Therapeutic Potential Research Articles

Aging-associated mechanisms of atrial fibrillation progression and their therapeutic potential

Atrial fibrillation (AF) is the most common sustained arrhythmia, with a particularly high prevalence in the elderly. As the global aging population rapidly expands, it is increasingly important to examine how alterations to the aging heart contribute to an increased AF susceptibility. This work critically reviews the key molecular mechanisms that may underpin the complex association between aging and AF. Moreover, we identify emerging novel opportunities for therapeutic intervention that may be able to prevent and/or improve the current treatment paradigms for age-related AF. This review contributes to a holistic understanding of the intricate relationship between aging and AF.

A Prospective Observational Study to Evaluate the Effectiveness of Platelet-Rich Plasma Therapy for Complex Wounds: Influential Clinical Variables on Wound Healing Outcomes.

Objective: Autologous platelet-rich plasma (PRP) has shown promising outcomes in treating wounds, but the profile of patients benefiting most from this therapy is not known. This study aimed to identify influential variables in the success of this therapy, analyzing its personalized therapeutic potential for complex wounds. Approach: A prospective observational study was conducted in elderly patients with complex wounds receiving autologous PRP. Patient's data about sociodemographic parameters, comorbidities, frailty (FI-VIG score), complete blood count including albumin, wound depth, location, chronicity, and etiology were collected at the beginning of the study. The wound area was monitored weekly. The data were analyzed using descriptive and inferential statistics, longitudinal data analysis, and survival analysis. Results: Ninety-seven elderly patients were included. The FI-VIG, baseline wound area, depth, and etiology were significantly correlated with wound outcome. Strong differences in wound area variation from treatment initiation were observed in healed wounds (13% reduction/week) compared with stagnant and complicated wounds (1 and 2% reduction/week, respectively). The healing time analysis showed that nearly 80% of patients required at least 15 weeks for complete healing. In addition, patients with smaller wound sizes, younger age, or lower FI-VIG scores had shorter healing times. Innovation: This is the first study that identifies prognostic indicators for wound outcomes to guide clinician decision-making for using autologous PRP. It also highlights the relevance of patient health baseline and wound features and evolution for the success of this therapy. Conclusion: This study demonstrates that personalizing autologous PRP therapy to treat complex wounds in elderly patients is possible.

Promoting Resilience and Well-Being of Young Adults with Diabetes Through Digital Storytelling in Arts-Based Research

ABSTRACT This arts-based research explores the role and impact of digital storytelling in supporting young adults with diabetes in China to face diabetes-related stigma and promote resilience and well-being. Twenty participants with diabetes recounted their experiences across three workshops and shared their perspectives on digital storytelling through semi-structured interviews. The results indicate that digital storytelling, as a health intervention, facilitates a comfortable environment for participants to articulate the traumatic impact of diabetes stigma. It encourages collective support and fosters a reinterpretation of the diabetes experience, enhancing participants’ capacity for future health management. The results also highlight the limitations of digital storytelling, particularly concerning its accessibility and transparency. Participants’ experiences underscore the need for careful consideration of these challenges to maximize the therapeutic potential of digital storytelling in the context of chronic illness management.

Unlocking the therapeutic potential and personalized therapy of testosterone: a comprehensive review.

Testosterone, the primary male sex hormone, orchestrates various physiological processes including sex differentiation, development of male characteristics, sperm production, and fertility. Its synthesis primarily occurs in Leydig cells within the testes, with smaller contributions from the ovaries and adrenal glands, all derived from cholesterol. Current therapeutic use of testosterone is mainly confined totreating hypergonadotropic hypogonadism, with limited off-label usage for augmenting muscle growth. This review delves into numerous studies investigating testosterone's therapeutic potential across various medical conditions as depicted in the figure given below. Of all the studies in this review, which show a positive therapeutic result by using testosterone, the most promising areas of potential usage of testosterone are anxiety and diabetes mellitus, followed by obesity and depression. By the medium if this study, we want to not only enlist the various potential therapeutic uses of testosterone, butalso promote a optimal hormonal balance, which can lead toprevention and/or better treatment outcomes for the mentioned diseases.

