Deciphering the miRNA-mRNA Interaction Landscape between Breast Cancer and Triple-Negative Breast Cancer: An Integrated Bioinformatics Approach.

Breast cancer (BC) is globally recognized as the second most prevalent form of cancer. It predominantly affects women and can be categorized into distinct types based on the overexpression of specific cancer receptors.The key receptors implicated in this context are the human epidermal growth factor receptor-2 (HER2), estrogen receptor (ER), and progesterone receptor (PR), alongside a particularly intricate subclass known as triple-negative breast cancer (TNBC). This subclassification is critical for the stratification of breast cancer and informs therapeutic decision-making processes. Due to a lack of therapeutic targets, such as growth factor receptors, TNBC is the most aggressive type. Hence, identifying targetable regulators such as miRNAs could pave the way for potential therapeutic interventions. To identify common differentially expressed mRNAs (DE-mRNAs) in BC, including TNBC, we leveraged two data sets from the GEO collection and The Cancer Genome Atlas (TCGA). Significant DE-mRNAs were identified through PPI, MCODE, CytoNCA, and CytoHubba analyses. Following this, miRNAs were predicted using mirDIP. We utilized GSE42568, GSE185645, and TCGA and identified 159 common DE-mRNAs. Using Cytoscape plug-ins, we identified the 10 most significant DE-mRNAs in BC. Using mirDIP, target miRNAs for 10 DE-mRNAs were identified. We conducted an advanced analysis on the TNBC GEO data set (GSE45498) to corroborate the significance of shared DE-mRNAs and DE-miRNAs in TNBC. We identified four downregulated DE-miRNAs, including hsa-miR-802, hsa-miR-1258, hsa-miR-548a-3p, and hsa-miR-2053, significantly associated with TNBC. Our study revealed significant miRNA-mRNA interactions, specifically hsa-miR-802/MELK, hsa-miR-1258/NCAPG, miR-548a-3p/CCNA2, and hsa-miR-2053/NUSAP1, in both BC and TNBC. The observed downregulation of hsa-miR-548a-3p is associated with diminished survival rates in BC patients, emphasizing their potential utility as prognostic indicators. Furthermore, the differential expression of mRNAs, including CCNB2, UBE2C, MELK, and KIF2C, correlates with reduced survival outcomes, signifying their critical role as potential targets for therapeutic intervention in both BC and TNBC. These findings highlight specific regulatory mechanisms that are potentially crucial for understanding and treating these cancer types.

Dissecting Crucial Gene Markers Involved in HPV-Associated Oropharyngeal Squamous Cell Carcinoma from RNA-Sequencing Data through Explainable Artificial Intelligence.

BACKGROUND: The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the etiology of the OPSCC to facilitate the administration of effective treatments. METHODS: This study confers an integrative genomics approach for identifying key oncogenic drivers involved in the OPSCC pathogenesis. The dataset contains RNA-Sequencing (RNA-Seq) samples of 46 Human papillomavirus-positive head and neck squamous cell carcinoma and 25 normal Uvulopalatopharyngoplasty cases. The differential marker selection is performed between the groups with a log2FoldChange (FC) score of 2, adjusted p-value < 0.01, and screened 714 genes. The Particle Swarm Optimization (PSO) algorithm selects the candidate gene subset, reducing the size to 73. The state-of-the-art machine learning algorithms are trained with the differentially expressed genes and candidate subsets of PSO. RESULTS: The analysis of predictive models using Shapley Additive exPlanations revealed that seven genes significantly contribute to the model's performance. These include ECT2, LAMC2, and DSG2, which predominantly influence differentiating between sample groups. They were followed in importance by FAT1, PLOD2, COL1A1, and PLAU. The Random Forest and Bayes Net algorithms also achieved perfect validation scores when using PSO features. Furthermore, gene set enrichment analysis, protein-protein interactions, and disease ontology mining revealed a significant association between these genes and the target condition. As indicated by Shapley Additive exPlanations (SHAPs), the survival analysis of three key genes unveiled strong over-expression in the samples from "The Cancer Genome Atlas". CONCLUSIONS: Our findings elucidate critical oncogenic drivers in OPSCC, offering vital insights for developing targeted therapies and enhancing understanding its pathogenesis.

Deciphering the Impact of Rare Missense Variants in EGFR-TKI-Resistant Non-Small-Cell Lung Cancer through Whole Exome Sequencing: A Computational Approach.

