Reduced Side Effects Research Articles

The effects of extracorporeal shock wave therapy in children with cerebral palsy: a systematic review.

Spastic Cerebral Palsy (CP) is a major cause of movement disorders in pediatric rehabilitation. Current treatments are often invasive and may lead to substantial discomfort. Extracorporeal shockwave therapy (ESWT) presents a potential alternative, offering a less invasive approach with a reduced side effect profile. However, the impact of ESWT on children with CP remains unclear. This systematic review aims to summarize the current evidence on ESWT's impact in children with spastic CP across various domains of the International Classification of Functioning, Disability, and Health for Children and Youth. To answer the main question, a systematic literature study is used. The studies, collected from four databases, were screened and data on outcome measures and methodological quality were extracted. Effect sizes were calculated to facilitate study comparison. In total, twelve randomized controlled trials met inclusion criteria, with PEDro scores ranging from three to eight. The combined study population included 421 children. Positive effects were observed on resistance to passive movements, passive range of motion, and gross motor skills, with effect sizes ranging from moderate (0.65) to very large (7.69). ESWT demonstrated positive effects across multiple domains in children with spastic CP.

Discovery of Novel pH-Sensitive μ-Opioid Receptor Agonists as Potent Analgesics with Reduced Side Effects

Discovery of Novel pH-Sensitive μ-Opioid Receptor Agonists as Potent Analgesics with Reduced Side Effects

Integrating Machine Learning and Pharmacophore Features for Enhanced Prediction of H1 Receptor Blockers.

Histamine Type I Receptor Antagonists (H1 blockers) are widely used to mitigate histamine-induced inflammation, particularly in allergic reactions. Histamine, a biogenic amine found in endothelial cells, vascular smooth muscle, bronchial smooth muscle, and the hypothalamus, is a key player in these responses. H1 blockers are essential in cough syrups and flu medications and are divided into two generations: first-generation H1 blockers, which are sedating and have numerous side effects, and second-generation blockers, which are non-sedating and generally less toxic but may still exhibit cross-reactivity with other receptors. In this study, a comprehensive database of compounds was utilized alongside fexofenadine as a benchmark to discover compounds with potentially superior efficacy and reduced side effect profiles. In particular, multidimensional K-means clustering, a machine-learning technique, was applied to identify compounds with chemical structures similar to fexofenadine. Utilizing computational prediction of pharmacokinetic profile and molecular docking experiments, the action of these drugs on the H1 receptor was assessed. Furthermore, the crossreactivity of antihistamines was investigated by conducting a structure-based pharmacophore feature analysis of the docked poses of highly toxic antihistamines with various receptors. By identifying and proposing the removal of common toxic features, we aim to facilitate the development of antihistamines with fewer adverse effects.

Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge

Preclinical studies have demonstrated that nanoparticles (NPs) hold significant potential for advancing cancer therapy by enhancing therapeutic efficacy while reducing side effects. Their effectiveness in solid tumors is, however, often constrained by insufficient accumulation and penetration. Understanding how the physicochemical properties of NPs – such as size, shape, and surface charge – influence their interaction with cells within the tumor is critical for optimizing NP design. In this study, we addressed the challenge of inconsistent NP behavior by systematically evaluating NP uptake in both 2D and 3D tumor models, and NP penetration in spheroids. Our results showed that larger NPs exhibited higher internalization rates in 2D models but limited penetration in 3D spheroids. Furthermore, negatively charged NPs consistently achieved superior accumulation and deeper penetration than neutral and positively charged NPs. Spherical NPs outperformed rod-shaped NPs in tumor accumulation and penetration. These findings underscore the importance of carefully tailoring NP properties to the complex tumor microenvironment for improved therapeutic outcomes in real tumors.

