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Search Results (44)

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Keywords = anti-aging and anti-tumor therapeutic agents

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19 pages, 1191 KiB  
Review
Targeting Senescence: A Review of Senolytics and Senomorphics in Anti-Aging Interventions
by Timur Saliev and Prim B. Singh
Biomolecules 2025, 15(6), 860; https://doi.org/10.3390/biom15060860 - 13 Jun 2025
Cited by 1 | Viewed by 3029
Abstract
Cellular senescence is a fundamental mechanism in aging, marked by irreversible growth arrest and diverse functional changes, including, but not limited to, the development of a senescence-associated secretory phenotype (SASP). While transient senescence contributes to beneficial processes such as tissue repair and tumor [...] Read more.
Cellular senescence is a fundamental mechanism in aging, marked by irreversible growth arrest and diverse functional changes, including, but not limited to, the development of a senescence-associated secretory phenotype (SASP). While transient senescence contributes to beneficial processes such as tissue repair and tumor suppression, the persistent accumulation of senescent cells is implicated in tissue dysfunction, chronic inflammation, and age-related diseases. Notably, the SASP can exert both pro-inflammatory and immunosuppressive effects, depending on cell type, tissue context, and temporal dynamics, particularly in early stages where it may be profibrotic and immunomodulatory. Recent advances in senotherapeutics have led to two principal strategies for targeting senescent cells: senolytics, which selectively induce their apoptosis, and senomorphics, which modulate deleterious aspects of the senescence phenotype, including the SASP, without removing the cells. This review critically examines the molecular mechanisms, therapeutic agents, and clinical potential of both approaches in the context of anti-aging interventions. We discuss major classes of senolytics, such as tyrosine kinase inhibitors, BCL-2 family inhibitors, and natural polyphenols, alongside senomorphics including mTOR and JAK inhibitors, rapalogs, and epigenetic modulators. Additionally, we explore the biological heterogeneity of senescent cells, challenges in developing specific biomarkers, and the dualistic role of senescence in physiological versus pathological states. The review also highlights emerging tools, such as targeted delivery systems, multi-omics integration, and AI-assisted drug discovery, which are advancing precision geroscience and shaping future anti-aging strategies. Full article
(This article belongs to the Special Issue Molecular Advances in Mechanism and Regulation of Lifespan and Aging)
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15 pages, 681 KiB  
Systematic Review
Impact of Pharmacological Treatments on Rheumatoid Arthritis-Associated Diffuse Interstitial Lung Disease: A Systematic Review and Meta-Analysis
by Ariam A. Muarif, Rana Algahtani, Lujain H. Alghamdi, Sarah S. Alghamdi, Lama Al Nemer, Reman Alsaqrah, Yazeed Alsulami, Maha Alsharif, Dana Alznbagi, Lena Aljehani, Ziyad Alsaeedi, Sultan Alghamdi, Taif A. Sayel, Basma Al Ghamdi and Ali Al Bshabshe
J. Pers. Med. 2025, 15(6), 239; https://doi.org/10.3390/jpm15060239 - 9 Jun 2025
Viewed by 867
Abstract
Background: Interstitial lung disease (ILD) is a prominent complication in the course of rheumatoid arthritis (RA), with a prevalence ranging from 5% to 60% and several phenotypes. The existing knowledge on the impact of different pharmacological interventions in individuals with rheumatoid arthritis-related [...] Read more.
Background: Interstitial lung disease (ILD) is a prominent complication in the course of rheumatoid arthritis (RA), with a prevalence ranging from 5% to 60% and several phenotypes. The existing knowledge on the impact of different pharmacological interventions in individuals with rheumatoid arthritis-related interstitial lung disease (RA-ILD) is inconclusive, and this variable response to treatment highlights the need for a personalized approach to the management of RA-associated ILD. Therefore, we aimed to evaluate the therapeutic effect and safety of different pharmacological agents, including conventional synthetic DMARDs (Cs DMARDs), biologic DMARDs (bDMARDs), targeted synthetic DMARDs (Ts DMARDs), and antifibrotic agents, in patients with RA-ILD. Method: This systematic review and meta-analysis searched for available randomized controlled trials (RCTs) and prospective cohort studies. A search was performed in the PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Eligible studies comprised those involving hospitalized patients diagnosed with RA-ILD, regardless of concomitant medications, who were of adult age (≥18 years); the studies measured the effect of pharmacological interventions, including methotrexate, leflunomide, tumor necrosis factor inhibitors (anti-TNF), abatacept, rituximab, JAK inhibitors, and antifibrotic agents, compared to placebo or other therapies for RA. Results: Out of 446 studies from 2002 to 2024, only 16 were included in this systematic review, including 14 prospective cohort studies and 2 placebo-controlled studies. Unfortunately, no RCTs were found that address our research question. The most relevant studies (n = 4) were performed in different countries (mainly Spain and the UK), with sample sizes varying from 23 to 381 patients (total: 2199 patients). The current study reveals that non-anti-TNF biologics were associated with a decreased risk of radiologic progression, while advanced therapies improved disease-related outcomes in patients requiring oxygen therapy. Methotrexate and other DMARDs were found to have inconsistent effects on ILD progression and mortality. Conclusions: Our review supports the integration of personalized medicine into the management of RA-ILD. By considering patient-specific factors and therapeutic responses, clinicians can better tailor interventions. We confirmed the high methodological quality of the trials, yielding solid evidence for the clinical management of RA-ILD. This review adds to the existing literature by identifying nintedanib as a potential disease-modifying therapy with the potential to slow the progression of lung disease. Full article
(This article belongs to the Section Personalized Therapy and Drug Delivery)
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24 pages, 7713 KiB  
Article
Resveratrol’s Pro-Apoptotic Effects in Cancer Are Mediated Through the Interaction and Oligomerization of the Mitochondrial VDAC1
by Tal Raviv, Anna Shteinfer-Kuzmine, Meital M. Moyal and Varda Shoshan-Barmatz
Int. J. Mol. Sci. 2025, 26(9), 3963; https://doi.org/10.3390/ijms26093963 - 22 Apr 2025
Viewed by 972
Abstract
Resveratrol is a naturally occurring phenolic compound found in various foods such as red wine, chocolate, peanuts, and blueberries. Both in-vitro and in-vivo studies have shown that it has a broad spectrum of pharmacological effects such as providing cellular protection and promoting longevity. [...] Read more.