Targeted therapy revolutionizes the treatment of non-small-cell lung cancer (NSCLC), harboring molecular change. Epidermal growth factor receptor(EGFR) mutations play a crucial role in the development of NSCLC, serving as a pivotal factor in its pathogenesis. We elucidated the mechanisms of resistance and potential therapeutic strategies in NSCLC resistant to the EGFR-tyrosine kinase inhibitor (EGFR-TKI). This is achieved by identifying rare missense variants through whole exome sequencing (WES). The goal is to enhance our understanding, identify biomarkers, and lay the groundwork for targeted interventions, thereby offering hope for an improved NSCLC treatment landscape. We conducted WES analysis on 16 NSCLC samples with EGFR-TKI-resistant NSCLC obtained from SRA-NCBI (PRJEB50602) to reveal genomic profiles within the EGFR-TKI. Our findings showed that 48% of the variants were missense, and after filtering with the Ensembl variant effect predictor, 53 rare missense variants in 23 genes were identified as highly deleterious. Further examination using pathogenic tools like PredictSNP revealed 12 deleterious rare missense variants in 7 genes: ZNF717, PSPH, ESRRA, SEMA3G, PTPN7, CAVIN4, and MYBBP1A. Molecular dynamics simulation (MDS) suggested that the L385P variant alters the structural flexibility of ESRRA, potentially leading to unfolding of ERRα proteins. This could impact their function and alter ERRα expression. These insights from MDS enhance our understanding of the structural and dynamic consequences of the L385P ESRRA variant and provide valuable implications for subsequent therapeutic considerations and targeted interventions.

Surface functionalization, particle size and pharmaceutical co-contaminant dependent impact of nanoplastics on marine crustacean - Artemia salina.

Despite a significant amount of research on micronanoplastics (MNPs), there is still a gap in our understanding of their function as transporters of other environmental pollutants (known as the Trojan horse effect) and the combined effects of ingestion, bioaccumulation, and toxicity to organisms. This study examined the individual effects of polystyrene nanoplastics (PSNPs) with various surface functionalizations (plain (PS), carboxylated (PS-COOH), and aminated (PS-NH2)), particle sizes (100 nm and 500 nm), and a pharmaceutical co-contaminant (metformin hydrochloride (MH), an anti-diabetic drug) on the marine crustacean - Artemia salina. The study specifically aimed to determine if MH alters the detrimental effects of PSNPs on A. salina. The potential toxicity of these emerging pollutants was assessed by examining mortality, hatching rate, morphological changes, and biochemical changes. Smaller nanoparticles had a more significant impact than larger ones, and PS-NH2 was more harmful than PS and PS-COOH. Exposure to the nanoparticle complex with MH resulted in a decrease in hatching rate, an increase in mortality, developmental abnormalities, an increase in reactive oxygen species, catalase, and lipid peroxidase, and a decrease in total protein and superoxide dismutase, indicating a synergistic effect. There were no significant differences between the complex and the individual nanoparticles. However, accumulating these particles in organisms could contaminate the food chain. These results highlight the potential environmental risks associated with the simultaneous exposure of aquatic species to plastics, particularly smaller PS, aminated PS, and pharmaceutical complex PS.

Genomic insights and advanced machine learning: characterizing autism spectrum disorder biomarkers and genetic interactions.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by altered brain connectivity and function. In this study, we employed advanced bioinformatics and explainable AI to analyze gene expression associated with ASD, using data from five GEO datasets. Among 351 neurotypical controls and 358 individuals with autism, we identified 3,339 Differentially Expressed Genes (DEGs) with an adjusted p-value (≤ 0.05). A subsequent meta-analysis pinpointed 342 DEGs (adjusted p-value ≤ 0.001), including 19 upregulated and 10 down-regulated genes across all datasets. Shared genes, pathogenic single nucleotide polymorphisms (SNPs), chromosomal positions, and their impact on biological pathways were examined. We identified potential biomarkers (HOXB3, NR2F2, MAPK8IP3, PIGT, SEMA4D, and SSH1) through text mining, meriting further investigation. Additionally, we shed light on the roles of RPS4Y1 and KDM5D genes in neurogenesis and neurodevelopment. Our analysis detected 1,286 SNPs linked to ASD-related conditions, of which 14 high-risk SNPs were located on chromosomes 10 and X. We highlighted potential missense SNPs associated with FGFR inhibitors, suggesting that it may serve as a promising biomarker for responsiveness to targeted therapies. Our explainable AI model identified the MID2 gene as a potential ASD biomarker. This research unveils vital genes and potential biomarkers, providing a foundation for novel gene discovery in complex diseases.

