Efficiency Of Therapy Research Articles

Nanotechnology and Artificial Intelligence in Dyslipidemia Management—Cardiovascular Disease: Advances, Challenges, and Future Perspectives

This narrative review explores emerging technologies in dyslipidemia management, focusing on nanotechnology and artificial intelligence (AI). It examines the current treatment recommendations and contrasts them with the future prospects enabled by these innovations. Nanotechnology shows significant potential in enhancing drug delivery systems, enabling more targeted and efficient lipid-lowering therapies. In parallel, AI offers advancements in diagnostics, cardiovascular risk prediction, and personalized treatment strategies. AI-based decision support systems and machine learning algorithms are particularly promising for analyzing large datasets and delivering evidence-based recommendations. Together, these technologies hold the potential to revolutionize dyslipidemia management, improving outcomes and optimizing patient care. In addition, this review covers key topics such as cardiovascular disease biomarkers and risk factors, providing insights into the current methods for assessing cardiovascular risk. It also discusses the current understanding of dyslipidemia, including pathophysiology and clinical management. Together, these insights and technologies hold the potential to revolutionize dyslipidemia management, improving outcomes and optimizing patient care.

Medical management pathways for Cushing’s disease in pituitary tumors centers of excellence (PTCOEs)

PurposeA recent update of consensus guidelines for the management of Cushing’s disease (CD) included indications for medical therapy. However, there is limited evidence regarding their implementation in clinical practice. This study aimed to evaluate current medical therapy approaches by expert pituitary centers through an audit conducted to validate the criteria of Pituitary Tumors Centers of Excellence (PTCOEs) and provide an initial standard of medical care for CD.MethodsBased on the activities of nine international PTCOEs between 2018 and 2020, we evaluated patients under medical treatment and their biochemical control rates.ResultsThe median number of active patients with CD per center was 117 (35–279), with a median number of 10 new patients with CD managed annually in the endocrinology units of PTCOEs (4–42). The median percentage of patients with CD receiving medical treatment was 13.3% (4.8–82.9). Ketoconazole was the most frequently used drug, with a median rate of usage of 26.5% (5-66.7) of those receiving medical therapy. The median rates of metyrapone and pasireotide use were 17.2% (0–50) and 9.3% (0-51.7), respectively. For cabergoline and osilodrostat, therapy, the median rates of use were 2.8% (0-33.3), and 1.7% (0–25), respectively. Combination therapy was reported to be utilized in 13.6% (0-45.5) of medically treated patients. Mifepristone was used in a single center, representing 1.1% of its medically treated patients. Overall, the median control rate in patients with CD receiving medical treatment was 75% (10–100).ConclusionAdrenal steroidogenesis inhibitors were the most commonly used medications amongst the centers. Despite the use of combination therapy, up to 25% of patients did not achieve disease control even in PTCOEs, highlighting the need for either more efficient combination therapies or novel therapeutic options.

Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.

Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells. The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers. Two clinical staging systems, Rai and Binet, provide prognostic information by using the results of physical examination and blood counts. Various biological and genetic markers provide additional prognostic information. Deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of the TP53 gene predict a shorter time to progression with most targeted therapies. The CLL international prognostic index (CLL-IPI) integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL. The CLL-IPI retains its significance in the era of targeted agents, but the overall prognosis of CLL patients with high-risk stages has improved. Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist: combinations of the BCL2 inhibitor venetoclax with obinutuzumab, or venetoclax with ibrutinib, or monotherapy with one of the inhibitors of Bruton tyrosine kinase (BTK). At relapse, the initial treatment may be repeated if the treatment-free interval exceeds 3 years. If the leukemia relapses earlier, therapy should be changed using an alternative regimen. Combinations of targeted agents now provide efficient therapies with a fixed duration that generate deep and durable remissions. These fixed-duration therapies have gained territory in the management of CLL, as they are cost-effective, avoid the emergence of resistance, and offer treatment free time to the patient. The cure rate of these novel combination regimens is unknown. Moreover, the optimal sequencing of targeted therapies remains to be determined. A medical challenge is to treat patients who are double-refractory to both BTK and BCL2 inhibitors. These patients need to be treated within experimental protocols using novel drugs.

Preparation and pharmacokinetic evaluation of a sertraline-methylpropyphenazone prodrug: a comparative metabolic study on the plasma and brain tissues of rats using LC-MS/MS analysis.

