Current Drug Targets - Online First

Treating neurological illnesses is challenging because the blood-brain barrier hinders therapeutic medications from reaching the brain. Recent advances in polymeric nanocarriers (PNCs), which improve medication permeability across the blood-brain barrier, may influence therapy strategies for neurological diseases. PNCs have several ways to deliver medications to the nervous system. This review article provides a summary of the parts and manufacturing methods involved in making PNCs. Additionally, it highlights the elements that result in PNCs having enhanced blood-brain barrier penetration. A combination of passive and active targeting strategies is used by PNCs intended to overcome the blood-brain barrier. Among these are micellar structures, nanogels, nanoparticles, cubosomes, and dendrimers. These nanocarriers, which are functionalized with certain ligands that target BBB transporters, enable the direct delivery of drugs to the brain. Mainly, the BBB prevents medications from entering the brain. Understanding the BBB's physiological and anatomical characteristics is necessary to get over this obstacle. Preclinical and clinical research demonstrates the safety and effectiveness of these PNCs, and their potential use in the treatment of neurological illnesses, including brain tumors, Parkinson's disease, and Alzheimer's disease, is discussed. Concerns that PNCs may have about their biocompatibility and possible toxicity are also covered in this review article. This study examines the revolutionary potential of PNCs in CNS drug delivery, potential roadblocks, ongoing research, and future opportunities for PNC design progress. PNCs open the door to more focused and efficient treatment for neurological illnesses by comprehending the subtleties of BBB penetration.

HAGLR Opposite Strand lncRNA (HAGLROS) is a long non-coding RNA (lncRNA) located on the long arm of human chromosome 2 at locus 2q31.1. Emerging evidence highlights HAGLROS as a pivotal player in human cancers, characterized by its significant upregulation across multiple malignancies where it functions as an oncogenic driver. Its aberrant expression is closely linked to the initiation and progression of 13 distinct cancer types, notably correlating with adverse clinical outcomes and reduced overall survival rates in 9 of these cancer types. Mechanistically, HAGLROS is under the regulatory influence of the transcription factor STAT3, exerts competitive binding to 9 miRNAs, activates 5 signaling pathways pivotal for cancer cell proliferation and metastasis, as well as intricately modulates gene expression profiles. Given its multifaceted roles, HAGLROS emerges as a promising candidate for cancer diagnostics and prognostics. Moreover, its potential as a therapeutic target holds considerable promise for novel treatment strategies in oncology. This review synthesizes current research on HAGLROS, covering its expression patterns, biological roles, and clinical significance in cancer. By shedding light on these aspects, this review aims to contribute new perspectives that advance our understanding of cancer biology, enhance diagnostic accuracy, refine prognostic assessments, and pave the way for targeted therapeutic interventions.

Obesity is a significant health concern due to its rapid increase worldwide. It has been linked to the pathogenic factors of renal diseases, cancer, cardiovascular diseases, hypertension, dyslipidemia, and type 2 diabetes. Notably, obesity raises the likelihood of developing chronic kidney disease (CKD), leading to higher adult mortality and morbidity rates. This study explores the molecular mechanisms that underlie obesity-associated nephropathy and its clinical implications. Obesity-Associated Nephropathy (OAN) develops and worsens due to insulin resistance and hyperinsulinemia, which promote renal sodium reabsorption, glomerular hyperfiltration, and hypertension, leading to progressive kidney damage. Renal damage is further aggravated by persistent inflammation and redox damage, mediated by adipokines and proinflammatory cytokines, such as TNF-α and IL-6. Furthermore, stimulation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) intensifies glomerular hypertension and fibrosis. These elements cause glomerular hyperfiltration, renal hypertrophy, and progressive kidney damage. Clinical manifestations of obesity-associated nephropathy include proteinuria, reduced glomerular filtration rate (GFR), and ultimately, CKD. Management strategies currently focus on lifestyle modifications, such as weight loss through diet and exercise, which have been effective in reducing proteinuria and improving GFR. Pharmacological treatments targeting metabolic pathways, including GLP-1 receptor agonists and SGLT2 inhibitors, have shown renoprotective properties. Additionally, traditional RAAS inhibitors offer therapeutic benefits. Early detection and comprehensive management of OAN are essential to prevent its progression and lessen the burden of CKD.

The second largest cause of cancer-related death worldwide, Hepatocellular Carcinoma (HCC) is also the most common primary liver cancer. HCC typically arises in patients with liver cirrhosis. Existing synthetic medicines for treating chronic liver disease are ineffective and come with undesirable side effects. Although herbal remedies have widespread popularity, there is still a long road ahead before they are fully accepted by the scientific community. Secondary metabolites and phytochemicals found in plants are abundant in both the human diet and the non-human environment. Natural plant chemicals have been shown to be beneficial as therapeutic and chemopreventive treatments for a wide variety of chronic disorders. Many diseases, including HCC, can be effectively treated with the help of phytochemicals found in food. Resveratrol, curcumin, urolithin A, silibinin, quercetin, N-trans-feruloyl octopamine, emodin, lycopene, caffeine, and phloretin are all examples. Approximately, 60% of all anticancer medications are determined to be derived from natural substances, according to recent studies. Plant derivatives have played an important role in cancer due to their capacity to scavenge free radicals, limit cell proliferation, and set off apoptosis. The progression of HCC is linked to inflammatory signaling pathways, and this study sought to look at how novel approaches, such as phytomedicines, are being used to fight cancer. Recent advancements in molecular mechanisms and drug targeting for HCC have been discussed in this review.