Comparative Atomistic Insights on Apo and ATP-I1171N/S/T in Nonsmall-Cell Lung Cancer.

Anaplastic lymphoma kinase (ALK) rearrangements occur in about 5% of nonsmall cell lung cancer (NSCLC) patients. Despite being first recognized as EML4-ALK, fusions with several additional genes have been identified, all of which cause constitutive activation of the ALK kinase and subsequently lead to tumor development. ALK inhibitors first-line crizotinib, second-line ceritinib, and alectinib are effective against NSCLC patients with these rearrangements. Patients progressing on crizotinib had various mutations in the ALK kinase domain. ALK fusion proteins are activated by oligomerization through the fusion partner, which leads to the autophosphorylation of the kinase's domain and consequent downstream activation. The proposed computational study focuses on understanding the activation mechanism of ALK and ATP binding of wild-type (WT) and I1171N/S/T mutations. We analyzed the conformational change of ALK I1171N/S/T mutations and ATP binding using molecular docking and molecular dynamics simulation approaches. According to principal component analysis and free energy landscape, it is clear that I1171N/S/T mutations in Apo and ATP showed different energy minima/unstable structures compared to WT-Apo. The results revealed that I1171N/S/T mutations and ATP binding significantly supported a change toward an active-state conformation, whereas WT-Apo remained inactive. We demonstrated that I1171N/S/T mutations are persistent in an active state and independent of ATP. The I1171S/T mutations showed greater intermolecular H-bonds with ATP than WT-ATP. The molecular mechanics Poisson-Boltzmann surface area analysis revealed that the I1171N/S/T mutation binding energy was similar to that of WT-ATP. This study shows that I1171N/S/T can form stable bonds with ATP and may contribute to a constitutively active kinase. Based on the Y1278-C1097 H-bond and E1167-K1150 salt bridge interaction, I1171N strongly promotes the constitutively active kinase independent of ATP. This structural mechanism study will aid in understanding the oncogenic activity of ALK and the basis for improving the ALK inhibitors.

Longitudinal assessment of HCV core antigen kinetics to monitor therapeutic response in the age of DAAs.

BACKGROUND: In the economy of therapeutic monitoring, an affordable viral marker is essential in the era of direct-acting antivirals (DAAs). We elucidated the kinetics of HCVcAg to delineate its precise role in monitoring therapeutic response. METHODS: In this longitudinal study, 3208 patients were tested for HCV RNA. A total of 423 patients were started on DAAs. Treatment response and kinetics of HCVcAg/RNA were assessed in treatment-naïve (n = 383) and previously treated (n = 40) patients with follow-up for 2 years. RESULTS: After the initiation of DAAs, the rate of relapse was significantly higher in the previously treated group than naive group [12.5% (5/40) Vs 2% (7/383), p<0.0001]. The response rate at RVR was significantly higher with HCVcAg than RNA in both groups (p<0.02). The kinetics of HCVcAg and RNA were significantly different at ETR and SVR12 in the naïve (p<0.04), but similar at all therapeutic points in the previously treated group. The correlation between HCVcAg and RNA was good at baseline, ETR and SVR, except RVR in both groups (r>0.6; p<0.0001). Furthermore, HCV genotypes, treatment regimen, CTP (<7/≥7) and MELD (<15/≥15) did not influence the therapeutic response and the viral replication kinetics (p>0.05). CONCLUSIONS: It is the first longitudinal study from India shows that the response rate and kinetics of HCVcAg are comparable to HCV RNA for an extended duration, except at RVR, irrespective of the HCV genotypes, treatment regimen, and liver disease severity. Hence, HCVcAg can be considered as a pragmatic marker to monitor therapeutic response and predict relapse in the era of DAAs.

A computational examination of the therapeutic advantages of fourth-generation ALK inhibitors TPX-0131 and repotrectinib over third-generation lorlatinib for NSCLC with ALK F1174C/L/V mutations.

