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Marine Drugs, Volume 23, Issue 10

2025 October - 42 articles

Cover Story: Sponges of the genus Latrunculia (family Latrunculiidae; class Demospongiae) are well known for producing cytotoxic pyrroloiminoquinone alkaloids called discorhabdins. Found mainly in Antarctic and North Pacific waters, these sponges yield diverse secondary metabolites, particularly highly pigmented discorhabdins with notable cytotoxic activity. In this study, three Antarctic Latrunculia specimens were investigated, leading to the isolation of five new pyrroloiminoquinone alkaloids and the known metabolite (+)-debromodiscorhabdin A. Three of the new compounds were brominated, while two contained a C-5/C-8 sulfur bridge and a C-2/N-18 linkage. Notably, three featured a previously unreported C-14 benzoyl substituent. Cytotoxicity assays against A549 cells showed IC₅₀ values of 4.3–23.9 µM. View this paper
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Articles (42)

  • Article
  • Open Access
3,235 Views
13 Pages

Cellulose and Cellulose Synthase in a Marine Pseudomonas Strain from Antarctica: Characterization, Adaptive Implications, and Biotechnological Potential

  • Maria Chiara Biondini,
  • Martina Di Sessa,
  • Alberto Vassallo,
  • Federica Chiappori,
  • Marco Zannotti,
  • Alessio Mancini,
  • Rita Giovannetti and
  • Sandra Pucciarelli

21 October 2025

Antarctic microorganisms have developed extraordinary strategies for adaptation. They have also demonstrated the ability to produce various biopolymers in response to environmental stress. The demand for biopolymers is constantly increasing and is ex...

  • Article
  • Open Access
1,216 Views
19 Pages

High-Seas Marine Microorganism Delivers an Extract That Dampens LPS-Driven Pro-Inflammatory Signaling: Galbibacter orientalis Strain ROD011

  • Minji Kim,
  • You-Jin Jeon,
  • Bomi Ryu,
  • Young-Mog Kim,
  • Jae-Il Kim,
  • Minkyeong Choi,
  • Sohee Kim,
  • Jihye Lee and
  • Jimin Hyun

18 October 2025

An ethyl acetate extract from the deep-sea bacterium Galbibacter orientalis strain ROD011 (GOEE), collected from international waters, was investigated as a potential anti-inflammatory agent. In lipopolysaccharide (LPS)-stimulated murine macrophages,...

  • Article
  • Open Access
1,317 Views
22 Pages

Biodiversity and Biological Interactions of Actinobacteria Associated with Deep Sea and Intertidal Marine Invertebrates

  • Hosea Isanda Masaki,
  • Yannik Karl-Heinz Schneider,
  • Ole Hinnerk Franz,
  • Espen Holst Hansen,
  • Jeanette Hammer Andersen and
  • Teppo Rämä

17 October 2025

Studying marine Actinobacteria across ecological niches is essential for discovering novel natural products and understanding microbial interactions. In this study, we investigated the diversity of Actinobacteria associated with five Arctic marine in...

  • Review
  • Open Access
5 Citations
4,029 Views
40 Pages

17 October 2025

In recent years, seaweed-derived polysaccharides have gained recognition as renewed potent bioactive compounds with significant antibacterial and antiviral properties. These polysaccharides include carrageenan, agar, agarose, and porphyran from red s...

  • Article
  • Open Access
788 Views
20 Pages

Valorization of Amphidinium carterae for Integrated Preparation of Peridinin and Diadinoxanthin Cycle Carotenoids

  • Yi Li,
  • Gengjie Zhuang,
  • Xuan Zhang,
  • Wei Cui,
  • Zhiwei Hong,
  • Jianhua Fan,
  • Jinrong Zhang and
  • Xiaojun Yan

17 October 2025

An integrated microalgae biorefinery producing high-purity xanthophylls using a sustainable and efficient strategy still faces critical challenges. In this study, the microalga Amphidinium carterae can accumulate peridinin and diadinoxanthin cycle ca...