A mutual prodrug of sertraline-methylpropyphenazone (SER-MP) was prepared and characterized using a spectral method. The yield of the prepared SER-MP was 90%, and its purity reached 98.8%. The metabolic fate of the prepared SER-MP versus sertraline (SER) was investigated in the plasma and brain tissues of rats. A solid-phase extraction procedure was developed and validated for the optimal recovery of SER, 3-hydroxymethylpropyphenazone (3-OHMP), and SER-MP from plasma and brain tissues. The extraction efficiency for the targeted analytes was improved from 93.5% to 98.0% using Chromabond® C8-100 mg solid-phase extraction columns. A high-performance liquid chromatography-triple-quad-mass spectrometric method was developed and validated to quantify the SER, SER-MP, and potential metabolites. The pharmacokinetic parameters showed that the time to reach the maximum plasma concentration (t max) for both SER and SER-MP was 6 hours, and the maximum plasma concentration of SER-MP reached 192 ng mL-1 with an elimination half-life time of 50 hours. The plasma level of SER, which was released as a metabolite of orally administered SER-MP, was increased by 2.4 times compared to SER HCl administered at equimolar doses. The concentration of SER-MP in the rat brains remained approximately stable at 100 ng g-1 for 0.5 to 192 hours. The serotonin level in the rat brain homogenate was 50 to 90 ng g-1 for both the group receiving SER and that receiving an equal molar dose of SER-MP. This observation was consistent during a time range of 1 to 192 h from oral administration. Thus, this approach could lead to the development of more efficient antidepressant therapies with reduced side effects. The findings indicate that SER-MP could minimize serotonin syndrome risks by maintaining steady serotonin levels in the brain, thus improving patient safety and compliance.

Amphiphilic Polyaspartamide Derivatives with Cholesterol Introduction Enhanced Ex Vivo mRNA Transfection Efficiency to Natural Killer Cells.

Engineered natural killer (NK) cells eliminate cancer cells by overexpressing a chimeric antigen receptor, producing highly efficient and safe NK cell therapies. This study investigated the polyplex formulation for the fusion protein GreenLantern-natural killer group 2D (NKG2D) mRNA to evaluate its ex vivo delivery efficacy into NK cells, wherein NKG2D on the surface of NK cells recognized its counterpart NKG2D ligands on cancer cells. Amphiphilic polyaspartamide derivatives Chol-PAsp(DET/CHE) were prepared by adding cyclohexylethylamine (CHE) and diethylenetriamine (DET) in the side chains and cholesterol (Chol) at the α-terminus to enhance endosomal escapability and optimize hydrophobicity. Chol-PAsp(DET/CHE) significantly improved mRNA delivery efficacy into NK-92mi cells, explained by increased polyplex stability and improved cellular uptake of mRNA. The NKG2D-overexpressing NK-92mi cells exhibited high anticancer efficacy against human colon cancer cells without affecting the viability of fibroblasts. Therefore, Chol-PAsp(DET/CHE) could be a promising mRNA delivery carrier for the ex vivo engineering of NK cells.

Bovine Serum Albumin Nanoparticle-Mediated Delivery of Ribavirin and Mycophenolic Acid for Enhanced Antiviral Therapeutics

The global spread of viral diseases is a public health issue. Ribavirin (RBV) and mycophenolic acid (MPA) are well-known wide-spectrum antiviral agents. The present study evaluated the potential of bovine serum albumin (BSA) nanoparticles (NPs) as a vehicle to improve the efficacy of molecules with antiviral activity. The results demonstrated that NPs offer a promising strategy for the delivery of antiviral drugs, improving their stability and reducing toxicity compared to free agents. BSA-based NPs effectively encapsulated hydrophilic molecules such as MPA and water-soluble compounds such as RBV, achieving encapsulation efficiencies of 10% and 20%, respectively. The purified NPs exhibited a particle size between 60 and 100 nm and did not show toxicity at the evaluated concentrations. In cellular viral infection models against Zika virus (ZIKV), Junín virus (JUNV), vesicular stomatitis virus (VSV) and herpes simplex virus (HSV-1), the BSA-based NPs loaded with MPA or RBV demonstrated antiviral properties superior to those of non-encapsulated agents, as well as 100- and 200-fold effective dose reductions, respectively. These findings clearly indicate the potential of BSA NPs as a novel platform for the development of safer and more efficient antiviral therapies.

