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Keywords = histopathology and transmission electron microscopy

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26 pages, 6652 KiB  
Article
Platelet-Rich Plasma (PRP) Mitigates Silver Nanoparticle (AgNP)-Induced Pulmonary Fibrosis via iNOS/CD68/CASP3/TWIST1 Regulation: An Experimental Study and Bioinformatics Analysis
by Shaimaa R. Abdelmohsen, Ranya M. Abdelgalil, Asmaa M. Elmaghraby, Amira M. Negm, Reham Hammad, Eleni K. Efthimiadou, Sara Seriah, Hekmat M. El Magdoub, Hemat Elariny, Islam Farrag, Nahla El Shenawy, Doaa Abdelrahaman, Hussain Almalki, Ahmed A. Askar, Marwa M. El-Mosely, Fatma El Zahraa Abd El Hakam and Nadia M. Hamdy
Int. J. Mol. Sci. 2025, 26(14), 6782; https://doi.org/10.3390/ijms26146782 - 15 Jul 2025
Viewed by 340
Abstract
Platelet-rich plasma (PRP) has become an increasingly valuable biologic approach for personalized regenerative medicine because of its potent anti-inflammatory/healing effects. It is thought to be an excellent source of growth factors that can promote tissue healing and lessen fibrosis. Although this treatment has [...] Read more.
Platelet-rich plasma (PRP) has become an increasingly valuable biologic approach for personalized regenerative medicine because of its potent anti-inflammatory/healing effects. It is thought to be an excellent source of growth factors that can promote tissue healing and lessen fibrosis. Although this treatment has demonstrated effectiveness in numerous disease areas, its impact on pulmonary fibrosis (PF) caused by silver nanoparticles (AgNPs) via its antiapoptotic effects remains to be explored. AgNPs were synthesized biologically by Bacillus megaterium ATCC 55000. AgNP characterization was carried out via UV–Vis spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) imaging to reveal monodispersed spheres with a mean diameter of 45.17 nm. A total of 48 male Wistar rats divided into six groups, with 8 rats per group, were used in the current study on the basis of sample size and power. The groups used were the PRP donor, control, AgNP, AgNP + PRP, AgNP + dexamethasone (Dexa) rat groups, and a recovery group. Body weights, hydroxyproline (HP) levels, and CASP3 and TWIST1 gene expression levels were assessed. H&E and Sirius Red staining were performed. Immunohistochemical studies for inducible nitric oxide synthase (iNOS) and cluster of differentiation 68 (CD68) with histomorphometry were conducted. A significant reduction in body weight (BWt) was noted in the AgNP group compared with the AgNP + PRP group (p < 0.001). HP, CASP3, and TWIST1 expression levels were significantly increased by AgNPs but decreased upon PRP (p < 0.001) treatment. Compared with those in the control group, the adverse effects of AgNPs included PF, lung alveolar collapse, thickening of the interalveolar septa, widespread lymphocytic infiltration, increased alveolar macrophage CD68 expression, and iNOS positivity in the cells lining the alveoli. This work revealed that PRP treatment markedly improved the histopathological and immunohistochemical findings observed in the AgNP group in a manner comparable to that of the Dexa. In conclusion, these results demonstrated the therapeutic potential of PRP in a PF rat model induced via AgNPs. This study revealed that PRP treatment significantly improved the histopathological and immunohistochemical alterations observed in the AgNP-induced group, with effects comparable to those of the Dexa. In conclusion, these findings highlight the therapeutic potential of PRP in a rat model of AgNP-induced PF. Full article
(This article belongs to the Special Issue New Advances in Cancer Genomics)
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17 pages, 22603 KiB  
Article
High-Fat Diet-Induced Diabetic Cardiomyopathy in Female Zebrafish: Cardiac Pathology and Functional Decline Mediated by Type 2 Diabetes
by Shuaiwang Huang, Zhanglin Chen, Haoming Li, Yunyi Zou, Bihan Wang, Wenjun Zhao, Lan Zheng, Zuoqiong Zhou, Xiyang Peng and Changfa Tang
Nutrients 2025, 17(13), 2209; https://doi.org/10.3390/nu17132209 - 2 Jul 2025
Viewed by 495
Abstract
Background: Diabetic cardiomyopathy (DCM) is characterized by progressive cardiac dysfunction, metabolic dysregulation, myocardial fibrosis, and mitochondrial impairment. Existing animal models, such as streptozotocin (STZ)-induced models, suffer from high mortality and fail to replicate chronic metabolic dysregulation induced by high-fat diets (HFD), whereas HFD [...] Read more.