  • Review
  • Open Access
1 Citations
1,931 Views
41 Pages

Microbial Blue Bioprospecting: Exploring the Advances of Compounds Post-Discovery

  • Cristiana Roberta Multisanti,
  • Valeria Celi,
  • Aurora Dibra,
  • Angela Pintus,
  • Rosario Calogero,
  • Carmen Rizzo and
  • Caterina Faggio

17 October 2025

Marine biotechnology is an emerging field of research. There is scientific evidence of the strong potential of a multitude of marine microorganisms in biotechnology, with applications spanning the medical, pharmaceutical, cosmeceutical, nutraceutical...

  • Article
  • Open Access
1,168 Views
16 Pages

Genomic and Metabolomic Insights into Metabolites of a Streptomyces Isolate Associated with Chromodoris quadricolor, a Red Sea Nudibranch

  • Samar M. Abdelrahman,
  • Zoe A. Pratte,
  • Manar El Samak,
  • Noura S. Dosoky,
  • Amro M. S. Hanora,
  • Frank J. Stewart and
  • Nicole B. Lopanik

17 October 2025

The marine invertebrate-associated microbiome has garnered significant interest in recent years due to its wealth of novel genes that can be explored for biomining. By combining genomics with untargeted data-dependent mass spectrometry (MS) and molec...

  • Review
  • Open Access
1 Citations
1,364 Views
34 Pages

Cancer Cell Cytotoxicity of Marinopyrroles, Pyrrolomycins, and Their Derivatives

  • Jeffrey M. Zimmerly,
  • Nicholas A. Armstrong,
  • Clare F. Euteneuer,
  • Brianna N. Davis,
  • M. Beth Griffis-Anchala,
  • Angelique Vargas and
  • Paul H. Davis

16 October 2025

Marine-derived secondary metabolites have emerged as a rich potential source of anticancer agents, with marinopyrroles and pyrrolomycins representing structurally distinct halogenated pyrroles of interest. Initially characterized for their potent ant...

  • Article
  • Open Access
2 Citations
920 Views
16 Pages

New Polyketides and a Ferroptosis Inhibitor from the Marine-Derived Fungus Diaporthe searlei CS-HF-1

  • Jicheng Xiao,
  • Peng Wu,
  • Yan Zhang,
  • Qi Lv,
  • Yulang Chi,
  • Wei Xu,
  • Wenzhen Lin and
  • Zhongbin Cheng

16 October 2025

As a driver of neurodegenerative disorders, ischemic injuries, and acute organ dysfunction, ferroptosis represents a therapeutic target, and its inhibition may provide novel therapies. In our ongoing efforts to discover ferroptosis inhibitors from fu...

  • Article
  • Open Access
1 Citations
3,549 Views
14 Pages

Novel Discorhabdin Derivatives from Antarctic Sponges of the Genus Latrunculia: Expanding the Chemical Diversity of Polar Marine Natural Products

  • Sam Afoullouss,
  • Stine S. H. Olsen,
  • Sydney Morrow,
  • Ezequiel Cruz Rosa,
  • Kaley Geu,
  • Nerida G. Wilson and
  • Bill J. Baker

15 October 2025

In this study, three Antarctic sponges of the genus Latrunculia were investigated, leading to the isolation of five unreported pyrroloiminoquinone alkaloids along with the known metabolite (+)-debromodiscorhabdin A (3). Three of the new metabolites w...

  • Review
  • Open Access
1 Citations
1,801 Views
30 Pages

Recent Advances in Secondary Metabolites from Marine Aspergillus

  • Zimin Wang,
  • Meirong Zhao,
  • Chenglin Li,
  • Yunxia Yu,
  • Zhiqiang Gong,
  • Fandong Kong and
  • Chengzhi Li

15 October 2025

Marine Aspergillus fungi, adapted to extreme marine environments (e.g., sediments, corals, mangroves), are prolific producers of structurally diverse secondary metabolites with significant bioactivities. This review comprehensively analyzes 340 novel...

  • Review
  • Open Access
2 Citations
1,251 Views
39 Pages

Marine-Derived Steroids for Cancer Treatment: Search for Potential Selective Glucocorticoid Receptor Agonists/Modulators (SEGRAMs)

  • Ekaterina M. Zhidkova,
  • Ekaterina D. Savina,
  • Ekaterina A. Yurchenko and
  • Ekaterina A. Lesovaya

14 October 2025

Steroids, particularly glucocorticoids, are essential components of cancer treatment for both hematological malignancies and solid tumors. The adverse effects of standard steroid-based drugs have forced drug discovery research to develop chemotherape...

