Therapeutic Potential Research Articles

Therapeutic and Health Promoting Potential of Terminalia chebula: An Exploratory Literature Review

: The plant Terminalia chebula has been used traditionally in many regions of the world for its therapeutic properties, especially in India. Its therapeutic and health-promoting potential has been recognized for centuries, and modern research continues to unveil its numerous benefits. One of the most significant applications of this plant is its antimicrobial and antioxidant potential. The plant contains high levels of phenolic compounds and flavonoids, which scavenge harmful free radicals in the body, reducing oxidative stress and cellular damage. This antioxidant action contributes to its anti-inflammatory effects, making it beneficial for a wide range of conditions, including arthritis, cardiovascular diseases, and neurodegenerative disorders. Furthermore, Terminalia chebula exhibits antimicrobial activity against various bacteria and fungi, including those responsible for common infections. It has been used to treat respiratory infections, urinary tract infections, and skin ailments. Its broad-spectrum antimicrobial effects make it a valuable natural remedy for combating microbial pathogens. Moreover, Terminalia chebula shows potential in managing diabetes and promoting cardiovascular health. Studies have indicated its ability to regulate blood sugar levels, improve insulin sensitivity, and reduce lipid abnormalities. These properties make it a promising adjunct therapy for individuals with diabetes or at risk of heart disease. In conclusion, Terminalia chebula possesses remarkable therapeutic and health-promoting potential. Its antioxidant, anti-inflammatory, antimicrobial, and digestive benefits make it a valuable natural remedy for various ailments. While research on Terminalia chebula is ongoing, its long-standing use in traditional medicine and emerging scientific evidence solidify its status as a potent medicinal plant with diverse applications in promoting overall well-being.

Facile bio-inspired fabrication of AgNPs from Salvia elegans leaf extract and determination of their cytotoxic DNA photocleavage potential

This study introduces a sustainable method for producing silver nanoparticles (AgNPs), focusing on sustainability and environmental protection. The technique includes the use of Salvia elegans aqueous leaf extract as a reducing agent. In addition, the research investigates the dose-dependent degradation of pUC19 DNA by silver nanoparticles, which is facilitated by the generation of singlet oxygen. The presence of S. elegans extract results in significant color changes, going from a colorless state to a dark brown hue, serving as an indication of the synthesis of AgNPs. A range of experimental methods were employed to analyze the biogenic silver nanoparticles, such as UV–visible absorption spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The meticulously produced AgNPs demonstrate a high level of uniformity, featuring a spherical shape and a particle size of 60 nm. DNA photo-cleavage studies show that singlet oxygen plays a crucial role in triggering DNA damage caused by AgNPs indicates their potential as powerful cytotoxic agents specifically aimed at cancer cells. Additional studies are required to clarify the effectiveness and specificity of AgNPs against various cancer cell types to assess their therapeutic potential. The cytotoxic effects of AgNPs, particularly in relation to DNA photocleavage, are of considerable interest in cancer research. This research holds promise for developing novel and sustainable cancer therapies based on the unique properties of biogenic silver nanoparticles.

Identification of Prognostic Markers and Potential Therapeutic Targets using Gene Expression Profiling and Simulation Studies in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of less than 10% making it one of the most fatal cancers. A lack of early measures of prognosis, challenges in molecular targeted therapy, ineffective adjuvant chemotherapy, and strong resistance to chemotherapy cumulatively make pancreatic cancer challenging to manage. The present study aims to enhance understanding of the disease mechanism and its progression by identifying prognostic biomarkers, potential drug targets, and candidate drugs that can be used for therapy in pancreatic cancer. Gene expression profiles from the GEO database were analyzed to identify reliable prognostic markers and potential drug targets. The disease's molecular mechanism and biological pathways were studied by investigating gene ontologies, KEGG pathways, and survival analysis to understand the strong prognostic power of key DEGs. FDA-approved anti-cancer drugs were screened through cell line databases, and docking studies were performed to identify drugs with high affinity for ARNTL2 and PIK3C2A. Molecular dynamic simulations of drug targets ARNTL2 and PIK3C2A in their native state and complex with nilotinib were carried out for 100 ns to validate their therapeutic potential in PDAC. Differentially expressed genes that are crucial regulators, including SUN1, PSMG3, PIK3C2A, SCRN1, and TRIAP1, were identified. Nilotinib as a candidate drug was screened using sensitivity analysis on CCLE and GDSC pancreatic cancer cell lines. Molecular dynamics simulations revealed the underlying mechanism of the binding of nilotinib with ARNTL2 and PIK3C2A and the dynamic perturbations. It validated nilotinib as a promising drug for pancreatic cancer. This study accounts for prognostic markers, drug targets, and repurposed anti-cancer drugs to highlight their usefulness for translational research on developing novel therapies. Our results revealed potential and prospective clinical applications in drug targets ARNTL2, EGFR, and PI3KC2A for pancreatic cancer therapy.