Background: Diabetic cardiomyopathy (DCM) is characterized by progressive cardiac dysfunction, metabolic dysregulation, myocardial fibrosis, and mitochondrial impairment. Existing animal models, such as streptozotocin (STZ)-induced models, suffer from high mortality and fail to replicate chronic metabolic dysregulation induced by high-fat diets (HFD), whereas HFD or HFD/STZ-combined rodent models require high maintenance costs. This study aimed to establish a zebrafish HFD-DCM model to facilitate mechanistic exploration and drug discovery. Methods: Eighty wild-type female zebrafish were divided into normal diet (N, 6% fat) and HFD (H, 24% fat) groups and fed the diet for 8 weeks. Metabolic phenotypes were evaluated using intraperitoneal glucose tolerance tests and insulin level analysis. Cardiac function was assessed by using echocardiography (ejection fraction, E peak). Structural, metabolic, and oxidative stress alterations were analyzed by histopathology (H&E, Masson, and Oil Red O staining), molecular assays (RT-qPCR, Western blotting), and mitochondrial structure/function evaluations (respiratory chain activity, transmission electron microscopy, and DHE staining). Results: HFD-fed zebrafish developed obesity, insulin resistance, and impaired glucose tolerance. Echocardiography revealed cardiac hypertrophy, reduced ejection fraction, and diastolic dysfunction. Excessive lipid accumulation, upregulated fibrosis/inflammatory markers, impaired mitochondrial respiration, elevated reactive oxygen species levels, and a disrupted redox balance were observed. Conclusions: We established a female zebrafish HFD model that recapitulates human DCM features, including hypertrophy, metabolic dysregulation, fibrosis, inflammation, and mitochondrial dysfunction. This model offers novel insights into DCM pathogenesis and serves as a valuable platform for mechanistic studies and targeted drug screening. Full article
(This article belongs to the Special Issue The Diabetes Diet: Making a Healthy Eating Plan)
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15 pages, 4413 KiB  
Article
Type I Interferons in SARS-CoV-2 Cutaneous Infection: Is There a Role in Antiviral Defense?
by Tatiana Mina Yendo, Raquel Leão Orfali, Naiura Vieira Pereira, Natalli Zanete Pereira, Yasmim Álefe Leuzzi Ramos, Joyce Tiyeko Kawakami, Amaro Nunes Duarte-Neto, Mirian Nacagami Sotto, Luiz Fernando Ferraz Silva, Alberto José da Silva Duarte, Maria Notomi Sato and Valeria Aoki
Int. J. Mol. Sci. 2025, 26(13), 6049; https://doi.org/10.3390/ijms26136049 - 24 Jun 2025
Viewed by 358
Abstract
SARS-CoV-2, a β-coronavirus, primarily affects the lungs, with non-specific lesions and no cytopathic viral effect in the skin. Cutaneous antiviral mechanisms include activation of TLR/IRF pathways and production of type I IFN. We evaluated the antiviral mechanisms involved in the skin of COVID-19 [...] Read more.
SARS-CoV-2, a β-coronavirus, primarily affects the lungs, with non-specific lesions and no cytopathic viral effect in the skin. Cutaneous antiviral mechanisms include activation of TLR/IRF pathways and production of type I IFN. We evaluated the antiviral mechanisms involved in the skin of COVID-19 patients, including skin samples from 35 deceased patients who had contracted COVID-19 before the launch of the vaccine. Detection of SARS-CoV-2 in the skin was performed using transmission electron microscopy and RT-qPCR. Microscopic and molecular effects of the virus in skin were evaluated by histopathology, RT-qPCR, and immunohistochemistry (IHC). The results revealed the presence of SARS-CoV-2 and microscopic changes, including microvascular hyaline thrombi, perivascular dermatitis, and eccrine gland necrosis. There was increased transcription of TBK1 and a reduction in transcription of TNFα by RT-qPCR in the COVID-19 group. IHC revealed reduced expression of ACE2, TLR7, and IL-6, and elevated expression of IFN-β by epidermal cells. In the dermis, there was decreased expression of STING, IFN-β, and TNF-α and increased expression of IL-6 in sweat glands. Our results highlight the role of type I IFN in the skin of COVID-19 patients, which may modulate the cutaneous response to SARS-CoV-2. Full article
(This article belongs to the Special Issue Novel Approaches to Potential COVID-19 Molecular Therapeutics)
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43 pages, 4992 KiB  
Article
Restorative Effects of Synbiotics on Colonic Ultrastructure and Oxidative Stress in Dogs with Chronic Enteropathy
by Dipak Kumar Sahoo, Tracey Stewart, Emily M. Lindgreen, Bhakti Patel, Ashish Patel, Jigneshkumar N. Trivedi, Valerie Parker, Adam J. Rudinsky, Jenessa A. Winston, Agnes Bourgois-Mochel, Jonathan P. Mochel, Karin Allenspach, Romy M. Heilmann and Albert E. Jergens
Antioxidants 2025, 14(6), 727; https://doi.org/10.3390/antiox14060727 - 13 Jun 2025
Viewed by 2454
Abstract
Synbiotics can be used to reduce intestinal inflammation and mitigate dysbiosis in dogs with chronic inflammatory enteropathy (CIE). Prior research has not assessed the colonic mucosal ultrastructure of dogs with active CIE treated with synbiotics, nor has it determined a possible association between [...] Read more.
