Key Signaling Pathways in Psoriasis: Recent Insights from Antipsoriatic Therapeutics.
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ABSTRACT:
SUBMITTER: Ben Abdallah H
PROVIDER: S-EPMC8254604 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prostate adenocarcinoma accounts for more than 20% of deaths among males due to cancer. It is the fifth-leading cancer diagnosed in males across the globe. The mortality rate is quite high due to prostate cancer. Despite the fact that advancements in diagnostics and therapeutics have been made, there is a lack of effective drugs. Metabolic pathways are altered due to the triggering of androgen receptor (AR) signaling pathways, and elevated levels of dihydrotestosterone are produced due to defects in AR signaling that accelerate the growth of prostate cancer cells. Further, PI3K/AKT/mTOR pathways interact with AR signaling pathway and act as precursors to promote prostate cancer. Prostate cancer therapy has been classified into luminal A, luminal B, and basal subtypes. Therapeutic drugs inhibiting dihydrotestosterone and PI3K have shown to give promising results to combat prostate cancer. Many second-generation Androgen receptor signaling antagonists are given either as single agent or with the combination of other drugs. In order to develop a cure for metastasized prostate cancer cells, Androgen deprivation therapy (ADT) is applied by using surgical or chemical methods. In many cases, Prostatectomy or local radiotherapy are used to control metastasized prostate cancer. However, it has been observed that after 1.5 years to 2 years of Prostatectomy or castration, there is reoccurrence of prostate cancer and high incidence of castration resistant prostate cancer is seen in population undergone ADT. It has been observed that Androgen derivation therapy combined with drugs like abiraterone acetate or docetaxel improve overall survival rate in metastatic hormone sensitive prostate cancer (mHSPC) patients. Scientific investigations have revealed that drugs inhibiting poly ADP Ribose polymerase (PARP) are showing promising results in clinical trials in the prostate cancer population with mCRPC and DNA repair abnormalities. Recently, RISUG adv (reversible inhibition of sperm under guidance) has shown significant results against prostate cancer cell lines and MTT assay has validated substantial effects of this drug against PC3 cell lines. Current review paper highlights the advancements in prostate cancer therapeutics and new drug molecules against prostate cancer. It will provide detailed insights on the signaling pathways which need to be targeted to combat metastasized prostate cancer and castration resistant prostate cancer.
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Project description:Psoriasis is a common, chronic, and inflammatory skin disease with a high burden on individuals, health systems, and society worldwide. With the immunological pathologies and pathogenesis of psoriasis becoming gradually revealed, the therapeutic approaches for this disease have gained revolutionary progress. Nevertheless, the mechanisms of less common forms of psoriasis remain elusive. Furthermore, severe adverse effects and the recurrence of disease upon treatment cessation should be noted and addressed during the treatment, which, however, has been rarely explored with the integration of preliminary findings. Therefore, it is crucial to have a comprehensive understanding of the mechanisms behind psoriasis pathogenesis, which might offer new insights for research and lead to more substantive progress in therapeutic approaches and expand clinical options for psoriasis treatment. In this review, we looked to briefly introduce the epidemiology, clinical subtypes, pathophysiology, and comorbidities of psoriasis and systematically discuss the signaling pathways involving extracellular cytokines and intracellular transmission, as well as the cross-talk between them. In the discussion, we also paid more attention to the potential metabolic and epigenetic mechanisms of psoriasis and the molecular mechanistic cascades related to its comorbidities. This review also outlined current treatment for psoriasis, especially targeted therapies and novel therapeutic strategies, as well as the potential mechanism of disease recurrence.
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Project description:Chronic and excessive inflammation in skin and joints causes significant morbidity in psoriasis patients. As a prevalent T lymphocyte-mediated disorder, psoriasis, as well as the side effects associated with its treatment, affects patients globally. In this review, recent progress is discussed in the areas of genetics, the immunological synapse, the untangling of the cytokine web and signaling pathways, xenotransplantation models, and the growing use of selectively targeted therapies. Since psoriasis is currently incurable, new management strategies are proposed to replace previous serendipitous approaches. Such strategic transition from serendipity to the use of novel selective agents aimed at defined targets in psoriatic lesions is moving rapidly from research benches to the bedsides of patients with this chronic and debilitating disease.
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Project description:Over the past couple of decades, lymphatics research has accelerated and gained a much-needed recognition in pathophysiology. As the lymphatic system plays heavy roles in interstitial fluid drainage, immune surveillance and lipid absorption, the ablation or excessive growth of this vasculature could be associated with many complications, from lymphedema to metastasis. Despite their growing importance in cancer, few anti-lymphangiogenic therapies exist today, as they have yet to pass phase 3 clinical trials and acquire FDA approval. As such, many studies are being done to better define the signaling pathways that govern lymphangiogenesis, in hopes of developing new therapeutic approaches to inhibit or stimulate this process. This review will cover our current understanding of the Ras signaling pathways and their interactions with Prox1, the master transcriptional switch involved in specifying lymphatic endothelial cell fate and lymphangiogenesis, in hopes of providing insights to lymphangiogenesis-based therapies.
