In Silico Design of Novel EpCAM-Binding Aptamers for Targeted Delivery of RNA Therapeutics.

Aptamers are short DNA or RNA sequences that adopt 3D structures and can bind to protein targets with high binding affinity and specificity. Aptamers exhibit excellent tissue penetration, are inexpensive to produce, and can be internalized by cells. Therefore, aptamers are attractive targeting ligands to direct the delivery of theranostic agents to the desired cells.

Global and regional mortality statistics of nipah virus from 1994 to 2023: a comprehensive systematic review and meta-analysis.

The mortality rate of Nipah virus (NiV) can vary in different regions, and its pattern across timelines has yet to be assessed. The primary objective is to perform a comparative analysis of mortality rates across different timelines and countries. Articles reporting NiV mortality from inception to November 2023 were analyzed in PubMed, Ovid Embase, Scopus, and Web of Science databases.

Targeting PD-L1 in cholangiocarcinoma using nanovesicle-based immunotherapy.

This study demonstrates the potential of using biological nanoparticles to deliver RNA therapeutics targeting programmed death-ligand 1 (PD-L1) as a treatment strategy for cholangiocarcinoma (CCA). RNA therapeutics offer prospects for intracellular immune modulation, but effective clinical translation requires appropriate delivery strategies. Milk-derived nanovesicles were decorated with epithelial cellular adhesion molecule (EpCAM) aptamers and used to deliver PD-L1 small interfering RNA (siRNA) or Cas9 ribonucleoproteins directly to CCA cells.

Therapeutic restoration of miR-126-3p as a multi-targeted strategy to modulate the liver tumor microenvironment.

Background: Impaired natural killer (NK) cell-mediated antitumor responses contribute to the growth of liver tumors. Expression of a disintegrin and metalloprotease 9 (ADAM9) increases shedding of membrane-bound major histocompatibility complex class I chain-related protein A and results in evasion from NK cell-mediated cytolysis. ADAM9 is also involved in angiogenesis and tumor progression and is a target of miR-126-3p, a tumor suppressor that is downregulated and alters tumor cell behavior in the liver and other cancers.

MiR-29b modulates DNA methylation in promoter region of miR-130b in mouse model of Diabetic nephropathy.

Unlabelled: Epigenetic modifications play a role in Diabetic Nephropathy (DN). Downregulation of miR-29b leads to modulation of DNA methylation via DNA methyl transferases (DNMTs) and hence exaggerated renal fibrosis in DN. Therefore, the main aim of the study was to evaluate effect of miR-29b expression in vivo on DNMTs, renal fibrosis, glomerular and tubular damage as well as renal morphology in DN.

Engineering Cell-Derived Nanovesicles for Targeted Immunomodulation.

Extracellular vesicles (EVs) show promise for targeted drug delivery but face production challenges with low yields. Cell-derived nanovesicles (CDNVs) made by reconstituting cell membranes could serve as EV substitutes. In this study, CDNVs were generated from mesenchymal stem cells by extrusion.

Extracellular vesicle RNA signaling in the liver tumor microenvironment.

The tumor microenvironment (TME) in liver cancers such as hepatocellular cancer (HCC) consists of a complex milieu of liver tissue-resident cells, infiltrated immune cells, and secreted factors that collectively serve to promote tumor growth and progression. Intercellular crosstalk contributes to tissue homeostasis, and perturbations during injury, inflammation and tumorigenesis that are important for tumor progression. Extracellular vesicle (EV)-mediated transfer of a payload of RNA molecules that serve as an intercellular signaling is an important contributor to tissue homeostasis within the TME.

Extracellular vesicle‑mediated miR‑126‑3p transfer contributes to inter‑cellular communication in the liver tumor microenvironment.

Extracellular vesicles (EVs) and their contents are gaining recognition as important mediators of intercellular communication through the transfer of bioactive molecules, such as non‑coding RNA. The present study comprehensively assessed the microRNA (miRNA/miR) content within EVs released from HepG2 liver cancer (LC) cells and LX2 hepatic stellate cells (HSCs) and determined the contribution of EV miRNA to intercellular communication. Using both transwell and spheroid co‑cultures of LC cells and HSCs, miR‑126‑3p within EV was established as a mediator of HSC to LC cell communication that influenced tumor cell migration and invasion, as well as the growth of multicellular LC/HSC spheroids.