The Yin and Yang of Microglia-Derived Extracellular Vesicles in CNS Injury and Diseases

Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining neural homeostasis but can also contribute to disease and injury when this state is disrupted or conversely play a pivotal role in neurorepair. One way that microglia exert their effects is through the secretion of small vesicles, microglia-derived exosomes (MGEVs). Exosomes facilitate intercellular communication through transported cargoes of proteins, lipids, RNA, and other bioactive molecules that can alter the behavior of the cells that internalize them. Under normal physiological conditions, MGEVs are essential to homeostasis, whereas the dysregulation of their production and/or alterations in their cargoes have been implicated in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), spinal cord injury (SCI), and traumatic brain injury (TBI). In contrast, MGEVs may also offer therapeutic potential by reversing inflammation or being amenable to engineering for the delivery of beneficial biologics or drugs. The effects of MGEVs are determined by the phenotypic state of the parent microglia. Exosomes from anti-inflammatory or pro-regenerative microglia support neurorepair and cell survival by delivering neurotrophic factors, anti-inflammatory mediators, and molecular chaperones. Further, MGEVs can also deliver components like mitochondrial DNA (mtDNA) and proteins to damaged neurons to enhance cellular metabolism and resilience. MGEVs derived from pro-inflammatory microglia can have detrimental effects on neural health. Their cargo often contains pro-inflammatory cytokines, molecules involved in oxidative stress, and neurotoxic proteins, which can exacerbate neuroinflammation, contribute to neuronal damage, and impair synaptic function, hindering neurorepair processes. The role of MGEVs in neurodegeneration and injury—whether beneficial or harmful—largely depends on how they modulate inflammation through the pro- and anti-inflammatory factors in their cargo, including cytokines and microRNAs. In addition, through the propagation of pathological proteins, such as amyloid-beta and alpha-synuclein, MGEVs can also contribute to disease progression in disorders such as AD and PD, or by the transfer of apoptotic or necrotic factors, they can induce neuron toxicity or trigger glial scarring during neurological injury. In this review, we have provided a comprehensive and up-to-date understanding of the molecular mechanisms underlying the multifaceted role of MGEVs in neurological injury and disease. In particular, the role that specific exosome cargoes play in various pathological conditions, either in disease progression or recovery, will be discussed. The therapeutic potential of MGEVs has been highlighted including potential engineering methodologies that have been employed to alter their cargoes or cell-selective targeting. Understanding the factors that influence the balance between beneficial and detrimental exosome signaling in the CNS is crucial for developing new therapeutic strategies for neurodegenerative diseases and neurotrauma.

Advanced platelet-rich fibrin versus connective tissue graft in maxillary gingival recession management.

Platelet concentrates have gained significant attention in periodontology due to their regenerative properties. This randomized clinical trial was aimed to compare the clinical efficacy of advanced platelet-rich fibrin (A-PRF) and connective tissue graft (CTG) in the management of recession defects. The objectives were to compare changes in recession height and root coverage percentage between the groups. Systemically healthy individuals presenting Cairo's RT1/RT2 gingival recession defects in the maxilla (n = 40) were treated with either A-PRF or CTG in combination with coronally advanced flap (CAF). Clinical parameters were measured at baseline, 3 months, and 6 months. Mean and complete root coverage percentages were calculated at 3 and 6 months. In both the test (CAF + A-PRF) and control (CAF + CTG) groups, a statistically significant reduction in mean recession height was seen from baseline values of 2.90 ± 0.55mm and 3.15 ± 0.87mm to 0.80 ± 0.95mm and 0.15 ± 0.48mm at 6 months, respectively (p < 0.001). In the test group, 10 sites had complete root coverage at 6 months with mean root coverage of 73.76 ± 29.58%. In the control group, 18 of 20 sites had complete root coverage with mean root coverage of 93.35 ± 23.1%. The control sites had a significantly greater reduction in recession height and higher mean and complete root coverage percentages at 6 months (p < 0.05). The study findings suggest that, the CTG had resulted in superior outcomes than A-PRF along with CAF. Question: To compare the efficacy of advanced platelet-rich fibrin (A-PRF) with connective tissue graft (CTG) in the management of gingival recession defects. Both interventions showed satisfactory healing. At 6 months, the CTG group demonstrated superior results than the A-PRF group. Meaning: CTG has a greater therapeutic potential than A-PRF in the management of gingival recessions. Platelet-derived membranes are widely used in various dental therapies due to their healing properties. Limited studies have been conducted using the novel platelet preparations in the management of receding gums. This study compared the effects of advanced platelet-rich fibrin membrane with conventional soft tissue harvested from the palate in the treatment of gum recession. Twenty-three patients requiring gum augmentation were recruited and treated with either platelet-derived membrane (test group) or tissue harvested from their palate (control group). Clinical parameters were measured at baseline (before intervention), 3 months, and 6 months. Both treatment modalities resulted in significant gum coverage at the end of 6 months. On comparison, the control sites had significantly greater improvements in all the measured clinical parameters indicating that tissue obtained from the palate had superior therapeutic potential.