  • Review
  • Open Access
1,319 Views
17 Pages

Methodologies for Detoxifying Bivalves from Marine Paralytic Shellfish Toxins

  • Adewale Aderogba,
  • Joana F. Leal and
  • Maria L. S. Cristiano

12 October 2025

The marine environment emerges as a key provider of food and sustainable products. However, these benefits are accompanied by numerous challenges owing to harmful algal blooms (HAB) and their associated biotoxins, which accumulate in organisms, like...

  • Review
  • Open Access
2 Citations
2,157 Views
23 Pages

9 October 2025

Diketopiperazines (DKPs) are biologically important cyclic dipeptides widespread in nature, associated primarily with microorganisms. This is the case for the 2,5-DKP derivative cyclo(L-Leu-L-Pro) (cLP), also known as gancidin W or PPDHMP, identified...

  • Systematic Review
  • Open Access
3 Citations
1,877 Views
36 Pages

Functionalization Strategies of Chitosan-Based Scaffolds with Growth Factors for Bone Regeneration: A Systematic Review

  • Jan Kiryk,
  • Mateusz Michalak,
  • Zuzanna Majchrzak,
  • Marzena Laszczyńska,
  • Sylwia Kiryk,
  • Sylwia Szotek,
  • Hanna Gerber,
  • Izabela Nawrot-Hadzik,
  • Jacek Matys and
  • Maciej Dobrzyński

9 October 2025

Bioactive agents can stimulate osteogenesis, angiogenesis, and cell proliferation; therefore, their application in bone regeneration offers significant therapeutic potential. The aim of this systematic review was to evaluate strategies for applying c...

  • Article
  • Open Access
1,054 Views
18 Pages

Enzymatic Spirulina Extract Enhances the Vasodilation in Aorta and Mesenteric Arteries of Aged Rats

  • Michal S. Majewski,
  • Mercedes Klett-Mingo,
  • Carlos M. Verdasco-Martín,
  • Cristina Otero and
  • Mercedes Ferrer

8 October 2025

Aging, one of the main factors associated with cardiovascular diseases, induces vascular modifications through nitric oxide (NO) release and oxidative stress. Based on the antioxidant properties of the non-enzymatic spirulina extract (non-Enz-Spir-E)...

  • Article
  • Open Access
1,180 Views
19 Pages

Carbon-Source Effects on Growth and Secondary Metabolism in the Marine Bacteroidota Tenacibaculum mesophilum and Fulvivirga kasyanovii

  • Luis Linares-Otoya,
  • Virginia Linares-Otoya,
  • Gladys Galliani-Huamanchumo,
  • Terecita Carrion-Zavaleta,
  • Jose Condor-Goytizolo,
  • Till F. Schäberle,
  • Mayar L. Ganoza-Yupanqui and
  • Julio Campos-Florian

4 October 2025

Marine Bacteroidota are recognized bacterial producers of bioactive metabolites, yet their biosynthetic potential remains cryptic under standard laboratory conditions. Here, we developed chemically defined media for Fulvivirga kasyanovii 48LL (Cytoph...

  • Article
  • Open Access
1,384 Views
19 Pages

In Vitro Antioxidant and Antidiabetic Effects of Atlantic Mackerel and Sardine By-Product Hydrolysates

  • Cristina Fuentes,
  • Samuel Verdú,
  • Raúl Grau,
  • José Manuel Barat and
  • Ana Fuentes

4 October 2025

This work evaluates the effect of raw material and protease enzymes on the antioxidant and antidiabetic potential of fish by-product hydrolysates. For this, mackerel (Scomber scombrus) and sardine (Sardina pilchardus) by-products were hydrolyzed usin...

  • Article
  • Open Access
2 Citations
1,377 Views
22 Pages

Purification, Identification, and In Silico Analysis of Anti-Obesity and Antidiabetic Peptides from the Red Seaweed Palmaria palmata

  • Sakhi Ghelichi,
  • Mona Hajfathalian,
  • Seyed Hossein Helalat,
  • Birte Svensson and
  • Charlotte Jacobsen

3 October 2025

This study investigates the anti-obesity and antidiabetic potential of P. palmata extracts produced through sequential enzymatic and alkaline treatments. Among the treatment groups, the extract treated solely with Alcalase® (Alc) demonstrated the...