Continuous local infiltration analgesia is equal to femoral and sciatic nerve block for total knee arthroplasty

BackgroundTotal knee arthroplasty (TKA) is associated with moderate to severe postoperative pain. Pain control is crucial for rapid mobilisation and reduces side effects as well as the length of hospital stay. In this context, a variety of multimodal pain control regimes show good pain relief, including several nerve blocks, iPACK and local infiltration analgesia (LIA). To compare the analgesic potency of LIA and the combination of continuous femoral nerve block + sciatic single-shot nerve block under general anaesthesia, we conducted a prospective, randomized, controlled, non-blinded single-centre study.Method 139 ASA I-III Patients were enrolled in the study, randomised into two groups. The LIA group received an intra- and periarticular infiltration containing a mix of ropivacaine 0,2%, adrenaline and ketorolac, followed by an infusion of the same mixture for 48 h via an intraarticular catheter. The patients in the FEM group received a combination of continuous femoral nerve block with a catheter using 30 ml prilocaine 1% and ropivacaine 0,2% plus a single-shot sciatic nerve block via an antero-medial approach (landmark-based technique) with 20 ml ropivacaine 0,75%. Postoperative pain scores were analysed during the first two postoperative days, as well as opioid consumption, the degree of knee movement and the occurrence of infections in both groups applying the Wilcoxon-Mann-Whitney test, Friedman chi-square test and the Log-rank-test.ResultsNo significant difference in pain scores, opioid consumption, time to first rescue analgesia, knee range of motion, age, height, weight and ASA could be detected. No severe side effects, such as secondary bleeding or infections, were reported.ConclusionBoth techniques are well established, provide equal pain relief for TKA and support early postoperative mobilisation.Trial RegistrationDRKS 00027145 08/12/2021. “retrospectively registered”.

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.

A Review on Microneedles Patches Transdermal Drug Delivery System

A revolutionary approach transdermal drug delivery has emerged as a viable alternative to traditional oral and injectable routes, offering improved patient compliance and reduces side effects. Microneedle patches have garnered significant attention in recent years as a primising technology for transdermal drug delivery. these microscopic needle arrays create micro- channels in the skin, enabling the delivery of therapeutics, including small molecules, peptides, proteins. Recent studies have demonstrated the efficacy of microneedle patches in delivering various therapeutics, including vaccines, hormones, and painkillers. The patches have shown improved bioavailability, reduced dosing frequency, and enhanced therapeutic outcomes. Additionally, microneedle patches have been found to be safe and well-tolerated, with minimal skin irritation and no significant adverse effects. Despite the promising results, challenges persist, including scalability, cost-effectiveness, and regulatory hurdles. Ongoing research aims to address these limitations, exploring new materials, designs, and manufacturing processes. The development of microneedle patches for transdermal drug delivery has the potential to transform the pharmaceutical industry, offering improved treatment outcomes, enhanced patient compliance, and reduced healthcare costs.

Enhanced Analgesic Efficacy and Reduced Side Effects of Morphine by Combination with PD-1 Agonist.

Chronic pain is a debilitating disease and remains challenging to treat. Morphine serves as the most commonly used drug for the treatment of pathological pain. However, detrimental side effects (e.g., hyperalgesia and tolerance) manifest during chronic administration, thus counteracting morphine analgesia. Investigators have sought methods to widen the therapeutic window of morphine in the management of chronic pain. Programmed cell death protein 1 (PD-1) is a recently validated analgesic target and is coexpressed with the mu opioid receptor (μOR) in dorsal root ganglion (DRG) sensory neurons. Here, we present evidence that PD-1 regulates the expression of μOR mRNA and influences μOR-mediated analgesia. Notably, the concomitant administration of PD-1 agonist H-20 greatly reduces the dosage of morphine needed for analgesia, thereby significantly decreasing opioid-related side effects. This new combination therapy may provide a solution for managing chronic pain in patients who require morphine.

Impact of nanostructured additives in tooth bleaching agents on enhancing color change and reducing side effects: a scoping review.