Targeting Menin in Acute Myeloid Leukemia: Therapeutic Advances and Future Directions

Germline mutations in the MEN1 gene encoding menin protein cause multiple endocrine neoplasia type 1 (MEN1) syndrome. Recent evidence suggests that inhibiting the interaction of menin with its crucial oncogenic protein partners represents a promising therapeutic strategy to AML. Menin plays a critical role in lysine methyltransferase 2A (KMT2A)-gene-rearranged and NPM1-m acute leukemias, both associated with adverse outcomes with current standard therapies, especially in the relapsed/refractory setting. Disrupting the menin–KMT2A interaction affects the proleukemogenic HOX/MEIS transcription program. This disruption leads to the differentiation of KMT2Ar and NPM1-m AML cells. Small molecular inhibitors of the menin–KMT2A interaction target the central cavity of MEN1 to inhibit the MEN1-KMT2A interaction and could target a similar transcriptional dependency in other leukemia subsets, broadening their therapeutic potential. These agents, both as monotherapies and in combination with synergistic drugs, are undergoing preclinical and clinical evaluation with promising early results. With the growing literature around menin inhibitors in AML, we discussed the biology of menin, its mechanism of action, its interacting partners in leukemia, possible inhibitors, their implications, synergistic drugs, and future therapeutic strategies in this review.

Can miRNAs in MSCs-EVs Offer a Potential Treatment for Hypoxic-ischemic Encephalopathy?

Neonatal hypoxic-ischemic encephalopathy (HIE) is a critical condition resulting from impaired oxygen and blood flow to the brain during birth, leading to neuroinflammation, neuronal apoptosis, and long-term neurological deficits. Despite the use of therapeutic hypothermia, current treatments remain inadequate in fully preventing brain damage. Recent advances in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer a novel, cell-free therapeutic approach, as these EVs can cross the blood-brain barrier (BBB) and deliver functional microRNAs (miRNAs) to modulate key pathways involved in inflammation and neuroprotection. This review examines how specific miRNAs encapsulated in MSC-EVs-including miR-21, miR-124, miR-146, and the miR-17-92 cluster-target the complex inflammatory responses that drive HIE pathology. By modulating pathways such as NF-κB, STAT3, and PI3K/Akt, these miRNAs influence neuroinflammatory processes, reduce neuronal apoptosis, and promote tissue repair. The aim is to assess the therapeutic potential of miRNA-loaded MSC-EVs in mitigating inflammation and neuronal damage, thus addressing the limitations of current therapies like therapeutic hypothermia.

Molecular Imaging Reveals Antineuroinflammatory Effects of HDAC6 Inhibition in Stroke Models.

Ischemic stroke is a devastating disease that causes neuronal death, neuroinflammation, and other cerebral damage. However, effective therapeutic strategies for ischemic stroke are still lacking. Histone deacetylase 6 (HDAC6) has been implicated in the pathogenesis of ischemic stroke, and the pharmacological inhibition of HDAC6 has shown promising neuroprotective effects. In this study, we utilized positron emission tomography (PET) imaging with the HDAC6-specific radioligand [18F]PB118 to investigate the dynamic changes of HDAC6 expression in the brain after ischemic injury. The results revealed a significant decline in [18F]PB118 uptake in the ipsilateral hemisphere on the first day after ischemia, followed by a gradual increase on days 4 and 7. To evaluate the therapeutic potential of HDAC6 inhibitors, we developed a novel brain-permeable and potent HDAC6 inhibitor, PB131, and assessed its neuroprotective effects in an ischemic stroke mouse model. PET imaging studies demonstrated that PB131 treatment alleviated the decline in [18F]PB118 uptake and reduced the infarct size in middle cerebral artery occlusion mice. Furthermore, PET imaging with the TSPO-specific radioligand [18F]FEPPA revealed that PB131 significantly suppressed neuroinflammation in the ischemic brain. These findings provide insights into the dynamic changes of HDAC6 in ischemic stroke and the potential of HDAC6 inhibitors as novel therapeutic agents for this condition.