Synbiotics can be used to reduce intestinal inflammation and mitigate dysbiosis in dogs with chronic inflammatory enteropathy (CIE). Prior research has not assessed the colonic mucosal ultrastructure of dogs with active CIE treated with synbiotics, nor has it determined a possible association between morphologic injury and signaling pathways. Twenty client-owned dogs diagnosed with CIE were randomized to receive either a hydrolyzed diet (placebo; PL) or a hydrolyzed diet supplemented with synbiotic-IgY (SYN) for 6 weeks. Endoscopic biopsies of the colon were obtained for histopathologic, ultrastructural, and molecular analyses and were compared before and after treatment. Using transmission electron microscopy (TEM), an analysis of the ultrastructural alterations in microvilli length (MVL), mitochondria (MITO), and rough endoplasmic reticulum (ER) was compared between treatment groups. To explore potential signaling pathways that might modulate MITO and ER stress, a transcriptomic analysis was also performed. The degree of mucosal ultrastructural pathology differed among individual dogs before and after treatment. Morphologic alterations in enterocytes, MVL, MITO, and ER were detected without significant differences between PL and SYN dogs prior to treatment. Notable changes in ultrastructural alterations were identified post-treatment, with SYN-treated dogs exhibiting significant improvement in MVL, MITO, and ER injury scores compared to PL-treated dogs. Transcriptomic profiling showed many pathways and key genes to be associated with MITO and ER injury. Multiple signaling pathways and their associated genes with protective effects, including fibroblast growth factor 2 (FGF2), fibroblast growth factor 7 (FGF7), fibroblast growth factor 10 (FGF10), synaptic Ras GTPase activating protein 1 (SynGAP1), RAS guanyl releasing protein 2 (RASGRP2), RAS guanyl releasing protein 3 (RASGRP3), thrombospondin 1 (THBS1), colony stimulating factor 1 (CSF1), colony stimulating factor 3 (CSF3), interleukin 21 receptor (IL21R), collagen type VI alpha 6 chain (COL6A6), ectodysplasin A receptor (EDAR), forkhead box P3 (FoxP3), follistatin (FST), gremlin 1 (GREM1), myocyte enhancer factor 2B (MEF2B), neuregulin 1 (NRG1), collagen type I alpha 1 chain (COL1A1), hepatocyte growth factor (HGF), 5-hydroxytryptamine receptor 7 (HTR7), and platelet derived growth factor receptor beta (PDGFR-β), were upregulated with SYN treatment. Differential gene expression was associated with improved MITO and ER ultrastructural integrity and a reduction in oxidative stress. Conversely, other genes, such as protein kinase cAMP-activated catalytic subunit beta (PRKACB), phospholipase A2 group XIIB (PLA2G12B), calmodulin 1 (CALM1), calmodulin 2 (CALM2), and interleukin-18 (IL18), which have harmful effects, were downregulated following SYN treatment. In dogs treated with PL, genes including PRKACB and CALM2 were upregulated, while other genes, such as FGF2, FGF10, SynGAP1, RASGRP2, RASGRP3, and IL21R, were downregulated. Dogs with CIE have colonic ultrastructural pathology at diagnosis, which improves following synbiotic treatment. Ultrastructural improvement is associated with an upregulation of protective genes and a downregulation of harmful genes that mediate their effects through multiple signaling pathways. Full article
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16 pages, 5155 KiB  
Article
Histopathological Study of Host–Pathogen Interactions Between Cordyceps javanica PSUC002 and Hypothenemus hampei
by Sinlapachai Senarat, Peerasak Bunsap, Pisit Poolprasert, Anjaree Inchan, Natthawut Charoenphon, Peerapon Sornying and Narit Thaochan
J. Fungi 2025, 11(6), 423; https://doi.org/10.3390/jof11060423 - 30 May 2025
Viewed by 1025
Abstract
The use of entomopathogenic fungi (EPF), such as Cordyceps javanica, to reduce insect pest populations is gaining traction since it is an environmentally safe approach that can control many pests at different life stages. Here, we focus on the histopathology of the [...] Read more.
