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10 pages, 462 KiB  
Article
Mutation Rates and Fitness Genes in Staphylococcus aureus Treated with the Medicinal Plant Synadenium glaucescens
by Zaituni Msengwa, Martin Saxtorph Bojer, Frank Rwegoshora, James Mwesongo, Magesa Mafuru, Faith Philemon Mabiki, Beda John Mwang’onde, Madundo Mkumbukwa Mtambo, Lughano Jeremy Kusiluka, Henrik Christensen, Robinson Hammerthon Mdegela and John Elmerdahl Olsen
Appl. Sci. 2025, 15(15), 8753; https://doi.org/10.3390/app15158753 (registering DOI) - 7 Aug 2025
Abstract
Extracts, fractions and the pure compound epifriedelanol of the medicinal plant Synadenium glaucescens have antibacterial properties. Herbal products are generally considered less prone to resistance development than conventional antimicrobials, as they contain multiple compounds, which makes bacteria less likely to develop resistance. However, [...] Read more.
Extracts, fractions and the pure compound epifriedelanol of the medicinal plant Synadenium glaucescens have antibacterial properties. Herbal products are generally considered less prone to resistance development than conventional antimicrobials, as they contain multiple compounds, which makes bacteria less likely to develop resistance. However, data supporting this notion are lacking. This study evaluated the development of resistance in Staphylococcus aureus subjected to extract, fractions and epifriedelanol of S. glaucescens. It also identified S. aureus fitness genes contributing to intrinsic resistance to extract of S. glaucescens. Fluctuation and gradient concentration assays were used to determine mutation rates and growth adaptation, respectively, which were lower following exposure to growth in crude extract than the pure compound epifriedelanol. By subjecting 1920 single gene mutants from the Nebraska Transposon Mutant Library to growth in the presence of extract of S. glaucescens, 12 genes were identified as important for natural resistance in S. aureus JE2; however, only mutation in the hemB gene decreased the minimum inhibitory concentration by greater than 4-fold (64-fold). In conclusion, purifying active antimicrobial compounds from S. glaucescens and using them as antibacterial substances as an alternative to crude extract increased the risk of resistance development. Further, the gene hemB appears to have a significant role in the natural resistance to the extracts obtained from S. glaucescens in this study. Full article
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42 pages, 1287 KiB  
Review
Antimicrobial Potential of Bee-Derived Products: Insights into Honey, Propolis and Bee Venom
by Agnieszka Grinn-Gofroń, Maciej Kołodziejczak, Rafał Hrynkiewicz, Filip Lewandowski, Dominika Bębnowska, Cezary Adamski and Paulina Niedźwiedzka-Rystwej
Pathogens 2025, 14(8), 780; https://doi.org/10.3390/pathogens14080780 - 6 Aug 2025
Abstract
Bee products, in particular honey, propolis and bee venom, are of growing scientific interest due to their broad spectrum of antimicrobial activity. In the face of increasing antibiotic resistance and the limitations of conventional therapies, natural bee-derived substances offer a promising alternative or [...] Read more.
Bee products, in particular honey, propolis and bee venom, are of growing scientific interest due to their broad spectrum of antimicrobial activity. In the face of increasing antibiotic resistance and the limitations of conventional therapies, natural bee-derived substances offer a promising alternative or support for the treatment of infections. This paper summarizes the current state of knowledge on the chemical composition, biological properties and antimicrobial activity of key bee products. The main mechanisms of action of honey, propolis and bee venom are presented, and their potential applications in the prevention and treatment of bacterial, viral and fungal infections are discussed. Data on their synergy with conventional drugs and prospects for use in medicine and pharmacology are also included. The available findings suggest that, with appropriate standardization and further preclinical and clinical analyses, bee products could become an effective support for the treatment of infections, especially those caused by pathogens resistant to standard therapies. Full article
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13 pages, 286 KiB  
Review
Drug Repurposing and Artificial Intelligence in Multiple Sclerosis: Emerging Strategies for Precision Therapy
by Pedro Henrique Villar-Delfino, Paulo Pereira Christo and Caroline Maria Oliveira Volpe
Sclerosis 2025, 3(3), 28; https://doi.org/10.3390/sclerosis3030028 - 6 Aug 2025
Abstract
Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional [...] Read more.
Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article
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41 pages, 3389 KiB  
Review
Fully Green Particles Loaded with Essential Oils as Phytobiotics: A Review on Preparation and Application in Animal Feed
by Maria Sokol, Ivan Gulayev, Margarita Chirkina, Maksim Klimenko, Olga Kamaeva, Nikita Yabbarov, Mariia Mollaeva and Elena Nikolskaya
Antibiotics 2025, 14(8), 803; https://doi.org/10.3390/antibiotics14080803 - 6 Aug 2025
Abstract
The modern livestock industry incorporates widely used antibiotic growth promoters into animal feed at sub-therapeutic levels to enhance growth performance and feed efficiency. However, this practice contributes to the emergence of antibiotic-resistant pathogens in livestock, which may be transmitted to humans through the [...] Read more.
The modern livestock industry incorporates widely used antibiotic growth promoters into animal feed at sub-therapeutic levels to enhance growth performance and feed efficiency. However, this practice contributes to the emergence of antibiotic-resistant pathogens in livestock, which may be transmitted to humans through the food chain, thereby diminishing the efficacy of antibiotics in treating bacterial infections. Current research explores the potential of essential oils from derived medicinal plants as alternative phytobiotics. This review examines modern encapsulation strategies that incorporate essential oils into natural-origin matrices to improve their stability and control their release both in vitro and in vivo. We discuss a range of encapsulation approaches utilizing polysaccharides, gums, proteins, and lipid-based carriers. This review highlights the increasing demand for antibiotic alternatives in animal nutrition driven by regulatory restrictions, and the potential benefits of essential oils in enhancing feed palatability and stabilizing the intestinal microbiome in monogastric animals and ruminants. Additionally, we address the economic viability and encapsulation efficiency of different matrix formulations. Full article
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33 pages, 5098 KiB  
Review
Medicinal Plants for Skin Disorders: Phytochemistry and Pharmacological Insights
by Nazerke Bolatkyzy, Daniil Shepilov, Rakhymzhan Turmanov, Dmitriy Berillo, Tursunay Vassilina, Nailya Ibragimova, Gulzat Berganayeva and Moldyr Dyusebaeva
Molecules 2025, 30(15), 3281; https://doi.org/10.3390/molecules30153281 - 6 Aug 2025
Abstract
Skin disorders are common and often chronic conditions with significant therapeutic challenges. Limitations of conventional treatments, such as adverse effects and antimicrobial resistance, have increased interest in plant-based alternatives. This article presents the phytochemical composition and pharmacological potential of several medicinal plants traditionally [...] Read more.
Skin disorders are common and often chronic conditions with significant therapeutic challenges. Limitations of conventional treatments, such as adverse effects and antimicrobial resistance, have increased interest in plant-based alternatives. This article presents the phytochemical composition and pharmacological potential of several medicinal plants traditionally used in the treatment of skin diseases, including Rubus vulgaris, Plantago major, Artemisia terrae-albae, and Eryngium planum. Based on an analysis of scientific literature, the presence of bioactive compounds—including flavonoids, anthocyanins, phenolic acids, tannins, and sesquiterpenes—is summarized, along with their antioxidant, anti-inflammatory, and antimicrobial effects. Emphasis is placed on the correlation between traditional ethnomedicinal applications and pharmacological mechanisms. The findings support the potential of these species as sources for dermatological phytotherapeutics. Further research is needed to standardize active constituents, assess safety, and conduct clinical validation. Full article
(This article belongs to the Special Issue Bioactive Molecules in Medicinal Plants)
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22 pages, 2630 KiB  
Review
Transfection Technologies for Next-Generation Therapies
by Dinesh Simkhada, Su Hui Catherine Teo, Nandu Deorkar and Mohan C. Vemuri
J. Clin. Med. 2025, 14(15), 5515; https://doi.org/10.3390/jcm14155515 - 5 Aug 2025
Abstract
Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency [...] Read more.
Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency and therapeutic outcomes. Methods: This review synthesizes the current literature and recent advancements in non-viral transfection technologies. It focuses on the mechanisms, advantages, and limitations of various delivery systems, including lipid nanoparticles, biodegradable polymers, electroporation, peptide-based carriers, and microfluidic platforms. Comparative analysis was conducted to evaluate their performance in terms of transfection efficiency, cellular uptake, biocompatibility, and potential for clinical translation. Several academic search engines and online resources were utilized for data collection, including Science Direct, PubMed, Google Scholar Scopus, the National Cancer Institute’s online portal, and other reputable online databases. Results: Non-viral systems demonstrated superior performance in delivering mRNA, siRNA, and antisense oligonucleotides, particularly in clinical applications. Biodegradable polymers and peptide-based systems showed promise in enhancing biocompatibility and targeted delivery. Electroporation and microfluidic systems offered precise control over transfection parameters, improving reproducibility and scalability. Collectively, these innovations address key challenges in gene delivery, such as stability, immune response, and cell-type specificity. Conclusions: The continuous evolution of transfection technologies is pivotal for advancing gene and cell-based therapies. Non-viral delivery systems, particularly LNPs and emerging platforms like microfluidics and biodegradable polymers, offer safer and more adaptable alternatives to viral vectors. These innovations are critical for optimizing therapeutic efficacy and enabling personalized medicine, immunotherapy, and regenerative treatments. Future research should focus on integrating these technologies to develop next-generation transfection platforms with enhanced precision and clinical applicability. Full article
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18 pages, 2432 KiB  
Article
Alkali Lignin-Based Biopolymer Formulations for Electro-Assisted Drug Delivery of Natural Antioxidants in Breast Cancer Cells—A Preliminary Study
by Severina Semkova, Radina Deneva, Georgi Antov, Donika Ivanova and Biliana Nikolova
Int. J. Mol. Sci. 2025, 26(15), 7481; https://doi.org/10.3390/ijms26157481 - 2 Aug 2025
Viewed by 271
Abstract
Recently, a number of natural biologically active substances have been proven to be attractive alternatives to conventional anticancer medicine or as adjuvants in contemporary combination therapies. Although lignin-based materials were previously accepted as waste materials with limited usefulness, recent studies increasingly report the [...] Read more.
Recently, a number of natural biologically active substances have been proven to be attractive alternatives to conventional anticancer medicine or as adjuvants in contemporary combination therapies. Although lignin-based materials were previously accepted as waste materials with limited usefulness, recent studies increasingly report the possibility of their use for novel applications in various industrial branches, including biomedicine. In this regard, the safety, efficiency, advantages and limitations of lignin compounds for in vitro/in vivo applications remain poorly studied and described. This study was carried out to investigate the possibility of using newly synthesized, alkali lignin-based micro-/nano-biopolymer formulations (Lignin@Formulations/L@F) as carriers for substances with antioxidant and/or anticancer effectiveness. Moreover, we tried to assess the opportunity for using an electro-assisted approach for achieving improved intracellular internalization. An investigation was conducted on an in vitro panel of breast cell lines, namely two breast cancer lines with different metastatic potentials and one non-tumorigenic line as a control. The characterization of all tested formulations was performed via DLS (dynamic light scattering) analysis. We developed an improved separation procedure via size/charge unification for all types of Lignin@Formulations. Moreover, in vitro applications were investigated. The results demonstrate that compared to healthy breast cells, both tested cancer lines exhibited slight sensitivity after treatment with different formulations (empty or loaded with antioxidant substances). This effect was also enhanced after applying electric pulses. L@F loaded with Quercetin was also explored only on the highly metastatic cancer cell line as a model for the breast cancer type most aggressive and non-responsive to traditional treatments. All obtained data suggest that the tested formulations have potential as carriers for the electro-assisted delivery of natural antioxidants such as Quercetin. Full article
(This article belongs to the Special Issue Natural Products in Cancer Prevention and Treatment)
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30 pages, 955 KiB  
Review
Breaking Barriers with Sound: The Implementation of Histotripsy in Cancer
by Ashutosh P. Raman, Parker L. Kotlarz, Alexis E. Giff, Katherine A. Goundry, Paul Laeseke, Erica M. Knavel Koepsel, Mosa Alhamami and Dania Daye
Cancers 2025, 17(15), 2548; https://doi.org/10.3390/cancers17152548 - 1 Aug 2025
Viewed by 376
Abstract
Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and [...] Read more.
Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and precisely destroy targeted tissue in a predefined volume while sparing critical structures like bile ducts, ureters, and blood vessels. Such precision is of value when treating tumors near vital structures. The FDA has cleared histotripsy for the treatment of all liver tumors. Major medical centers are currently spearheading clinical trials, and some institutions have already integrated the technology into patient care. Histotripsy is now being studied for a host of other cancers, including primary kidney and pancreatic tumors. Preclinical murine and porcine models have already revealed promising outcomes. One of histotripsy’s primary advantages is its non-thermal mechanical actuation. This feature allows it to circumvent the limitations of heat-based techniques, including the heat sink effect and unpredictable treatment margins near sensitive tissues. In addition to its non-invasive ablative capacities, it is being preliminarily explored for its potential to induce immunomodulation and promote abscopal inhibition of distant, untreated tumors through CD8+ T cell responses. Thus, it may provide a multilayered therapeutic effect in the treatment of cancer. Histotripsy has the potential to improve precision and outcomes across a multitude of specialties, from oncology to cardiovascular medicine. Continued trials are crucial to further expand its applications and validate its long-term efficacy. Due to the speed of recent developments, the goal of this review is to provide a comprehensive and updated overview of histotripsy. It will explore its physics-based mechanisms, differentiating it from similar technologies, discuss its clinical applications, and examine its advantages, limitations, and future. Full article
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18 pages, 1518 KiB  
Systematic Review
Effectiveness of Psychological Therapy for Treatment-Resistant Depression in Adults: A Systematic Review and Meta-Analysis
by Sabrina Giguère, Alexandra Fortier, Julie Azrak, Charles-Édouard Giguère, Stéphane Potvin and Alexandre Dumais
J. Pers. Med. 2025, 15(8), 338; https://doi.org/10.3390/jpm15080338 - 1 Aug 2025
Viewed by 353
Abstract
Background: Depression that is resistant to two or more adequate treatment trials—treatment-resistant depression (TRD)—is a prevalent clinical challenge. Although psychotherapies have been recommended by clinical guidelines as an alternative or adjunctive treatment strategy, the effectiveness of psychotherapy in individuals with TRD has not [...] Read more.
Background: Depression that is resistant to two or more adequate treatment trials—treatment-resistant depression (TRD)—is a prevalent clinical challenge. Although psychotherapies have been recommended by clinical guidelines as an alternative or adjunctive treatment strategy, the effectiveness of psychotherapy in individuals with TRD has not yet been evaluated through meta-analytic methods, primarily due to a limited number of trials. This highlights the necessity of personalized research targeting this specific population. This systematic review and meta-analysis aimed to summarize the evidence on psychotherapy in treating TRD. Methods: A systematic search was conducted following the Guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles were included if they quantitatively examined the efficacy of psychotherapy on depression symptoms in individuals diagnosed with depression who had not responded to at least two prior treatments (i.e., pharmacotherapy and/or psychotherapy). Results: A total of 12 studies were included. The quality of evidence was evaluated as being globally moderate. When pooling all psychotherapies, a small-to-moderate, but significant, effect on depressive symptoms was observed compared to the control group (SMD = −0.49, CI = −0.63; −0.34). The observed effect remained unchanged after removing the outlier (SMD = −0.47, CI = −0.62; −0.32). When examining depressive symptoms by type of psychotherapy, Mindfulness-Based Cognitive Therapy (SMD = −0.51, CI = −0.76; −0.25), Cognitive Behavioral Therapy (SMD = −0.53, CI = −0.92; −0.14), and Cognitive Therapy (SMD = −0.51, CI = −1.01; −0.01) showed a moderately significant effect on depressive symptoms compared to the control group. Conclusions: Although this potentially represents the first meta-analysis in this area, the number of studies specifically addressing this complex population remains limited, and the existing literature is still in its early stages. Research focusing on TRD is notably sparse compared to the broader body of work on depression without treatment resistance. Consequently, it was not possible to conduct meta-analyses by type of psychotherapy across all treatment modalities and by type of control group. Due to several study limitations, there is currently limited evidence available about the effectiveness of psychotherapy for TRD, and further trials are needed. Beyond the treatments usually offered for depression, it is possible that TRD requires a personalized medicine approach. Full article
