Pharmacology
New Phenylpropanoid from Croton velutinus (Euphorbiaceae) as Potential Anticancer Natural Product Targeting MAPKs: Review with Docking Approach
Cancer encompasses a group of diseases characterized by uncontrolled cell growth and the ability to invade or spread to other parts of the body. It is considered a major public health issue being the second leading cause of death worldwide. A crucial signaling pathway altered in many cancers is the Mitogen-Activated Protein Kinase (MAPK) pathway which is associated with the regulation of cell proliferation differentiation and survival playing a central role in the development and maintenance of malignant tumors. Natural products have made significant contributions to pharmacotherapy particularly in the field of cancer treatment. The Euphorbiaceae family comprising approximately 300 genera and over 5000 species is known for its rich diversity of bioactive compounds. Croton velutinus (Euphorbiaceae) a species predominantly found in Northeast Brazil has recently garnered attention due to its novel phenylpropanoids isolated from its roots. Among these (E)-4-(1-epoxy-78-propen) phenylbenzoate (CV2) has demonstrated potential cytotoxic activity against various human tumor cell lines including B16F10 MCF-7 HL60 HCT-116 and HepG2. This review aims to highlight the antitumor activity of phenylpropanoids derived from the Euphorbiaceae family. Furthermore through molecular docking studies we explored the binding efficacy of CV2 with MAPKs (ERK JNK p38) comparing it to 25 other phenylpropanoid compounds reported in the literature revealing promising interactions that could be further investigated for therapeutic applications.
Sugammadex in Perioperative Neuromuscular Management: Current Advances and Best Practices
Neuromuscular blocking agents (NMBAs) are crucial for anesthesia enabling intubation and optimal surgical conditions. Timely reversal of blockade is critical for safe extubation and recovery. While neostigmine a traditional reversal agent is effective for moderate blockade it has limitations in reversing deep blockade and requires anticholinergics to mitigate side effects. Sugammadex a novel agent addresses these limitations by selectively encapsulating aminosteroid NMBAs like rocuronium providing rapid and reliable reversal. It demonstrates significant advantages including faster recovery and reduced postoperative complications especially in high-risk populations such as elderly patients or those with organ dysfunction. However challenges such as high costs and potential adverse effects including hypersensitivity and cardiovascular events restrict its routine use. This review explores sugammadex’s pharmacological features clinical applications and cost-effectiveness offering strategies to optimize its use in complex surgical scenarios while addressing current limitations.
Exploration of Pharmacological Mechanism of Kaempferol in Treating Rheumatoid Arthritis based on Network Pharmacology, Molecular Modelling, and Experimental Validation
The autoimmune inflammatory disease known as rheumatoid arthritis (RA) has a complicated and poorly understood etiology. Fibroblast-like synoviocytes (FLSs) have tumor-like characteristics in RA including aggressive growth and heightened activation that leads to the release of pro-inflammatory factors. These processes are essential for the gradual deterioration of joint tissues. Kaempferol with the chemical formula 357-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one is found in many different types of plants and plant families. The pharmacological effects of this substance have been well-documented. The benefits of this substance encompass protection for the heart and brain as well as fighting inflammation bacteria cancer osteoporosis and allergies. It also has properties that can help with anxiety pain relief and hormonal balance. However its precise function in the management of RA is still unclear.
To investigate the effect of kaempferol on apoptosis in RA FLSs and elucidate the underlying mechanisms.
We used the CCK-8 assay to assess the effects of different kaempferol concentrations on RA FLSs. We also used flow cytometry with Annexin V-FITC/PI staining to analyse cell cycle distribution and quantify apoptotic cells. To verify apoptosis the TUNEL test was employed. Important proteins associated with apoptosis were verified to be expressed using western blotting. Finally network pharmacology analysis was used to identify potential kaempferol targets and their interactions with AKT1 PIK3R1 and HSP90AA1 proteins were studied using molecular docking and molecular dynamics simulations.
Kaempferol treatment significantly increased apoptosis in RA FLSs up-regulating the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl-2. Specifically kaempferol at 100 and 200 μM increased the apoptosis index to 29.77 ± 6.02% and 55.63 ± 11.05% respectively compared to the control. The induction of caspase-9 and caspase-3 cleavage was observed indicating the activation of the mitochondrial pathway. Kaempferol also inhibited the phosphorylation of PI3K and Akt with a significant reduction in their activation. Molecular docking studies demonstrated that kaempferol interacted with AKT1 PIK3R1 and HSP90AA1 proteins with binding energies of -6.51 -4.26 and -6.51 kcal/mol respectively suggesting a strong affinity and potential direct impact on these proteins.
