GLP-1/GIP Agonist as an Intriguing and Ultimate Remedy for Combating Alzheimer's Disease through its Supporting DPP4 Inhibitors: A Review.

BACKGROUND: Alzheimer's disease (AD) is a widespread neurological illness in the elderly, which impacted about 50 million people globally in 2020. Type 2 diabetes has been identified as a risk factor. Insulin and incretins are substances that have various impacts on neurodegenerative processes. Preclinical research has shown that GLP-1 receptor agonists decrease neuroinflammation, tau phosphorylation, amyloid deposition, synaptic function, and memory formation. Phase 2 and 3 studies are now occurring in Alzheimer's disease populations. In this article, we present a detailed assessment of the therapeutic potential of GLP-1 analogues and DPP4 inhibitors in Alzheimer's disease. AIM: This study aimed to gain insight into how GLP-1 analogues and associated antagonists of DPP4 safeguard against AD. METHODS: This study uses terms from search engines, such as Scopus, PubMed, and Google Scholar, to explore the role, function, and treatment options of the GLP-1 analogue for AD. RESULTS: The review suggested that GLP-1 analogues may be useful for treating AD because they have been linked to anti-inflammatory, neurotrophic, and neuroprotective characteristics. Throughout this review, we discuss the underlying causes of AD and how GLP signaling functions. CONCLUSION: With a focus on AD, the molecular and pharmacological effects of a few GLP-1/GIP analogs, both synthetic and natural, as well as DPP4 inhibitors, have been mentioned, which are in the preclinical and clinical studies. This has been demonstrated to improve cognitive function in Alzheimer's patients.

The Emergence of Nanotechnology in the Prognosis and Treatment of Myocardial Infarctions.

Myocardial infarction (MI), commonly known as a heart attack, is a critical cardiovascular condition associated with high morbidity and mortality rates worldwide. Despite significant advancements in traditional treatment modalities, there remains a need for innovative approaches to improve the prognosis and treatment outcomes of MI. The emergence of nanotechnology has provided a promising avenue for revolutionizing the management of this life-threatening condition. This manuscript aims to explore the role of nanotechnology in the prognosis and treatment of myocardial infarctions. Nanotechnology offers unique advantages in the field of cardiovascular medicine, including targeted drug delivery, precise imaging and diagnosis, regenerative medicine approaches, biosensors and monitoring, and the integration of therapy and diagnostics (theragnostic). One of the key advantages of nanotechnology is the ability to deliver therapeutic agents directly to the affected site. Nanoparticles can be engineered to carry drugs specifically to damaged heart tissue, enhancing their efficacy while minimizing off-target effects. Additionally, nanoparticles can serve as contrast agents, facilitating high-resolution imaging and accurate diagnosis of infarcted heart tissue. Furthermore, nanotechnology-based regenerative approaches show promise in promoting tissue healing and regeneration after MI. Nanomaterials can provide scaffolding structures or release growth factors to stimulate the growth of new blood vessels and support tissue repair. This regenerative potential holds significant implications for restoring cardiac function and minimizing long-term complications. Nanotechnology also enables real-time monitoring of critical parameters within the heart, such as oxygen levels, pH, and electrical activity, through the utilization of nanoscale devices and sensors. This capability allows for the early detection of complications and facilitates timely interventions. Moreover, the integration of therapy and diagnostics through nanotechnology-based platforms, known as theragnostic, holds tremendous potential. Nanoparticles can simultaneously deliver therapeutic agents while providing imaging capabilities, enabling personalized treatment strategies tailored to individual patients. This manuscript will review the recent advancements, clinical trials, and patents in nanotechnology for the prognosis and treatment of myocardial infarctions. By leveraging nanotechnology's unique properties and applications, researchers and clinicians can develop innovative therapeutic approaches that enhance patient outcomes, improve prognosis, and ultimately revolutionize the management of myocardial infarctions.

Regulation of omega-3 fatty acids production by different genes in freshwater fish species: a review.

The present study aims to compare the gene expression of three different fish species (common carp, tilapia, and trout) with varying levels of fatty acids (FA). Based on transcriptome analysis and RNA sequencing, various genes and their associated metabolic pathways are identified. Pathways are categorized based on the genes they encode. Genes that were differentially expressed and their promoter's methylation patterns were revealed by RNA-seq analysis in common carp. Furthermore, fatty acid-enriched pathways, such as ARA4 and adipocytokine signaling, were also identified. Many genes and pathways may influence tilapia's growth and omega-3 content. Using the mTOR pathway, trout with differential expression were discovered to be involved in producing omega-3 fatty acids. This study revealed major pathways in fish species to produce omega-3 fatty acids.

Epsilon poly-lysine in buffalo semen extender: A step towards reducing the development of antibiotic resistance.