Resveratrol is a naturally occurring phenolic compound found in various foods such as red wine, chocolate, peanuts, and blueberries. Both in-vitro and in-vivo studies have shown that it has a broad spectrum of pharmacological effects such as providing cellular protection and promoting longevity. These effects include antioxidant, anti-inflammatory, neuroprotective, and anti-viral properties, as well as improvements in cardio-metabolic health and anti-aging benefits. Additionally, resveratrol has demonstrated the ability to induce cell death and inhibit tumor growth across different types and stages of cancer. However, the dual effects of resveratrol—acting to support cell survival in some contexts, while inducing cell death in others—is still not fully understood. In this study, we identify a novel target for resveratrol: the voltage-dependent anion channel 1 (VDAC1), a multi-functional outer mitochondrial membrane protein that plays a key role in regulating both cell survival and death. Our findings show that resveratrol increased VDAC1 expression levels and promoted its oligomerization, leading to apoptotic cell death. Additionally, resveratrol elevated intracellular Ca2+ levels and enhanced the production of reactive oxygen species (ROS). Resveratrol also induced the detachment of hexokinase I from VDAC1, a key enzyme in metabolism, and regulating apoptosis. When VDAC1 expression was silenced using specific siRNA, resveratrol-induced cell death was significantly reduced, indicating that VDAC1 is essential for its pro-apoptotic effects. Additionally, both resveratrol and its analog, trans-2,3,5,4′-tetrahydroxystilbene-2-O-glucoside (TSG), directly interacted with purified VDAC1, as revealed by microscale thermophoresis, with similar binding affinities. However, unlike resveratrol, TSG did not induce VDAC1 overexpression or apoptosis. These results demonstrate that resveratrol-induced apoptosis is linked to increased VDAC1 expression and its oligomerization. This positions resveratrol not only as a protective agent, but also as a pro-apoptotic compound. Consequently, resveratrol offers a promising therapeutic approach for cancer, with potentially fewer side effects compared to conventional treatments, due to its natural origins in plants and food products. Full article
(This article belongs to the Collection Feature Papers in Molecular Oncology)
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15 pages, 3208 KiB  
Article
Safety Profile of Solanum tuberosum-Derived Exosomes: Evidence from In Vitro Experiments and Human Skin Tests
by Yeji Lee, Radwa Wahid Mohamed and Sanghwa Yang
Pharmaceuticals 2025, 18(4), 458; https://doi.org/10.3390/ph18040458 - 24 Mar 2025
Viewed by 1529
Abstract
Background/Objectives: Potato (Solanum tuberosum)-derived exosomes (SDEs) are extracellular vesicles (66 nm in diameter) with therapeutic potential. SDEs suppress matrix metallopeptidases (MMPs) 1, 2, and 9, tumor necrosis factor (TNF), and interleukin 6 (IL6), while exhibiting [...] Read more.