Lung-on-chip microdevices to foster pulmonary drug discovery.

Respiratory diseases account for unprecedented mortality owing to a lack of personalized or insufficient therapeutic interventions. Fostering pulmonary research into managing pulmonary threat requires a potential alternative approach that can mimick the complexities of the human body. The miniaturized bionic simulation of the lung holds great potential in the quest for a successful therapeutic intervention.

'Transfersome-embedded-gel' for dual-mechanistic delivery of anti-psoriatic drugs to dermal lymphocytes.

Aim: Develop a platform for co-delivering clobetasol propionate (CP) and cyclosporine (CyA) to the epidermis and dermis to treat psoriasis.

Methods: The transfersomes were prepared by thin-film hydration method. Transfersomes were characterised by dynamic light scattering and transmission electron microscope (TEM).

Tunneling Nanotube-Mediated Communication: A Mechanism of Intercellular Nucleic Acid Transfer.

Tunneling nanotubes (TNTs) are thin, F-actin-based membranous protrusions that connect distant cells and can provide e a novel mechanism for intercellular communication. By establishing cytoplasmic continuity between interconnected cells, TNTs enable the bidirectional transfer of nuclear and cytoplasmic cargo, including organelles, nucleic acids, drugs, and pathogenic molecules. TNT-mediated nucleic acid transfer provides a unique opportunity for donor cells to directly alter the genome, transcriptome, and metabolome of recipient cells.

Targeting specificity protein 1 with miR-128-3p overcomes TGF-β1 mediated epithelial-mesenchymal transition in breast cancer: An in vitro study.

Background: Specificity protein 1 (SP1) was found to play a critical role in the regulation of TGF-β1 driven epithelial-mesenchymal transition (EMT). Recent clinical findings demonstrated a significant drop in the expression of miR-128-3p with the cancer progression in breast cancer patients. However, the impact of miR-128-3p on the SP1 expression in breast cancer remains unknown.

Mesenchymal Stem Cell-Derived Exosomes Loaded with miR-155 Inhibitor Ameliorate Diabetic Wound Healing.

Diabetic wounds are one of the debilitating complications that affect up to 20% of diabetic patients. Despite the advent of extensive therapies, the recovery rate is unsatisfactory, and approximately, 25% of patients undergo amputation, thereby demanding alternative therapeutic strategies. On the basis of the individual therapeutic roles of the miR-155 inhibitor and mesenchymal stem cells (MSC)-derived exosomes, we conjectured that the combination of the miR-155 inhibitor and MSC-derived exosomes would have synergy in diabetic wound healing.

Role of miRNAs in Cancer Diagnostics and Therapy: A Recent Update.

The discovery of microRNAs (miRNAs) has been one of the revolutionary developments and has led to the advent of new diagnostic and therapeutic opportunities for the management of cancer. In this regard, miRNA dysregulation has been shown to play a critical role in various stages of tumorigenesis, including tumor invasion, metastasis as well as angiogenesis. Therefore, miRNA profiling can provide accurate fingerprints for the development of diagnostic and therapeutic platforms.

Structural features regulated photoluminescence intensity and cell internalization of carbon and graphene quantum dots for bioimaging.

Carbon-based nanostructures with nanometer dimensions have been identified as potential photoluminescence probes for bioimaging due to their biocompatibility, tunable bandgap, and resistance to photobleaching. However, the influence of structural features of carbon quantum dots (CQDs) and graphene quantum dots (GQDs) in bioimaging has not been explored previously. In the present investigation, we elucidated the mechanism of higher PL in GQDs as compared to CQDs as a function of their structural features.

Engineered nanoplex mediated targeted miRNA delivery to rescue dying podocytes in diabetic nephropathy.