Kaempferol induces apoptosis in RA FLSs by inhibiting phosphorylation of the PI3K/Akt signaling pathway increasing levels of pro-apoptotic proteins and decreasing levels of anti-apoptotic proteins. Thus kaempferol a naturally occurring flavonoid has great promise in the management of RA.
Cytotoxic Effects of Dysphania ambrosioides Extracts on Oral Squamous Cell Carcinoma
Dysphania ambrosioides commonly known as “mastruz” is a medicinal plant traditionally used for its therapeutic properties including antimicrobial and anti-inflammatory effects. Previous studies have also suggested its antitumor potential. However its role in oral squamous cell carcinoma (OSCC) remains unexplored. This study aimed to evaluate the in vitro cytotoxic effects of D. ambrosioides extracts on SCC4 (OSCC) and HaCaT (human keratinocyte) cell lines.
Crude extracts were obtained using different methods including hexanic ethanolic hydroethanolic (7:3) and aqueous extractions all performed ultrasonic-assisted extraction. The extracts were tested at concentrations ranging from 7.81 µg/mL to 1000 µg/mL using 2-fold serial dilutions. Cell viability was assessed after 48 hours of treatment using the MTT assay with DMSO as the control.
The extracts exhibited concentration-dependent cytotoxic effects on both cell lines with HaCaT cells showing greater sensitivity. However the lack of selectivity toward tumor cells over normal cells suggests a broad-spectrum cytotoxic activity without tumor-specific therapeutic targeting.
These findings highlight the need for further fractionation of the extracts and identification of the bioactive compounds responsible for the observed effects. Although the extracts demonstrated significant cytotoxic activity their therapeutic potential should not be limited to cytotoxicity alone. Future studies should explore additional biological activities such as anti-inflammatory or immunomodulatory properties to fully understand the therapeutic applications of D. ambrosioides.
Design, Molecular Docking, In Vitro and In Vivo Evaluation of Dimenhydrinate-Cyclodextrin Complex for Fast-Disintegrating Tablet
This study aimed to formulate and evaluate dimenhydrinate (DMH) as fast-disintegrating tablets (FDTs) complexed with β-cyclodextrin (β-CD) to enhance its solubility dissolution profile and pharmacological performance.
A DMH:β-CD inclusion complex was prepared at a 1:1 molar ratio using the kneading method. Characterization was performed through phase solubility studies FTIR analysis molecular docking and in vitro dissolution testing. FDTs were developed using various superdisintegrants and assessed for quality attributes of a tablet including hardness friability wetting time water absorption ratio and drug content.
Phase solubility and FTIR analyses confirmed the formation of a stable DMH:β-CD complex. Molecular docking indicated a binding affinity of -4.2 kcal/mol between β-CD and diphenhydramine. Among the FDT formulations CP3 containing 9% crospovidone showed the best performance with a disintegration time of 4.3 seconds and the highest drug release rate. In vivo pharmacological tests demonstrated enhanced sedative and antiemetic activities of the optimized FDTs compared to conventional DMH formulations.
The findings suggest that cyclodextrin-based complexation combined with orodispersible tablet technology can significantly enhance DMH's pharmacological efficacy and patient compliance. However additional investigations on long-term stability pharmacokinetics and clinical scalability are warranted.
The DMH:β-CD FDTs developed in this study offer promising improvements in solubility dissolution and therapeutic performance indicating their potential for better clinical outcomes and patient acceptability.
Integrated Network Pharmacology and Molecular Modeling Approach for Potential PTGS2 Inhibitors against Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic inflammatory condition of the joints and a leading cause of global disability. However the use of current anti-inflammatory treatments is often limited by serious side effects and multi-organ toxicity necessitating the exploration of safer alternatives.
This study aims to investigate the anti-rheumatic potential of natural compounds of Cassia angustifolia as small-molecule inhibitors of PTGS2.
The therapeutic potential of C. angustifolia was evaluated through antioxidant and anti-inflammatory assays. Gas chromatography-mass spectrometry (GC-MS) was used to identify its constituents. ADMET profiling (absorption distribution metabolism excretion and toxicity) network pharmacology and molecular dynamics simulation were employed to uncover the active compounds against PTGS2 for RA treatment.