Piperine solubility enhancement via DES formation: Elucidation of intermolecular interactions and impact of counterpart structure via computational and spectroscopic approaches

The development of new forms of existing APIs with enhanced physicochemical properties is critical for improving their therapeutic potential. In this context, ionic liquids (ILs) and deep eutectic solvents (DESs) have gained significant attention in recent years due to their unique properties and potential for solubility enhancement. In this study, we explore the role of different counterparts in the formation of IL/DESs with piperine (PI), a poorly water-soluble drug. After screening a library of fourteen counterpart molecules, ten liquid PI-counterpart systems were developed and investigated. Thermal analysis confirmed the formation of IL/DES, while computational and spectroscopic studies revealed that hydrogen bonding played a crucial role in the interaction between PI and the counterparts, confirming DES formation. The solubility enhancement of PI in these systems ranged from ∼ 36 % to 294 %, with PI-Oxalic acid (OA) exhibiting the highest saturation solubility (49.71 μg/mL) and PI-Ibuprofen (IB) the lowest (17.23 μg/mL). The presence of hydrogen bonding groups in counterparts was key to successful DES formation. A negative correlation was observed between solubility and logP (r = − 0.75, p* = 0.0129), while a positive correlation was found between solubility and normalized polar surface area (PSA) (r = 0.68, p* = 0.029). PI-OA and PI-IB were located at the extreme ends of these regression lines, further validating the relationship between these properties and solubility enhancement. These findings highlight essential aspects of rational IL/DES design, optimizing their properties for broader applications.

In-silico based Designing of benzo[d]thiazol-2-amine Derivatives as Anal-gesic and Anti-inflammatory Agents.

Benzo[d]thiazoles represent a significant class of heterocyclic com-pounds renowned for their diverse pharmacological activities, including analgesic and anti-inflammatory properties. This molecular scaffold holds substantial interest among medicinal chemists owing to its structural versatility and therapeutic potential. Incorporating the benzo[d]thiazole moiety into drug molecules has been extensively investigated as a strategy to craft novel therapeutics with heightened efficacy and minimized adverse effects. The aim of the present research work was to design, synthesize and characterize the new benzo[d]thiazol-2-amine derivatives as potent analgesic and anti-inflammatory agents. The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMR spectroscopy, 13CNMR spectroscopy and Mass spectroscopy methods were used to characterize the structural properties of all 13 newly syn-thesized derivatives. The molecular properties of these newly synthesized derivatives were estimated to study the attributes of drug-like candidates. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Analgesic and anti-inflammatory activities of synthesized compounds were evaluated by us-ing albino rats. Findings of the research suggested that compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8andG10 showed lower binding affinity than Indometha-cin when docking was performed with enzyme COX-2.In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities was performed for synthesized compounds. Compounds G10 and G11 exhibited significant COX-1 and COX-2 enzyme in-hibitory action with an IC50 value of 5.0 and 10 μM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. Highest analgesic action was exhibited by derivative G11 and the compound G10 showed the highest anti-inflammatory response. Inhibition of COX may be considered as a mechanism of action of these compounds. It was concluded that synthesized derivatives G10 and G11 exhibited significant analgesic and anti-inflammatory effect; therefore, the said compounds may be subjected to further clinical investigation for establishing these as future compounds for the treatment of pain and inflammation.