  • Article
  • Open Access
1 Citations
855 Views
20 Pages

The Effect of Ultraviolet Light Irradiation on Pigment Performance in Microwave-Assisted Extraction of Arthrospira platensis

  • Anna Trubetskaya,
  • Roland Haseneder,
  • Maximilian Lippold,
  • Rob J. F. van Haren,
  • Volker Herdegen,
  • Lisa Ditscherlein,
  • James J. Leahy,
  • Italo Pisano,
  • Yvonne Joseph and
  • Jan Zuber
  • + 1 author

30 September 2025

Phycocyanin, a blue pigment from Arthrospira platensis, is widely used as a natural colorant in food products, but its application is limited by its sensitivity to light and temperature during extraction and storage. This study explored the impact of...

  • Article
  • Open Access
1,003 Views
21 Pages

Ulvan-Na, an Ulvan Subjected to Na+ Cation Exchange, Improves Intestinal Barrier Function in Age-Related Leaky Gut

  • Yuka Maejima,
  • Yuki Morioka,
  • Yusei Sato,
  • Masanori Hiraoka,
  • Ayumu Onda and
  • Takushi Namba

30 September 2025

The global increase in life expectancy underscores the need to promote healthy aging, particularly by addressing age-related leaky gut syndrome, which contributes to systemic inflammation and chronic disease. This study focused on the sustainable pro...

  • Review
  • Open Access
1,431 Views
15 Pages

Marine-Derived Ligands of Nicotinic Acetylcholine Receptors in Cancer Research

  • Igor E. Kasheverov,
  • Irina V. Shelukhina,
  • Yuri N. Utkin and
  • Victor I. Tsetlin

30 September 2025

Marine sources contain compounds that act on a wide variety of systems, including ligand-gated ion channels. This review will focus on the effectors of nicotinic acetylcholine receptors (nAChRs), for which the diversity of ligands and modulators from...

  • Article
  • Open Access
1 Citations
955 Views
17 Pages

Nemertide Alpha-1 as a Biopesticide: Aphid Deterrence, Antimicrobial Activity, and Safety Aspects

  • Quentin Laborde,
  • Katarzyna Dancewicz,
  • Erik Jacobsson,
  • Adam A. Strömstedt,
  • Taj Muhammad,
  • Camilla Eriksson,
  • Blazej Slazak,
  • Ulf Göransson and
  • Håkan S. Andersson

29 September 2025

Aphid control often relies on synthetic pesticides, but their overuse has raised concerns about resistance development and negative impact on wildlife and human health. Consequently, the search for new biopesticide agents has gained significant atten...

  • Article
  • Open Access
967 Views
16 Pages

28 September 2025

A series of guaiazulene derivatives were efficiently synthesized by one-step reaction using guaiazulene as the substrate. Their structures were fully characterized by comprehensive spectroscopic methods, and their antiviral activities against influen...

  • Article
  • Open Access
1 Citations
1,501 Views
41 Pages

A Robust Marine Collagen Peptide–Agarose 3D Culture System for In Vitro Modeling of Hepatocellular Carcinoma and Anti-Cancer Therapeutic Development

  • Lata Rajbongshi,
  • Ji-Eun Kim,
  • Jin-Eui Lee,
  • Su-Rin Lee,
  • Seon-Yeong Hwang,
  • Yuna Kim,
  • Young Mi Hong,
  • Sae-Ock Oh,
  • Byoung Soo Kim and
  • Sik Yoon
  • + 1 author

27 September 2025

The development of physiologically relevant three-dimensional (3D) culture systems is essential for modeling tumor complexity and improving the translational impact of cancer research. We established a 3D in vitro model of human hepatocellular carcin...

  • Review
  • Open Access
1 Citations
2,425 Views
26 Pages

27 September 2025

Tumor immunotherapy, a revolutionary cancer treatment, is hindered by inadequate immune cell activation, immunosuppressive tumor microenvironment (TME), and off-target toxicities of immunotherapeutics. These bottlenecks necessitate innovative strateg...