This study aimed to determine whether incorporating nanostructured additives into bleaching agents enhances efficacy and reduces side effects while identifying gaps for further investigation. A comprehensive search was conducted in electronic databases, including PubMed/Medline, Embase, Scopus, and ISI Web of Science. Two reviewers independently screened articles based on predefined criteria, resolving discrepancies through discussion or consultation with a third reviewer. Data extraction focused on key details, including study design, interventions, and outcomes. Twenty-one articles were reviewed, consisting of nine clinical studies, one in vivo/in situ study, and 11 in vitro studies on tooth bleaching protocols. Hydrogen peroxide was the most commonly used bleaching agent. The primary nanostructured additives studied were titanium dioxide nanoparticles, polymeric carbamide peroxide nanoparticles, chitosan nanoparticles, nano-hydroxyapatite, SiO2/MgO/Fe2O3 nanocomposite spheres, and nano-bioactive glass. Most studies demonstrated an enhanced bleaching effect, reduced bleaching sensitivity, decreased cytotoxicity, reduced hydrogen peroxide penetration into the pulp chamber, and protection of the tooth surface against mineral and structural loss when nanostructured additives were incorporated into the bleaching agent. Incorporating nanostructured additives into tooth-bleaching agents improved efficacy and reduced side effects, especially with titanium oxide nanoparticles. Further clinical studies and systematic reviews are needed to establish strong evidence for safe clinical practice. Including nanostructured additives in bleaching agents, such as titanium oxide nanoparticles, might be a valuable approach to enhancing the bleaching potential while reducing bleaching sensitivity and cytotoxicity, offering safer alternatives for clinical protocols.

Innovating alopecia treatment: nanostructured lipid carriers as advanced delivery platforms.

Alopecia, a common dermatological condition, poses significant psychological and social challenges. Despite the availability of various treatments, their efficacy is often limited by poor bioavailability and delivery challenges. Nanostructured lipid carriers have emerged as promising advanced drug delivery systems for alopecia treatment due to their ability to encapsulate both hydrophilic and lipophilic compounds, enhancing their stability, solubility, and controlled release. This manuscript explores the potential of Nanostructured lipid carriers as innovative delivery platforms for alopecia therapeutics, focusing on their formulation, characterization, and application in topical treatments. The unique properties of Nanostructured lipid carriers, including their small size, biocompatibility, and ability to target specific skin layers, are discussed in relation to improving the penetration and therapeutic efficacy of active ingredients such as minoxidil, finasteride, and plant-derived compounds. Additionally, we highlight the role of Nanostructured lipid carriers in improving scalp penetration, reducing side effects, and offering a more efficient alternative to conventional treatments. The manuscript concludes with insights into future trends, challenges, and the clinical potential of Nanostructured lipid carriers-based formulations in revolutionizing alopecia treatment.

Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment strategy for schizophrenia.

Schizophrenia is a chronic and severe mental disorder. It is currently treated with antipsychotic drugs (APD). However, APD's work only in a limited number of patients and may have cognition impairing side effects. A growing body of evidence points out the potential involvement of abnormal sphingolipid metabolism in the pathophysiology of schizophrenia. Here, an analysis of human gene polymorphisms and brain gene expression in schizophrenia patients identified an association of SMPD1 and SMPD3 genes coding for acid- (ASM) and neutral sphingomyelinase-2 (NSM). In a rat model of psychosis using amphetamine hypersensitization, we found a locally restricted increase of ASM activity in the prefrontal cortex (PFC). Short-term haloperidol (HAL) treatment reversed behavioral symptoms and the ASM activity. A sphingolipidomic analysis confirmed an altered ceramide metabolism in the PFC during psychosis. Targeting enhanced ASM activity in a psychotic-like state with the ASM inhibitor KARI201 reversed psychotic like behavior and associated changes in the sphingolipidome. While effective HAL treatment led to locomotor decline and cognitive impairments, KARI201 did not. An RNA sequencing analysis of the PFC suggested a dysregulation of numerous schizophrenia related genes including Olig1, Fgfr1, Gpr17, Gna12, Abca2, Sox1, Dpm2, and Rab2a in the rat model of psychosis. HAL and KARI201 antipsychotic effects were associated with targeting expression of other schizophrenia associated genes like Col6a3, Slc22a8, and Bmal1, or Nr2f6a, respectively, but none affecting expression of sphingolipid regulating genes. Our data provide new insight into a potentially pathogenic mechanism of schizophrenia and suggest a new pharmaco-treatment strategy with reduced side effects.

Green chemistry: Modern therapies using nanocarriers for treating rare brain cancer metastasis from colon cancer.