Background/Objectives: Potato (Solanum tuberosum)-derived exosomes (SDEs) are extracellular vesicles (66 nm in diameter) with therapeutic potential. SDEs suppress matrix metallopeptidases (MMPs) 1, 2, and 9, tumor necrosis factor (TNF), and interleukin 6 (IL6), while exhibiting radical-scavenging activity against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro and mitigating hydrogen peroxide (H2O2)-induced oxidative stress in HaCaT cells. SDEs upregulate the antioxidant gene glutathione S-transferase alpha 4 (GSTA4), prevent UVB damage, and regenerate photodamaged HaCaT cells. This study evaluates SDEs’ safety and skin-enhancing properties to improve their beauty-related and medical applications. Methods: The SDEs purified via ultracentrifugation were tested for their cytotoxic effects on HaCaT cell viability in scratch wound healing assays and for skin barrier gene modulation in HaCaT keratinocytes and Detroit 551 fibroblasts. A reverse transcription–polymerase chain reaction (RT-PCR) was used to analyze the changes in skin barrier gene expression following the SDE treatment. Cosmetic prototypes containing SDEs were assessed for skin irritation, cooling effects, periorbital wrinkle reduction, elasticity, and whitening properties. Results: The cytotoxicity and human topical tests confirmed the safety of SDE application. The SDEs accelerated wound closure, elevated the skin barrier gene expression level, and improved the clinical parameters, including wrinkle reduction, elasticity enhancement, and whitening. No irritation or side effects were observed. Conclusions: This study identified natural, edible potato-derived exosomes (SDEs) as highly safe agents that significantly enhance wound healing and promote skin barrier-related gene expression. Their multifunctional anti-aging efficacy—reducing wrinkles, enhancing elasticity, and promoting whitening without irritation—positions them as promising candidates for cosmetic and dermatological innovations. These findings warrant further exploration of SDEs for therapeutic applications, including inflammatory skin disorders and drug delivery systems. Full article
(This article belongs to the Section Pharmaceutical Technology)
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30 pages, 4118 KiB  
Review
Lactic Acid Bacteria in Vinegar Fermentation: Diversity, Functionality and Health Benefits
by Elahesadat Hosseini, Zenebe Tadesse Tsegay, Slim Smaoui and Theodoros Varzakas
Foods 2025, 14(4), 698; https://doi.org/10.3390/foods14040698 - 18 Feb 2025
Cited by 4 | Viewed by 3737
Abstract
Vinegar, frequently distilled by solid fermentation or liquid processes, was generated through the synergistic effect of a microbial community in open or semi-open environments. Based on the studied raw materials, researchers distributed the vinegar into three classes: grain, fruit and animal, with lactic [...] Read more.
Vinegar, frequently distilled by solid fermentation or liquid processes, was generated through the synergistic effect of a microbial community in open or semi-open environments. Based on the studied raw materials, researchers distributed the vinegar into three classes: grain, fruit and animal, with lactic acid bacteria (LAB) playing a pivotal role in their fermentation and contributing significantly to their functional and sensory qualities. Typically, the natural maturation of fresh vinegar necessitates a long period and vast space, engendering a reduced efficiency. To accelerate the vinegar aging process, some physical methods, viz. micro-oxygenation, ozone, ultrasound, microwave, gamma rays, infrared, electric fields and high pressure, have been developed. Produced or enriched by LAB, key bioactive vinegar components are organic acids, phenolic compounds, melanoidins, and tetramethylpyrazine. These active compounds have antibacterial, antioxidant, anti-inflammatory functions; aid in the regulation of liver protection metabolism and glucose control; and have blood pressure, anti-tumor, anti-fatigue and metabolic regulatory effects. The review explores advancements in vinegar production, including modernized fermentation processes and optimized aging techniques, which enhance these beneficial compounds and ensure product consistency and safety. By examining the LAB variety strains and the bioactive profiles of different vinegar types, this study highlights vinegar’s value beyond a culinary product, as a potential therapeutic agent in human nutrition and health. The findings underscore vinegar’s relevance not only in dietary and preventive healthcare but also as a potential functional food ingredient. Further research is needed to explore the mechanisms of action through which LAB contribute to the development of several new healthy vinegars. Full article
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18 pages, 640 KiB  
Article
Anti-Tumor Necrosis Factor-α Use in Pediatric Inflammatory Bowel Disease—Reports from a Romanian Center
by Roxana Matran, Andra-Mihaela Diaconu, Andreea Maria Iordache, Irina Dijmărescu, Alexandra Coroleucă, Daniela Păcurar and Cristina Becheanu
Pharmaceuticals 2025, 18(1), 84; https://doi.org/10.3390/ph18010084 - 11 Jan 2025
Cited by 1 | Viewed by 1648
Abstract
Background/Objectives: The introduction of anti-tumor necrosis factor-α (anti-TNF-α) agents, particularly infliximab (IFX) and adalimumab (ADA), has significantly expanded the therapeutic arsenal for inflammatory bowel disease (IBD). While these biologics have demonstrated substantial efficacy, they are associated with a spectrum of potential adverse events [...] Read more.