Perceptions and Use of Extended-Duration Exposure Therapy Amongst Psychologists.

Extended-duration exposure therapy, in which treatment is delivered over a single prolonged session or cluster of long-duration sessions, is a highly efficacious and efficient treatment for anxiety disorders such as specific phobias. Despite this, little is known about the use of extended-duration exposure therapy in clinical practice. In the present study we investigated the perceptions and use of extended-duration exposure therapy amongst a sample of Australian psychologists via a survey, and the Therapist Beliefs about Exposure Scale. Additionally, we compared theoretical understanding of exposure therapy, and therapy delivery strategies (using a case study vignette), between psychologists who deliver exposure therapy via an extended-duration mode, versus the more traditional multi-session mode. Extended-duration exposure therapy is widely underutilised, and this is associated with negative beliefs about exposure therapy in general, as well as several practical barriers. There were no differences in the reported theoretical mechanisms of exposure therapy between those who do and do not use extended-duration exposure therapy. However, psychologists who use extended-duration exposure therapy reported greater use of strategies with demonstrated efficacy (e.g., more intense delivery) and less use of therapy-interfering strategies (e.g., distress reduction techniques) relative to those who do not use extended-duration exposure therapy. These findings identify potential mechanisms accounting for extended-duration exposure therapy's efficiency and point to strategies that may increase the uptake of extended-duration exposure therapy in clinical practice.

Current Landscape and Prospects of CAR-T Cell Therapy in Prostate Cancer: A Clinical Trial Review

This review talks about the causes and dangers of prostate cancer. The widespread of prostate cancer and the shortcomings of traditional therapies are discovered, and the principles, significance, and prospects of CAR-T therapy were discussed. Through discussing the significance of CAR-T therapy and the progress of clinical trials. This paper talks about the relevant targets of CAR-T therapy for prostate cancer such as PSMA, PSCA, reviews the purpose, process and results of currently approved clinical trials. This review hopes to find the focus and shortcomings of current CAR-T therapies in the clinical trials and contributes to the development of more efficient CAR-T therapies

Efficient Biochemical Method for Characterizing and Classifying Related Amyloidogenic Peptides.

Amyloidosis is a group of proteinopathies characterized by the systemic or organ-specific deposition of proteins in the form of amyloid fibers. Nearly 40 proteins play a role in these pathologies, and the structures of the associated fibers are beginning to be determined by Cryo-EM. However, the molecular events underlying the process, such as fiber nucleation and elongation, are poorly understood, which impairs developing efficient therapies. In most cases, only a few dozen amino acids of the pathological protein are found in the final structure of the fibers, while amyloid peptides comprising five to 10 amino acids are involved in the fiber nucleation process. The identification and biochemical characterization of these peptides are therefore of major scientific and clinical importance. We demonstrated that in silico approaches are limited due to the peptides' small size and long-distance intra- and intermolecular interactions that occur during nucleation. To address this problem, we developed a novel biochemical method for characterizing and classifying batches of related peptides. Initial work to optimize our approach is based on the reference peptide PHF6 (β1) from Microtubule-Associated Protein Tau (MAPT) as compared to 22 related peptides. Depending on their biochemical properties and using the Garnier-Delamarche plot we propose, we classified these peptides into three groups: aggregative, amyloid, and soluble (neither aggregative nor amyloid). We emphasize that our biochemical classification method is applicable to any family of peptides and could be scaled up for high-throughput analyses.

Lauryl-NrTP6 lipopeptide self-assembled nanorods for nuclear-targeted delivery of doxorubicin.

Targeted delivery offers solutions for more efficient therapies with fewer side effects. Here, lipopeptides (LPs) prepared by conjugation of the nuclear-targeting peptide analogue H-YKQSHKKGGKKGSG-NH2 (NrTP6) and two lauric acid chains are used to encapsulate the chemotherapeutic agent doxorubicin (DX) through a solvent-exchange protocol. LPs spontaneously form nanosized rod-like assemblies in phosphate buffer. DX is trapped in the peptide regions of the assemblies. Confocal laser scanning microscopy shows that the peptide assemblies translocate into the nucleus. Cytotoxicity studies over 72 h in A549 and HeLa cancer cell lines show less toxicity for the LP encapsulated DX than for free DX. In contrast, subtoxic doses of encapsulated DX are more effective than free DX in avoiding colony formation over 14 days, with a complete absence of colonies for the LP-encapsulated DX. The results show a more efficient and slow delivery of DX to the nucleus through LP encapsulation, paving the way for the use of lower DX doses as a chemotherapeutic agent.

