Hepatocellular carcinoma (HCC), a liver cancer originating from hepatocytes, is a major health concern and among the most common malignancies worldwide. Sorafenib, approved by the U.S. F.D.A., is the primary first-line treatment for patients with advanced HCC. While the preferred first-line systemic regimen for HCC is immunotherapy with Atezolizumab plus bevacizumab or Tremelimumab-actl + durvalumab, Sorafenib is still an alternative recommended regimen. While some patients with advanced HCC may benefit from Sorafenib treatment, most eventually develop resistance, leading to poor prognosis. Long noncoding RNAs (lncRNAs) have been found to play a critical role in tumorigenesis and the development of HCC, as well as other cancers. They are also key players in tumor drug resistance, though the mechanisms of lncRNAs in Sorafenib resistance in HCC remain poorly understood. This review summarizes the molecular mechanisms contributing to Sorafenib resistance in HCC with their potential correlation with lncRNAs, including the roles of transporters, receptors, cell death regulation, and other influencing factors.

While chronic pain is challenging to manage, it always co-exists with depression. Currently, chronic pain and depression are usually treated separately with distinct approaches, yet effectiveness remains elusive. Consequently, the development of integrated therapeutic strategies for pain while addressing depression is a high public health priority and unmet need that affects millions of people. This study aims to determine if the combination of the two phytocannabinoids Beta-Caryophyllene (BCP) and cannabidiol (CBD) is effective for chronic pain while simultaneously showing antidepressant effects. We used a chronic inflammatory pain model (Complete Freund's Adjuvant, CFA) and a battery of pain and depression-like behavior tests in mice. Proteomics and immunohistochemistry (IHC) were used to explore the potential mechanisms of the effect of the combination on pain and depression. We found that mice treated with the CBD and BPC combination produced a synergistic pain-relieving effect in the chronic inflammatory pain model and exhibited antidepressant properties. Our IHC data also show that the CBD and BCP combination significantly reduced the neuroinflammation produced by CFA, and the proteomics showed downregulation of selected proteins involved in inflammation by the combination, compared to the individual effects of CBD and BCP. In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic pain-relief effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for chronic pain and related depression.

Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and cellular signaling in cancer. Their functions are primarily mediated through interactions with specific protein partners that modulate chromatin structure, epigenetic remodeling, transcription, and signal transduction. In this review, we explore reports and strategies for the proteomic characterization of lncRNA-associated proteins, particularly emphasizing high-throughput liquid chromatography–mass spectrometry (LC-MS)-based techniques. Affinity-based methods such as RNA pull-down, ChIRP MS, RAP-MS, BioID-MS, and SILAC-MS enable sensitive and specific mapping of lncRNA and protein complexes. These approaches reveal cancer-specific proteomic signatures, post-translational modifications, and mechanistic insights into tumor biology. The use of label-free quantification, bituminization, and crosslinking strategies further enhances the resolution of dynamic RNA–protein networks. Validation tools following bioinformatic analyses, such as Western blotting, immunohistochemistry, immunofluorescence, and ELISA, are used to prioritize and confirm findings. Candidate biomarkers from hepatocellular carcinoma to colorectal and prostate cancers, profiling lncRNA-associated proteins, hold promise for identifying clinically actionable biomarkers and therapeutic targets. This review highlights the translational relevance of lncRNA protein studies and advocates for their broader adoption in oncological research. In LC-MS workflows, proteins bound to lncRNAs are enzymatically digested into peptides, separated via nano-LC, and analyzed using high-resolution tandem MS. Label-free or isotope-labeled methods quantify differential enrichment, followed by bioinformatics-driven pathway annotation.

Hepatocellular carcinoma (HCC) is a liver cancer that originates from hepatocytes. It is a primary health issue and one of the most common malignant tumors. The US FDA approved Sorafenib as the first-line anti-cancer drug for advanced HCC patients. A few patients with advanced HCC may benefit from Sorafenib treatment, but most of the patients eventually develop resistance to Sorafenib, which leads to its poor prognosis. Long-noncoding RNAs (lncRNA) have been found to play a critical role in tumorigenesis and the development of HCC, as well as various cancers. It also plays a vital role in tumor drug resistance, while the mechanisms of LncRNAs in HCC sorafenib resistance have not been characterized yet. In this review article, we summarized the molecular mechanisms, such as the involvement of transporters, receptors, cell death regulation, and other factors impacting sorafenib resistance in HCC.

Background/Objectives: Neuropathic pain is one of the most severe types of chronic pain. Although it is difficult to manage, it often co-occurs with depression. Yet, no medication addresses the neuropathic pain and depression comorbidity. Therefore, developing integrated treatment strategies that address both pain and depression is a major public health priority and an unmet need affecting millions. Methods: In this study, we investigated the effect of combining a terpene, Beta-Caryophyllene (BCP), and cannabidiol (CBD) on neuropathic pain and associated depression. We employed a chronic constriction injury (CCI) neuropathic pain model and a series of behavioral tests to evaluate how oral administration of this combination influences neuropathic pain and depression-like behaviors in mice. We employed immunohistochemistry and proteomics approaches to explore the mechanism. Results: The analgesic effect of combining CBD and BCP is synergistic in neuropathic pain and also shows an antidepressant effect. Additionally, we found that this combination decreases neuroinflammation associated with CCI and affects specific genes involved in the inflammation. Conclusions: This work provides preclinical scientific evidence supporting the potential usefulness of this combination for neuropathic pain and associated depression.

Background/Objectives: To develop a novel method for isolating proteins associated with Long Non-coding RNAs (LncRNAs) using high-throughput Liquid Chromatography Mass Spectrometry (LC-MS) and proteomics approaches for identifying cancer-associated proteins involved in post-translational modifications (PTMs) such as glycosylation, phosphorylation, citrullination, methylation, and acetylation. Additionally, the focus is on identifying and quantifying differentially modulated or regulated proteins associated with LncRNAs to discover novel molecular signatures or biomarkers. Methods: Identification, quantification, and characterization of LncRNAs associated pro-teins by using Label free Quantification (LFQ) of proteins by Nono LC-Mass Spectrometry (LC-MS)., use Employ bioinformatics, biostatistics analysis for find out the differentially expressed, exclusive protein or modulated., find outInvestigate the mechanisms and pathways involving these unique or specific proteins analysis of unique/specific proteins and Validation of these unique/specific proteins by Immunohistochemistry (IHC) and western blotting/ enzyme-linked immunosorbent assay (ELISA) for to achieve better out-come. Conclusions: Identified and validated novel proteins associated with LncRNAs could be early detective molecular biomarkers of cancer and it could be useful in clinical practice for diagnosis, prognosis of liver, colorectal and other several types of cancer types.