Background/Objectives: The introduction of anti-tumor necrosis factor-α (anti-TNF-α) agents, particularly infliximab (IFX) and adalimumab (ADA), has significantly expanded the therapeutic arsenal for inflammatory bowel disease (IBD). While these biologics have demonstrated substantial efficacy, they are associated with a spectrum of potential adverse events (AEs). This study aims to evaluate and document these AEs to facilitate optimal patient selection and monitoring strategies of patients undergoing these therapies. Methods: This retrospective, single-center study examined pediatric IBD patients receiving anti-TNF-α therapy at the “Grigore Alexandrescu” Emergency Hospital for Children in Bucharest, Romania, from January 2015 to October 2024. AEs were categorized into non-infectious complications (acute infusion reactions, anti-drug antibody formation), dermatological effects (erythema nodosum, vasculitis), neurological effects (Guillain–Barré syndrome), and infections. AEs were analyzed in relation to the specific anti-TNF-α agent administered and comprehensively characterized. Results: Of 40 patients enrolled, 22 (55%) had Crohn’s disease (CD). The median (IQR) age at diagnosis was 14.8 years [10.8–15.9]. IFX was used in 34 (85%) patients while 6 (15%) patients received either ADA or IFX/ADA sequential therapy. Twenty-seven AEs were documented in 19 (47.5%) patients, the most prevalent being antidrug antibody formation (44.4%), infections (22.2%), and acute infusion reactions (22.2%). All ADA-exposed patients experienced at least one AE, compared to 41.2% (n = 14) patients treated with IFX, p = 0.01. Conclusions: AEs were observed in approximately half of the study cohort, with anti-drug antibody formation emerging as the most frequent complication. ADA therapy was associated with a significantly higher rate of AEs compared to IFX. These findings underscore the critical importance of vigilant monitoring for patients undergoing anti-TNF-α therapy in pediatric IBD management. Full article
(This article belongs to the Section Pharmacology)
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23 pages, 2980 KiB  
Article
Nebulized Hybrid Nanoarchaeosomes: Anti-Inflammatory Activity, Anti-Microbial Activity and Cytotoxicity on A549 Cells
by Sofia Giuliana Guerin Stabile, Noelia Perez, Horacio Emanuel Jerez, Yamila Roxana Simioni, Estefanía Butassi, Martin Daniel Mizrahi, Matias Leonardo Nobile, Ana Paula Perez, Maria Jose Morilla, Leticia Herminia Higa and Eder Lilia Romero
Int. J. Mol. Sci. 2025, 26(1), 392; https://doi.org/10.3390/ijms26010392 - 4 Jan 2025
Cited by 1 | Viewed by 3862
Abstract
The properties of two hybrid nanoarchaeosomes (hybrid nanoARCs) made of archaeolipids extracted from the halophilic archaea Halorubrum tebenquichense and combining the properties of archaeolipid bilayers with metallic nanoparticles are explored here. BS-nanoARC, consisting of a nanoARC loaded with yerba mate (Ilex paraguariensis) [...] Read more.
The properties of two hybrid nanoarchaeosomes (hybrid nanoARCs) made of archaeolipids extracted from the halophilic archaea Halorubrum tebenquichense and combining the properties of archaeolipid bilayers with metallic nanoparticles are explored here. BS-nanoARC, consisting of a nanoARC loaded with yerba mate (Ilex paraguariensis) extract (YME)-biogenic silver nanoparticles (BSs), and [BS + BS-nanoARC], consistent of a BS-nanoARC core covered by an outer shell of BSs, were structurally characterized and their therapeutic activities screened. By employing 109 ± 5 µg gallic acid equivalents (GAEs) and 73.4 µg chlorogenic acid/ YME mg as a silver reductive agent, spherical, heterogeneously sized (~80 nm diameter), −27 mV ζ potential, 90% Ag0 and λmax 420 nm BSs were obtained. We further prepared ~100–200 nm diameter, −57 mV ζ potential BS-nanoARC and ~300 nm diameter, −37 mV ζ potential [BS + BS-nanoARCs]. Freshly prepared and nebulized BS-nanoARCs reduced the release of TNF-α, IL-6 and IL-8 by LPS-irritated THP-1-macrophages and were highly anti-planktonic against S. aureus (MIC90: 13 ± 0.8 µg Ag/mL). While the nanoARCs and BS-nanoARCs were innocuous, freshly prepared [BS + BS-nanoARCs] magnified the cytotoxicity of BSs (IC50 12 µg Ag/mL vs. IC50 ~36 µg Ag/mL) on A549 cells. Such cytotoxicity remained after 30 days in the dark at 4 °C, while that of BSs was lost. Freshly prepared BSs also lost activity upon nebulization, whereas freshly prepared [BS + BS-nanoARCs] did not. However, the cytotoxicity of the [BS + BS-nanoARCs] was also lost when nebulized after 30 days of storage. Despite the harmful effects of storage and mechanical stress on the structure of the more active [BS + BS-nanoARCs], hybrid nanoARCs are promising examples of nanomedicines combining the properties of archaeolipids with antimicrobial silver nanoparticles and anti-inflammatory polyphenols that could complement oncologic therapies, reducing the usage of classical antitumoral agents, corticosteroids, and, importantly, of antibiotics, as well as their waste. Full article
(This article belongs to the Special Issue Recent Research on Novel Lipid-Based Nano Drug Delivery Systems)
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20 pages, 4034 KiB  
Article
Nicotinamide Mononucleotide Restores NAD+ Levels to Alleviate LPS-Induced Inflammation via the TLR4/NF-κB/MAPK Signaling Pathway in Mice Granulosa Cells
by Mehboob Ahmed, Umair Riaz, Haimiao Lv, Muhammad Amjad, Sohail Ahmed, Shaokat Ali, Muhammad Usman Ghani, Guohua Hua and Liguo Yang
Antioxidants 2025, 14(1), 39; https://doi.org/10.3390/antiox14010039 - 31 Dec 2024
Cited by 6 | Viewed by 1905
Abstract
Inflammation disrupts the normal function of granulosa cells (GCs), which leads to ovarian dysfunction and fertility decline. Inflammatory conditions such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI), endometriosis, and age-related ovarian decline are often associated with chronic low-grade inflammation. Nicotinamide mononucleotide [...] Read more.