Brain metastasis (BM) from colon cancer is associated with a poor prognosis and restricted treatment alternatives, largely due to issues related to blood-brain barrier (BBB) permeability and the negative effects of standard chemotherapy. Nanotechnology improves treatment efficacy by enabling targeted and controlled drug delivery. This review article evaluates the potential of nanotechnology-based therapies for treating colon cancer BM, emphasizing their capacity to cross the BBB, diminish metastatic growth, and enhance overall survival rates. A review of multiple studies evaluated nanoparticles (NPs) as carriers for chemotherapy, focusing on parameters including particle size, surface charge, and drug-loading capacity. The study also reviewed studies that examined BBB penetration, in vitro tumor accumulation, and in vivo tumor growth inhibition. In vitro findings indicated that NPs accumulate more efficiently in BM tissue than in healthy brain tissue and show significant BBB penetration. In vivo, nanotherapy markedly inhibited tumor growth and prolonged survival relative to conventional chemotherapy or control treatments while also exhibiting reduced side effects. Recent studies demonstrated that plant extracts can effectively and safely synthesize nanomaterials, positioning them as a viable and environmentally friendly precursor for nanomaterial production. Nanotechnology-based therapies demonstrate significant potential in the treatment of colon cancer BM by minimizing systemic toxicity, enhancing therapeutic efficacy, and facilitating more targeted drug delivery. Further research is required to confirm these findings and implement them in clinical practice.

The application of nanomaterials in drug delivery system

Drug delivery system (DDS) is a key technology platform for optimizing the distribution of drugs in the body. It improves the the efficiency of drug treatment and reduces side effects by regulating the dose, time and target location. This review focuses on the application progress of nanomaterials in DDS. Liposomes, albumin nanoparticles and magnetic iron oxide nanoparticles are widely used due to their good biocompatibility, targeted drug release ability and imaging application potential. However, these materials also have certain limitations. Liposomes have low drug loading capacity, and their product Doxil shows low tolerance and certain adverse reactions. New nanomaterials are being developed and tried to be used in DDS. Innovative materials such as nano gels and metal organic frameworks (MOFs) have the capacity of reprinting a large number of drugs and low toxicity and application potential. These materials are in the research stage and are expected to play a significant role in future clinical applications.

Advances in Migraine Treatment: A Comprehensive Clinical Review.

Migraine is a neurological disease that, while not inherently causing "chronic headaches," can evolve into a chronic condition over time including major symptoms such as nausea, and light, sound, and allodynia, particularly in cases of frequent episodic migraine or due to factors such as medication overuse or inadequate management. This condition's complex pathophysiology makes treatment difficult. Genetics, trigeminovascular system activation, and cortical spreading depression are involved. Epidemiological research estimates that one in seven persons worldwide are affected, mostly women. Migraine prevalence has increased dramatically in recent decades; however, it varies by demographic and location. This review covers pharmaceutical and non-pharmacological migraine therapy methods and their future. Second-generation triptans have reduced side effects and administration issues, however, Zolmitriptan and Sumatriptan still treat migraines. Monoclonal antibodies that target calcitonin gene-related peptides may prevent migraines; however, their accessibility and safety are problems. Antiepileptics, beta-blockers, and neuromodulation devices are also available. Wearable technology offers customized monitoring and intervention. Precision medicine and gene-based medicines provide hope for tailored migraine treatments, but access, privacy, and informed consent raises ethical concerns. Stakeholder engagement must promote patient autonomy and well-being, responsible implementation, and equal access to novel therapies. A holistic and multidisciplinary approach is needed to manage migraines, taking into consideration present and future therapy developments and new challenges. Research, collaboration, and ethics can improve migraine outcomes and quality of life.

Comparative analysis of warm needle moxibustion and gua sha nursing care on sleep quality and psychological stress in insomnia patients undergoing eszopiclone tablet treatment: A retrospective study.