Background: In non-small-cell lung cancer (NSCLC), a pivotal factor in promoting cancer development is the rearrangement in the anaplastic lymphoma kinase ALK gene, resulting in elevated ALK protein expression. F1174C/L/V is the acquired secondary resistant mutation in ALK. Significant survival improvements have been seen while tyrosine kinase inhibitors specifically target ALK. Nevertheless, the emergence of drug resistance hinders the clinical effectiveness of these drugs. Objective: This research sought to find the binding affinity/inhibitory effects of the existing drug lorlatinib (LOR) and upcoming TPX-0131 (zotizalkib/TPX) and repotrectinib (TPX-0005/REP) inhibitors against ALK F1174C/L/V mutations using computational approaches to identify potential strategies over resistance. Methods: We conducted molecular docking, molecular dynamics simulation, and MMPBSA calculations to investigate how compact macrocyclic inhibitors, such as TPX-0131 and repotrectinib, fit within the ATP-binding boundary and differ from LOR. Results: Our results demonstrated that TPX-0131 and repotrectinib contributed to higher binding energy in F1174C and F1174L mutations than LOR. Repotrectinib showed greater binding energy in the F1174V mutation, whereas LOR and TPX-0131 exhibited similar binding energy. However, all three inhibitors showed significant binding energy toward F1174C/L/V mutations found in NSCLC. Conclusion: This comparative study of the potential binding effects of fourth-generation inhibitors TPX-0131 and repotrectinib and third-generation inhibitor LOR for ALK F1174C/L/V mutations revealed the atomistic insights of the binding mechanism. These computational findings enable us to carry out further research for the clinical implementation of fourth-generation ALK inhibitors on ALK-positive NSCLC.

3-Hydroxypropane-1,2-Diyl Dipalmitoleate-A Natural Compound with Dual Roles (CB1 Agonist/FAAH1 Blocker) in Inhibiting Ovarian Cancer Cell Line.

Though it was once known that upregulated Cannabinoid Receptor (CB1) and downregulated Fatty Acid Amide Hydrolase (FAAH1) are associated with tumour aggressiveness and metastasis, it is now clear that upregulated CB1 levels more than a certain point cause accumulation of ceramide and directs cells to apoptosis. Hence, CB1 analogues/FAAH1 blockers are explored widely as anticancer drugs. There are reports on CB1-agonists and FAAH1-blockers separately, however, dual activities along with ovarian cancer-specific links are not established for any natural compound. With this setting, we describe for the first time the isolation of 3-hydroxypropane-1,2-diyl dipalmitoleate (564.48 Da) from a marine snail, Conus inscriptus, which binds to both CB1 and FAAH1 (glide energies: -70.61 and -30.52 kcal/mol, respectively). MD simulations indicate stable compound-target interaction for a minimum of 50 nanoseconds with relative invariabilities in Rg. The compound inhibited ovarian cancer cell line, PA1 at 1.7 µM. Structural and chemical interpretation of the compound (C2) was done using FT-IR, GC-MS, ESI-MS, 1H and 13C-NMR (1 and 2D). Furthermore, a probable route for gram-scale synthesis of C2 is hinted herein. With the available preliminary data, molecular mechanisms involving dual roles for this potent molecule must be elucidated to understand the possibilities of usage as an anticancer drug.

Molecular insights of the G2019S substitution in LRRK2 kinase domain associated with Parkinson's disease: A molecular dynamics simulation approach.

The G2019S substitution in the Leucine-rich repeat kinase 2 (LRRK2) is significantly associated with Parkinson's disease (PD). This substitution was identified in both familial and sporadic forms of PD with a higher frequency. Few computational studies have reported the impact of G2019S substitution on inhibitors of the kinase domain of LRRK2. However, no computational study deeply investigated the possible impact of the G2019S substitution on the kinase domain in its Apo conformation. Therefore, in this study, we used 200 ns molecular dynamic simulation using the GROMACS 5.1.4 package software to investigate the impact of the G2019S substitution on the structure of the kinase domain of LRRK2. Our results indicate that the G2019S substitution affects the dynamics and stability of LRRK2 by decreasing the flexibility and increasing the compactness of the kinase domain and showing its tendency to be in an active conformation for long time interval because of the high energy barrier between active and inactive conformation. This study predicts the molecular pathogenicity mechanism of the G2019S on patients with PD and provides a potential platform for developing therapeutics for patients with PD that harbor this amino acid substitution.

Inhibition of the ATPase Domain of Human Topoisomerase IIa on HepG2 Cells by 1, 2-benzenedicarboxylic Acid, Mono (2-ethylhexyl) Ester: Molecular Docking and Dynamics Simulations.