Inflammation disrupts the normal function of granulosa cells (GCs), which leads to ovarian dysfunction and fertility decline. Inflammatory conditions such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI), endometriosis, and age-related ovarian decline are often associated with chronic low-grade inflammation. Nicotinamide mononucleotide (NMN) is an important precursor of NAD+ and has gained attention for its potential to modulate cellular metabolism, redox homeostasis, and mitigate inflammation. This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs. The results of this experiment demonstrated that LPS had negative effects on GCs in term of reduced viability and proliferation rates and upregulated the production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-α). Notably, the levels of NAD+ and NAD+/NADH ratio in GCs were reduced in response to inflammation. On the other hand, NMN supplementation restored the NAD+ levels and the NAD+/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels. It also enhanced cell viability and proliferation rates of GCs. Furthermore, NMN also reduced apoptosis rates in GCs by downregulating pro-apoptotic markers, including Caspase-3, Caspase-9, and Bax while upregulating anti-apoptotic marker Bcl-2. NMN supplementation significantly reduced reactive oxygen species ROS and improved steroidogenesis activity by restoring the estradiol (E2) and progesterone (P4) levels in LPS-treated GCs. Mechanistically, this study found that NMN suppressed the activation of the TLR4/NF-κB/MAPK signaling pathways in GCs, which regulates inflammatory processes. In conclusion, the findings of this study revealed that NMN has the potential to reduce LPS-mediated inflammatory changes in GCs by modulating NAD+ metabolism and inflammatory signaling pathways. NMN supplementation can be used as a potential therapeutic agent for ovarian inflammation and related fertility disorders. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
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25 pages, 1928 KiB  
Review
The Potential Application of Resveratrol and Its Derivatives in Central Nervous System Tumors
by Agnieszka Nowacka, Martyna Śniegocka, Wojciech Smuczyński, Sara Liss, Ewa Ziółkowska, Dominika Bożiłow, Maciej Śniegocki and Michał Wiciński
Int. J. Mol. Sci. 2024, 25(24), 13338; https://doi.org/10.3390/ijms252413338 - 12 Dec 2024
Cited by 5 | Viewed by 2690
Abstract
Resveratrol, a naturally occurring polyphenolic compound found in various plants, has been extensively studied for its broad spectrum of beneficial biological effects. These encompass its potent antioxidant properties, anti-inflammatory activities, anti-aging capabilities, cardioprotective functions, and neuroprotective potential. The diverse biological actions of resveratrol [...] Read more.
Resveratrol, a naturally occurring polyphenolic compound found in various plants, has been extensively studied for its broad spectrum of beneficial biological effects. These encompass its potent antioxidant properties, anti-inflammatory activities, anti-aging capabilities, cardioprotective functions, and neuroprotective potential. The diverse biological actions of resveratrol extend beyond these well-established properties. It also exerts a significant impact on metabolic processes and bioavailability, and critically, it demonstrates the ability to effectively traverse the blood–brain barrier. This capacity to penetrate the central nervous system renders resveratrol a promising therapeutic agent for the management of central nervous system malignancies, as it has been shown to inhibit tumor cell proliferation, induce apoptosis, and modulate key signaling cascades, such as PI3K/Akt, JAK/STAT, and NF-kB. The multifaceted nature of resveratrol’s biological effects, including its influence on diverse physiological processes, underscores its potential as a valuable therapeutic option for the treatment of central nervous system tumors. Full article
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25 pages, 2431 KiB  
Review
Green Tea Catechins and Skin Health
by Xin-Qiang Zheng, Xue-Han Zhang, Han-Qing Gao, Lan-Ying Huang, Jing-Jing Ye, Jian-Hui Ye, Jian-Liang Lu, Shi-Cheng Ma and Yue-Rong Liang
Antioxidants 2024, 13(12), 1506; https://doi.org/10.3390/antiox13121506 - 10 Dec 2024
Cited by 7 | Viewed by 9259
Abstract
Green tea catechins (GTCs) are a group of bioactive polyphenolic compounds found in fresh tea leaves (Camellia sinensis (L.) O. Kuntze). They have garnered significant attention due to their diverse health benefits and potential therapeutic applications, including as antioxidant and sunscreen agents. [...] Read more.
