A Case of Hypernatremia With Dementia.

The authors report a case of hypernatremia in a patient with a history of dementia. This case highlights the challenges and scope of taking care of such patients. It also highlights the hardships in diagnosing and caring for patients with inadequate documentation of past diagnoses and treatments.

ß-Cyclodextrin-crosslinked synthetic neuropeptide Y-based nanosponges in epilepsy by contributing GABAergic signal.

Neuropeptide Y (NPY) is a polypeptide sequence useful in regulating physiological functions like homeostasis, feeding, etc., but its usage is restricted due to its short half-life. ß-cyclodextrin-crosslinked nanosponges improve the drug release and stability due to its wide cavity, which is helpful to deliver therapeutics. The present work aimed to formulate synthetic NPY-based nanocarriers as sponges by polymer condensation mechanism using design experiment to improve the peptide release and stability. The validated nanosponges exhibited a particle size of 423.42 ± 5.32 nm, 75.82 ± 7.43 % entrapment efficiency and 83.50 ± 6.54 % NPY release for 24 h. The NPY and ß-cyclodextrin interaction was confirmed by X-ray diffraction, Fourier transform infrared and nuclear magnetic resonance spectroscopy. The NPY-loaded nanosponges were found stable for 6 months at two conditions (5 ± 2 °C and 25 ± 2 °C). The cross-linked nanocarriers of synthetic peptide-based nanosponges powder at different doses were administered intranasally using a metered-dose inhaler in the animal model to check its antiepileptic activity. The synthetic NPY-loaded nanosponges at higher doses showed significant antiepileptic effects equivalent to the standard drug (administered orally) in maximal electroshock and chemically-induced seizures with an increase of NPY in the brain directly proportional to GABAergic signalling by increase in GABA levels resulting in convulsions attenuation.

Dual-action of colloidal ISCOMs: an optimized approach using Box-Behnken design for the management of breast cancer.

Neuropeptide Y (NPY) occurs in G-protein-coupled receptors and offers targeted effects at the active sites for therapeutic action in various conditions like depression, stress, obesity and cancer. Immune stimulating complexes (ISCOMs) associate peptides with the lipid systems for enhancing antigen targeting to provide site-specific action and B-cell response. The present study focused on the encapsulation of NPY in ISCOMs to comprise dual action in the form of immunity modulation and management of breast cancer by arresting G0/G1 phase. The colloidal ISCOMs were prepared by coupling method and further optimized by Box-Behnken design of Design of Experiment (DoE) software. The NPY-loaded ISCOMs (formulation ISCN) were characterized by various parameters with higher % encapsulation efficiency of 87.99 ± 1.87% and in-vitro release of 84.16±3.2% of NPY for 24 h. The study of MTT assay on MCF-7 cell line for formulation ISCN exhibited a significant decrease in the cell growth of 66.41±4.7% at 10 µg/mL compared to plain NPY (52.21±0.04%). The MCF-7 cells showed a significant reduction in cytokine levels in the presence of formulation ISCN wherein TH1(TNF-α) and TH2(IL-10) levels were found to be 25.12±3.11 pg/mL and 35.76±4.23 pg/mL, respectively. The cell cycle study demonstrated that significant cells were blocked in the G0/G1 phase with 57.8±3.02% of cell apoptosis using formulation ISCN. The formulation ISCN was found to prolong t1/2 and increase AUC than plain NPY via intravenous administration due to complex formation with phospholipid. Hence, ISCOMs-based NPY system will be a promising approach for dual action as immunomodulation and anticancer effects by controlling the release of NPY.

Experimental aspects of NPY-decorated gold nanoclusters using randomized hybrid design against breast cancer cell line.

Gold nanoclusters (AuNCs) are potential carrier system for bioactive like proteins and peptides used in various therapeutics against various ailments. Neuropeptide Y (NPY) is consists of 36 amino acids used to treat depression, obesity, epilepsy, and so on. but possess instability at higher temperatures causing its limited usage. The present study focused on the NPY-decorated AuNCs prepared using desolvation reduction technique and optimized through randomized hybrid design. ATR-FTIR, 1 H NMR and CD spectroscopic studies confirmed the AuNCs structure interaction with NPY. The optimized NPY-decorated AuNCs possessed 85.6 ± 2.08% of entrapment efficiency with 85.32 ± 7.55% of NPY release for 24 h. It displayed dose-dependent cell cytotoxicity, IC50 value of 0.7 ± 0.05 µg mL-1 and apoptosis of 68.48 ± 7.35% with controlled cell migration causing G0G1 cell arrest by penetrating cancer cell membrane on MCF-7 cell line. Furthermore, the AuNCs caused surface disruption of the cancerous cell further interrupting the protein synthesis by MAPK pathway leading to cell death. The AuNCs were stable for 3 months at 25 ± 2°C due to steric hindrance. Hence, NPY-decorated AuNCs were found to be effective on MCF-7 cell line with a significant anti-apoptotic effect, further emerging as a novel therapeutic delivery system in the management of breast cancer.