Innovative Glucagon-Based Therapies for Obesity

Abstract Obesity poses a significant global health challenge, with an alarming rise in prevalence rates. Traditional interventions, including lifestyle modifications, often fall short of achieving sustainable weight loss, ultimately leading to surgical interventions, which carry a significant burden and side effects. This necessitates the exploration of effective and relatively tolerable pharmacological alternatives. Among emerging therapeutic avenues, glucagon-based treatments have garnered attention for their potential to modulate metabolic pathways and regulate appetite. This paper discusses current research on the physiological mechanisms underlying obesity and the role of glucagon in energy homeostasis. Glucagon, traditionally recognized for its glycemic control functions, has emerged as a promising target for obesity management due to its multifaceted effects on metabolism, appetite regulation, and energy expenditure. This review focuses on the pharmacological landscape, encompassing single and dual agonist therapies targeting glucagon receptors (GcgRs), glucagon-like peptide-1 receptors (GLP-1Rs), glucose-dependent insulinotropic polypeptide receptors (GIPRs), amylin, triiodothyronine, fibroblast growth factor 21 (FGF21), and peptide tyrosine tyrosine. Moreover, novel triple-agonist therapies that simultaneously target GLP-1R, GIPR, and GcgR show promise in augmenting further metabolic benefits. This review paper tries to summarize key findings from preclinical and clinical studies, elucidating the mechanisms of action, safety profiles, and therapeutic potential of glucagon-based therapies in combating obesity and its comorbidities. Additionally, it explores ongoing research endeavors, including phase III trials, aimed at further validating the efficacy and safety of these innovative treatment modalities.

Mechanisms and Therapeutic Potential of GPX4 in Pain Modulation.

Pain, a complex symptom encompassing both sensory and emotional dimensions, constitutes a significant global public health issue. Oxidative stress is a pivotal factor in the complex pathophysiology of pain, with glutathione peroxidase 4 (GPX4) recognized as a crucial antioxidant enzyme involved in both antioxidant defense mechanisms and ferroptosis pathways. This review systematically explores GPX4's functions across various pain models, including neuropathic, inflammatory, low back, and cancer-related pain. Specifically, the focus includes GPX4's physiological roles, antioxidant defense mechanisms, regulation of ferroptosis, involvement in signal transduction pathways, and metabolic regulation. By summarizing current research, we highlight the potential of GPX4-targeted therapies in pain management.

Reproducible routes: reliably navigating the connectome to enrich personalized brain stimulation strategies

Non-invasive brain stimulation (NIBS) technologies, such as repetitive transcranial magnetic stimulation (rTMS), offer significant therapeutic potential for a growing number of neuropsychiatric conditions. Concurrent with the expansion of this field is the swift evolution of rTMS methodologies, including approaches to optimize stimulation site planning. Traditional targeting methods, foundational to early successes in the field and still widely employed today, include using scalp-based heuristics or integrating structural MRI co-registration to align the transcranial magnetic stimulation (TMS) coil with anatomical landmarks. Recent evidence, however, supports refining and personalizing stimulation sites based on the target's structural and/or functional connectivity profile. These connectomic approaches harness the network-wide neuromodulatory effects of rTMS to reach deeper brain structures while also enabling a greater degree of personalization by accounting for heterogenous network topology. In this study, we acquired baseline multimodal magnetic resonance (MRI) at two time points to evaluate the reliability and reproducibility of distinct connectome-based strategies for stimulation site planning. Specifically, we compared the intra-individual difference between the optimal stimulation sites generated at each time point for (1) functional connectivity (FC) guided targets derived from resting-state functional MRI and (2) structural connectivity (SC) guided targets derived from diffusion tensor imaging. Our findings suggest superior reproducibility of SC-guided targets. We emphasize the necessity for further research to validate these findings across diverse patient populations, thereby advancing the personalization of rTMS treatments.

Advanced Nanomaterials for Cancer Therapy: Gold, Silver, and Iron Oxide Nanoparticles in Oncological Applications.

Cancer remains one of the most challenging health issues globally, demanding innovative therapeutic approaches for effective treatment. Nanoparticles, particularly those composed of gold, silver, and iron oxide, have emerged as promising candidates for changing cancer therapy. This comprehensive review demonstrates the landscape of nanoparticle-based oncological interventions, focusing on the remarkable advancements and therapeutic potentials of gold, silver, and iron oxide nanoparticles. Gold nanoparticles have garnered significant attention for their exceptional biocompatibility, tunable surface chemistry, and distinctive optical properties, rendering them ideal candidates for various cancer diagnostic and therapeutic strategies. Silver nanoparticles, renowned for their antimicrobial properties, exhibit remarkable potential in cancer therapy through multiple mechanisms, including apoptosis induction, angiogenesis inhibition, and drug delivery enhancement. With their magnetic properties and biocompatibility, iron oxide nanoparticles offer unique cancer diagnosis and targeted therapy opportunities. This review critically examines the recent advancements in the synthesis, functionalization, and biomedical applications of these nanoparticles in cancer therapy. Moreover, the challenges are discussed, including toxicity concerns, immunogenicity, and translational barriers, and ongoing efforts to overcome these hurdles are highlighted. Finally, insights into the future directions of nanoparticle-based cancer therapy and regulatory considerations, are provided aiming to accelerate the translation of these promising technologies from bench to bedside.

