Organelle-targeted drug delivery (OTDD) is an advanced strategy in the field of precision medicine, which delivers therapeutic agents to subcellular organelles. The OTDD provides a more targeted and efficient approach for neurodegenerative, cancer, and metabolic disorders, by addressing the root cause of diseases that are associated with organelle dysfunction. The recent advances in nanotechnology have enabled intelligent drug carriers, which have the potential to target organelles. This study aimed to explore the recent advancements in OTDD, emphasizing the role of nanocarriers, targeting approaches, and stimulus-responsive systems to enhance therapeutic accuracy and overcome major challenges in clinical translation. This review discusses advanced progress in OTDD, focusing on various nanocarriers. It discusses the function of targeting moieties, including peptides and ligands, as well as stimuli-responsive drug delivery systems that are activated by intracellular stimuli, like pH or reactive oxygen species, capable of targeting the delivery of the drug using organelles. Moreover, challenges in clinical translation, regulatory issues, and patient-specific factors are analyzed. OTDD advancements have shown promising preclinical and clinical outcomes in enhancing drug targeting and therapeutic efficiency. However, its clinical use involves barriers in standardization, regulatory approvals, and disease-specific variation, which primarily hinder its clinical application. Personalized strategies need to be employed to enhance the outcome of therapy. The OTDD has the potential to revolutionize subcellular precision medicine by providing specific drugs for different diseases. Interdisciplinary collaboration is required to address the existing challenges and facilitate clinical translation, thereby improving patient- specific therapeutic approaches.

Introduction: Parkinson's Disease (PD) is a common neurodegenerative disorder with limited treatment options. Thus, there's a need for new therapies. Mucuna pruriens (MP) seeds are used in traditional treatments for PD, but their mechanisms are not well understood. This research uses in silico methods to explore MP's pharmacological effects as a potential PD treatment.

Methods: We registered the active ingredients in MP and their targets, then analyzed genes related to Parkinson's Disease (PD). This led to the creation of a Protein-Protein Interaction (PPI) network. We examined the binding interactions between hub proteins and compounds using molecular docking and confirmed the results with molecular dynamics analysis.

Results: We revealed sixteen substances in MP seeds that target 113 therapeutic points in PD. The proteins identified in the enrichment analysis regulate actin, endocytosis, and various other cellular processes. Ultimately, we identified eleven hub proteins (TP53, AKT1, MAPK8, ESR1, MAPK3, BCL2, HSP90AA1, PRKACA, CASP3, EGFR, and IL6) that interact with the sixteen active compounds, a finding confirmed by molecular docking and molecular dynamics.

Discussion: The identified hub proteins are key therapeutic targets that regulate crucial processes in Parkinson's disease, highlighting the neuroprotective potential of bioactive compounds in MP seeds. These findings justify further experimental studies to confirm their therapeutic potential in treating Parkinson's disease.

Conclusion: Our findings suggest that, in addition to L-DOPA, other compounds in MP seeds may act synergistically to produce antiparkinsonian effects.

Recent studies have established that cytokeratin 8 (CK8) is closely linked to glycogen synthesis; however, its mechanistic role in hepatic glycogen synthesis in type 2 diabetes mellitus (T2DM) remains unclear. This study aimed to elucidate the effects and underlying molecular mechanisms of CK8.

Preeclampsia (PE) is the second-leading global cause of maternal mortality, affecting 5% of primigravidas. Owing to the substantial heterogeneity of clinical manifestations in PE, an urgent need arises to quantitatively evaluate the efficacy of existing diagnostic methods based on positive proteinuria (PRO) and to develop novel biomarkers to enhance diagnostic accuracy.

Immunotherapy has revolutionized cancer treatment, however, its effectiveness remains limited by weak tumor immunogenicity and immunosuppressive microenvironments. Mitochondria have emerged as a strategic therapeutic target, given their central role in regulating immune cell activation, proliferation, and function through metabolic reprogramming and signaling pathway modulation. Mitochondria-targeted nanoformulations offer a promising approach to amplify anti-tumor immunity by enhancing immune responses at the cellular and molecular levels.

Hereditary Angioedema (HAE) is a rare, autosomal dominant disorder characterized by episodic, non-pruritic, non-pitting swelling of the skin, respiratory tract, and gastrointestinal system resulting from C1 esterase inhibitor (C1-INH) deficiency or dysfunction. It is frequently underdiagnosed, particularly in developing countries like India, due to its nonspecific presentation and overlap with allergic angioedema.