Green tea catechins (GTCs) are a group of bioactive polyphenolic compounds found in fresh tea leaves (Camellia sinensis (L.) O. Kuntze). They have garnered significant attention due to their diverse health benefits and potential therapeutic applications, including as antioxidant and sunscreen agents. Human skin serves as the primary barrier against various external aggressors, including pathogens, pollutants, and harmful ultraviolet radiation (UVR). Skin aging is a complex biological process influenced by intrinsic factors such as genetics and hormonal changes, as well as extrinsic factors like environmental stressors, among which UVR plays a pivotal role in accelerating skin aging and contributing to various dermatological conditions. Research has demonstrated that GTCs possess potent antioxidant properties that help neutralize free radicals generated by oxidative stress. This action not only mitigates cellular damage but also supports the repair mechanisms inherent in human skin. Furthermore, GTCs exhibit anti-carcinogenic effects by inhibiting pathways involved in tumor promotion and progression. GTCs have been shown to exert anti-inflammatory effects through modulation of inflammatory signaling pathways. Chronic inflammation is known to contribute significantly to both premature aging and various dermatological diseases such as psoriasis or eczema. By regulating these pathways effectively, GTCs may alleviate symptoms associated with inflammatory conditions. GTCs can enhance wound healing processes by stimulating angiogenesis. They also facilitate DNA repair mechanisms within dermal fibroblasts exposed to damaging agents. The photoprotective properties attributed to GTCs further underscore their relevance in skincare formulations aimed at preventing sun-induced damage. Their ability to screen UV light helps shield underlying tissues from harmful rays. This review paper aims to comprehensively examine the beneficial effects of GTCs on skin health through an analysis encompassing in vivo and in vitro studies alongside insights into molecular mechanisms underpinning these effects. Such knowledge could pave the way for the development of innovative strategies focused on harnessing natural compounds like GTCs for improved skincare solutions tailored to combat environmental stresses faced by the human epidermis. Full article
(This article belongs to the Special Issue Antioxidants for Skin Health)
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16 pages, 4022 KiB  
Article
Berberine Mitigates Sepsis-Associated Acute Kidney Injury in Aged Rats by Preserving Mitochondrial Integrity and Inhibiting TLR4/NF-κB and NLRP3 Inflammasome Activations
by Ruedeemars Yubolphan, Anongporn Kobroob, Apisek Kongkaew, Natthakarn Chiranthanut, Natthanicha Jinadang and Orawan Wongmekiat
Antioxidants 2024, 13(11), 1398; https://doi.org/10.3390/antiox13111398 - 15 Nov 2024
Cited by 5 | Viewed by 1664
Abstract
Sepsis-associated acute kidney injury (SA-AKI) presents a severe challenge in the elderly due to increasing incidence, high mortality, and the lack of specific effective treatments. Exploring novel and secure preventive and/or therapeutic approaches is critical and urgent. Berberine (BBR), an isoquinoline alkaloid with [...] Read more.
Sepsis-associated acute kidney injury (SA-AKI) presents a severe challenge in the elderly due to increasing incidence, high mortality, and the lack of specific effective treatments. Exploring novel and secure preventive and/or therapeutic approaches is critical and urgent. Berberine (BBR), an isoquinoline alkaloid with anti-inflammatory, antioxidant, and immunomodulatory properties, has shown beneficial effects in various kidney diseases. This study examined whether BBR could protect against SA-AKI in aged rats. Sepsis was induced in 26-month-old male Wistar rats by cecal ligation and puncture (CLP), either with or without BBR pretreatment. CLP induction led to SA-AKI, as indicated by elevated serum levels of malondialdehyde, tumor necrosis factor-alpha, urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL), along with histopathological features of kidney damage. Key indicators of kidney oxidative stress, mitochondrial dysfunction, apoptosis, and activations of the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling, including the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome pathway, were also elevated following CLP induction. BBR pretreatment substantially mitigated these adverse effects, suggesting that it protects against SA-AKI in aged rats by reducing oxidative stress, preserving mitochondrial integrity, and inhibiting key inflammatory pathways. These findings highlight the potential of BBR as a therapeutic agent for managing SA-AKI in elderly populations. Full article
(This article belongs to the Special Issue Oxidative Stress in Renal Health)
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18 pages, 5379 KiB  
Article
Trastuzumab Potentiates Antitumor Activity of Thiopyrano[2,3-d]Thiazole Derivative in AGS Gastric Cancer Cells
by Piotr Roszczenko, Olga Klaudia Szewczyk-Roszczenko, Agnieszka Gornowicz, Robert Czarnomysy, Andrii Lozynskyi, Krzysztof Bielawski, Roman Lesyk and Anna Bielawska
Molecules 2024, 29(21), 5117; https://doi.org/10.3390/molecules29215117 - 30 Oct 2024
Viewed by 1811
Abstract
Gastric cancer remains a significant therapeutic challenge, highlighting the need for new strategies to improve treatment efficacy. This study investigates the potential of combined therapy with the novel Thiopyrano[2,3-d]Thiazole derivative LES-6400 and the anti-HER2 antibody trastuzumab in AGS gastric cancer cells. [...] Read more.