Blocking GP130 binding in interleukin-11 through site-specific PEGylation attenuates bleomycin-induced pulmonary fibrosis in mice

Recent insights have identified interleukin-11 (IL-11) as a pivotal profibrotic cytokine, with its signaling through IL-11Rα and GP130 receptors emerging as a promising therapeutic target for fibrotic diseases. Herein, we developed receptor-biased IL-11 via site-specific PEGylation at the GP130 binding interface, aiming to explore its therapeutic potential for bleomycin-induced pulmonary fibrosis in mice. By conducting single site-directed cysteine mutagenesis at site II or site III of IL-11, we refined the conjugation site, demonstrating that mutation at site III exhibits heightened sensitivity to GP130 binding and signaling. Cysteine-based PEGylation substantially attenuated the ability of GP130 to bind to IL-11 W147C, while almost entirely preserving its IL-11Rα binding ability. These PEGylated IL-11 W147C analogs showed potent inhibition of TF-1 cell proliferation and significant antagonism to TGF-β1-induced human lung fibroblasts (HLFs) differentiation into myofibroblasts. Moreover, PEGylation significantly prolonged the half-life of IL-11 W147C in healthy rats. Subcutaneous administration of PEGylated analogs, particularly PEG20/40 k-IL-11 W147C, effectively mitigated extracellular matrix deposition, preserved alveolar architecture, and attenuated the progression of pulmonary fibrosis in mice. The finding of this study not only underscores the therapeutic potential of IL-11 modulation, but also provides a general strategy for the design of cytokine-based biased antagonists and agonists targeting these multifaceted signaling pathways.

Effects of Laurus extract against cadmium-induced neurotoxicity in rats

Cadmium (Cd) is a hazardous heavy metal with widespread environmental presence, posing significant threats to human and animal health. This study investigates the neurotoxic effects of Cd exposure and explores the therapeutic efficacy of Laurus nobilis L. in counteracting these adverse effects. Cd exposure induces oxidative stress and neurotoxicity, leading to neuronal damage and histopathological alterations. Laurus, known for its antioxidant properties, is assessed for its potential in mitigating Cd-induced neurotoxicity through in vitro antioxidant assays, GC–MS analysis, HPLC profiling, and experimental animal models. Results demonstrate that Laurus ethanolic extract exhibits significant antioxidant activity, attributed to its phenolic and flavonoid constituents. GC–MS analysis reveals various bioactive compounds in the extract, including Hexadecanoic acid methyl ester and (Z)-13-Docosenamide, which posses neuroprotective properties. HPLC analysis identifies phenolic compounds such as ellagic acid and flavonoids like rutin and kaempferol in the extract. In vivo studies in rats exposed to Cd demonstrate that Laurus extract administration mitigates Cd-induced alterations in body and brain weight, hematological parameters, liver and kidney function, oxidative stress markers, and acetylcholinesterase (AchE) activity. Histopathological examination confirms the protective effects of Laurus against Cd-induced neuronal damage. The SOD model, validated with high resolution (2.05 Å) and strong R values (work: 0.192, free: 0.236, observed: 0.194), shows strong structural stability (C-score: 0.30). Docking studies reveal high binding affinities of kaempferol (−8.1 kcal/mol) and rutin (−8.7 kcal/mol) with SOD with kaempferol demonstrating superior solubility, lipophilicity, and drug-likenessSimulation analysis confirms the protein’s flexibility and adaptability, highlighting its therapeutic potential, especially with kaempferol. These findings suggest the therapeutic potential of Laurus. as a natural remedy for Cd-induced neurotoxicity, highlighting its antioxidant and neuroprotective properties.

Ro 90-7501 suppresses colon cancer progression by inducing immunogenic cell death and promoting RIG-1-mediated autophagy.

Colon cancer is one of the leading causes of cancer-related mortality worldwide. Current treatments, including surgery, chemotherapy, and radiation therapy, often have limited efficacy due to tumor heterogeneity and resistance mechanisms. Therefore, there is a critical need for novel therapeutic strategies that can enhance the immune response against colon cancer cells while promoting their efficient clearance. In this study, we investigated the anti-tumor effects of Ro 90-7501, a specific small molecule, in colon cancer cell lines (HCT8 and SW480) and in vivo models. MTS, EdU, Scratch Wound and Transwell assays were performed to detect the cell proliferation and metastasis. Additionally, flow cytometry and immunofluorescence staining were used to analyze changes in apoptosis and necrosis. Furthermore, we examined its ability to induce immunogenic cell death (ICD) and promote retinoic acid-inducible gene I (RIG-I)-mediated autophagy. The expression levels of key molecules involved in ICD and autophagy were assessed using Western blot analysis, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Our findings demonstrated that Ro 90-7501 significantly suppressed colon cancer cell proliferation and metastasis, inducing apoptosis and necrosis. Mechanistically, Ro 90-7501 triggered ICD by upregulating the exposure of calreticulin (CRT) on the cell surface and increasing the release of high mobility group box 1 (HMGB1) and extracellular ATP levels. Concurrently, it promoted RIG-I-mediated autophagy via the MAVS-TRAF6 signaling axis, evidenced by increased expression of autophagy-related genes, such as microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 proteins, coupled with a reduction in P62 protein. Additionally, Ro 90-7501 treatment activated the RIG-I-MAVS-TRAF6 signaling axis in colon cancer cells. Furthermore, Ro 90-7501 enhanced the secretion of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα), thereby activating the immune response. In conclusion, Ro 90-7501 exhibits potent anti-tumor activity against colon cancer by inducing ICD and promoting RIG-I-mediated autophagy. These results suggest that Ro 90-7501 may serve as a promising therapeutic candidate for colon cancer treatment by enhancing both intrinsic cellular processes and adaptive immune responses. Further studies are warranted to elucidate the detailed mechanisms underlying these effects and to evaluate its therapeutic potential in clinical settings.