The use of entomopathogenic fungi (EPF), such as Cordyceps javanica, to reduce insect pest populations is gaining traction since it is an environmentally safe approach that can control many pests at different life stages. Here, we focus on the histopathology of the coffee berry borer, Hypothenemus hampei, infected by C. javanica. Morphological observation revealed that C. javanica conidia germinated within 12 h following inoculation according to light microscopic and ultrastructural levels. The fungus thoroughly penetrated the fat body and muscular tissue between 84 and 120 h post-inoculation. Transmission electron microscopy (TEM) confirmed the hyphal invasion of the cuticle at 12 h post-inoculation, with progressive tissue disruption and organelle degeneration, especially mitochondria and rough endoplasmic reticulum in adipocytes. All organelles were completely degenerated at 96 h post-inoculation. There was evidence of a connection between C. javanica activity and the coffee berry borer that might cause histopathological changes in the host defense against the pathogen, pointing to increased mortality and potential control of coffee berry borer in natural populations. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) confirmed that apoptotic cells were slightly increased in the adipose tissue and integument of the coffee berry borer. The ability of C. javanica to fatally infect the coffee berry borer suggests that it could be deployed as a biological control agent in the field. Full article
(This article belongs to the Special Issue Current Trends in Mycological Research in Southeast Asia)
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19 pages, 26737 KiB  
Article
Caffeic Acid Phenethyl Ester Protects Against Doxorubicin-Induced Cardiotoxicity via Inhibiting the ROS-MLKL-Mediated Cross-Talk Between Oxidative Stress and Necroptosis
by Chenying Jiang, Tinghuang Zhang, Jiawen Gu, Chenjun Shen, Hang Gao, Hai An, Chen Wang, Jiahui Lu, Shengzhang Lin, Huajun Zhao and Zhihui Zhu
Biomolecules 2025, 15(6), 783; https://doi.org/10.3390/biom15060783 - 28 May 2025
Cited by 1 | Viewed by 661
Abstract
Purpose: Doxorubicin (DOX) is a broad-spectrum anti-tumor anthracycline drug. However, its clinical application is greatly limited due to the side effect of cardiotoxicity. Caffeic acid phenethyl ester (CAPE) is one of the major biologically active compounds isolated from propolis, which is effective in [...] Read more.
Purpose: Doxorubicin (DOX) is a broad-spectrum anti-tumor anthracycline drug. However, its clinical application is greatly limited due to the side effect of cardiotoxicity. Caffeic acid phenethyl ester (CAPE) is one of the major biologically active compounds isolated from propolis, which is effective in the treatment of cardiovascular diseases. The purpose of this study aimed to explore the possible mechanism of CAPE’s protective effect on DOX-induced cardiotoxicity (DIC). Methods: In vivo, a DIC model was established by the intraperitoneal injection of 3 mg/kg DOX. The cardiac function of mice was monitored by electrocardiograms. Histopathological changes in myocardial tissue were detected by H&E staining. Serum samples were tested for the level of markers of myocardial injury. In vitro, transmission electron microscopy was used to assess the mitochondrial damage. Oxidative stress was measured by flow cytometry and mitochondrial respiration analysis. Necroptosis pathway changes were detected by Western blotting. Furthermore, the overexpression plasmid of a key necroptosis gene, necroptosis inhibitor or ROS inducer/inhibitor was applied to H9c2 and AC16 cells to explore whether CAPE exerted a protective effect against DIC through the cross-talk mediated by ROS and MLKL. Results: CAPE could improve the cardiac function and protect against myocardial tissue. CAPE pre-administration treatment attenuated the DOX-induced generation of ROS, protected mitochondrial functions and inhibited necroptosis. Moreover, there was cross-talk between the ROS and necroptosis. CAPE could protect against DIC by inhibiting the ROS-MLKL signaling that regulated the cross-talk. Conclusions: CAPE alleviated the oxidative stress and necroptosis of DIC, indicating that the cross-talk mediated by ROS-MLKL signaling may be a potential therapeutic mechanism for clinical DIC. Full article
(This article belongs to the Section Molecular Biology)
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22 pages, 3529 KiB  
Article
Chitosan-Folic Acid-Coated Quercetin-Loaded PLGA Nanoparticles for Hepatic Carcinoma Treatment
by Anil Kumar Sahdev, Chaitany Jayprakash Raorane, Mohammad Ajmal Ali, Khalid Mashay Al-Anazi, Ranjith Kumar Manoharan, Vinit Raj and Anita Singh
Polymers 2025, 17(7), 955; https://doi.org/10.3390/polym17070955 - 31 Mar 2025
Cited by 1 | Viewed by 776
Abstract
Hepatocellular carcinoma (HCC) causes the third highest mortality worldwide. Liver ablation, surgery, and embolization are conventional methods for treatment. However, these methods have limitations. To overcome these issues, nanomedicines have potential due to their high stability, high drug load capacity, and controlled release. [...] Read more.