C. angustifolia extract contained significant phenolic (18.2 ± 0.008 mg GAE/g DW) and flavonoid (27.57 ± 0.03 mg RE/g DW) content. GC-MS yielded 288 compounds of which four passed the toxicity parameters. Protein-protein interaction analysis revealed 10 RA-related targets with PTGS2 emerging as the most prominent one. Molecular docking and simulations revealed that compound-2 [2-Benzo [13] dioxol-5-yl-8-methoxy-3-nitro-2H-chromene] and compound-4 [alpha-hydroxy-N-[2-methoxyphenyl]-benzene propanamide] binds strongly with PTGS2 (-7.7 kcal/mol and -7.9 kcal/mol respectively) predicting its stable interaction.
C. angustifolia compounds present a significant potential as PTGS2 inhibitors warranting further in vitro and in vivo investigations to confirm their therapeutic efficacy against RA.
New Standards in the Treatment of Advanced Metastatic Melanoma: Immunotherapy and BRAF-Targeted Therapies as Emerging Paradigms
Although cutaneous melanoma accounts for only about 2% of skin cancers its rapid progression makes it an aggressive skin cancer with a high mortality rate. As of 2018 the SEER database estimated that the 5-year overall survival (OS) rate is 29.8% in patients with stage IV disease at diagnosis in the United States. Non-cutaneous melanoma including mucosal and uveal subtypes carries a generally worse prognosis. Once considered refractory to conventional treatments such as chemotherapy and radiation therapy the advent of immunotherapy including immune checkpoint inhibitors (ICIs) vaccines and tumor-infiltrating lymphocytes (TIL) and of targeted therapy over the past decade has resulted in dramatic improvements in melanoma. Importantly ICIs have resulted in long-term remission for patients with melanoma thus introducing the possibility of a cure for some patients with metastatic disease. These include antibodies against programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) cytotoxic T-lymphocyte antigen-4 (CTLA-4) and lymphocyte activation gene-3 (LAG-3). In this review we will provide an overview of metastatic melanoma while focusing on its current pharmacologic armamentarium toxicities of treatment including ICIs and targeted therapy and its therapeutic clinical strategies. The therapeutic advances presented in this review serve as the foundation for an ever-expanding repertoire of innovative approaches. These include mRNA vaccines oncolytic viruses bispecific engagers oral immunomodulators and novel cytokines. Adoptive cellular strategies are evolving to TILS transduced with conditional gene expression cassettes as well as non-T cell approaches involving dendritic cells and natural killer (NK) cells. Targeted therapy strategies have broadened to include upstream components of RAS other MAP kinase pathways and HDAC inhibitors among others. All these new paradigms translate into increasingly complex decision-making for the treatment team a burden that is more than offset by the tremendous benefit for melanoma patients. This is truly the beginning of a new era.
Pre-clinical Safety Study of Cold Atmospheric Plasma (CAP) Produced by an Inbuilt CAP Device and ROS Mediated Apoptotic Activity in Human Skin Melanoma Cells
In recent decades Cold Atmospheric Plasma (CAP) has become increasingly popular in healthcare for managing diseases especially skin cancer. This study aimed to assess the preclinical safety of an indigenously developed dielectric barrier discharge-CAP (DBD) device and its cytotoxic efficacy against melanoma cells while adhering to OECD 402 guidelines for acute dermal toxicity study. The safety evaluation includes ex vivo studies on mouse peritoneal exudates and in vivo acute dermal toxicity tests on Wistar rats.
The ex vivo study of mice peritoneal cells treated for up to 120 seconds showed a survival rate of over 90% up to 90 seconds of CAP treatment for applied voltage 18.6 kV at 20 kHz with no significant difference with control. In the acute dermal toxicity tests CAP exposure for up to 30 seconds caused minimal inflammatory cell infiltration and no significant Dermal Inflammation Scoring (DIS) (<1).
The efficacy study against G361 human melanoma cells showed reduced cell viability by ~50% (MTT assay) upon 30 seconds of CAP treatment for applied voltage 24 kV at 20 kHz through ROS-mediated apoptosis confirmed by a 3-fold increase in intracellular reactive oxygen species levels and nuclear fragmentation (4'6-diamidino-2-phenylindole staining). Annexin V/PI (propium iodide) staining further revealed ~30% apoptosis after 24 hours of incubation. These findings establish the developed DBD-CAP device is safe for rat skin exposure durations of up to 30 seconds and effective in inducing apoptosis in melanoma cells.
This study supports CAP's optimization for clinical applications and its integration with existing therapies for enhanced outcomes. However further study is needed to examine the possible risks associated with using CAP devices in the biomedical field.