Polyplexes of retinoic acid: an in vitro study of complex nanostructures against colorectal cancer cell line (HCT-15).

Despite recent advances in the treatment of human colon cancer, the chemotherapeutic efficacy against colon cancer is still unsatisfactory. The complexity in colorectal cancer treatment leads to new research in combination therapy to overcome multidrug resistance in cancer and increase apoptosis. The objective of the present research work was to develop polyplexes for co-delivery of plasmid DNA with retinoic acid against colorectal cancer cell line (HCT-15). Plain polyplexes were prepared using chitosan and hyaluronic acid solution (0.1% w/v), whereas retinoic acid polyplexes were prepared using ethanol: water (1:9 v/v) system. The particle size was observed in the order of chitosan solution > blank polyplex > retinoic acid-loaded polyplex. Encapsulation efficiency of retinoic acid was found to be 81.51 ± 4.33% for retinoic acid-loaded polyplex formulation. The drug release was observed to be in a controlled pattern with 72.23 ± 1.32% release of retenoic acid from polyplex formulation. Cell line studies of the formulation displayed better cell inhibition and low cytotoxicity for the retinoic acid-loaded polyplexes in comparison to pure retinoic acid, thus demonstrating better potential action against colorectal cancer cell line HCT-15. Retinoic acid-loaded polyplexes indicated higher potential for the delivery of the active whereas the cell line studies displayed the efficacy of the formulation against colorectal cancer cell line HCT-15.

Integration of Internet of Things with Quantum Dots: A State-of-the-art of Medicine.

Internet of Things (IoT) emerges as disruptive innovation and development in the fields of drug delivery and biomedical sciences using on-target active transportation, sensors, wearable devices, real-time diagnostics, etc. Semiconducting fluorescence emitting material, quantum dots on integration with IoT displayed interesting results in the healthcare sector, especially in hospitals and pathological laboratories. Presently, the integrated system is used to improve productivity without the interference of human and offer a cost-effective system. This integrated system can be used for the detection of various diseases like epilepsy, cancer, diabetes, etc., and various biomedical applications like energy storage, lights, sensor technology, light filters, etc. The integrated technology is implemented into the field of medicine for simplifying the approaches in therapeutics and diagnostic applications. The collected and analyzed data are further useful for healthcare professionals to find patient-centric solutions. Artificial Intelligence-aided IoT emerges as a novel technology for transmitting and securing health data. Despite some of the limitations like e-waste and the risk of hacking, an IoT-based QD system will be considered as a modern healthcare provider with life-saving products for enriching the medical quality and real-time accessibility.

Potential of Chimeric Antigen Receptor T-Cells in Cancer Therapy.

Novel approaches for targeted delivery like nanoparticles, liposomes, polymer conjugates, etc. with better safety profile needs to be developed for cancer treatment. Chimeric antigen receptors (CAR) with modified thymus cells (T-cells) showed greater potential as a therapy due to its direct effect on immune system responsible for destruction of pathogens and said equivalent to the living drug. On activation of T-cell, it binds to the antigen domains treating refractory or relapsed cancers. The receptors are termed chimeric as it consists of T-cells functioning as well as antigen-binding combined in sole receptor. This therapy showed positive success towards hematological cancers and engineered for specific protein targeting. Though the therapy is associated to several challenges like incompetence towards tumor lysis and cytokine release rate, termination of cytotoxic activity after completion of tumor eradication, etc. The control mechanisms used by CAR T-cells are apoptosis by suicide genes, dual-antigen receptor, ON-switch tumor attack and bispecific molecules as activation switch. In solid tumors, CAR T-cell therapy showed promising signs of efficacy becoming a game-changing cell therapy. CAR T-cells are optimized using different engineering resolutions and lead to broadways for therapy adoption to benefit the cancer patients.

Nanoconjugates-Based Stem Cell Therapy for the Management of COVID-19.

A potential ability of stem cells (SCs) is to regenerate and repair tissues in the human body by providing great prospects for therapeutic applications in the field of medicine. Currently, SC therapy is used in various conditions like diabetes, neurodegenerative disorders, etc. but faces some limitations like patient biocompatibility and chances of cross-infection. SCs are further modulated with nanoconjugates to overcome such challenges and will offer an advantage in the treatment of COVID-19. This pandemic requires design and development of proper treatment to save the life of human beings. Advancements in SC-based nanoconjugated therapy will open new avenues and create a significant impact in the development of futuristic nanomedicine. It may also emerge as a potential therapy for the management of infection in patients suffering from SARS-CoV-2 and related diseases such as pneumonia and virus-induced lung injuries. Graphical abstract Mechanisms of stem cell-based nanoconjugates for inhibition of replication of corona virus.