Wnt Signaling Pathway in Tumor Biology.

Relapse and metastasis are the major challenges that stand in the way of cancer healing and survival, mainly attributed to cancer stem cells (CSCs). Their capabilities of self-renewal and tumorigenic potential leads to treatment resistance development. CSCs function through signaling pathways such as the Wnt/β-catenin cascade. While commonly involved in embryogenesis and adult tissues homeostasis, the dysregulation of the Wnt pathway has direct correlations with tumorigenesis, metastasis, and drug resistance. The development of therapies that target CSCs and bulk tumors is both crucial and urgent. However, the extensive crosstalk present between Wnt and other signaling networks (Hedgehog and Notch) complicates the development of efficient long-term therapies with minimal side-effects on normal tissues. Despite the obstacles, the emergence of Wnt inhibitors and subsequent modulation of the signaling pathways would provide dynamic therapeutic approaches to impairing CSCs and reversing resistance mechanisms.

Parenteral Nutrition in the Health-Care Setting: A Comprehensive Review

Parenteral Nutrition (PN) is a critical therapeutic technique that delivers necessary nutrients straight into the circulation, bypassing the gastrointestinal system. This strategy is critical for people who are unable to acquire appropriate nourishment through oral or enteral routes owing to a variety of medical issues. PN first appeared in the mid-twentieth century, primarily to help those who were very malnourished or recuperating from significant surgery. As medical understanding of nutrition grew, so did the complexity and customization of PN formulations, allowing for personalized nutritional support depending on metabolic demands. The indications for PN are diverse, including gastrointestinal diseases, cancer therapies, severe illnesses, neurological issues, and pediatric demands. Patients suffering with Crohn's illness, short gut syndrome, and severe malnutrition caused by cancer therapies frequently rely on PN to maintain their nutritional status. Furthermore, critically sick patients in intensive care settings typically encounter elevated metabolic demands, needing efficient nutritional therapies that oral feeding cannot deliver. While PN has considerable advantages, such as increased recovery, malnutrition prevention, and quality of life, it is not without hazards. Infections, metabolic abnormalities, and liver dysfunction are all possible complications, emphasizing the importance of thorough monitoring and following best practices in PN administration. A multidisciplinary approach including healthcare specialists from several professions is required to achieve the best outcomes for patients seeking PN. Looking ahead, technological developments, personalized dietary techniques, and artificial intelligence integration promise to improve the safety and efficacy of PN. Continuous research and innovation are required to solve current difficulties and enhance the overall quality of care for patients requiring parenteral feeding. As the healthcare environment shifts, PN will remain an important component of nutritional support, requiring continuing attention and development in clinical practice.

Desloratadine mitigates hepatocellular carcinoma in rats: Possible contribution of TLR4/MYD88/NF-κB pathway.

Chemotherapeutic medication-induced systemic toxicity makes cancer treatment less effective. Thus, the need for drug repurposing, which aids in the development of safe and efficient cancer therapies, is urgent. The primary goal of this research was to assess desloratadine hepatoprotective abilities and its capacity to attenuate TLR4/MyD88/NF-κB inflammatory pathway in hepatocellular carcinoma (HCC) induced by thioacetamide (TAA). Male Sprague Dawely rats received TAA injections (200mg/kg, i.p., 2 times/week) for 16weeks. To confirm the development of HCC, liver function biomarkers and histopathological analysis were evaluated. Desloratadine (5mg/kg, p.o.) was administered to rats in 2 treatment groups; HCC+DES 1 group received desloratadine with TAA for 1month from week 13-16, HCC+DES 2 group received desloratadine with TAA for 2months from week 9-16. Chronic TAA administration resulted in considerable overexpression of the profibrogenic cytokine TGF-β and elevation in protein expression of NF-κB besides levels of TLR4, MyD88, TRAF6, TAK1 and IL-1β. Desloratadine administration showed a significant improvement in liver function tests, as well as an increase in tissue antioxidant enzymes and an improvement in the liver's histopathological features. Collectively, desloratadine through modulating TLR4/MyD88/TRAF6/TAK1/NF-κB and acting as an antioxidant, is a promising treatment for HCC induced by TAA.