Mucosal Melanoma: An Overview of Recent Therapies
Mucosal Melanoma (MM) is an aggressive disease that is distinct from cutaneous melanoma in risk factors prognosis and treatment. Surgical treatment is currently the treatment of choice for localized disease; however the recurrence rate is common. For advanced or metastatic disease immunotherapy with PD-1 inhibitors and anti-CTLA is generally first-line treatment however the overall responses to immunotherapy in MM are often lower and less robust when compared to that observed in cutaneous melanoma. Adoptive-TIL therapy has shown great promise. Other advances particularly through the exploration of novel and combination therapies are a step forward and a hope to improve outcomes in patients with mucosal melanoma. In this review we summarize current treatment options for MM and we updated future clinical trials available for this population of patients.
Dermoscopic Aspects of Cutaneous Melanoma and Non-Melanoma Skin Cancer
Dermoscopy is a very important diagnostic tool in clinical practice. It increases accuracy in skin cancer detection. Melanoma and its major variants have distinct dermoscopic patterns and structures described as well as cutaneous keratynocytic tumors such as basal cell carcinoma and squamous cell carcinomas. Superficial spreading melanoma may show dermoscopic structures varying from atypical network atypical hyperpigmentation atypical globules and dots and atypical streaks to negative network; lentigo maligna lesions demonstrate dermoscopic structures associated with the tumour progression around follicular openings; nodular lesions may be suspected mainly by colors (pink or blue and black) and the recognition of peculiar patterns such as the parallel ridge pattern may facilitate vascular structures and acral lentiginous. The histopathologic subtype of BCC is an important determinant of the dermoscopic pattern of the tumor being the vascular strucutures a significant clue for its diagnosis. Invasive squamous cell carcinoma may also be differentiated from in situ lesions by clinical and dermoscopic aspects such as vascular and hyperkeratotic structures. The aim of this review was to provide a comprehensive overview of the major dermoscopic patterns and structures described for the diagnosis of major melanoma variants and for cutaneous carcinomas. It also gives some insights about sequential digital imaging for patients with multiple melanocytic nevi.
Surgical Excision Margins in Skin Melanomas with Breslow Thickness Greater than 2 mm: A Systematic Review and Meta-Analysis
This systematic review and meta-analysis aimed to evaluate the efficacy of narrow compared to wide surgical excision margins in the treatment of cutaneous malignant melanomas (MM) with Breslow thickness greater than 2 mm. All prior meta-analyses included studies analyzing patients with a variety of Breslow indexes. There is no prior meta-analysis analyzing the survival of the subgroup of MM patients with MMs > 2 mm in Breslow thickness. Hence the aim of the present meta-analysis and systematic review was to examine the survival of the subgroup of MM patients with MMs > 2 mm in Breslow thickness.
We followed the Cochrane Handbook for Systematic Reviews of Interventions and reported our findings in accordance with PRISMA guidelines. We included randomized controlled trials (RCTs) that compared narrow (1-2 cm) versus wide (3-4 cm) surgical excision margins for cutaneous melanomas thicker than 2 mm. Studies on non-cutaneous melanomas observational studies and non-randomized trials were excluded. Ten-year mortality rate and overall survival were the primary outcomes. Our searches were conducted in EMBASE and PUBMED databases.
Three RCTs were included with a total of 2304 randomized patients. This meta-analysis showed no significant difference in 10-year all-cause mortality between narrow (2 cm) and wide (4 cm) margins (risk difference: 3.3% 95% CI: -1.7% to 8.2% p=0.202). Similarly there was no significant difference in overall survival between narrow (1-2 cm) and wide (3-4 cm) margins (hazard ratio: 1.09 95% CI: 0.974-1.214 p=0.3). Heterogeneity was low and non-significant.
This meta-analysis supports the non-inferiority of narrow (1-2 cm) surgical margins compared to wide (3-4 cm) margins for localized cutaneous melanomas with Breslow thickness greater than 2 mm. These findings suggest that narrow margins could be considered in surgical practice although a 1 cm margin may be inadequate based on the results of individual studies. Further RCTs focusing on patients with localized MM thicker than 2 mm and taking into account modern adjuvant therapies and sentinel lymph node biopsies are recommended to refine surgical guidelines.