  • Article
  • Open Access
3,628 Views
20 Pages

A Stable Delivery System for Meretrix meretrix Derived Immunomodulatory Peptide (QLNWD): Fabrication and Characterization of Glycosylated Protein Nanoparticle

  • Wanyi Wu,
  • Zhixuan Wu,
  • Jiamin Cai,
  • Wenhong Cao,
  • Haisheng Lin,
  • Jialong Gao,
  • Xiuping Fan,
  • Huina Zheng and
  • Xiaoming Qin

27 September 2025

In this study, nanoparticles prepared by the heat-induced self-assembly of bovine serum albumin-dextran conjugates (BSA-DX) were utilized as an effective delivery system for the immunoregulatory peptide Gln-Leu-Asn-Trp-Asp (QLNWD) from Meretrix meret...

  • Article
  • Open Access
1,027 Views
22 Pages

Sustainable and Integral Valorization of Dosidicus gigas Pen Waste: Combined Production of Chitosan with Antibacterial Properties and Human and Marine Probiotics

  • Marta Lima,
  • Adrián Pedreira,
  • Noelia Sanz,
  • José Antonio Vázquez,
  • Míriam R. García,
  • Filipe Mergulhão and
  • Jesus Valcarcel

27 September 2025

This study details a biorefinery approach to valorize Dosidicus gigas squid pen waste. The process starts with the enzymatic deproteinization of squid pens, which prove effective with both Alcalase and Novozym, with the latter exhibiting a slightly h...

  • Review
  • Open Access
1,380 Views
23 Pages

Ecological Characteristics and Nutritional Values of Australia-Native Brown Algae Species

  • Chao Dong,
  • Cundong Xie,
  • Ziqi Lou,
  • Zu Jia Lee,
  • Colin J. Barrow and
  • Hafiz A. R. Suleria

26 September 2025

This review focuses on five native Australian brown algae species—Cystophora torulosa, Durvillaea potatorum, Ecklonia radiata, Hormosira banksii, and Phyllospora comosa—evaluating their environmental adaptability, biochemical composition,...

  • Article
  • Open Access
930 Views
19 Pages

26 September 2025

Age-related macular degeneration (AMD) progresses to vision-threatening dry and wet forms, with no effective dry AMD treatments available. The sulfated polysaccharide (GNP, 25.8 kDa) derived from Gelidium crinale exhibits diverse biological activitie...

  • Article
  • Open Access
1,081 Views
22 Pages

26 September 2025

Triple-negative breast cancers (TNBC) lack estrogen, progesterone, and express little, if any, HER2 receptors on their surface. No targeted therapies exist for this aggressive form of breast cancer. A library of enriched fractions from marine organis...

  • Article
  • Open Access
1,183 Views
22 Pages

Characterization of YKL-40 Binding to Extracellular Matrix Glycosaminoglycans

  • Unnur Magnusdottir,
  • Yiming Yang Jonatansdottir,
  • Kristinn R. Oskarsson,
  • Jens G. Hjorleifsson,
  • Jon M. Einarsson and
  • Finnbogi R. Thormodsson

26 September 2025

YKL-40 is a chitinase-like glycoprotein implicated in various pathological processes, yet its glycosaminoglycan (GAG) binding profile beyond heparin has not been examined. In this study, we performed a Microscale Thermophoresis (MST) analysis on the...

  • Review
  • Open Access
3 Citations
3,536 Views
37 Pages

26 September 2025

Mangroves represent a promising yet underexplored source of natural products. Sonneratia caseolaris (mangrove apple) is a widely distributed species with a long history of use in traditional medicine, and it is receiving increasing recognition for it...

  • Article
  • Open Access
883 Views
15 Pages

Novel Cyclic Tetrapeptides as Neuraminidase Inhibitors from a Sponge-Associated Penicillium sp. SCSIO41035

  • Weihao Chen,
  • Xiangliu Chen,
  • Mengjing Cong,
  • Jianglian She,
  • Xiaoyan Pang,
  • Shengrong Liao,
  • Bin Yang,
  • Xuefeng Zhou,
  • Yonghong Liu and
  • Junfeng Wang
  • + 1 author

26 September 2025

Four new compounds and three new natural products (17), including three novel cyclic tetrapeptides (penicopeptides B−D), along with three known spiroquinazoline analogs (810), were isolated from rice medium cultures of a sponge-as...