(This article belongs to the Special Issue Personalized Medicine in Psychiatry: Challenges and Opportunities)
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20 pages, 1899 KiB  
Case Report
Ruptured Posterior Inferior Cerebellar Artery Aneurysms: Integrating Microsurgical Expertise, Endovascular Challenges, and AI-Driven Risk Assessment
by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc
J. Clin. Med. 2025, 14(15), 5374; https://doi.org/10.3390/jcm14155374 - 30 Jul 2025
Viewed by 457
Abstract
Background/Objectives: Posterior inferior cerebellar artery (PICA) aneurysms are one of the most difficult cerebrovascular lesions to treat and account for 0.5–3% of all intracranial aneurysms. They have deep anatomical locations, broad-neck configurations, high perforator density, and a close association with the brainstem, which [...] Read more.
Background/Objectives: Posterior inferior cerebellar artery (PICA) aneurysms are one of the most difficult cerebrovascular lesions to treat and account for 0.5–3% of all intracranial aneurysms. They have deep anatomical locations, broad-neck configurations, high perforator density, and a close association with the brainstem, which creates considerable technical challenges for either microsurgical or endovascular treatment. Despite its acceptance as the standard of care for most posterior circulation aneurysms, PICA aneurysms are often associated with flow diversion using a coil or flow diversion due to incomplete occlusions, parent vessel compromise and high rate of recurrence. This case aims to describe the utility of microsurgical clipping as a durable and definitive option demonstrating the value of tailored surgical planning, preservation of anatomy and ancillary technologies for protecting a genuine outcome in ruptured PICA aneurysms. Methods: A 66-year-old male was evaluated for an acute subarachnoid hemorrhage from a ruptured and broad-necked fusiform left PICA aneurysm at the vertebra–PICA junction. Endovascular therapy was not an option due to morphology and the center of the recurrence; therefore, a microsurgical approach was essential. A far-lateral craniotomy with a partial C1 laminectomy was carried out for proximal vascular control, with careful dissection of the perforating arteries and precise clip application for the complete exclusion of the aneurysm whilst preserving distal PICA flow. Results: Post-operative imaging demonstrated the complete obliteration of the aneurysm with unchanged cerebrovascular flow dynamics. The patient had progressive neurological recovery with no new cranial nerve deficits or ischemic complications. Long-term follow-up demonstrated stable aneurysm exclusion and full functional independence emphasizing the sustainability of microsurgical intervention in challenging PICA aneurysms. Conclusions: This case intends to highlight the current and evolving role of microsurgical practice for treating posterior circulation aneurysms, particularly at a time when endovascular alternatives are limited by anatomy and hemodynamics. Advances in artificial intelligence cerebral aneurysm rupture prediction, high-resolution vessel wall imaging, robotic-assisted microsurgery and new generation flow-modifying implants have the potential to revolutionize treatment paradigms by embedding precision medicine principles into aneurysm management. While the discipline of cerebrovascular surgery is expanding, it can be combined together with microsurgery, endovascular technologies and computational knowledge to ensure individualized, durable, and minimally invasive treatment options for high-risk PICA aneurysms. Full article
(This article belongs to the Special Issue Neurovascular Diseases: Clinical Advances and Challenges)
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50 pages, 937 KiB  
Review
Precision Neuro-Oncology in Glioblastoma: AI-Guided CRISPR Editing and Real-Time Multi-Omics for Genomic Brain Surgery
by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc
Int. J. Mol. Sci. 2025, 26(15), 7364; https://doi.org/10.3390/ijms26157364 - 30 Jul 2025
Viewed by 413
Abstract
Precision neurosurgery is rapidly evolving as a medical specialty by merging genomic medicine, multi-omics technologies, and artificial intelligence (AI) technology, while at the same time, society is shifting away from the traditional, anatomic model of care to consider a more precise, molecular model [...] Read more.