Hepatocellular carcinoma (HCC) causes the third highest mortality worldwide. Liver ablation, surgery, and embolization are conventional methods for treatment. However, these methods have limitations. To overcome these issues, nanomedicines have potential due to their high stability, high drug load capacity, and controlled release. Thus, we prepared quercetin-loaded polylactic-co-glycolic acid (PLGA) nanoparticles coated with folic acid-chitosan (QPCF-NPs) to improve drug delivery and targetability applications of quercetin for the treatment of HCC. We prepared QPCF-NPs by solvent evaporation and coated them with chitosan-folic acid (CS-FA). QPCF-NPs were examined using Fourier-Transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). In addition, the drug release rate and cytotoxicity were studied. Moreover, in vivo HCC studies such as histopathology and biochemical parameters were conducted. Subsequently, QPCF-NPs with a spherical shape and an average size of 200–290 nm have been demonstrated to have formed by FTIR, XRD, SEM, and TEM. Further, we observed sustained drug release from QPCF-NPs compared to quercetin. Cellular cytotoxicity showed significant inhibition in the HEPG2-cell line with QPCF-NPs treatment. Biochemical estimate and oxidative stress regulation were considerably more regulated in the treatment groups than the HCC group in a dose-dependent way after subcutaneous administration of QPCF-NPs. ELISA of interleukin and caspase-3 demonstrated the anticipated results in comparison to the carcinogen control group. Compared to earlier preparations, the QPCF-NPs generated demonstrated better drug targetability and potency for treating HCC. Full article
(This article belongs to the Section Polymer Applications)
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20 pages, 22332 KiB  
Article
Ginsenoside Rb1 Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1/PGC-1α/PPARα Signaling Pathway
by Ziwei Zhou, Zhimin Song, Xiaomeng Guo, Qi Wang, Meijing Li, Minyu Zhang and Muxin Gong
Pharmaceuticals 2025, 18(4), 500; https://doi.org/10.3390/ph18040500 - 30 Mar 2025
Cited by 1 | Viewed by 638
Abstract
Background: Heart failure (HF), the terminal stage of cardiovascular disease with high morbidity and mortality, remains poorly managed by current therapies. Ventricular remodeling in HF is fundamentally characterized by myocardial fibrosis. While ginsenoside Rb1 has demonstrated anti-fibrotic effects in HF, the underlying [...] Read more.
Background: Heart failure (HF), the terminal stage of cardiovascular disease with high morbidity and mortality, remains poorly managed by current therapies. Ventricular remodeling in HF is fundamentally characterized by myocardial fibrosis. While ginsenoside Rb1 has demonstrated anti-fibrotic effects in HF, the underlying mechanism remains unclear. Twist1, an upstream regulator of energy metabolism factors PGC-1α and PPARα, may attenuate fibrosis by preserving systemic energy homeostasis, suggesting its pivotal role in HF pathogenesis. This study explores ginsenoside Rb1′s anti-HF mechanisms through the regulation of ginsenoside Rb1 on these metabolic regulators. Methods: Sprague Dawley rats were subjected to a ligation of the left anterior descending coronary artery to induce an HF model, followed by ginsenoside Rb1 treatment for 6 weeks. Therapeutic effects were evaluated through cardiac function assessment, myocardial histopathological staining (HE, Masson, immunofluorescence, immunohistochemistry), mitochondrial morphology observation (transmission electron microscopy), energy metabolism analysis (electron transport chain efficiency, mitochondrial membrane potential, ATP content), and protein expression profiling (Twist1, PGC-1α, PPARα, GLUT4, PPARγ). Additionally, H9c2 cells induced with endothelin-1 to model HF were employed as an in vitro model to further investigate ginsenoside Rb1′s regulatory effects on the Twist1/PGC-1α/PPARα signaling pathway. Results: Ginsenoside Rb1 can restore cardiac function in HF rats, improve mitochondrial function, alleviate energy metabolism disorders, and inhibit ventricular remodeling. By modulating the Twist1/PGC-1α/PPARα signaling pathway, ginsenoside Rb1 suppressed the abnormal overexpression of Twist1 and maintained normal expression of downstream PGC-1α and PPARα. In vitro experiments further demonstrated that ginsenoside Rb1 significantly inhibited Twist1 expression in H9c2 cardiomyocytes with HF while promoting PGC-1α and PPARα expression, thereby restoring myocardial energy metabolism and mitigating ventricular remodeling in HF. Conclusions: Ginsenoside Rb1 can inhibit the upregulation of Twist1 and activate the expression of its downstream PGC-1α and PPARα expression, by modulating the Twist1/PGC-1α/PPARα signaling pathway, alleviating ventricular remodeling in HF patients and improving myocardial energy metabolism dysfunction. Twist1 may be a key target for the treatment of HF. This study not only elucidates the mechanism by which ginsenoside Rb1 alleviates HF, but also provides new insights into the clinical treatment of HF. Full article
(This article belongs to the Section Pharmacology)
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16 pages, 4715 KiB  
Article
Respiratory Muscle Injury Following Acute Monocled Cobra (Naja kaouthia) Envenoming: Histopathological Study in Rat Diaphragm
by Wanida Chuaikhongthong, Wipapan Khimmaktong, Natyamee Thipthong, Nissara Lorthong and Janeyuth Chaisakul
Curr. Issues Mol. Biol. 2025, 47(2), 86; https://doi.org/10.3390/cimb47020086 - 29 Jan 2025
Viewed by 1599
Abstract
Clinical symptoms of monocled cobra (Naja kaouthia) envenoming include the paralysis of extraocular muscles, local tissue necrosis and death through respiratory failure. These neurotoxic outcomes are mainly due to the inhibitory action of postsynaptic neurotoxins to nicotinic acetylcholine receptors. However, injuries [...] Read more.