Is choline kinase alpha a drug target for obesity?

Choline kinase alpha (ChoKα) is a therapeutic target being developed for a variety of diseases, from cancer to rheumatoid arthritis and from parasites to bacterial infections. Nevertheless, the therapeutic potential of this drug target seems not exhausted and may end up as a possible solution for a larger variety of conditions. Here we present our working model for how ChoKα could play a role in obesity and for how drugs being developed as therapeutics for other diseases using ChoKα as a target, could be repurposed as prophylactic treatments for obesity. We also present preliminary observations in support of our model.

The inhibitory effect of Hypericum japonicum on H9N2 avian influenza virus

The H9N2 subtype of avian influenza virus (AIV) causes severe immunosuppression and high mortality in view of its frequent co-infection with other pathogens, resulting in significant economic losses in the poultry industry. Current vaccines provide suboptimal immune protection against H9N2 AIV owing to antigenic variations, highlighting the urgent need for safe and effective antiviral drugs for the prevention and treatment of this virus. This study aimed to investigate the inhibitory effects of Hypericum japonicum extract on H9N2 AIV. Our findings revealed that the extract obtained through resin column separation using 60% ethanol (S06-60%) inhibited H9N2 AIV replication in Madin-Daby canine kidney cells in a dose-dependent manner. The maximum safe concentration of the water-soluble S06-60% extract was determined to be 0.05 mg/mL. Time-course experiments indicated that S06-60% primarily exerted its antiviral effects during the viral pretreatment and adsorption stages. Furthermore, in vivo experiments conducted on specific pathogen-free chickens confirmed the effectiveness of S06-60% in inhibiting H9N2 AIV infection and mitigating associated damage to tracheal and lung tissues. Overall, our study highlights the therapeutic potential of Hypericum japonicum extract S06-60% as a viable antiviral candidate against H9N2 AIV, offering promising implications for its application in poultry health management to reduce the economic impact on the poultry industry.

Exploring the Intracellular Distribution of Se Compounds Delivered by Biodegradable Polyelectrolyte Capsules Using X‐Ray Fluorescence Imaging

AbstractSelenium (Se) compounds hold promise as potential therapeutics for cancer due to their diverse biological functions and redox‐regulating properties. In this study, the encapsulation of a hydrophobic selenium compound inside 5 µm sized biodegradable polyelectrolyte capsules consisting of poly‐L‐arginine and dextran is investigated. While the encapsulated form of the compound showed comparable cellular uptake and cytotoxicity as the free drug, e.g. no improved anti‐cancer efficacy is achieved, the investigation yielded crucial insights. Utilizing subcellular resolution synchrotron X‐ray fluorescence imaging (XFI), the intracellular location of the Se compound is successfully visualized by demonstrating the degradation of the capsules and the following redistribution of the compound, without exogenous labeling. By applying a quantitative fitting approach, the intracellular Se mass is determined to be 0.09 ± 0.01 pg after degradation of the carrier. This highlights the potential of XFI as a powerful tool for tracking intracellular dynamics of metal‐based drugs, which may facilitate drug development in the clinic.

Therapeutic potential and agricultural benefits of curcumin: a comprehensive review of health and sustainability applications