Non-surgical Synergistic Interventions for the Treatment of Skin Cancer
Skin cancer is broadly classified into two categories i.e. non-melanoma skin cancer (NMSC) and malignant melanoma (MM) with MM having a greater fatality rate than NMSC. A large number of treatment strategies currently exist for these skin cancer types ranging from monotherapies to complex multifaceted synergistic interventions including dual therapies trimodality therapy and multicomponent combinations therapy. These combinatorial cancer treatments have delivered more favorable results when compared with monotherapies and although combination treatments increase the cost of treatment these regimens have lower side effect profiles decreased resistance high efficacy and an improved long-term response. Synergistic combination treatments for skin cancer are often complex wide-ranging and encompass diverse platforms with various mechanisms of action. An understanding of the physiological potential as well the efficacy of such treatments is therefore vital to ensure patients receive the best possible treatment. This review therefore focuses on the current advancements and existing non-surgical combinative drug delivery methods utilized for treating skin cancer. It encompasses the diverse pharmaceutical delivery systems clinical outcomes and oncology strategies employed and aims to highlight the role of non-surgical combination therapies in enhancing patient compliance reducing treatment durations and improving overall survival rates while addressing relapses and metastasis. The promising outlook of the research being conducted in this field has also been provided as well as the barriers to the effective treatment of this complex condition.
Elucidating the Complex Etiology of Schizophrenia: Comprehensive Insights into the Therapeutic Roles of Natural Compounds and Pharmacological Interventions
Schizophrenia (SCZ) remains a captivating mental disorder marked by complex symptomatology. Despite the success of the current therapeutic options for psychosis a definitive cure remains elusive. Hence this review explores mechanisms underlying SCZ pathophysiology examining their potential as novel therapeutic targets. This is a narrative review of literature that has been critically analyzed following retrieval from PubMed PubMed Central and Google Scholar. Nearly 30% of patients of SCZ show no response to first- and second-generation antipsychotic drugs and continue to suffer from cognitive and negative symptoms including medication-induced adverse effects. Apart from the social and environmental factors SCZ has been strongly linked to epigenetic factors and alterations in protein expression. Epigenetic modifications include histone modification and DNA methylation. Epigenetic alterations gained through environmental factors known as molecular scars also influence to some extent the brain functions throughout the life span of a human being. Epigenetic mechanisms are now recognized as significant contributors to the development and progression of SCZ. Epigenetics is critical in SCZ etiology through DNA methylation and histone modification. Herbal medicines offer promise by targeting genetic and epigenetic pathways albeit with safety concerns. These approaches offer potential as supplementary therapies alongside conventional treatments or alternative preventive measures. By thoroughly investigating these methods we may uncover new possibilities in SCZ care ultimately paving the path for more effective and holistic therapeutic approaches.
An in silico Approach for Identification of Novel Natural Selective ALR2 Inhibitors from Cynomorium songaricum for Treating Diabetic Complications
Aldose reductase-2 (ALR2) is a key enzyme in the polyol pathway whose overexpression is implicated in several diabetic complications including neuropathy nephropathy retinopathy and atherosclerotic plaque formation. Under hyperglycemic conditions the intracellular accumulation of sorbitol and the depletion of NADPH lead to osmotic imbalance and oxidative stress driven by the formation of reactive oxygen species and advanced glycation end products. Although various ALR2 inhibitors have been developed their clinical application has been hampered by nonselective inhibition of both ALR2 and the homologous enzyme ALR1.
In this study we employed a comprehensive in silico approach to evaluate the inhibitory potential of natural compounds from Cynomorium songaricum against ALR2. Our workflow integrated with ADMET molecular docking with scoring function and glide XP molecular dynamics (MD) simulations PCA FEL and MM/GBSA. Through this analysis four natural compounds of C. songaricum (Compound Name: p-Coumaric acid Vanillic acid 4-Oxoniobenzoate and Phloroglucinol) displayed significant bonds formation including hydrogen and hydrophobic bonds with the target protein.
These bonds exhibited the ligand stability. Further the MD simulation analysis followed by post-simulation analysis verified the dynamic stability of these four natural compounds and compared them with the native ligand of the target protein. These natural compounds exhibit particularly stable binding within the ALR2 selectivity pocket demonstrating an inhibitory effect over ALR1 when compared with the reference inhibitor Epalrestat.
These promising in silico findings suggest that CID: 8468 and CID: 135 merit further evaluation through in vitro in vivo and clinical studies as potential selective inhibitors for the treatment of diabetic complications.