This retrospective study aims to assess the adjunctive efficacy of warm needle moxibustion and gua sha care in the treatment of eszopiclone tablets on sleep quality and psychological stress in insomnia patients. Data of 138 insomnia patients from Gansu Baoshihua hospital between January and December 2022 were collected. Patients were bifurcated into 2 groups: those solely treated with eszopiclone (n = 71) and those administered a combined regimen of eszopiclone, warm needle moxibustion, and gua sha (n = 67). Sleep quality, psychological stress, and daytime drowsiness were assessed using the Pittsburgh Sleep Quality Index (PSQI), Perceived Stress Scale-10 (PSS-10), and Epworth Sleepiness Scale (ESS), respectively. Adverse effects were also monitored. Baseline demographics and clinical characteristics were comparable between the 2 groups. Post-intervention, the intervention group exhibited significant reductions in PSQI and ESS scores (P < .05), whereas the control group showed no significant changes. The PSS-10 scores remained unchanged in both groups post-intervention. The intervention group reported a significant decrease in the prevalence of nausea and dizziness posttreatment (P < .05), with a notably lower post-intervention nausea prevalence compared to the control group (P < .05). Incorporating warm needle moxibustion and gua sha nursing care into the eszopiclone treatment regimen potentially amplify sleep quality while reducing side effects in patients with insomnia.

Synthetic Strategies for the Development of Ibuprofen Derivatives: A Classified Study.

Ibuprofen, a widely used NSAID from the aryl propionic acid class, effectively relieves pain, fever, and inflammation. On prolonged use, it leads to gastrointestinal, hepatic, and renal toxicities, particularly gastrointestinal ulcers. These side effects are largely attributed to the carboxylic acid functional group common to NSAIDs. The present review highlights the different modifications done to the carboxylic group in Ibuprofen, by various researchers such as estersgramma, amides, hydroxamic acids, and N-substituted hydrazides, along with the integration of heterocyclic moieties like triazoles, tetrazoles, and oxadiazoles. Additionally, Ibuprofen has been hybridized with other drugs and complexed with metals to enhance therapeutic effects. The different synthetic strategies that were employed were esterification, amidation, condensation, Schiff's base formation, etc. These modifications have resulted in derivatives with antimicrobial, antifungal, anticancer, and other biological activities, aiming to reduce side effects while retaining or enhancing antiinflammatory, analgesic, and antipyretic properties.

Effect of a Novel Food Rich in Miraculin on the Intestinal Microbiome of Malnourished Patients with Cancer and Dysgeusia.

Dysgeusia contributes to malnutrition and worsens the quality of life of patients with cancer. Despite the different strategies, there is no effective treatment for patients suffering from taste disorders provided by the pharmaceutical industry. Therefore, we developed a novel strategy for reducing side effects in cancer patients by providing a novel food supplement with the taste-modifying glycoprotein miraculin, which is approved by the European Union, as an adjuvant to medical-nutritional therapy. A pilot randomized, parallel, triple-blind, and placebo-controlled intervention clinical trial was carried out in which 31 malnourished patients with cancer and dysgeusia receiving antineoplastic treatment were randomized into three arms-standard dose of dried miracle berries (DMBs) (150 mg DMB/tablet), high dose of DMBs (300 mg DMB/tablet), or placebo (300 mg freeze-dried strawberry)-for three months. Patients consumed a DMB or placebo tablet before each main meal (breakfast, lunch, and dinner). Using stool samples from patients with cancer, we analyzed the intestinal microbiome via nanopore methodology. We detected differences in the relative abundances of genera Phocaeicola and Escherichia depending on the treatment. Nevertheless, only the Solibaculum genus was more abundant in the standard-dose DMB group after 3 months. At the species level, Bacteroides sp. PHL 2737 presented a relatively low abundance in both DMB groups, whereas Vescimonas coprocola presented a relatively high abundance in both treatment groups after 3 months. Furthermore, a standard dose of DMB was positively associated with TNF-α levels and Lachnoclostridium and Mediterraneibacter abundances, and a high dose of DMB was negatively associated with TNF-α levels and the relative abundance of Phocaeicola. Following the administration of a high dose of DMB, a positive correlation was observed between erythrocyte polyunsaturated fatty acids and the presence of Lachnoclostridium and Roseburia. Additionally, a positive association was identified between Phocaeicola and the acetic acid concentration of feces. There was a negative association between the relative abundance of Phocaeicola and taste perception in the high-dose DMB group. The combination of DMB intake with nutritional treatment and individualized dietary guidance results in positive changes in the intestinal microbiome of patients with cancer and dysgeusia. Changes observed in the intestinal microbiome might contribute to maintaining an appropriate immune response in cancer patients. As the current pilot study included a limited number of participants, further clinical trials on a larger group of patients are needed to draw robust findings.