Precision neurosurgery is rapidly evolving as a medical specialty by merging genomic medicine, multi-omics technologies, and artificial intelligence (AI) technology, while at the same time, society is shifting away from the traditional, anatomic model of care to consider a more precise, molecular model of care. The general purpose of this review is to contemporaneously reflect on how these advances will impact neurosurgical care by providing us with more precise diagnostic and treatment pathways. We hope to provide a relevant review of the recent advances in genomics and multi-omics in the context of clinical practice and highlight their transformational opportunities in the existing models of care, where improved molecular insights can support improvements in clinical care. More specifically, we will highlight how genomic profiling, CRISPR-Cas9, and multi-omics platforms (genomics, transcriptomics, proteomics, and metabolomics) are increasing our understanding of central nervous system (CNS) disorders. Achievements obtained with transformational technologies such as single-cell RNA sequencing and intraoperative mass spectrometry are exemplary of the molecular diagnostic possibilities in real-time molecular diagnostics to enable a more directed approach in surgical options. We will also explore how identifying specific biomarkers (e.g., IDH mutations and MGMT promoter methylation) became a tipping point in the care of glioblastoma and allowed for the establishment of a new taxonomy of tumors that became applicable for surgeons, where a change in practice enjoined a different surgical resection approach and subsequently stratified the adjuvant therapies undertaken after surgery. Furthermore, we reflect on how the novel genomic characterization of mutations like DEPDC5 and SCN1A transformed the pre-surgery selection of surgical candidates for refractory epilepsy when conventional imaging did not define an epileptogenic zone, thus reducing resective surgery occurring in clinical practice. While we are atop the crest of an exciting wave of advances, we recognize that we also must be diligent about the challenges we must navigate to implement genomic medicine in neurosurgery—including ethical and technical challenges that could arise when genomic mutation-based therapies require the concurrent application of multi-omics data collection to be realized in practice for the benefit of patients, as well as the constraints from the blood–brain barrier. The primary challenges also relate to the possible gene privacy implications around genomic medicine and equitable access to technology-based alternative practice disrupting interventions. We hope the contribution from this review will not just be situational consolidation and integration of knowledge but also a stimulus for new lines of research and clinical practice. We also hope to stimulate mindful discussions about future possibilities for conscientious and sustainable progress in our evolution toward a genomic model of precision neurosurgery. In the spirit of providing a critical perspective, we hope that we are also adding to the larger opportunity to embed molecular precision into neuroscience care, striving to promote better practice and better outcomes for patients in a global sense. Full article
(This article belongs to the Special Issue Molecular Insights into Glioblastoma Pathogenesis and Therapeutics)
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33 pages, 2605 KiB  
Article
Phytochemical Profile, Vasodilatory and Biphasic Effects on Intestinal Motility, and Toxicological Evaluation of the Methanol and Dichloromethane Extracts from the Aerial Parts of Ipomoea purpurea Used in Traditional Mexican Medicine
by Valeria Sánchez-Hernández, Francisco J. Luna-Vázquez, María Antonieta Carbajo-Mata, César Ibarra-Alvarado, Alejandra Rojas-Molina, Beatriz Maruri-Aguilar, Pedro A. Vázquez-Landaverde and Isela Rojas-Molina
Pharmaceuticals 2025, 18(8), 1134; https://doi.org/10.3390/ph18081134 - 30 Jul 2025
Viewed by 392
Abstract
Background: Cardiovascular diseases, particularly hypertension, and gastrointestinal disorders represent major public health concerns in Mexico. Although a range of pharmacological treatments exists, their use is associated with adverse effects, highlighting the need for safer therapeutic alternatives. Species of the Ipomoea genus are widely [...] Read more.