Exploring the Promising Role of Guggulipid in Rheumatoid Arthritis Management: An In-depth Analysis.

Guggulipid, an oleo-gum resin extracted from the bark of Commiphora wightii of the Burseraceae family, holds a significant place in Ayurvedic medicine due to its historical use in treating various disorders, including inflammation, gout, rheumatism, obesity, and lipid metabolism imbalances. This comprehensive review aims to elucidate the molecular targets of guggulipids and explore their cellular responses. Furthermore, it summarizes the findings from in-vitro, in-vivo, and clinical investigations related to arthritis and various inflammatory conditions. A comprehensive survey encompassing in-vitro, in-vivo, and clinical studies has been conducted to explore the therapeutic capacity of guggulipid in the management of rheumatoid arthritis. Various molecular pathways, such as cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), PI3-kinase/AKT, JAK/STAT, nitric oxide synthase (iNOS), and NFκB signaling pathways, have been targeted to assess the antiarthritic and anti-inflammatory effects of this compound. The research findings reveal that guggulipid demonstrates notable antiarthritic and anti-inflammatory effects by targeting key molecular pathways involved in inflammatory responses. These pathways include COX-2, VEGF, PI3-kinase/AKT, JAK/STAT, iNOS, and NFκB signaling pathways. in-vitro, in-vivo, and clinical studies collectively support the therapeutic potential of guggulipid in managing rheumatoid arthritis and related inflammatory conditions. This review provides a deeper understanding of the therapeutic mechanisms and potential of guggulipid in the management of rheumatoid arthritis. The collective evidence strongly supports the promising role of guggulipid as a therapeutic agent, encouraging further research and development in guggulipid-based treatments for these conditions.

Integrating Network Pharmacology and Transcriptomic Strategies to Explore the Pharmacological Mechanism of Paeoniflorin Exerts Antidepressant Effects

Background: Paeoniflorin has been proven to have neuroprotective and antidepressant effects in several studies. However, there is currently no comprehensive elaboration of its antidepressant effects through network pharmacology combined with transcriptomics analysis. The purpose of this study is to explore the potential mechanisms by which paeoniflorin exerts its antidepressant effects using network pharmacology and transcriptomics sequencing approaches. Methods: We utilized metascape to enrich the intersecting targets for paeoniflorin and depression for enrichment analyses. Additionally, we employed Cytoscape software to construct target pathway networks. For the screening of differentially expressed genes (DEGs) altered by paeoniflorin, we sequenced mRNA from the hippocampal tissue of CUMS model mice using the BMKCloud platform. We further enriched their biological functions and signaling pathways by using the Omishare database. The study utilized a combination of network pharmacology and transcriptomics analysis to evaluate the interactions between paeoniflorin and key targets. The results were then verified through a molecular docking process and a subsequent Western blot experiment. Results: According to a comprehensive analysis, paeoniflorin has 19 key targets that are closely related to its therapeutic effect. Molecular docking revealed that paeoniflorin has a high affinity for HIF-1α, VEGFA, and other targets. Furthermore, protein expression and immunofluorescence staining analysis showed that paeoniflorin significantly increased the expression level of HIF-1α and VEGFA in the hippocampus of depression model mice. Conclusion: These findings suggest that paeoniflorin may have therapeutic potential in depression through the activation of the HIF-1α-VEGFA pathway.

Ten Reasons Why Neurologists Should Refer Patients With Alzheimer Dementia to Music Therapy.