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by the accumulation of mutant huntingtin protein (mHTT) with expanded polyglutamine (polyQ) tracts. These aggregates contribute to neuronal toxicity and disease progression. Targeting aggregation, especially at the N-terminal domain (N17), may offer a therapeutic strategy. This study aims to identify potential small-molecule inhibitors that can bind to aggregation-prone regions of mHTT using computational methods.

Cardiovascular diseases (CVDs) are the most prominent leading cause of morbidity and mortality in developed and developing countries. Bone Morphogenetic Protein-7 (BMP-7), a member of the transforming growth factor-β (TGF-β) superfamily, has served as a crucial mediator in the progression of pathogenesis of numerous CVDs. A narrative literature review was conducted using PubMed, Scopus, and Web of Science databases. Studies addressing BMP-7 and cardiovascular implications were included for this review. BMP-7 is considered significant for its cardioprotective properties, providing anti-fibrotic, anti-inflammatory, and pro-regenerative effects. Additionally, BMP-7 interacts with other signaling molecules, including TGF-β/Smad2/3 signaling, PI3K/Akt pathway, PTEN-Akt pathway, and NF-kB signaling, positioning BMP-7 as a potential therapeutic target for mitigating CVDs. Current research into BMP-7 analogs and gene therapy identifies its potential in personalized medicine for CVDs. Conclusively, BMP-7 serves as a multi- -targeting regulator in the pathogenesis of CVDs by influencing the progression of a spectrum of complex molecular interactions of CVDs. Therefore, the present review provides a detailed description of the mechanisms by which it interacts with other molecular targets in the pathogenesis of CVDs, aiming to generate new avenues for targeted intervention and biomarker development in cardiovascular medicine.

Digital twin technology has emerged as a breakthrough development in healthcare, providing personalised transdermal drug delivery systems for chronic pain treatment. Digital twins provide accurate, customised therapy to enhance therapeutic outcomes and reduce risks by combining patient-specific computational models. This article aims to explore the applicability of digital twin technology in improving the transdermal delivery of drugs for successful chronic pain management. It is enabling personalised treatment through patient-specific simulations. By integrating physiological data with computational models, digital twins optimise drug absorption, patch application, and dosage adjustments in real-time, enhancing therapeutic outcomes while minimising side effects. Recent advancements highlight improvements in fentanyl patch optimisation, site-specific drug delivery, and thermally controlled systems. However, challenges such as ethical concerns, data security, and standardisation need to be addressed. Future research should focus on integrating AI and IoT to refine digital twin applications in precision medicine. It can be concluded from the findings of various studies that digital twin technology offers a promising future for precise and individualised transdermal drug delivery in chronic pain, paving the way for safer and more effective therapeutic interventions.

Nanotechnology in drug delivery has revolutionized modern therapeutics by addressing the limitations of conventional drug delivery methods. This review article explores the significant advancements in nanoparticle-based drug delivery systems, highlighting their role in enhancing therapeutic efficacy and overcoming drug resistance. Nanoparticles, including lipid-based, polymer- based, inorganic, and biological types, offer improved solubility, stability, targeted delivery, and controlled release of therapeutic agents. By enabling precise delivery to specific tissues or cells, these advancements minimize off-target effects and toxicity, particularly in cancer therapy. Additionally, nanomedicine facilitates the delivery of drugs across biological barriers such as the blood-brain barrier, which opens new avenues for treating neurological disorders. The ability to co-encapsulate multiple therapeutic agents in nanoparticles also supports combination therapies that target multiple pathways simultaneously, thereby reducing the development of resistance. As research progresses, the integration of nanotechnology in drug delivery promises to transform healthcare by providing more effective, safer, and personalized treatments. This article advocates for continued exploration and innovation in the field by emphasizing the need for interdisciplinary collaboration to fully realize the potential of nanomedicine in improving patient outcomes and addressing unmet clinical needs.

Astragalus mongholicus is distributed in Inner Mongolia, China, and has a certain therapeutic effect on silicosis. However, the regulatory mechanisms of Astragalus mongholicus mediated by alternative splicing (AS) in silicosis pathology and treatment remain unclear.