Gastric cancer remains a significant therapeutic challenge, highlighting the need for new strategies to improve treatment efficacy. This study investigates the potential of combined therapy with the novel Thiopyrano[2,3-d]Thiazole derivative LES-6400 and the anti-HER2 antibody trastuzumab in AGS gastric cancer cells. The antitumor effects of the combined therapy were evaluated using various techniques, including the MTT assay for cell viability, [3H]-thymidine incorporation for DNA synthesis, and flow cytometry to assess apoptosis (Annexin V-FITC/PI staining), mitochondrial membrane potential (MMP), and inflammatory cytokine levels. ELISA was employed to measure the levels of IL-6, p53, and cytochrome C. The combination of LES-6400 (1 µM) and trastuzumab (10 µg/mL) demonstrated superior antitumor activity compared to monotherapy with either agent in AGS gastric cancer cells. The combination therapy enhanced apoptosis, presumably by inducing oxidative stress in the cells and disrupting mitochondrial membrane potential. Additionally, a significant increase in p53 protein levels and modulation of interleukin levels, including a marked reduction in IL-6 levels, were observed, suggesting an impact on apoptotic and inflammatory responses. These findings indicate that the combined use of LES-6400 and trastuzumab is a promising therapeutic strategy for gastric cancer, warranting further investigation into the mechanisms of action and potential clinical applications of this combined approach. Full article
(This article belongs to the Special Issue Targeted Cancer Therapy: Small Molecules and Immunotherapy)
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18 pages, 2326 KiB  
Systematic Review
A Systematic Review of Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Treatment for Glioblastoma
by Edoardo Agosti, Sara Antonietti, Tamara Ius, Marco Maria Fontanella, Marco Zeppieri and Pier Paolo Panciani
Brain Sci. 2024, 14(11), 1058; https://doi.org/10.3390/brainsci14111058 - 25 Oct 2024
Cited by 2 | Viewed by 2193
Abstract
Background: Glioblastoma (GBM) is an extremely aggressive brain tumor that has few available treatment options and a dismal prognosis. Recent research has highlighted the potential of extracellular vesicles (MSC-EVs) produced from mesenchymal stem cells as a potential treatment approach for GBM. MSC-EVs, including [...] Read more.
Background: Glioblastoma (GBM) is an extremely aggressive brain tumor that has few available treatment options and a dismal prognosis. Recent research has highlighted the potential of extracellular vesicles (MSC-EVs) produced from mesenchymal stem cells as a potential treatment approach for GBM. MSC-EVs, including exosomes, microvesicles, and apoptotic bodies, perform a significant function in cellular communication and have shown promise in mediating anti-tumor effects. Purpose: This systematic literature review aims to consolidate current findings on the therapeutic potential of MSC-EVs in GBM treatment. Methods: A systematic search was conducted across major medical databases (PubMed, Web of Science, and Scopus) up to September 2024 to identify studies investigating the use of MSC-derived EVs in GBM therapy. Keywords included “extracellular vesicles”, “mesenchymal stem cells”, “targeted therapies”, “outcomes”, “adverse events”, “glioblastoma”, and “exosomes”. Inclusion criteria were studies published in English involving GBM models both in vivo and in vitro and those reporting on therapeutic outcomes of MSC-EVs. Data were extracted and analyzed based on EV characteristics, mechanisms of action, and therapeutic efficacy. Results: The review identified several key studies demonstrating the anti-tumor effects of MSC-EVs in GBM models. A total of three studies were included, focusing on studies conducted between 2021 and 2023. The review included three studies that collectively enrolled a total of 18 patients. These studies were distributed across two years, with two trials published in 2023 (66.7%) and one in 2021 (33.3%). The mean age of the participants ranged from 37 to 57 years. In terms of gender distribution, males were the predominant group in all studies. Prior to receiving MSC-EV therapy, all patients had undergone standard treatments for GBM, including surgery, chemotherapy (CT), and, in some cases, radiation therapy (RT). In all three studies, the targeted treatment involved the administration of herpes simplex virus thymidine kinase (HSVtk) gene therapy delivered to the tumor site, then 14 days of ganciclovir treatment. Outcomes across the studies indicated varying levels of efficacy for the MSC-EV-based therapy. The larger 2023 study reported fewer encouraging outcomes, with a median PFS of 11.0 months (95% CI: 8.3–13.7) and a median OS of 16.0 months (95% CI: 14.3–17.7). Adverse effects were reported in only one of the studies, the 2021 trial, where patients experienced mild-to-moderate side effects, including fever, headache, and cerebrospinal fluid leukocytosis. A total of 11 studies on preclinical trials, using in vitro and in vivo models, were included, covering publications from 2010 to 2024. The studies utilized MSCs as delivery systems for various therapeutic agents (interleukin 12, interleukin 7, doxorubicin, paclitaxel), reflecting the versatility of these cells in targeted cancer therapies. Conclusions: MSC-derived EVs represent a promising therapeutic approach for GBM, offering multiple mechanisms to inhibit tumor growth and enhance treatment efficacy. Their ability to deliver bioactive molecules and modulate the tumor microenvironment underscores their potential as a novel, cell-free therapeutic strategy. Future studies should optimize EV production and delivery methods and fully understand their long-term effects in clinical settings to harness their therapeutic potential in GBM treatment. Full article
(This article belongs to the Special Issue New Trends and Technologies in Modern Neurosurgery)
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21 pages, 7423 KiB  
Article
Nanotherapy for Cancer and Biological Activities of Green Synthesized AgNPs Using Aqueous Saussurea costus Leaves and Roots Extracts
by Mina A. Almayouf, Raihane Charguia, Manal A. Awad, Abir Ben Bacha and Imen Ben Abdelmalek
Pharmaceuticals 2024, 17(10), 1371; https://doi.org/10.3390/ph17101371 - 15 Oct 2024
Cited by 1 | Viewed by 1554
Abstract
Background/Objectives: Nanoparticles derived from medicinal plants are gaining attention for their diverse biological activities and potential therapeutic applications. Methods: This study explored the antioxidant, anti-inflammatory, anti-tumoral, and antimicrobial properties of green synthesized silver nanoparticles (AgNPs) using the aqueous leaf and root [...] Read more.