BACKGROUND: The major attention has been received by the natural products in the prevention of diseases due to their pharmacological role. OBJECTIVE: The major focus of the study was to search for highly potential anti-cancer compounds from marine Streptomyces sp. VITJS4 (NCIM No. 5574). METHODS: Cytotoxic assay was examined by MTT assay on HepG2 cells. Bioassay-guided fractionation of the ethyl acetate extract from the fermented broth led to the isolation of the compound. The lead compound structure was elucidated by combined NMR and MS analysis, and the absolute configuration was assigned by extensive spectroscopic analysis. RESULTS: On the basis of spectroscopic data, the compound was identified as 1, 2 benzenedicarboxylic acid, mono 2-ethylhexyl (BMEH). The compound exhibited in vitro anticancer potential against liver (HepG2) cancer cells. Based on the flow cytometric analysis, it was evident that the BMEH was also effective in arresting the cell cycle at G1 phase. Further, the Western blotting analysis confirmed the down-regulation of Bcl-2 family proteins, and activation of caspase-9 and 3. The molecular docking and dynamics simulation were performed to reveal the activity of the compound over a time period of 10ns. From the molecular dynamics studies, it was found that the stability and compactness were attained by the protein by means of the compound interaction. CONCLUSION: This study highlights our collaborative efforts to ascertain lead molecules from marine actinomycete. This is the first and foremost report to prove the mechanistic studies of the purified compound 1, 2-benzene dicarboxylic acid, mono(2-ethylhexyl) ester isolated from marine Streptomyces sp.VITJS4 against HepG2 cells.

Prevalence of nephropathy in type 1 diabetes in the Arab world: A systematic review and meta-analysis.

The aim of this study was to conduct a systematic review and meta-analysis and determine the prevalence of diabetic nephropathy (DN) among Arab patients with T1D. A systematic literature search was conducted using 4 different literature databases (PubMed, ScienceDirect, Web of Science, and Embase) to capture all relevant data about Arab patients with T1D that had DN. Meta-analysis and systematic review were performed using the random effect model, and the heterogeneity of the studies was assessed using the Q-test, I2, and Tau-squared statistics. Publication bias was assessed using the funnel-plot test. Our search strategy captured 372 studies in only 10 out of the 22 Arab countries in a period of 48 years (1969-2017); of which, 41 met our inclusion criteria for full article analysis, of those, 15 were eligible for meta-analysis. We estimated the prevalence of DN among Arab people with T1D to be 18.2% (95% confidence interval 13.1%-24.8%). In conclusion, DN prevalence is underexplored among Arab patients with T1D and represents a significant risk for the well-being of Arab patients with T1D. Therefore, there is an urgent need for comprehensive epidemiological studies for DN among Arab patients with T1D.

Interaction of Catechu Dye with DNA: Spectroscopic and In Silico Approach.

Catechin, a yellow colored molecule obtained from the wood of Acacia catechu was analyzed for its interaction with synthetic DNA duplexes using spectroscopic analysis. UV-Visible spectroscopic analysis revealed the non-intercalative binding mode. Fourier Transform Infrared spectroscopy (FTIR) analysis expose chemical shift indicated by various vibrational stretches and an increase in the intensity of base stacking was observed by Circular Dichroism (CD), respectively. This inference was further confirmed through nuclear staining technique and also in electrophoretic technique; the dye quenches the fluorescent intensity of ethidium bromide. The result of fluorescence spectroscopy was in concordance with the electrophoretic technique. In addition, the spectroscopic results were in accordance with the molecular docking studies of specific catechin compound from the catechu dye with CT-DNA. This kind of site specificity is a gain in the medicinal field as the drug can be DNA targeted for cancer therapeutics. The present work reveals that catechu dye has a noteworthy application in the field of medical bioscience.

Functionality study of santalin as tyrosinase inhibitor: A potential depigmentation agent.

Excessive melanin production leads to hyperpigmentation disorders which results in distressing aesthetic values. Though there are some synthetic depigmentation agents available it has been reported to possess cytotoxic and mutagenic effects. Hence there is a need for the development of safe and non toxic natural tyrosinase inhibitors. Here we report the role of santalin, the chief constituent of Pterocarpus santalinus in inhibition of tyrosinase and melanin synthesis. Santalin inhibited tyrosinase activity dose dependently. Inhibitory kinetic studies revealed mixed type of inhibition with reversible mechanism. Santalin was found to interact with the fluorophore amino acid residue of tyrosinase. Analysis of circular dichroism spectra showed the binding of santalin to tyrosinase which induced the loss of secondary helical structure. Molecular docking result suggested that santalin interact with the catalytic core of tyrosinase through strong hydrogen and hydrophobic bonding. The results of in vitro studies showed santalin inhibited melanogenesis through down regulation of MITF, tyrosinase, TRP-1 and TRP-2 without any cytotoxic effects towards B16F0 melanoma cells. Therefore, our results suggested that santalin possesses anti-tyrosinase activity, which could be utilized as a safe depigmentation agent in the cosmetic field for the treatment of hyperpigmentation disorder.