AbstractTurmeric (Curcuma longa L.), the plant from which curcumin is derived, is renowned for its wide range of therapeutic and agricultural benefits. Curcumin, the key bioactive compound, is highly valued for its potent anti-provocative, antioxidant, and antimicrobial properties, which contribute to its effectiveness in treating various human diseases and improving plant resilience to environmental stresses. The therapeutics potential of curcumin is notable owing its abilities to combat microbes act as an oxidant and reduce inflammation. Its effectiveness in treating a range of human disease such as tumor, cardiac problems, and brain degenerative ailments stems from its ability to modulate various cellular process and signaling pathways. Despite its low bioavailability, innovations in delivery system such as nanoparticles and liposomal formulations, have enhanced its therapeutic efficacy by improving solubility and systemic absorption. In agriculture, curcumin's antimicrobial properties provide a natural alternative to chemical pesticides, offering protection against pathogens and enhancing plant resilience to specific environmental stresses such as drought, salinity, and oxidative stress. Nanotechnology applications have furthered these benefits by facilitating the efficient uptake and distribution of curcumin within plant tissues, promoting growth and stress tolerance. This review also highlights curcumin's nutritional benefits, including its impact on gut health and metabolic syndrome. Synergistic interactions with dietary nutrients can amplify its health benefits, making it a valuable dietary supplement. However, ongoing research is needed to fully understand curcumin's mechanisms of action and long-term safety. Overall, curcumin holds promise as a versatile agent in both medical and agricultural fields, supporting sustainable practices and advancing health outcomes. Future research should focus on optimizing curcumin formulations and translating preclinical findings into clinical successes. Graphical abstract

The proteomic landscape of extracellular vesicles derived from human intervertebral disc cells.

Extracellular vesicles (EVs) function as biomarkers and are crucial in cell communication and regulation, with therapeutic potential for intervertebral disc (IVD)-related low back pain (LBP). EV cargo is often affected by tissue health, which may affect the therapeutic potential. There is currently limited knowledge of how the cargo of IVD cell-derived EVs varies with tissue health and how differences in proteomic profile affect the predicted biological functions. Our study purified EVs from human IVD cell conditioned media by size-exclusion chromatography. Nanoparticle tracking analysis was conducted to measure EV size and concentration. Transmission electron microscopy and Western blot were performed to examine EV structure and markers. Tandem mass tag-mass spectrometry was conducted to determine protein cargo. Most EVs were exosomes and intermediate microvesicles with an increasing amount linked to disease progression. Of the proteins detected, 88.6% were shared across the non-degenerate, mildly-degenerate, and degenerate samples. GO and KEGG analyses revealed that cargo from the mildly-degenerate samples was the most distinct, with the proteins in high abundance strongly associated with extracellular matrix (ECM) organization and structure. Shared proteins, highly expressed in the non-degenerate and degenerate samples, showed strong associations with cell adhesion, ECM-receptor interaction, and vesicle-mediated transport, respectively. Our findings indicate that EVs from IVD cells from tissue with different degrees of degeneration share a majority of the cargo proteins. However, the level of expression differs with degeneration grade. Cargo from the mildly-degenerate samples exhibits the most differences. A better understanding of changes in EV cargo in the degenerative process may provide novel information related to molecular mechanisms underlying IVD degeneration and suggest new potential treatment modalities for IVD-related LBP.

Insights of gut-liver axis in hepatic diseases: Mechanisms, clinical implications, and therapeutic potentials

With the rising prevalence of chronic liver diseases worldwide, there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease. Currently, the most common causes of liver disease are non-alcoholic fatty liver disease, hepatitis, and alcoholic liver disease. Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis. In this review, we analyse the relationship between the gut and liver and their significance in liver disease. This two-way relationship has interesting effects on each other in liver diseases. The gut microbiota, through its metabolites, influences the metabolism in numerous ways. Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases. Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.

Therapeutic Potential of Ramalin Derivatives with Enhanced Stability in the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) remains a significant public health challenge with limited effective treatment options. Ramalin, a compound derived from Antarctic lichens, has shown potential in the treatment of AD because of its strong antioxidant and anti-inflammatory properties. However, its instability and toxicity have hindered the development of Ramalin as a viable therapeutic agent. The primary objective of this study was to synthesize and evaluate novel Ramalin derivatives with enhanced stabilities and reduced toxic profiles, with the aim of retaining or improving their therapeutic potential against AD. The antioxidant, anti-inflammatory, anti-BACE-1, and anti-tau activities of four synthesized Ramalin derivatives (i.e., RA-Hyd-Me, RA-Hyd-Me-Tol, RA-Sali, and RA-Benzo) were evaluated. These derivatives demonstrated significantly improved stabilities compared to the parent compound, with RA-Sali giving the most promising results. More specifically, RA-Sali exhibited a potent BACE-1 inhibitory activity and effectively reduced tau phosphorylation, a critical factor in AD pathology. Despite exhibiting reduced antioxidant activities compared to the parent compound, these derivatives represent a potential multi-targeted approach for AD treatment, marking a significant step forward in the development of stable and effective AD therapeutics.