Alzheimer dementia (AD) constitutes a major societal problem with devastating neuropsychiatric involvement. Pharmaceutical interventions carry a heightened risk of side effects; thus, nonpharmacological interventions such as music-based interventions (MBIs), including music therapy, are recommended. The 2023 Neurology release of the Music Based Intervention Toolkit for Brain Disorders of Aging showcased music's emerging role as an intervention to manage symptoms of various brain disorders while defining the building blocks of MBIs to guide research in the exploration of music's therapeutic potential. This study extends beyond the research aspects of the MBI Toolkit to clinical applications by providing neurologists with a summary of MBIs, the MBI Toolkit, how board-certified music therapists (MT-BCs) administered music therapy is a unique MBI, and 10 reasons why they should make referrals to music therapy for their patients with AD.

Antioxidant potential and cytotoxicity of Cordyceps militaris in vitro culture extracts

Cordyceps militaris is an entomopathogenic fungus with therapeutic potential in humans. The focus is on its hydroalcoholic extracts, which were obtained from biomass cultured in vitro in molasses. The media were subjected to a colourimetric chemical screening, an in vitro antioxidant potential evaluation by DPPH, ABTS and FRAP, and a cytotoxicity test by MTT assay. The results evidenced the presence of reducing sugars, alkaloids, coumarins, cardiac glycosides, and sesquiterpene lactones in both extracts. Additionally, tannins and quinones were identified exclusively in EHM. EHG exhibited a higher concentration of phenolic compounds (6.6 µg GAE/mg), while EHM demonstrated a higher concentration of phytates (40 µg PAE/mg), and both exhibited similar amounts of saponins (2.55±0.18 µg DGE/mg).The antioxidant potential of the extracts was assessed using the DPPH, ABTS and FRAP assays. The results demonstrated that EHG exhibited a greater effect in both assays, with 60.98 % and 80.70 % inhibition, respectively. In contrast, no significant difference was observed in the DPPH assay, with an average inhibition of 77.83 %. Both extracts exhibited no cytotoxicity at the concentrations tested, demonstrating 100 % viability (LC50 > 300 µg/mL). It was concluded that the use of different carbon sources in both enriched media for the in vitro culture of C. militaris resulted in a modified chemical profile of the obtained biomass, which exhibited greater phytochemical complexity when cultured with molasses. In contrast, the biomass cultured with glucose showed a notable antioxidant potential in vitro, and no extract exhibited cytotoxicity in the tested cell lines.

Neuroglobin protects dopaminergic neurons in a Parkinson’s cell model by interacting with mitochondrial complex NDUFA10

The study aimed to validate the protective effect of neuroglobin (Ngb) in a cell model of Parkinson’s disease (PD) and explore its therapeutic potential. Lentivirus-Ngb (LvNgb) and siRNA-Ngb (siNgb) were used to achieve Ngb overexpression and knockdown, respectively, in a sporadic PD cell model. Apoptosis was evaluated by flow cytometry-based Annexin V/propidium iodide assays. Activation of the pro-apoptotic factor, Caspase-9, was detected by immunoblotting, and Complex I activities were detected by using enzyme-linked immunosorbent assay (ELISA). Mitochondrial dysfunction was examined by measuring the mitochondrial membrane potential (MMP), NAD+/NADH ratios, and reactive oxygen species (ROS) levels. Additionally, coimmunoprecipitation (Co-IP) assays were conducted in mouse neuroblastoma cell line 9D (MN9D) cells to determine the interactions of Ngb with the Complex I subunit NDUFA10. The results showed that Ngb overexpression reduced the percentages of apoptotic cells, total caspase-9 levels and restored Complex I activities in the PD cell model. Conversely, knockdown of Ngb resulted in an increase in apoptotic cells, higher total caspase-9 levels, and decreased Complex I activities. Furthermore, Ngb overexpression restored MMP and NAD+/NADH ratios and alleviated ROS-mediated oxidative stress in MN9D cells. Finally, Co-IP confirmed the interaction between Ngb and NDUFA10 in MN9D cells. In conclusion, Ngb protects MN9D cells against apoptosis by interacting with Complex I subunit NDUFA10, rescuing its activity and inhibiting the mitochondrial pathway of apoptosis in the MPP+-mediated PD model.

Deciphering the cellular landscape and potential targets of nasopharyngeal and oral cancers using single-cell RNA sequencing.