Abstract B004: Ovarian cancer long intergenic noncoding RNA 1 is a potential therapeutic target in advanced ovarian cancer by promoting glycolytic pathway and hypoxic response

Abstract Ovarian cancer (OvC) is often diagnosed as an advanced disease because symptoms do not develop at earlier stages. Besides current treatments, alternative efficient therapies for OvC need to be established. We have previously identified that a novel long intergenic noncoding RNA (lincRNA) originated from chromosome 10q21 was predominantly expressed in clinical ovarian cancer tissues, designated as ovarian cancer lincRNA 1 (OIN1). Silencing of OIN1 in OvC cell lines substantially exhibited the inhibition of in vitro and in vivo cell proliferation, by upregulating apoptosis-related genes. In the present study, we aimed to evaluate whether OIN1 can be a therapeutic target in advanced OvC and how OIN1 drives the progression of OvC. We established long-term culturable spheroid cultures of OvC patient-derived cells (OvC-PDCs) from ascites of OvC patients as an advanced OvC model. The OvC-PDC spheroid cultures abundantly expressed OIN1 and stemness-related genes. OIN1-targeted siRNAs could suppress the spheroid growth and upregulate apoptosis-related genes such as RASSF5 and ADORA1 in OvC-PDC cultures. In a bloody ascites-generating xenograft in vivo model of mice intraperitoneally injected with OvC-PDC, OIN1-targeted siRNA treatment engineered by drug delivery system alleviated ascites production and prolonged the mice survival time. Based on transcriptomic analysis of OIN1 silencing in OvC-PDC cultures, we found that OIN1 inhibition exerts the downregulation of genes involved in glycolytic pathway and hypoxic response. We further demonstrated that OIN1 modulates HIF1a-mediated transcriptional regulation in OvC- PDCs. The present findings provide promising evidence that OIN1 can be a potential therapeutic target for advanced OvC. Citation Format: Kuniko Horie, Wataru Sato, Kazuhiro Ikeda, Satoshi Inoue. Ovarian cancer long intergenic noncoding RNA 1 is a potential therapeutic target in advanced ovarian cancer by promoting glycolytic pathway and hypoxic response [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B004.

Prodigiosin Demonstrates Promising Antiviral Activity Against Dengue Virus and Zika Virus in In-silico Study.

Dengue (DENV) and Zika virus (ZIKV), transmitted by Aedes mosquitoes, pose significant public health challenges. Effective treatments for these viruses remain elusive, highlighting the urgent need for new efficient antiviral therapies. This study explores prodigiosin, a microbial tripyrrole pigment, as an antiviral agent against both DENV and ZIKV employing advanced analytical approaches which integrate molecular docking, CASTp 3.0 validation and molecular dynamics (MD) simulations providing insights into molecular interactions at an atomic level. Prodigiosin exhibited favourable drug-likeness properties, meeting Lipinski's rule of five and demonstrating optimal physicochemical and pharmacokinetic characteristics according to Ghose's, Veber's, Egan's and Muegge's filters, essential for oral bioavailability. Absorption, Distribution, Metabolism, Excretion, and Toxicity profiling indicated high intestinal absorption, minimal risk for drug-drug interactions and a low toxicity profile, with no AMES toxicity, hepatotoxicity, or skin sensitization. Molecular docking revealed prodigiosin's strong binding affinities to NS5 methyltransferases of both DENV (-7.6kcal/mol) and ZIKV (-7.7kcal/mol) viruses, suggesting potential disruption of viral replication. Notably, prodigiosin's binding affinities were comparable to ribavirin-5'-triphosphate and chloroquine, known inhibitors of DENV and ZIKV, respectively. MD simulations confirmed stable and specific interactions with prodigiosin with low root-mean-square deviation values. Additional analyses, including root-mean-square fluctuation, radius of gyration and solvent-accessible surface area, indicated compact and stable complexes. These multi-parametric in-silico analytical strategies provide a novel perspective of prodigiosin as an antiviral agent, demonstrating its drug interactions at the molecular level. These promising results suggest that prodigiosin could serve as a broad-spectrum antiviral agent against both DENV and ZIKV, warranting further experimental validation for therapeutic development against flaviviral infections.

Exploring the Therapeutic Potential of Ginkgo biloba Polyphenols in Targeting Biomarkers of Colorectal Cancer: An In-silico Evaluation.