Aging is a complex biological process marked by progressive cellular and tissue decline, leading to an increased risk of age-related diseases. Plant-based natural compounds, including polyphenols, flavonoids, carotenoids, alkaloids, and terpenoids, have gained attention for their potential in mitigating aging-related damage through antioxidant, anti-inflammatory, and cellular repair mechanisms. The review identified that plant-derived bioactive compounds target key pathways involved in aging, including Sirtuins (SIRT1), AMP-activated protein kinase (AMPK), and Nuclear Factor-kappa B (NF-κB). These compounds address key hallmarks of aging, such as oxidative stress, mitochondrial dysfunction, cellular senescence, and chronic inflammation. Evidence suggests their potential in preventing or delaying age-related disorders, including neurodegenerative diseases, cardiovascular conditions, and skin aging. Plant-derived compounds offer a promising alternative to synthetic anti-aging interventions due to their efficacy, safety, and sustainability. However, challenges such as low bioavailability and limited clinical validation must be addressed. Advances in drug delivery systems and comprehensive clinical trials are critical to realizing their full therapeutic potential. Plant-based bioactive compounds represent a significant opportunity for developing safer and more sustainable anti-aging therapies. Continued research is essential to overcome existing limitations and facilitate the integration of these approaches into mainstream healthcare practices.

Cancer is a significant human health concern due to its increasing mortality rate and profound impact on public health and healthcare systems. The cytotoxic, antiproliferative, immunosuppressive, and apoptogenic properties of scorpion venom proteins and peptides have been observed in various cancer cell lines. Therefore, the purpose of this study was to investigate the potential use of proteins derived from scorpion venom in cancer treatment. In this study, the effects of different scorpion venoms on transmembrane channels, the inhibition of angiogenesis, the inhibition of invasion and metastasis, the inhibition of proliferation, and the induction of apoptosis were investigated, as were their clinical applications in the treatment of hepatocellular carcinoma and breast, cervical, prostate, colorectal, and melanoma cancers. The results showed that various scorpion venoms can suppress cell growth, stimulate apoptosis, reduce tumor size, and enhance the immune response, thereby serving as alternative drugs for treating various types of cancers and their metastasis. This review suggests a positive association between scorpion venom (SV) proteins and the treatment of these cancers. Future research should focus on understanding the underlying mechanisms, identifying biomarkers to predict response, and exploring potential combination therapies to increase the efficacy of scorpion venom proteins in cancer treatment.

Lung cancer, particularly non-small cell lung cancer, is a leading cause of global mortality, with many cases diagnosed at advanced stages. The Toll-Like Receptor (TLR) signaling pathway plays a crucial role in linking inflammation to lung cancer progression, with both pro-tumor and anti-tumor effects. This perspective delves into the complex functions of TLR proteins in lung cancers, elucidating their involvement in tumor growth, angiogenesis, and metastasis. In addition, we highlight the therapeutic potentials of TLR agonists and antagonists, emphasizing their interplay with immune checkpoint inhibitors like PD-1/PD-L1 blockers to overcome immunosuppressive barriers. Nevertheless, the paradoxical effects of TLR activation, balancing immune stimulation and suppression, demand precise targeting strategies. Collectively, our study synthesizes the current understanding of TLR signaling pathways in lung cancers, offering insights into their potential for advancing lung cancer therapies.

Long intergenic non-coding RNA 01123 (LINC01123) is a lncRNA located on the human chromosome 2q13. It is upregulated in various cancers and has been identified as an oncogene. Its expression is associated with the risk and poor prognosis of multiple cancers.

Double homeobox A pseudogene 9 (DUXAP9), also known as long intergenic non-coding RNA 1296 (LINC01296) and lymph node metastasis-associated transcript 1 (LNMAT1), is an emerging lncRNA encoded by a pseudogene. It has been reported to be upregulated in various tumor types and functions as an oncogenic factor. The high expression of DUXAP9 is closely related to clinical pathological features and poor prognosis in 16 types of malignant tumors. DUXAP9 is transcriptionally activated by YY-1 and Twist1 and functions as a guide or scaffold for biomolecular complexes and chromatin modifiers, or as a 'decoy' for miRNAs, mRNAs, and proteins, thereby regulating gene expression. Moreover, the PI3K/AKT, NF-κB, MAPK/ERK, and Wnt/β- catenin signaling pathways are variously activated or inhibited by DUXAP9, subsequently influencing the biological behaviors of tumor cells, including proliferation, apoptosis, cell cycle arrest, migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance. This review summarizes recent research on DUXAP9 in oncology, offering insights into its expression characteristics, biological functions, molecular mechanisms, and clinical significance for cancer diagnosis, treatment, and prognosis.