Cellular heterogeneity in nasopharyngeal cancer (NPC) and oral cancer remains unclear. In the current study, using single-cell RNA sequencing techniques, we investigated the cellular landscape in NPC and oral cancers. We identified a diverse range of cell types within the tumor microenvironment (TME) and variations in cell infiltration between NPC and oral cancer. In oral cancer, we observed a predominant infiltration of epithelial cells, fibroblasts, and endothelial cells (ECs), while T cells were the main infiltrating cell population in NPCs. We further classified these infiltrating cells into subclusters. Additionally, we observed complex interactions among cells that led to distinct trajectories. In particular, a unique epithelial subcluster with high expression of major histocompatibility complex class II (MHC-II) molecules was correlated with a favorable outcome and infiltration of CD4+ T cells. In addition, MHC-II+ epithelial cells inhibited mouse tumor growth and promoted T-cell infiltration. Consequently, our findings provide a deep understanding of the TME showing a significant prognostic value and therapeutic potential.

Trifolin Attenuates Hypertension-Mediated Cardiac Injury by Inhibiting Cardiomyocyte Apoptosis: Mechanistic Insights and Therapeutic Potential

BackgroundHypertension-induced cardiac disease is a common complication and a significant contributor to mortality in hypertensive patients, largely due to cardiomyocyte apoptosis. Although Trifolin has been identified as a potential antihypertensive compound, its therapeutic role in hypertension-induced cardiac injury remains uncertain. PurposeThis study aims to evaluate the protective effects of Trifolin and explore the underlying mechanisms of its action against hypertension-induced cardiac injury. MethodsIn vivo, mice were infused with Angiotensin II (AngII, 500 ng/kg/min) or saline via osmotic pumps and treated with Trifolin (0.1, 1.0, or 10.0 mg/kg/day) or Valsartan (10 mg/kg/day) for four weeks. In vitro, H9C2 cells were stimulated with AngII (1 μM) and treated with Trifolin (25, 50, or 100 μM). Various assays, including echocardiography, hematoxylin and eosin staining, TUNEL assay, Annexin-V/propidium iodide staining, and JC-1 staining, were used to assess Trifolin's therapeutic effects on hypertension-related cardiac injury and cardiomyocyte apoptosis. Potential pharmacological mechanisms were analyzed through network pharmacology and confirmed via Western blotting. ResultsTrifolin treatment improved cardiac function by increasing left ventricular ejection fraction and fractional shortening while reducing tissue disorganization in AngII-treated mice. It also reduced cardiomyocyte apoptosis, reversing the upregulation of Bax and cleaved caspase-3 and the downregulation of Bcl-2. Network pharmacology identified 314 common targets of Trifolin linked to hypertensive heart disease, with involvement in apoptosis, MAPK, PI3K/AKT, and HIF-1 signaling pathways. Trifolin treatment increased p-PI3K/PI3K and p-AKT/AKT ratios while decreasing p-ERK/ERK, p-p38 MAPK/p38 MAPK, and p-JNK/JNK ratios in both mouse and cell models. ConclusionTrifolin alleviates AngII-induced cardiac injury and cardiomyocyte apoptosis, potentially through the regulation of MAPK, PI3K/AKT, and HIF-1 signaling pathways.

Hydroxypropyl methylcellulose stabilized clove oil nanoemulsified orodispersible films: Study of physicochemical properties, release profile, mucosal permeation, and anti-bacterial activity.

Hydroxypropyl methylcellulose (HPMC)-based nanoemulsions for quick dissolving orodispersible (OD) films were prepared to encapsulate clove oil (CO) to harness its anti-bacterial properties. The influence of additives maltodextrin, pectin, and glycerol on the OD films was studied. The nanoemulsion particle size varied from 135 nm to 195 nm. A decrease in tensile strength and, an increase in elongation at break and opacity were observed in OD films compared to neat HPMC film. The AFM images showed an increase in HPMC films' average roughness from 6.95 to 90 nm after adding CO and additives. The additives controlled CO in-vitro release from HPMC following the Higuchi model. The ex-vivo permeation through porcine mucosal membrane was 9-33 % while the permeation coefficient and flux were 0.282-0.879 cm s-1 and 0.191-1.318 μg cm-2 s-1, respectively. The OD films exhibited significant inhibition of Staphylococcus aureus, Streptococcus mutans, and Porphyromonas gingivalis suggesting their therapeutic potential in oral healthcare.