Bear Bile Powder Alleviates Corticosterone-induced Depression-like Behavior in Female Mice by Protecting Hippocampal Neurons via the BDNF/TrkB/ CREB Pathway
Bear bile powder (BBP) has been traditionally used in Chinese medicine for calming the liver pacifying the mind and relieving convulsions as recorded in Ben Jing Feng Yuan and Yu Qiu Yao Jie. Although the antidepressant effects of BBP have been previously reported the underlying neurological mechanisms have yet to be fully elucidated. This study aimed to investigate the antidepressant effects of BBP on corticosterone (CORT)-induced depression-like behaviors in female mice and to explore the involvement of the BDNF/TrkB/CREB signaling pathway.
Female mice received subcutaneous CORT injections to induce depression-like behaviors followed by oral administration of BBP at doses of 50 100 and 200 mg/kg. Behavioral assessments biochemical analyses UPLC-MS/MS immunohistochemistry and Western blotting were conducted to evaluate antidepressant effects. Additionally a CORT-induced HT22 cell injury model was established to assess the neuroprotective mechanisms of BBP with or without the TrkB antagonist K252a focusing on the BDNF/TrkB/CREB pathway.
BBP significantly alleviated depression-like behaviors in CORT-treated female mice. It restored neurotransmitter levels reduced neuronal necrosis in the hippocampal CA3 region increased DCX-positive cells in the dentate gyrus and activated hippocampal BDNF/TrkB/CREB signaling. In vitro BBP attenuated CORT-induced apoptosis and promoted proliferation in HT22 cells. Applying K252a confirmed that BBP’s neuroprotective and antidepressant effects were mediated via the BDNF/TrkB/CREB pathway.
These findings suggest that BBP exerts notable antidepressant and neuroprotective effects in female depression models by modulating neurotransmitters and enhancing neurogenesis through the BDNF/TrkB/CREB pathway. Using both in vivo and in vitro models strengthens the evidence for BBP’s mechanism of action. However further studies involving additional brain regions and upstream regulatory mechanisms are warranted.
BBP effectively alleviates CORT-induced depressive-like behaviors in female mice by restoring neurotransmitter balance protecting hippocampal neurons and promoting neurogenesis via the BDNF/TrkB/CREB pathway. These results provide a theoretical basis for the potential application of BBP in managing female depression.
Electrospun Food Nanofibers for Hormonal Delivery: New Strategy in Sustainable Pharmaceutical Delivery System
Electrospinning is an innovative process that produces polymeric fibres for a variety of purposes including controlled hormone administration. These fibres are made from biopolymers like chitosan cellulose alginate and starch and have attracted interest for their capacity to encapsulate hormones and release them in a regulated way therefore Increasing bioavailability and stability. The article investigates the utilization of smart electrospun fibers for hormone delivery alongside a focus on their potential to improve therapeutic results. Electrospun fibres can encapsulate hormones such as insulin melatonin and contraceptives for regulated and prolonged release. This method addresses difficulties in traditional hormone delivery like frequent insulin injections or hormone instability in biological circumstances. Techniques like coaxial electrospinning enable the development of core-shell structures which further optimize release profiles. The use of these fibres for diabetic management wound healing and long-term contraception represents substantial advances in patient care. The flexibility of fibres also allows for precise regulation of drug release kinetics which improves the efficacy of hormone therapy while reducing adverse effects. Smart electrospun food fibres have enormous promise for the future of hormone administration providing longer-lasting more focused and effective therapies. Their flexibility along with ongoing advances in electrospinning processes positions them as a viable tool in contemporary medicine.
Expanding the Potential of Gene Therapy for Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene leading to progressive muscle degeneration loss of ambulation cardiomyopathy and early mortality. While advances in multidisciplinary care and pharmacological interventions including corticosteroids and exon-skipping therapies have improved patient outcomes current treatments primarily provide symptomatic relief without addressing the underlying genetic defect. Gene therapy has emerged as a promising approach to modify disease progression particularly through the use of adeno-associated virus (AAV)-mediated delivery of micro-dystrophin constructs. These truncated genes retain essential functional domains enabling the restoration of dystrophin expression within the packaging limits of AAV vectors. Early-phase clinical trials have demonstrated encouraging safety profiles and transgene expression; however challenges such as immune responses variability in functional improvement and long-term durability remain. Recent innovations including optimized AAV capsids immunomodulatory strategies and genome editing technologies like CRISPR-Cas9 are actively being explored to overcome these barriers. Additionally scalable vector manufacturing and the integration of real-world data are essential for broader clinical translation. This review synthesizes current advancements clinical milestones and future directions in gene therapy for DMD emphasizing the need for precise dosing long-term efficacy and equitable access to fully realize the therapeutic potential of these evolving strategies.