubin in biological materials.\u0000","PeriodicalId":10868,"journal":{"name":"Current Signal Transduction Therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43005183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}