The use of antibiotics in semen extenders can contribute to the development of antibiotic resistance. The objective of the study was to evaluate epsilon-polylysine (Ɛ-PL) as a substitute for antibiotics in the buffalo semen extender. For this, 20 semen ejaculates were collected from four Murrah buffalo bulls. Each ejaculate was divided into three equal aliquots and extended into an egg yolk-based semen extender containing either antibiotics (strepto-penicillin) or different concentrations of Ɛ-PL (0.64 and 1.28 g/L) to make the final concentration 80 million sperm/mL and cryopreserved as per the standard procedure. The antibiogram sensitivity test confirmed that Ɛ-PL is an effective antimicrobial against microbes present in buffalo semen ejaculates. Furthermore, the addition of Ɛ-PL in the semen extender significantly reduces the colony forming unit (CFU)/mL in cryopreserved semen equivalent to strepto-penicillin. The sperm motility and kinematic parameters assessed by a computer-assisted sperm analyser showed that Ɛ-PL did not inhibit either sperm motility not kinematic parameters of cryopreserved sperm. The flow-cytometric evaluation of frozen-thawed sperm revealed interesting results. The extender supplemented with Ɛ-PL protected sperm acrosome and mitochondrial membrane potential greater than the extender supplemented with strepto-penicillin. Further, Ɛ-PL reduced significantly the production of superoxide anions from mitochondria during the cryopreservation process. In this way, Ɛ-PL may be a suitable alternative to antibiotics in semen extenders. In conclusion, Ɛ-PL at a concentration of 0.64 g/L acts as an effective antimicrobial as well as antioxidant in semen extender for cryopreservation of buffalo sperm.

Effect of mitochondria-targeted antioxidant on the regulation of the mitochondrial function of sperm during cryopreservation.

Sperm mitochondrion is one of the major susceptible organelles that get damaged during cryopreservation. The study aimed to minimize mitochondrial dysfunction and oxidative stress during sperm cryopreservation using mitochondria-specific antioxidants. For this, semen was collected from five buffalo bulls (3 ejaculates/bull). The ejaculates were diluted in an low-density lipoprotein-based extender and divided into four equal aliquots. Mitochondria-targeted antioxidant (MitoQ) was added at a final concentration of 0 (control), 0.02, 0.2 and 2 µM separately in each aliquotes and cryopreserved. The addition of MitoQ at a concentration of 0.02 µM improved post-thaw sperm motility, plasma membrane integrity and able to sustain sperm motility for a longer time. To investigate MitoQ's effects on mitochondrial function, we measured mitochondrial membrane potential (MMP) using JC-1 dye, superoxide production using Mitosox assay, and lipid peroxidation by TBARS assay. The supplementation of 0.02 µM MitoQ in the extender prevented the significant reduction of MMP and reduced superoxide production resulting in lower lipid peroxidation of sperm plasma membrane after cryopreservation. Further, we found that a higher concentration of MitoQ decreases MMP and increases mitochondrial superoxide production. In conclusion, MitoQ @ 0.02 µM can alleviate oxidative stress by regulating mitochondrial functionality in spermatozoa during cryopreservation.

Aryldiazoquinoline based multifunctional small molecules for modulating Aß42 aggregation and cholinesterase activity related to Alzheimer's disease.

Research continues to find a breakthrough for the treatment of Alzheimer's Disease (AD) due to its complicated pathology. Presented herein is a novel series of arydiazoquinoline molecules investigated for their multifunctional properties against the factors contributing to Alzheimer's disease (AD). The inhibitory properties of fourteen closely related aryldiazoquinoline derivatives have been evaluated for their inhibitory effect on Aß42 peptide aggregation. Most of these molecules inhibited Aß42 fibrillation by 50-80%. Selected molecules were also investigated for their binding behaviour to preformed Aß40 aggregates indicating a nanomolar affinity. In addition, these compounds were further investigated as cholinesterase inhibitors. Interestingly, some of the compounds turned out to be moderate in vitro inhibitors for AChE activity with IC50 values in low micro molar range. The highest anti-AChE activity was shown by compound labelled as 2a with an IC50 value of 6.2 µM followed by 2b with IC50 value of 7.0 µM. In order to understand the inhibitory effect, binding of selected molecules to AChE enzyme was studied using molecular docking. In addition, cell toxicity studies using Neuro2a cells were performed to assess their effect on neuronal cell viability which suggests that these molecules possess a non-toxic molecular framework. Overall, the study identifies a family of molecules that show good in vitro anti-Aß-aggregation properties and moderately inhibit cholinesterase activity.

A comparative evaluation of fracture load of monolithic and bilayered zirconia crowns with and without a cervical collar: an in vitro study.

INTRODUCTION: The use of zirconia based all-ceramic restorations are preferred nowadays owing to superior biologic and esthetic properties. However, these restorations have also reported higher incidences of fracture and chipping. The clinical success may be enhanced by optimizing the core design, through the introduction of monolithic zirconia, or the layered crowns can be strengthened by adding the cervical collar to them. OBJECTIVE: This study was performed with the objective to compare and evaluate the fracture load of monolithic and bilayered zirconia crowns with and without a cervical collar. METHODS: A prospective observational study was carried out to compare 45 fabricated zirconia crowns of three different designs on a customized metal mould. The samples were oriented on the metal mould and subjected to confocal microscope for the evaluation of marginal integrity followed by cementing the crown on the metal mould and subjecting it to the universal testing machine for the analysis for the flexural strength. Data were analyzed using one way Anova and t- test for inter and intra groups. The significance level was set at P ≤ 0.05. RESULTS: The monolith zirconia crowns and layered zirconia crowns with cervical collar reported more flexural strength. CONCLUSION: The amount of force required to fracture the zirconia crowns was higher in the case of monolith zirconia crown and layered zirconia crown with cervical collar as compared to the layered zirconia crown without cervical collar.