Colorectal cancer (CRC) is a major contributor to cancer-related deaths worldwide, driving the need for effective anticancer therapies with fewer side effects. The exploration of Ginkgo biloba, a natural source, offers a hopeful avenue for novel treatments targeting key colorectal biomarkers involved in CRC treatment. The aim of this study was to explore the binding affinity of natural molecules derived from G. biloba to essential biomarkers associated with CRC, including Kirsten rat sarcoma virus, neuroblastoma RAS mutations, serine/threonine-protein kinase B-Raf, phosphatidylinositol 3'-kinase, and deleted colorectal cancer, using molecular docking. The focus of this research was to evaluate how effectively these molecules bind to specified targets in order to identify potential inhibitors for the treatment of CRC. A total of 152 polyphenolic compounds from G. biloba were selected and subjected to molecular docking simulations to evaluate their interactions with CRC-related biomarkers. The docking results were analysed to identify ligands exhibiting strong affinities towards the targeted genes, suggesting potential inhibitory effects. Docking simulations unveiled the strong binding affinities between selected polyphenolic compounds derived from G. biloba and genes associated with CRC. The complex glycoside structures that are found in flavonols are of significant importance. These compounds, including derivatives with distinctive arrangements, exhibited promising docking scores, signifying substantial interactions with the targeted biomarkers. The study demonstrates the potential of G. biloba-derived molecules as effective anticancer agents for colorectal cancer. The identified ligands exhibit strong interactions with crucial CRC-related biomarkers, suggesting potential inhibition ability. Further in vitro and in vivo investigations are needed to validate and build upon these promising findings, advancing the development of novel and efficient CRC therapies.

Recent Advancements and SAR Studies of Synthetic Coumarins as MAO-B Inhibitors: An Updated Review.

The oxidative deamination of a wide range of endogenous and exogenous amines is catalyzed by a family of enzymes known as monoamine oxidases (MAOs), which are reliant on flavin-adenine dinucleotides. Numerous neurological conditions, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are significantly correlated with changes in the amounts of biogenic amines in the brain caused by MAO. Hydrogen peroxide, reactive oxygen species, and ammonia, among other toxic consequences of this oxidative breakdown, can harm brain cells' mitochondria and cause oxidative damage. The prime objective of this review article was to highlight and conclude the recent advancements in structure-activity relationships of synthetic derivatives of coumarins for MAO-B inhibition, published in the last five years' research articles. The literature (between 2019 and 2023) was searched from platforms like Science Direct, Google Scholar, PubMed, etc. After going through the literature, we have found a number of coumarin derivatives being synthesized by researchers for the inhibition of MAO-B for the management of diseases associated with the enzyme such as Alzheimer's Disease and Parkinson's Disease. The effect of these coumarin derivatives on the enzyme depends on the substitutions associated with the structure. The structure-activity relationships of the synthetic coumarin derivatives that are popular nowadays have been described and summarized in the current study. The results revealed the updated review on SAR studies of synthetic coumarins as MAO-B inhibitors, specifically for Alzheimer's Disease and Parkinson's Disease. The patents reported on coumarin derivatives as MAO-B inhibitors were also highlighted. Recently, coumarins, a large class of chemicals with both natural and synthetic sources, have drawn a lot of attention because of the vast range of biological actions they have that are linked to neurological problems. Numerous studies have demonstrated that chemically produced and naturally occurring coumarin analogs both exhibited strong MAO-B inhibitory action. Coumarins bind to MAO-B reversibly thereby preventing the breakdown of neurotransmitters like dopamine leading to the inhibition of the enzyme A number of MAO-B blockers have been proven to be efficient therapies for treating neurological diseases like Alzheimer's Disease and Parkinson's Disease. To combat these illnesses, there is still an urgent need to find effective treatment compounds.

Reverse Vaccinology Integrated with Biophysics Techniques for Designing a Peptide-Based Subunit Vaccine for Bourbon Virus.