Synthesis and Characterization of Brucine Gold Nanoparticles for Targeted Breast Cancer Therapy: Mechanistic Insights Into Apoptosis and Antioxidant Disruption in MCF-7 Cells.

Globally, breast cancer continues to be the leading type of cancer affecting women, with rising mortality rates projected by 2030. This highlights the importance of developing new, affordable treatments, like drug delivery systems that use nanoparticles. Gold nanoparticles (AuNPs), including their exceptional optical and physical attributes, make them an attractive vehicle for targeted treatment, allowing for accurate and focused delivery of medication directly to cancerous cells while reducing harmful side effect. This study focuses on the synthesis and characterization of brucine-gold nanoparticles (BRU-AuNPs) for targeted breast cancer therapy by evaluating their antioxidant and apoptotic mechanism. BRU-AuNPs were synthesized and characterized (UV-Vis spectroscopy, Fourier transform infrared [FTIR], scanning electron microscopy [SEM], x-ray diffraction [XRD], dynamic light scattering [DLS], and zeta potential) to confirm successful synthesis, size, and stability. Invitro studies were assessed using MCF-7 breast cancer cell lines to evaluate cell cytotoxicity, antioxidant balance, reactive oxygen species (ROS) generation, mitochondrial membrane potential, apoptosis induction, cell migration, and pro-apoptotic gene expression. Characterization results confirmed the successful synthesis of BRU-AuNPs with an average crystal size of 85.40nm and stable surface charge. Results demonstrated that BRU-AuNPs reduced MCF-7 cell viability in a dose-dependent manner, with an IC50 value of 11.47µg/mL. Treatment with BRU-AuNPs altered the antioxidant balance, increased ROS generation, depolarized mitochondrial membranes, and induced apoptosis. Additionally, BRU-AuNPs inhibited cell migration and upregulated pro-apoptotic gene expression. The synthesized BRU-AuNPs exhibit potential as a highly effective targeted delivery system for breast cancer treatment. Their ability to directly deliver BRU to tumor cells while reducing side effects and enhancing therapeutic efficacy underscores their promise in advancing breast cancer therapy. Further studies are warranted to explore their clinical potential and optimize therapeutic outcomes.

A novel rapalog shows improved safety vs. efficacy in a human organoid model of polycystic kidney disease.

The mammalian target of rapamycin (mTOR) pathway is a therapeutic target in polycystic kidney disease (PKD), but mTOR inhibitors such as everolimus have failed to show efficacy at tolerated doses in clinical trials. Here, we introduce AV457, a novel rapalog developed to reduce side effects, and assess its dose-dependent safety and efficacy versus everolimus in PKD1-/- and PKD2-/- human kidney organoids, which form cysts in a PKD-specific way. Both AV457 and everolimus reduce cyst growth over time. At intermediate doses, AV457 exhibits an improved safety profile relative to everolimus, with comparable efficacy. Target engagement assays confirm mTOR pathway inhibition and greater selectivity of AV457 for mTOR complex 1 versus complex 2, compared to everolimus. AV457 thus provides a more favorable balance of safety and efficacy for PKD compared to everolimus and merits further consideration as an investigational therapeutic.

The Exosome and its Application in Skin Wound Healing: A Systematic Review on In vitro Studies.

Wound healing is a complex procedure frequently delayed in patients with underlying chronic conditions. Despite essential advances in tissue engineering and regenerative medicine, wound healing remains challenging, warranting novel methods for promoting wound healing. It has been demonstrated that exosomes are one of the main secretory products of different cell types, such as Mesenchymal Stem Cells (MSCs), for regulating various biological processes, including wound healing. Henceforth, understanding these exosome effects might assist in improving wound management and highlight a novel therapeutic model for cell-free therapies with reduced side effects for repairing wounds. This systematic review involved conducting research electronically on scholarly scientific databases, including PubMed, Science Direct, and Scopus. Eligibility checks were performed based on predefined selection criteria. Finally, thirty-nine studies were considered. Exosomes have been indicated to use multitargeted pathways to improve wound healing by modulating numerous dysregulated signaling cascades involved in cell proliferation, cell cycle regulation, metastasis, apoptosis, and angiogenesis. The outcome of this review might guide pre-clinical and clinical studies on the role of exosomes in skin wound healing.