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Project description:BackgroundPsoriasis is a chronic inflammatory skin disease, the pathogenesis of which is more complicated and often requires long-term treatment. In particular, moderate to severe psoriasis usually requires systemic treatment. Psoriasis is also associated with many diseases, such as cardiometabolic diseases, malignant tumors, infections, and mood disorders. Psoriasis can appear at any age, and lead to a substantial burden for individuals and society. At present, psoriasis is still a treatable, but incurable, disease. Previous studies have found that microRNAs (miRNAs) play an important regulatory role in the progression of various diseases. Currently, miRNAs studies in psoriasis and dermatology are relatively new. Therefore, the identification of key miRNAs in psoriasis is helpful to elucidate the molecular mechanism of psoriasis.AimTo identify key molecular markers and signaling pathways to provide potential basis for the treatment and management of psoriasis.MethodsThe miRNA and mRNA data were obtained from the Gene Expression Omnibus database. Then, differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were screened out by limma R package. Subsequently, DEmRNAs were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomics functional enrichment. The "WGCNA" R package was used to analyze the co-expression network of all miRNAs. In addition, we constructed miRNA-mRNA regulatory networks based on identified hub miRNAs. Finally, in vitro validation was performed. All experimental procedures were approved by the ethics committee of Chinese PLA General Hospital (S2021-012-01).ResultsA total of 639 DEmRNAs and 84 DEmiRNAs were identified. DEmRNAs screening criteria were adjusted P (adj. P) value < 0.01 and |logFoldChange| (|logFC|) > 1. DEmiRNAs screening criteria were adj. P value < 0.01 and |logFC| > 1.5. KEGG functional analysis demonstrated that DEmRNAs were significantly enriched in immune-related biological functions, for example, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, and chemokine signaling pathway. In weighted gene co-expression network analysis, turquoise module was the hub module. Moreover, 10 hub miRNAs were identified. Among these 10 hub miRNAs, only 8 hub miRNAs predicted the corresponding target mRNAs. 97 negatively regulated miRNA-mRNA pairs were involved in the miRNA-mRNA regulatory network, for example, hsa-miR-21-5p-claudin 8 (CLDN8), hsa-miR-30a-3p-interleukin-1B (IL-1B), and hsa-miR-181a-5p/hsa-miR-30c-2-3p-C-X-C motif chemokine ligand 9 (CXCL9). Real-time polymerase chain reaction results showed that IL-1B and CXCL9 were up-regulated and CLDN8 was down-regulated in psoriasis with statistically significant differences.ConclusionThe identification of potential key molecular markers and signaling pathways provides potential research directions for further understanding the molecular mechanisms of psoriasis. This may also provide new research ideas for the prevention and treatment of psoriasis in the future.
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Project description:Advances in omics technologies have made it possible to unravel biomarkers from different biological levels. Intensive studies have been carried out to uncover the dysregulations in psoriasis and to identify molecular signatures associated with the pathogenesis of psoriasis. In this review, we presented an overview of the current status of the omics-driven biomarker research and emphasized the transcriptomic, epigenomic, proteomic, metabolomic, and glycomic signatures proposed as psoriasis biomarkers. Furthermore, insights on the limitations and future directions of the current biomarker discovery strategies were discussed, which will continue to comprehend broader visions of psoriasis research, diagnosis, and therapy especially in the context of personalized medicine.
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Project description:The incidence of hepatocellular carcinoma (HCC) ranks first among primary liver cancers, and its mortality rate exhibits a consistent annual increase. The treatment of HCC has witnessed a significant surge in recent years, with the emergence of targeted immune therapy as an adjunct to early surgical resection. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has shown promising results in other types of solid tumors. This article aims to provide a comprehensive overview of the intricate interactions between different types of TILs and their impact on HCC, elucidate strategies for targeting neoantigens through TILs, and address the challenges encountered in TIL therapies along with potential solutions. Furthermore, this article specifically examines the impact of oncogenic signaling pathways activation within the HCC tumor microenvironment on the infiltration dynamics of TILs. Additionally, a concise overview is provided regarding TIL preparation techniques and an update on clinical trials investigating TIL-based immunotherapy in solid tumors.
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Project description:MotivationSeveral types of studies, including genome-wide association studies and RNA interference screens, strive to link genes to diseases. Although these approaches have had some success, genetic variants are often only present in a small subset of the population, and screens are noisy with low overlap between experiments in different labs. Neither provides a mechanistic model explaining how identified genes impact the disease of interest or the dynamics of the pathways those genes regulate. Such mechanistic models could be used to accurately predict downstream effects of knocking down pathway members and allow comprehensive exploration of the effects of targeting pairs or higher-order combinations of genes.ResultsWe developed methods to model the activation of signaling and dynamic regulatory networks involved in disease progression. Our model, SDREM, integrates static and time series data to link proteins and the pathways they regulate in these networks. SDREM uses prior information about proteins' likelihood of involvement in a disease (e.g. from screens) to improve the quality of the predicted signaling pathways. We used our algorithms to study the human immune response to H1N1 influenza infection. The resulting networks correctly identified many of the known pathways and transcriptional regulators of this disease. Furthermore, they accurately predict RNA interference effects and can be used to infer genetic interactions, greatly improving over other methods suggested for this task. Applying our method to the more pathogenic H5N1 influenza allowed us to identify several strain-specific targets of this infection.AvailabilitySDREM is available from http://sb.cs.cmu.edu/sdrem.Supplementary informationSupplementary data are available at Bioinformatics online.
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