MicroRNAs (miRNA) is vital for gene expression regulation and normal kidney function. Mainly, miRNA-30a is responsible for the homeostasis of podocytes. In the diabetic nephropathic condition, miRNA-30a is directly and primarily suppressed by hyperglycemic kidney induced Notch signaling pathway leads to podocyte damage and apoptosis.

MiR-155 Inhibitor-Laden Exosomes Reverse Resistance to Cisplatin in a 3D Tumor Spheroid and Xenograft Model of Oral Cancer.

Cisplatin resistance is one of the major concerns in the treatment of oral squamous cell carcinoma (OSCC). Accumulating evidence suggests microRNA (miRNA) dysregulation as one of the mediators of chemoresistance. Toward this, our previous study revealed the role of exosomal microRNA-155 (miR-155) in cisplatin resistance via downregulation of FOXO3a, a direct target of miR-155, and induction of epithelial-to-mesenchymal transition in OSCC.

miR-29b attenuates histone deacetylase-4 mediated podocyte dysfunction and renal fibrosis in diabetic nephropathy.

Purpose: As epigenetic modifications like chromatin histone modifications have been suggested to play a role in the pathophysiology of Diabetic Nephropathy (DN) and are also found to be regulated by microRNAs. Our main purpose was to explore the role of microRNA in histone modulations associated with DN. There is downregulation of miR-29b due to advanced glycation end products in diabetes.

Exosome-mediated delivery of miR-30a sensitize cisplatin-resistant variant of oral squamous carcinoma cells via modulating Beclin1 and Bcl2.

Exosomes facilitate cross-talk amongst tumor cells, and thus also possess the potential to influence tumor-microenvironment and chemo-resistance. miRNAs, the important constituent of exosomes, are often dysregulated in cancer. They have been shown to play an essential role in tumor progression, metastasis, invasion, and resistance developed against different therapies.

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model.

Diabetic nephropathy (DN), a chronic progressive kidney disease, is a significant complication of diabetes mellitus. Dysregulation of the histone deacetylases (HDACs) gene has been implicated in the pathogenesis of DN. Hence, the HDAC-inhibitors have emerged as a critical class of therapeutic agents in DN; however, the currently available HDAC4-inhibitors are mostly nonselective in nature as well as inhibit multiple HDACs.

Exosome mediated miR-155 delivery confers cisplatin chemoresistance in oral cancer cells via epithelial-mesenchymal transition.

Cisplatin is used as chemotherapeutic drug for oral squamous cell carcinoma (OSCC). However, OSCC cells develop resistance following long-term cisplatin exposure. Resistance against cisplatin chemo-therapy is accredited to the process of epithelial-to-mesenchymal transition, which in-turn has been linked to tumor-recurrence.

MicroRNA-29b Modulates β-Secretase Activity in SH-SY5Y Cell Line and Diabetic Mouse Brain.

Hyperglycemia is one of the major risk factors responsible for memory impairment in diabetes which may lead to Alzheimer's disease (AD) at a later stage. MicroRNAs are a class of non-coding RNAs that are found to play a role in diabetes. Downregulation of microRNA-29b in diabetes is well reported.

Role of Omega-3 Fatty Acids and Butter Oil in Targeting Delivery of Donepezil Hydrochloride Microemulsion to Brain via the Intranasal Route: a Comparative Study.

In order to investigate the possible role of butter oil (BO) and omega-3 fatty acids-rich fish oil (O3FO) in the delivery of donepezil hydrochloride microemulsion (DH-ME) to the brain via intranasal route, the present study was conducted. DH:BO and DH:O3FO binary mixtures (9:1 to 1:9) were prepared by simple physical mixing and subjected to in vitro diffusion study. Ratios of DH:BO and DH:O3FO, which showed the highest diffusion, were selected for further development of microemulsion (ME).

Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease.

Diabetes mellitus (DM) is a gradually rising metabolic disease which is currently affecting millions of people worldwide. Diabetes is associated with various complications like nephropathy, neuropathy, retinopathy, diabetic foot, cognitive impairment, and many more. Evidence suggests that cognitive dysfunction is a rising complication of diabetes which adversely affects the brain of patients suffering from diabetes.