Clinical symptoms of monocled cobra (Naja kaouthia) envenoming include the paralysis of extraocular muscles, local tissue necrosis and death through respiratory failure. These neurotoxic outcomes are mainly due to the inhibitory action of postsynaptic neurotoxins to nicotinic acetylcholine receptors. However, injuries involving respiratory muscles have rarely been investigated. In this study, we determined the effect of N. kaouthia envenoming on morphological changes in the rat diaphragm. The efficacy of cobra monovalent antivenom in neutralising the histopathological effects of N. kaouthia venom was also evaluated. The intramuscular (i.m.) administration of N. kaouthia venom (2 mg/kg) caused skeletal muscle fibre atrophy and ruptures of myofibrils shown via a light microscope study. Transmission electron microscopy (TEM) revealed the zig-zagging of the Z-band, mitochondrial damages and degeneration of the synaptic fold of the neuromuscular junction following experimental cobra envenoming for 4 h. Intravenous administration of cobra antivenom at manufacturer-recommended doses diminished histopathological changes in the diaphragm following the administration of cobra venom. The expression of NF-kB and MuRF1 in the experimentally N. kaouthia-envenomed diaphragm indicated inflammation and tissue atrophy in the immunofluorescence analysis, respectively. In this study, we found that there were respiratory muscle injuries following N. kaouthia envenoming. The early administration of monovalent N. kaouthia antivenom is capable of neutralising neurotoxic outcomes following cobra envenoming. Full article
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16 pages, 2416 KiB  
Article
Sustainable Nanomedicine: Enhancement of Asplatin’s Cytotoxicity In Vitro and In Vivo Using Green-Synthesized Zinc Oxide Nanoparticles Formed via Microwave-Assisted and Gambogic Acid-Mediated Processes
by Hatem A. F. M. Hassan, Nada K. Sedky, Mohamed S. Nafie, Noha Khalil Mahdy, Iten M. Fawzy, Toka Waleed Fayed, Eduard Preis, Udo Bakowsky and Sherif Ashraf Fahmy
Molecules 2024, 29(22), 5327; https://doi.org/10.3390/molecules29225327 - 12 Nov 2024
Cited by 1 | Viewed by 2419
Abstract
Chemoresistance encountered using conventional chemotherapy demands novel treatment approaches. Asplatin (Asp), a novel platinum (IV) prodrug designed to release cisplatin and aspirin in a reductive environment, has demonstrated high cytotoxicity at reduced drug resistance. Herein, we investigated the ability of green-synthesized nanocarriers to [...] Read more.
Chemoresistance encountered using conventional chemotherapy demands novel treatment approaches. Asplatin (Asp), a novel platinum (IV) prodrug designed to release cisplatin and aspirin in a reductive environment, has demonstrated high cytotoxicity at reduced drug resistance. Herein, we investigated the ability of green-synthesized nanocarriers to enhance Asp’s efficacy. Zinc oxide nanoparticles (ZnO-NPs) were synthesized using a green microwave-assisted method with the reducing and capping agent gambogic acid (GA). These nanoparticles were then loaded with Asp, yielding Asp@ZnO-NPs. Transmission electron microscopy was utilized to study the morphological features of ZnO-NPs. Cell viability studies conducted on MDA-MB-231 breast cancer cells demonstrated the ability of the Asp@ZnO-NPs treatment to significantly decrease Asp’s half-maximal inhibitory concentration (IC50) (5 ± 1 µg/mL). This was further demonstrated using flow cytometric analysis that revealed the capacity of Asp@ZnO-NPs treatment to significantly increase late apoptotic fractions. Furthermore, in vivo studies carried out using solid Ehrlich carcinoma-bearing mice showed significant tumor volume reduction with the Asp@ZnO-NPs treatment (156.3 ± 7.6 mm3), compared to Asp alone (202.3 ± 8.4 mm3) and untreated controls (342.6 ± 10.3 mm3). The histopathological analysis further demonstrated the increased necrosis in Asp@ZnO-NPs-treated group. This study revealed that Asp@ZnO-NPs, synthesized using an eco-friendly approach, significantly enhanced Asp’s anticancer activity, offering a sustainable solution for potent anticancer formulations. Full article
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14 pages, 8177 KiB  
Article
The Protective Role of Intermedin in Contrast-Induced Acute Kidney Injury: Enhancing Peritubular Capillary Endothelial Cell Adhesion and Integrity Through the cAMP/Rac1 Pathway
by Tingting Gao, Ruiyuan Gu, Heng Wang, Lizheng Li, Bojin Zhang, Jie Hu, Qinqin Tian, Runze Chang, Ruijing Zhang, Guoping Zheng and Honglin Dong
Int. J. Mol. Sci. 2024, 25(20), 11110; https://doi.org/10.3390/ijms252011110 - 16 Oct 2024
Viewed by 1444
Abstract
Contrast-induced acute kidney injury (CIAKI) is a common complication with limited treatments. Intermedin (IMD), a peptide belonging to the calcitonin gene-related peptide family, promotes vasodilation and endothelial stability, but its role in mitigating CIAKI remains unexplored. This study investigates the protective effects of [...] Read more.