Structure-activity-relationship of amide and sulfonamide analogs of omarigliptin.

A series of novel substituted-[(3R)-amino-2-(2,5-difluorophenyl)]tetrahydro-2H-pyran analogs have been prepared and evaluated as potent, selective and orally active DPP-4 inhibitors. These efforts lead to the discovery of a long acting DPP-4 inhibitor, omarigliptin (MK-3102), which recently completed phase III clinical development and has been approved in Japan.

Nanoparticle based insulin delivery system: the next generation efficient therapy for Type 1 diabetes.

Diabetic cases have increased rapidly in recent years throughout the world. Currently, for type-1 diabetes mellitus (T1DM), multiple daily insulin (MDI) injections is the most popular treatment throughout the world. At this juncture, researchers are trying to develop different insulin delivery systems, especially through oral and pulmonary route using nanocarrier based delivery system. This next generation efficient therapy for T1DM may help to improve the quality of life of diabetic patients who routinely employ insulin by the subcutaneous route. In this paper, we have depicted various next generation nanocarrier based insulin delivery systems such as chitosan-insulin nanoparticles, PLGA-insulin nanoparticles, dextran-insulin nanoparticles, polyalkylcyanoacrylated-insulin nanoparticles and solid lipid-insulin nanoparticles. Modulation of these insulin nanocarriers may lead to successful oral or pulmonary insulin nanoformulations in future clinical settings. Therefore, applications and limitations of these nanoparticles in delivering insulin to the targeted site have been thoroughly discussed.

Structural signature of the G719S-T790M double mutation in the EGFR kinase domain and its response to inhibitors.

Some individuals with non-small-cell lung cancer (NSCLC) benefit from therapies targeting epidermal growth factor receptor (EGFR), and the characterization of a new mechanism of resistance to the EGFR-specific antibody gefitinib will provide valuable insight into how therapeutic strategies might be designed to overcome this particular resistance mechanism. The G719S and T790M mutations and their combination were involved in causing different conformational redistribution of EGFR. In the present computational study, we analyzed the impact and structural influence of G719S/T790M double mutation (DM) in EGFR with ligand (gefitinib) through molecular dynamic simulation (50 ns) and docking analysis. We observed the escalation in distance between the functional loop and activation loop with respect to T790M mutation compared to the G719S mutation. Furthermore, we confirmed that the G719S mutation causes the ligand to move closer to the hinge region, whereas T790M makes the ligand escape from the binding pocket. Obtained results provide with an explanation for the resistance induced by T790M and a vital clue for the design of drugs to combat gefitinib resistance.

TNF/TNFR: drug target for autoimmune diseases and immune-mediated inflammatory diseases.

Tumor necrosis factor, a regulatory cytokine, is extremely important signaling protein in the immune system. Among TNF family, TNF-alpha, TNF-beta are most the significant family members. Receptor of TNF namely TNFR1 and TNFR2 stimulates two different signaling pathways. TNFR1 signaling induces apoptosis pathway. Conversely, TNFR2 signaling triggers cell survival pathways. In this paper, we discuss about the TNF family with special reference to TNF-alpha/TNF-beta, different hypothesis related to autoimmunity and role of TNF, structure of TNF-alpha/TNF-beta, distribution and normal activity in human body of TNF, receptors and signaling pathway for drug targeting. Finally, we also discuss about the therapy for autoimmune diseases and immune-mediated inflammatory diseases (IMIDs) using small molecules or therapeutic proteins.

Novel biomarker for prostate cancer diagnosis by MRS.

Magnetic resonance spectroscopy (MRS) is a prospective tool for characterization of the chemical composition of tissues. In vivo MRS can be used for metabolite profiling in the prostate tissue to discriminate non-invasively carcinomas and healthy prostate. In this article different prostate metabolites have been discussed and how to exploit the MRS technique for the estimation of metabolites in prostate tissue quantitatively is elucidated. Choline, citrate, creatine, myo-inositol metabolites can be considered as biomarker for localization of malignancy in the prostate and their ratio can be used for the determination of cancer tissue in the prostate gland.