An innovative phase 2 chronic pain master protocol design to assess novel mechanisms in multiple pain types.

The phase 2 chronic pain master protocol (CPMP) presented here provides a construct to accelerate the investigation of novel analgesics, broadly referred to here as mechanisms. Designed to address historical challenges in analgesic research and development, such as the choice of indication, this protocol enables the efficient evaluation of potential therapeutics with different mechanisms of action in 3 pain types: nociceptive pain (osteoarthritis), neuropathic pain (diabetic peripheral neuropathic pain), and mixed pain (chronic low back pain). The study design was determined before the identification of any specific molecule. Statistical simulations were conducted to optimize the methodology and design, the culmination of which were submitted to and accepted by the Complex Innovative Trial Design Pilot Meeting Program, a unique collaboration with the United States Food and Drug Administration. Benefits of the CPMP include limiting the number of study participants exposed to placebo and reducing the total sample size over time by leveraging placebo data across studies within a pain type and efficacy data across pain types for a specific molecule. The CPMP design enables: (1) efficient evaluation of multiple novel mechanisms of action; (2) the study of multiple molecules simultaneously or serially; (3) direct statistical comparison of molecules within a pain type; and (4) efficient planning and conduct of clinical studies. ClinicalTrials.gov ID NCT05986292. By evaluating novel mechanisms across different pain types, therapeutic potential can be assessed more efficiently compared with traditional individual clinical studies.

Delivery Systems for Plasma-reactive Species and their Applications in the Field of Biomedicine.

Cold atmospheric plasma (CAP) is an ionized matter with potential applications in various medical fields, ranging from wound healing and disinfection to cancer treatment. CAP's clinical usefulness stems from its ability to act as an adjustable source of reactive oxygen and nitrogen species (RONS), which are known to function as pleiotropic signaling agents within cells. Plasma-activated species, such as RONS, have the potential to be consistently and precisely released by carriers, enabling their utilization in a wide array of biomedical applications. Furthermore, understanding the behavior of CAP in different environments, including water, salt solutions, culture medium, hydrogels, and nanoparticles, may lead to new opportunities for maximizing its therapeutic potential. This review article sought to provide a comprehensive and critical analysis of current biomaterial approaches for the targeted delivery of plasma-activated species in the hope to boost therapeutic response and clinical applicability.

Functional Food Candidate from Indonesian Green Algae Caulerpa racemosa (Försskal) J. Agardh by Two Extraction Methods: Metabolite Profile, Antioxidant Activity, and Cytotoxic Properties

There is an urgent need to explore natural sources like Caulerpa racemosa (Försskal) J. Agardh for bioactive compounds with strong antioxidant and therapeutic potential, providing sustainable alternatives for health and pharmaceutical innovation. This study aimed to determine the phytochemical profile and biological activities of extracts from edible green algae–known as sea grapes (C. racemosa). This present study has successfully identified secondary metabolites through untargeted metabolomic profiling by liquid chromatography-high resolution mass spectrometry (LC-HRMS) as well as a bioactive peptide. The antioxidant activity and cytotoxicity of extracts from C. racemosa and compounds were determined. A total of 103 metabolites were identified in the C. racemosa extract obtained by the maceration (ME), while 48 metabolites were detected in the soxhlet extract (SE). The sequence of the identified peptide was ELWKTF (Glu-Leu-Trp-Lys-Thr-Phe; C41H58N8O) and its abundance was identified in the α-chymotrypsin hydrolysate of C. racemosa. In the antioxidant activity test, SE and purified fraction 1 (PF1) had EC50<EC50 of control or Glutathione (GSH) in terms of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) inhibition, and PF1 had EC50<EC50 of control or Trolox in terms of 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) inhibition. In general, C. racemosa contains antioxidant nutrients, metabolites, and bioactive peptides, suggesting its promising potential as a functional food and pharmaceutical.

Neuro-regeneration or Repair: Cell Therapy of Neurological Disorders as A Way Forward.

The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression. Cell therapy for neurological disorders offers several therapeutic potentials and provides hope for many patients. Here we provide a general overview of cell therapy in neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), stroke and traumatic brain injury (TBI), involving many forms of stem cells, including embryonic stem cells and induced pluripotent stem cells. We also address the current concerns and perspectives for the future. Most studies for cell therapy in neurological diseases are in the pre-clinical stage, and there is still a great need for further research to translate neural replacement and regenerative therapies into clinical settings.