Strategic Aspects of NPY-Based Monoclonal Antibodies for Diagnosis and Treatment of Breast Cancer.

Immunotherapy emerges as a treatment strategy for breast cancer marker, diagnosis and treatment. In this review, monoclonal antibodies (mAbs)-based passive and peptide vaccines as active immunotherapy approaches like activation of B-cells and T-cells are studied. Passive immunotherapy is mAbs-based therapy effective against tumor cells, which acts by targeting HER2, IGF 1R, VEGF, BCSC and immune checkpoints. Neuropeptide Y (NPY) and GPCR are the areas of interest to target BC metastases for on-targeting therapeutic action. Neuropeptide S (NPS) or NPS receptor 1, acts as a biomarker for Neuroendocrine tumors (NET), mostly characterized by synaptophysin and chromogranin-A expression or Ki-67 proliferation index. The protein fusion technologies arise as a promising avenue in plant expression systems for increased recombinant Ab accumulation and cost-efficient purification. Recently, mAbs-based immunotherapy effectiveness is appreciated as a novel therapeutic combination of chemotherapy and immunotherapy to reduce the side effects and improve therapeutic responsiveness. Synthetic drug resistance will be overcome by mAbs-based therapy through several clinical trials and detection methods need to be optimized for accuracy and precision. Pharmacokinetic attributes need to be accessed for preferred receptor-agonist activity without ligand accumulation.

Physiological and Therapeutic Roles of Neuropeptide Y on Biological Functions.

Neuropeptide Y (NPY), an amino acid, used for various physiological processes for management and treatment of various ailments related to central nervous system, cardiovascular system, respiratory system, gastro-intestinal system and endocrinal system. In nasal mucosa, high concentrations of NPY are stored with noradrenaline in sympathetic nerve fibers. NPY Y1 receptor mediates nitric oxide levels and reduction in blood flow in nasal mucosa of the human. NPY plays a role in dietary consumption via various factors like signaling the CNS for a prerequisite of energy in hypothalamus by mediating appetite and shows orexigenic effect. NPY emerges as a natural ligand of G-protein coupled receptors which activates the Y-receptors (Y1-Y6). But applications of NPY are limited due to shows the cost inefficiency and stability issues in the formulation design and development. In this review, authors present the findings on various therapeutic applications of NPY on different organ systems. Moreover, its role in food intake, sexual behavior, blood pressure, etc. by inhibiting calcium and activating potassium channels. The combination therapies of drugs with neuropeptide Y and its receptors will show new targets for treating diseases. Further evaluation and detection of NPY needs to be investigated for animal models of various diseases like retinal degeneration and immune mechanisms.

Role of Solid-Gas Interface of Nanobubbles for Therapeutic Applications.

The development of nanoscale particles offers tremendous potential for the formulation of nanobubbles, an area of great interest in therapeutic ultrasound, detection, diagnosis, and drug delivery systems. This review compiles information for designing nanobubbles tailored to various applications such as color Doppler imaging, multidrug-resistant treatment, cosmeceuticals, gene therapy, cancer treatment, water treatment, and so forth. Nanobubbles also extend a path for convenient and eco-friendly systems for cleaning conducting surfaces. We anticipate that this review will provide insights into nanobubble formulation, applications, and future approaches. It also focuses on newer technologies and formulation of gases, polymers, and excipients. Nanobubbles emerge as novel biocompatible, nontoxic carriers for clinical and commercial applications in healthcare but have yet to be explored in other fields.

Factor VIII ectopically targeted to platelets is therapeutic in hemophilia A with high-titer inhibitory antibodies.

Inhibitory immune response to exogenously infused factor VIII (FVIII) is a major complication in the treatment of hemophilia A. Generation of such inhibitors has the potential to disrupt gene therapy for hemophilia A. We explore what we believe to be a novel approach to overcome this shortcoming. Human B-domain-deleted FVIII (hBDDFVIII) was expressed under the control of the platelet-specific alphaIIb promoter in platelets of hemophilic (FVIIInull) mice to create 2bF8trans mice. The FVIII transgene product was stored in platelets and released at the site of platelet activation. In spite of the lack of FVIII in the plasma of 2bF8trans mice, the bleeding phenotype of FVIIInull mice was corrected. More importantly, the bleeding phenotype was corrected in the presence of high inhibitory antibody titers introduced into the mice by infusion or by spleen cell transfer from recombinant hBDDFVIII-immunized mice. Our results demonstrate that this approach to the targeted expression of FVIII in platelets has the potential to correct hemophilia A, even in the presence of inhibitory immune responses to infused FVIII.