Background: Cardiovascular diseases, particularly hypertension, and gastrointestinal disorders represent major public health concerns in Mexico. Although a range of pharmacological treatments exists, their use is associated with adverse effects, highlighting the need for safer therapeutic alternatives. Species of the Ipomoea genus are widely employed in Mexican traditional medicine (MTM) for their purgative, anti-inflammatory, analgesic, and sedative properties. Particularly, Ipomoea purpurea is traditionally used as a diuretic and purgative; its leaves and stems are applied topically for their anti-inflammatory and soothing effects. This study aimed to determine their phytochemical composition and to evaluate the associated vasodilatory activity, modulatory effects on intestinal smooth-muscle motility, and toxicological effects of the methanolic (ME-Ip) and dichloromethane (DE-Ip) extracts obtained from the aerial parts of I. purpurea. Methods: The phytochemical composition of the ME-Ip and DE-Ip extracts of I. purpurea was assessed using UPLC-QTOF-MS and GC-MS, respectively. For both extracts, the vasodilatory activity and effects on intestinal smooth muscle were investigated using ex vivo models incorporating isolated rat aorta and ileum, respectively, whereas acute toxicity was evaluated in vivo. Results: Phytochemical analysis revealed, for the first time, the presence of two glycosylated flavonoids within the Ipomoea genus; likewise, constituents with potential anti-inflammatory activity were detected. The identified compounds in I. purpurea extracts may contribute to the vasodilatory, biphasic, and purgative effects observed in this species. The EC50 values for the vasodilatory effects of the methanolic (ME-Ip) and dichloromethane (DE-Ip) extracts were 0.80 and 0.72 mg/mL, respectively. In the initial phase of the experiments on isolated ileal tissues, both extracts induced a spasmodic (contractile) effect on basal motility, with ME-Ip exhibiting higher potency (EC50 = 27.11 μg/mL) compared to DE-Ip (EC50 = 1765 μg/mL). In contrast, during the final phase of the experiments, both extracts demonstrated a spasmolytic effect, with EC50 values of 0.43 mg/mL for ME-Ip and 0.34 mg/mL for DE-Ip. In addition, both extracts exhibited low levels of acute toxicity. Conclusions: The phytochemical profile and the vasodilatory and biphasic effects of the I. purpurea extracts explain, in part, the use of I. purpurea in MTM. The absence of acute toxic effects constitutes a preliminary step in the toxicological safety assessment of I. purpurea extracts and demonstrates their potential for the development of phytopharmaceutic agents as adjuvants for the treatment of cardiovascular and gastrointestinal disorders. Full article
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17 pages, 2131 KiB  
Article
Investigating Neuroprotective Effects of Berberine on Mitochondrial Dysfunction and Autophagy Impairment in Parkinson’s Disease
by Hae-Rim Cha, Jin-Seok Kim, Jin-Hyeob Ryu and Hyun-Jeong Cho
Int. J. Mol. Sci. 2025, 26(15), 7342; https://doi.org/10.3390/ijms26157342 - 29 Jul 2025
Viewed by 717
Abstract
Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. [...] Read more.
Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. In this study, we investigated the therapeutic potential and underlying mechanisms of berberine in both cellular and animal models of PD. In vitro, SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA) exhibited decreased viability and increased oxidative stress, both of which were significantly alleviated by berberine treatment based on cell viability assays and DCFH-DA staining. Western blot analysis revealed that berberine modulated the AMPK–PGC-1α–SIRT1 signaling pathway and restored the expression of autophagy-related proteins LC3B and P62, suggesting that berberine could improve mitochondrial function and autophagy balance. In vivo studies using a 6-OHDA-induced PD mouse model further confirmed these effects, showing that berberine could improve motor function and lead to molecular changes consistent with in vitro studies. Additionally, safety evaluations indicated no significant hepatotoxicity based on AST and ALT levels. Body weight also remained stable throughout treatment. Collectively, our findings suggest that berberine can not only alleviate PD-related symptoms but also target key pathological mechanisms, supporting its potential as a therapeutic candidate for PD and other neurodegenerative diseases. Full article
(This article belongs to the Section Molecular Neurobiology)
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26 pages, 1171 KiB  
Review
Current Context of Cannabis sativa Cultivation and Parameters Influencing Its Development
by Andreia Saragoça, Ana Cláudia Silva, Carla M. R. Varanda, Patrick Materatski, Alfonso Ortega, Ana Isabel Cordeiro and José Telo da Gama
Agriculture 2025, 15(15), 1635; https://doi.org/10.3390/agriculture15151635 - 29 Jul 2025
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Abstract
Cannabis sativa L. is a versatile plant with significant medicinal, industrial, and recreational applications. Its therapeutic potential is attributed to cannabinoids like THC and CBD, whose production is influenced by environmental factors, such as radiation, temperature, and humidity. Radiation, for instance, is essential [...] Read more.
Cannabis sativa L. is a versatile plant with significant medicinal, industrial, and recreational applications. Its therapeutic potential is attributed to cannabinoids like THC and CBD, whose production is influenced by environmental factors, such as radiation, temperature, and humidity. Radiation, for instance, is essential for photosynthetic processes, acting as both a primary energy source and a regulator of plant growth and development. This review covers key factors affecting C. sativa cultivation, including photoperiod, light spectrum, cultivation methods, environmental controls, and plant growth regulators. It highlights how these elements influence flowering, biomass, and cannabinoid production across different growing systems, offering insights for optimizing both medicinal and industrial cannabis cultivation. Studies indicate that photoperiod sensitivity varies among cultivars, with some achieving optimal flowering and cannabinoid production under extended light periods rather than the traditional 12/12 h cycle. Light spectrum adjustments, especially red, far-red, and blue wavelengths, significantly impact photosynthesis, plant morphology, and secondary metabolite accumulation. Advances in LED technology allow precise spectral control, enhancing energy efficiency and cannabinoid profiles compared to conventional lighting. The photoperiod plays a vital role in the cultivation of C. sativa spp., directly impacting the plant’s developmental cycle, biomass production, and the concentration of cannabinoids and terpenes. The response to photoperiod varies among different cannabis cultivars, as demonstrated in studies comparing cultivars of diverse genetic origins. On the other hand, indoor or in vitro cultivation may serve as an excellent alternative for plant breeding programs in C. sativa, given the substantial inter-cultivar variability that hinders the fixation of desirable traits. Full article
(This article belongs to the Section Ecosystem, Environment and Climate Change in Agriculture)
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Review
Drug Repurposing of New Treatments for Neuroendocrine Tumors
by Stefania Bellino, Daniela Lucente and Anna La Salvia
Cancers 2025, 17(15), 2488; https://doi.org/10.3390/cancers17152488 - 28 Jul 2025
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Abstract
Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for [...] Read more.
Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metastatic. In this context, drug repurposing has emerged as a promising strategy to improve treatment options due to the limited number of effective treatments and the heterogeneity of the disease. Indeed, a large number of non-oncology drugs have the potential to address more than one target that could be therapeutic for cancer patients. Although many repurposed drugs are used off-label, efficacy for the new use must be demonstrated in clinical trials. Within regulatory frameworks, both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have procedures to reduce the need for extensive new studies and to expedite the review of drugs for serious conditions when preliminary evidence indicates substantial clinical improvement over available therapy. In spite of several advantages, including reduced development time, lower costs, known safety profiles, and faster regulatory approval, difficulty in obtaining new patents for old drugs with limited protection for intellectual property may reduce commercial returns and disincentivize investments. This review aims to provide comprehensive information on some marketed drugs currently under investigation to be repurposed or used in clinical practice for NETs and to discuss the major clinical challenges. Although drug repurposing is a useful strategy for early access to medicines, the monitoring of the clinical benefit of oncologic drugs during the post-marketing authorization is crucial to support the safety and effectiveness of treatments. Full article
(This article belongs to the Special Issue Advances in Drug Repurposing to Overcome Cancers)
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