Despite the seriousness of the disease carried by ticks, little is known about the Bourbon virus. Only three US states have recorded human cases of Bourbon virus (BRBV) infection; in all cases, a tick bite was connected with the onset of the illness. The Bourbon virus (BRBV) belongs to the Orthomyxoviridae family and Thogotovirus genus, originating in the states of the US, i.e., Kansas, Oklahoma and Missouri. The growing rates of BRBV infections in various parts of the US highlight the necessity for a thorough analysis of the virus's transmission mechanisms, vector types and reservoir hosts. Currently, there are no vaccines or efficient antiviral therapies to stop these infections. It is imperative to produce a vaccination that is both affordable and thermodynamically stable to reduce the likelihood of future pandemics. Various computational techniques and reverse vaccinology methodologies were employed to identify specific B- and T-cell epitopes. After thorough examination, the linker proteins connected the B- and T-cell epitopes, resulting in this painstakingly constructed vaccine candidate. Furthermore, 3D modeling directed the vaccine construct toward molecular docking to determine its binding affinity and interaction with TLR-4. Human beta-defensin was used as an adjuvant and linked to the N-terminus to boost immunogenicity. Furthermore, the C-IMMSIM simulation resulted in high immunogenic activities, with activation of high interferon, interleukins and immunoglobulin. The results of the in silico cloning process for E. coli indicated that the vaccine construct will try its utmost to express itself in the host, with a codon adaptation CAI value of 0.94. A net binding free energy of -677.7 kcal/mol obtained during docking showed that the vaccine has a high binding affinity for immunological receptors. Further validation was achieved via molecular dynamic simulations, inferring the confirmational changes during certain time intervals, but the vaccine remained intact to the binding site for a 100 ns interval. The thermostability determined using an RMSF score predicted certain changes in the mechanistic insights of the loop region with carbon alpha deviations, but no major changes were observed during the simulations. Thus, the results obtained highlight a major concern for researchers to further validate the vaccine's efficacy using in vitro and in vivo approaches.

Evaluation Secondary Metabolite Extract Produced by Aspergillus terreus Isolated from Poultry Droppings as Anticancer Agent

Malignant diseases are considered one of the problems of our time, and cancer is defined as the abnormal growth of malignant cells. It is widely accepted as the leading cause of death. There is currently no proven cancer cure. As a result, scientists have concentrated on creating secure and efficient therapies. Research has been done on the effects of naturally occurring substances that have been extracted from living things, such fungus on cancer cells. This study sought to determine the natural products' efficacy against human cancer cell line MCF-7. After A. terreus was isolated from samples of chicken droppings, it was grown on potato and Sabouraud Dextrose Agars (SDA and PDA) with chloramphenicol media. It was then identified using the extracted genomic DNA, the internal transcribed spacer (ITS) region was amplified and sequenced. After 30 days of incubation at 27°C, natural metabolite products were also recovered from the fermentation medium using the ethyl acetate extraction technique. The effectiveness of the fungal extract against the human cancer cell line MCF-7 and the normal human cell line NHF cell was also determined after incubation for 27 hours with the natural extract. The treated human cancer cell line MCF-7 showed decrease of proliferation, whereas the normal human cell line NHF showed no effect. Significant inhibitor compared to cancer line. The IC50 values for MCF-7 cell lines and NHF normal human cell lines were 7.672 and 1431 μg/mL, respectively. In summary, MCF-7 was affected by the natural extract extracted from A. terreus, in contrast to the control. When these results were combined, they showed that the fungal extract is an effective anti-cancer treatment.

Photothermal‐Mediated In Situ Delivery of Polycations Into Bacteria via Alternating Polymer‐Modified Nanoparticles for Targeted Bacterial Killing and Enhanced Biofilm Penetration

AbstractTo achieve targeted clearance of bacteria and their biofilms, a straightforward strategy to integrate antimicrobial alternating polymers with photothermal polydopamine nanoparticles (PDA NPs) is proposed. By manipulating the alternating distribution of electrostatic, hydrophobic, and hydrogen bonding units in the polymer backbone, the thermal stability of polymer‐particle interaction can be tuned, enabling photothermal‐mediated in situ delivery of cationic antimicrobial polymers into bacteria. The alternating polymer coating significantly enhances the penetration capability of NPs into the Methicillin‐resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) biofilm, achieving a 99% bactericidal rate within the biofilm at a low concentration after 10 min of near‐infrared irradiation, whereas pristine PDA NPs shows negligible effects. The in‐vitro co‐culture model demonstrates that alternating‐polymer‐loaded NPs selectively eradicate 1 × 107 CFU mL−1 of MRSA and E. coli while preserving over 75% viability of the mammalian cells, including mice fibroblasts, human kidney cells, human cervical cancer cells, and macrophages. The efficacy of these biocompatible NPs in targeting bacteria is further validated in a mouse MRSA‐infected wound model. This approach represents a significant advancement in developing safe and efficient antimicrobial therapies with targeted bacterial killing and minimal off‐target effects based on alternating cationic polymers.