The global prevalence of Diabetes Mellitus is rising; this complex metabolic disorder marked with hyperglycemia comes with increased morbidity and more associated health risks. Type 1 Diabetes Mellitus, an autoimmune disorder primarily affecting young individuals, lacks innovative pharmacological therapies. While current treatments for Type 2 Diabetes Mellitus-including lifestyle interventions and medications-can be effective, many patients still struggle with glycemic control. This review aims to highlight recent advances in diabetes mellitus management, emphasizing novel therapeutics and drug delivery systems that aim to decrease dosage frequency, target the manifestation of side effects, and enhance anti-diabetic effectiveness.

Antimicrobial peptides (AMPs), part of the body's innate immune response, are natural compounds that inhibit bacteria during bacterial infections. Despite their important role in counteracting cellular pathogens, the precise mechanism of generating AMPs in response to bacterial infection remains elusive. However, recent findings demonstrate that the proteasome, a cellular complex involved in the degradation of intracellular proteins, plays a key role in generating AMPs during bacterial infection. Intriguingly, bacterial infections have been shown to mediate the remodeling of the proteasome, resulting in altered cleavage activity that increases the generation of antimicrobial peptides and helps reduce intracellular bacterial load. Additionally, the 11S proteasome subunit PSME3 has been identified as the key regulatory particle responsible for triggering proteasome remodeling in response to bacterial stress. Remarkably, given the burgeoning research on antimicrobial agents, the recent findings uncover an important anti-bacterial functional role of the proteasome and open avenues for investigating strategies to modulate or enhance the cell's natural defense against pathogens to develop new antimicrobial therapeutics.

Depression is a debilitating psychiatric disorder characterized by loss of interest, anhedonia, and social isolation, which is projected to become the leading cause of disability worldwide by 2030. Despite the greater economic and social burden imposed by depression, the precise pathophysiology underlying the development of depression remains elusive. Betaine (N, N, N-trimethylglycine), an amino acid derivative, is widely distributed in various animals and plants and has been shown to have numerous beneficial effects, including antioxidant activities, anti-inflammatory functions, regulation of energy metabolism, and reduction of endoplasmic reticulum stress. It has been used to treat Alcohol-Associated Liver Disease (AALD), type 2 diabetes, cancer, obesity, and Alzheimer's Disease (AD). Interestingly, accumulating evidence has shown that betaine exerts a significant role in alleviating depressive-like behavior in patients and animals resulting from chronic stress. Although the antidepressant effects of betaine have not been compared with traditional antidepressants with insufficient verification, based on the neurobiological mechanisms of depression, it may be a potential alternative medicine for the treatment of depression. This is the first review aiming to provide a comprehensive overview of the remarkable effects of betaine in the pathophysiology of depression. These pieces of evidence are of great importance for deepening our understanding of the antidepressant mechanism of betaine, so as to develop betaine supplements for the supplementary treatment of depression.

Amylin is a thirty-seven amino acid peptide hormone that is secreted from the pancreas with insulin. The peptide hormone amylin activates its receptors in the brain to regulate blood glucose and food appetite. Interestingly, the amylin receptor is the heterodimer of the calcitonin receptor (which is the receptor for the peptide hormone calcitonin) and an accessory protein called receptor activity-modifying protein. Amylin receptor activation has emerged as a promising drug target for the treatment of diabetes and obesity. Recent pharmaceutical efforts with amylin receptor activators have focused on developing drugs for the treatment of obesity. Multiple amylin analogs have been tested in pre-clinical settings, and some are currently being tested in clinical trials. In this review, recent research publications and available information regarding drug development targeting amylin receptors were searched. It summarizes the amylin receptor activators currently being tested in clinical trials for the treatment of obesity. In addition, recent research achievements were demonstrated, such as the introduction of mutations that enhanced receptor affinity/potency and the development of a method for measuring selective amylin receptor activation. Potential issues along with peptide drug development were described, including lipidation to achieve a long-acting property. The combination of an amylin analog and other anti-obesity peptide drugs has demonstrated higher clinical efficacy in reducing body weight than monotherapy. The combination therapy is likely to be the first drug therapy where an amylin analog is used for obesity treatment. In addition, amylin receptor activators may have an adverse effect profile more favorable than that of GLP-1 receptor activators, which could be a potential benefit of amylin receptor activators.