  • Article
  • Open Access
884 Views
11 Pages

Therapeutic Potential of DPHC, A Brown Seaweed Polyphenol, Against TNF-α-Induced Inflammatory Muscle Loss

  • Minji Kim,
  • Won-Woo Lee,
  • Kil-Nam Kim,
  • Young-Mog Kim,
  • You-Jin Jeon,
  • Fengqi Yang,
  • Seo-Young Kim and
  • Hyo-Geun Lee

26 September 2025

Inflammatory muscle loss results from excessive inflammatory responses, causing muscle damage and weakness. In the current investigation, we evaluated the protective effects of diphlorethohydroxycarmalol (DPHC) against tumor necrosis factor-alpha (TN...

  • Article
  • Open Access
1 Citations
1,152 Views
25 Pages

Marine Collagen from European Sea Bass (Dicentrarchus labrax) Waste for the Development of Chitosan/Collagen Scaffolds in Skin Tissue Engineering

  • Alessandro Coppola,
  • Maria Oliviero,
  • Noemi De Cesare,
  • Nello Russo,
  • Noemi Nappo,
  • Carmine Buonocore,
  • Gerardo Della Sala,
  • Pietro Tedesco,
  • Fortunato Palma Esposito and
  • Daniela Coppola
  • + 3 authors

25 September 2025

Over the past years, with the growing interest in sustainable biomaterials, marine collagen has been emerging as an interesting alternative to bovine collagen. It is more easily absorbed by the body and has higher bioavailability. In this study, coll...

  • Article
  • Open Access
1 Citations
1,071 Views
21 Pages

25 September 2025

Polysaccharides derived from green algae have garnered significant attention owing to their distinctive structural characteristics and biological activities. In particular, sulfated polysaccharides from these algae represent a promising frontier in t...

  • Article
  • Open Access
1 Citations
863 Views
13 Pages

25 September 2025

The survival and efficacy of probiotic bacteria depend on their ability to grow under optimal conditions and withstand environmental stresses, and marine macroalgae are emerging as promising prebiotic sources that may enhance their viability. In this...

  • Article
  • Open Access
1,380 Views
21 Pages

The Synergistic Role of Sargassum horneri Fucoidan and Lactobacillus plantarum: Microbiome and Gut Barrier Restoration in Zebrafish Colitis

  • N. M. Liyanage,
  • D. P. Nagahawatta,
  • H. H. A. C. K. Jayawardhana,
  • Jun-Geon Je,
  • Li Yiqiao,
  • Fengqi Yang,
  • Young-Sang Kim,
  • Kyung Yuk Ko and
  • You-Jin Jeon

25 September 2025

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by disruption of the intestinal barrier and gut microbiota imbalance, leading to significant impairment in patient quality of life. This study investigated the therapeutic efficac...

  • Article
  • Open Access
1 Citations
988 Views
18 Pages

25 September 2025

Ulva sp. is a fast-growing, widely distributed marine alga with significant potential across various sectors, yet it remains underutilised. This study optimised pressurised liquid extraction (PLE) to obtain high-value fractions from Ulva biomass. Usi...

  • Article
  • Open Access
783 Views
13 Pages

Cytotoxic Mechanism of Deep-Sea Fungus Chaetomium globosum YP-106 Metabolite Chaetomugilin O in Thyroid Cancer Cells

  • Yaqin Fan,
  • Wenhui Xiong,
  • Yuting Qiu,
  • Yang Li,
  • Xin Liu,
  • Peiqing He and
  • Guian Huang

24 September 2025

This study investigated the potential of the deep-sea-derived fungal metabolite, chlorinated azaphilone compound chaetomugilin O, in the treatment of thyroid cancer. Chaetomugilin O was extracted from the fungus Chaetomium globosum YP-106 and subject...

  • Review
  • Open Access
4,082 Views
23 Pages

Jellyfish Venom-Induced Cardiotoxicity and Immune Responses: Mechanisms and Potential Therapeutic Strategies

  • Yueyue Li,
  • Zhiwen Qiu,
  • Bingbing Li,
  • Xiaoyu Geng,
  • Xuelu Yu,
  • Yue Li,
  • Wei Li and
  • Jishun Yang

23 September 2025

Jellyfish stings represent a significant global marine hazard, causing injuries from localized skin damage to fatal systemic complications. While skin reactions are the most common symptom, heart toxicity (cardiotoxicity) is the primary cause of deat...

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Mar. Drugs - ISSN 1660-3397