Contrast-induced acute kidney injury (CIAKI) is a common complication with limited treatments. Intermedin (IMD), a peptide belonging to the calcitonin gene-related peptide family, promotes vasodilation and endothelial stability, but its role in mitigating CIAKI remains unexplored. This study investigates the protective effects of IMD in CIAKI, focusing on its mechanisms, particularly the cAMP/Rac1 signaling pathway. Human umbilical vein endothelial cells (HUVECs) were treated with iohexol to simulate kidney injury in vitro. The protective effects of IMD were assessed using CCK8 assay, flow cytometry, ELISA, and Western blotting. A CIAKI rat model was utilized to evaluate renal peritubular capillary endothelial cell injury and renal function through histopathology, immunohistochemistry, immunofluorescence, Western blotting, and transmission electron microscopy. In vitro, IMD significantly enhanced HUVEC viability and mitigated iohexol-induced toxicity by preserving intercellular adhesion junctions and activating the cAMP/Rac1 pathway, with Rac1 inhibition attenuating these protective effects. In vivo, CIAKI caused severe damage to peritubular capillary endothelial cell junctions, impairing renal function. IMD treatment markedly improved renal function, an effect negated by Rac1 inhibition. IMD protects against renal injury in CIAKI by activating the cAMP/Rac1 pathway, preserving peritubular capillary endothelial integrity and alleviating acute renal injury from contrast media. These findings suggest that IMD has therapeutic potential in CIAKI and highlight the cAMP/Rac1 pathway as a promising target for preventing contrast-induced acute kidney injury in at-risk patients, ultimately improving clinical outcomes. Full article
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24 pages, 4163 KiB  
Article
Biosynthesis of Zinc Oxide Nanoparticles Using Seaweed: Exploring Their Therapeutic Potentials
by Sohaila I. Abotaleb, Saly F. Gheda, Nanis G. Allam, Einas H. El-Shatoury, João Cotas, Leonel Pereira and Ali M. Saeed
Appl. Sci. 2024, 14(16), 7069; https://doi.org/10.3390/app14167069 - 12 Aug 2024
Cited by 2 | Viewed by 2579
Abstract
This study aimed to biosynthesize zinc oxide nanoparticles (ZnO-NPs) using extracts from various seaweeds, including Ulva lactuca, Ulva intestinalis (Chlorophyta), and Sargassum muticum (Phaeophyceae). The biosynthesized ZnO-NPs were characterized using UV spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and [...] Read more.
This study aimed to biosynthesize zinc oxide nanoparticles (ZnO-NPs) using extracts from various seaweeds, including Ulva lactuca, Ulva intestinalis (Chlorophyta), and Sargassum muticum (Phaeophyceae). The biosynthesized ZnO-NPs were characterized using UV spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and zeta potential analysis. Their antimicrobial activity was assessed using the disk diffusion method, revealing significant efficacy against two bacterial species (Klebsiella pneumoniae and Escherichia coli) and two fungal species (Candida albicans and Aspergillus niger). Additionally, the antioxidant potential of the ZnO-NPs was evaluated based on the total antioxidant capacity, ferric reducing antioxidant power, and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assays. The antioxidant activity of the ZnO-NPs was confirmed using the three antioxidant assays. The ZnO-NPs of U. lactuca recorded the highest antioxidant activity. The cytotoxicity of the ZnO-NPs was tested on different cell lines using the MTT assay. The ZnO-NPs of U. lactuca showed very weak cytotoxic effects on WI 38 (84.98 ± 4.6 µg/mL) and 23, and this result confirmed its safety on normal cells. The ZnO-NPs of U. lactuca showed moderate cytotoxic effects on the HepG-2 (46.66 ± 2.8 µg/mL) and MCF-7 (30.60 ± 2.1 µg/mL) cell lines. In an in vivo study, the ZnO-NPs of U. lactuca showed a decrease in tumor volume, weight, and serum malondialdehyde in experimental mice, while the total antioxidant capacity of the serum was increased. Histopathological changes in ZnO-NPs indicated a reduction in tumor size, a lower number of mitosis divisions, and a rise in apoptosis correlated with the ZnO-NPs of the U. lactuca-treated groups. In conclusion, biosynthesized ZnO-NPs from seaweed showed potent antimicrobial, antioxidant, and antitumor activities, which can be used in the pharmaceutical industry. Full article
(This article belongs to the Section Applied Biosciences and Bioengineering)
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18 pages, 10482 KiB  
Article
Basal Linear Deposit: Normal Physiological Ageing or a Defining Lesion of Age-Related Macular Degeneration?
by Akshaya Lakshmi Thananjeyan, Jennifer Arnold, Mitchell Lee, Cheryl Au, Victoria Pye, Michele C. Madigan and Svetlana Cherepanoff
J. Clin. Med. 2024, 13(16), 4611; https://doi.org/10.3390/jcm13164611 - 7 Aug 2024
Viewed by 1312
Abstract
Objective: To determine if basal linear deposit (BLinD) is a specific lesion of age-related macular degeneration (AMD). Methods: The cohort was selected from a clinically and histopathologically validated archive (Sarks Archive) and consisted of 10 normal eyes (age 55–80 years) without any macular [...] Read more.