Background/Objectives: Nanoparticles derived from medicinal plants are gaining attention for their diverse biological activities and potential therapeutic applications. Methods: This study explored the antioxidant, anti-inflammatory, anti-tumoral, and antimicrobial properties of green synthesized silver nanoparticles (AgNPs) using the aqueous leaf and root extracts of Saussurea costus (S. costus). The physicochemical characterizations of both biosynthesized AgNPs using the aqueous leaf extract (L-AgNPs) and root extract (R-AgNPs) were examined using UV spectroscopy, fluorescence spectroscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, dynamic light scattering, and Fourier-transform infrared spectroscopy. The antioxidant activity measured using ABTS, DPPH, and FRAP assays showed that AgNPs, particularly from roots, had higher activity than aqueous extracts, attributed to phenolic compounds acting as capping and antioxidant agents. Results: Enzyme inhibition studies indicated that AgNPs exhibited remarkable anti-inflammatory effects, inhibiting COX-1, 5-LOX, and secreted PLA2 enzymes by over 99% at 120 µg/mL, comparable to standard drugs. The anti-tumoral effects were evaluated on the human cancer cell lines HCT-116, LoVo, and MDA-MB-231, with AgNPs inhibiting cell proliferation dose-dependently and IC50 values between 42 and 60 µg/mL, demonstrating greater potency than extracts. The AgNPs also showed enhanced antimicrobial activities against various microbial strains, with IC50 values as low as 14 µg/mL, which could be linked to nanoparticle interactions with microbial cell membranes, causing structural damage and cell death. Conclusions: These findings suggest that S. costus-derived AgNPs are promising natural, biodegradable agents for various biological applications and potential new therapeutic agents, necessitating further research to explore their mechanisms and applications. Full article
(This article belongs to the Topic Enzymes and Enzyme Inhibitors in Drug Research)
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21 pages, 4856 KiB  
Article
Inhibitory Effects of Reynoutria japonica Houtt. on Pain and Cartilage Breakdown in Osteoarthritis Based on Its Multifaceted Anti-Inflammatory Activity: An In Vivo and In Vitro Approach
by Hee-Geun Jo, Chae Yun Baek, Juni Lee, Yeseul Hwang, Eunhye Baek, Aejin Song, Ho Sueb Song and Donghun Lee
Int. J. Mol. Sci. 2024, 25(19), 10647; https://doi.org/10.3390/ijms251910647 - 3 Oct 2024
Cited by 1 | Viewed by 1609
Abstract
In the past 30 years, the number of years lived with disability due to osteoarthritis (OA) has doubled, making it an increasing global health burden. To address this issue, interventions that inhibit the progressive pathology driven by age-related low-grade inflammation, the primary mechanism [...] Read more.
In the past 30 years, the number of years lived with disability due to osteoarthritis (OA) has doubled, making it an increasing global health burden. To address this issue, interventions that inhibit the progressive pathology driven by age-related low-grade inflammation, the primary mechanism of OA, are being actively pursued. Recent investigations have focused on modulating the age-related low-grade inflammatory pathology of this disease as a therapeutic target. However, no agent has successfully halted the disease’s progression or reversed its irreversible course. Reynoutria japonica Houtt. (RJ), a promising East Asian herbal medicine, has been utilized for several diseases due to its potent anti-inflammatory activity. This study aims to determine RJ’s capacity to inhibit OA symptoms and associated inflammation, exploring its potential for further development. In vivo and in vitro experiments demonstrated RJ’s anti-OA activity and modulation of multifaceted inflammatory targets. RJ significantly inhibited pain, gait deterioration, and cartilage destruction in a monosodium iodoacetate-induced OA rat model, with its analgesic effect further confirmed in an acetic acid-induced writhing model. RJ exhibited consistent anti-inflammatory activity against multiple targets in serum and cartilage of the OA rat model and lipopolysaccharide-induced RAW 264.7 cells. The inhibition of inflammatory cytokines, including interleukin-1β, interleukin-6, matrix metalloproteinase-13, tumor necrosis factor-α, and nitric oxide synthase 2, suggests that RJ’s alleviation of OA manifestations relates to its multifaceted anti-inflammatory activity. These results indicate that RJ merits further investigation as a disease-modifying drug candidate targeting OA’s inflammatory pathology. To further characterize the pharmacological properties of RJ, future studies with expanded designs are warranted. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Strategies of Inflammatory Pain)
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