Objective: To determine if basal linear deposit (BLinD) is a specific lesion of age-related macular degeneration (AMD). Methods: The cohort was selected from a clinically and histopathologically validated archive (Sarks Archive) and consisted of 10 normal eyes (age 55–80 years) without any macular basal laminar deposit (BLamD) (Sarks Group I) and 16 normal aged eyes (age 57–88 years) with patchy BLamD (Sarks Group II). Only eyes with in vivo fundus assessment and corresponding high-resolution transmission electron microscopy (TEM) micrographs of the macula were included. Semithin sections and fellow-eye paraffin sections were additionally examined. BLinD was defined as a diffuse layer of electron-lucent vesicles external to the retinal pigment epithelium (RPE) basement membrane by TEM and was graded as follows: (i) Grade 0, absence of a continuous layer; (ii) Grade 1, a continuous layer up to three times the thickness of the RPE basement membrane (0.9 µm); (iii) Grade 2, a continuous layer greater than 0.9 µm. Bruch’s membrane (BrM) hyalinisation and RPE abnormalities were determined by light microscopic examination of corresponding semithin and paraffin sections. Results: BLinD was identified in both normal (30%) and normal aged (62.5%) eyes. BLinD was thicker in normal aged eyes (p = 0.045; 95% CI 0.04–3.4). BLinD thickness positively correlated with both the degree of BrM hyalinisation (p = 0.049; 95% CI 0.05–2.69) and increasing microscopic RPE abnormalities (p = 0.022; 95% CI 0.188–2.422). RPE abnormalities were more likely to be observed in eyes with increased BrM hyalinisation (p = 0.044; 95% CI 0.61–4.319). Conclusions: BLinD is most likely an age-related deposit rather than a specific lesion of AMD. Its accumulation is associated with increasing BrM hyalinisation and microscopic RPE abnormalities, suggesting a relationship with dysregulated RPE metabolism and/or transport. Full article
(This article belongs to the Special Issue Vitreoretinal Disease: Clinical Insights and Treatment Strategies)
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30 pages, 6481 KiB  
Article
Enhanced Antibacterial Activity of Clindamycin Using Molecularly Imprinted Polymer Nanoparticles Loaded with Polyurethane Nanofibrous Scaffolds for the Treatment of Acne Vulgaris
by Sammar Fathy Elhabal, Rehab Abdelmonem, Rasha Mohamed El Nashar, Mohamed Fathi Mohamed Elrefai, Ahmed Mohsen Elsaid Hamdan, Nesreen A. Safwat, Mai S. Shoela, Fatma E. Hassan, Amira Rizk, Soad L. Kabil, Nagla Ahmed El-Nabarawy, Amal Anwar Taha and Mohamed El-Nabarawi
Pharmaceutics 2024, 16(7), 947; https://doi.org/10.3390/pharmaceutics16070947 - 17 Jul 2024
Cited by 17 | Viewed by 3234
Abstract
Acne vulgaris, a prevalent skin condition, arises from an imbalance in skin flora, fostering bacterial overgrowth. Addressing this issue, clindamycin molecularly imprinted polymeric nanoparticles (Clin-MIP) loaded onto polyurethane nanofiber scaffolds were developed for acne treatment. Clin-MIP was synthesized via precipitation polymerization using methacrylic [...] Read more.
Acne vulgaris, a prevalent skin condition, arises from an imbalance in skin flora, fostering bacterial overgrowth. Addressing this issue, clindamycin molecularly imprinted polymeric nanoparticles (Clin-MIP) loaded onto polyurethane nanofiber scaffolds were developed for acne treatment. Clin-MIP was synthesized via precipitation polymerization using methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), and azoisobutyronitrile (AIBN) as functional monomers, crosslinkers, and free-radical initiators, respectively. MIP characterization utilized Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) before being incorporated into polyurethane nanofibers through electrospinning. Further analysis involved FTIR, scanning electron microscopy (SEM), in vitro release studies, and an ex vivo study. Clin-MIP showed strong antibacterial activity against S. aureus, with inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.39 and 6.25 μg/mL, respectively. It significantly dropped the bacterial count from 1 × 108 to 39 × 101 CFU/mL in vivo and has bactericidal activity within 180 min of incubation in vitro. The pharmacodynamic and histopathology studies revealed a significant decrease in infected animal skin inflammation, epidermal hypertrophy, and congestion upon treatment with Clin-MIP polyurethane nanofiber and reduced pro-inflammatory cytokines (NLRP3, TNF-α, IL-1β, and IL-6) conducive to acne healing. Consequently, the recently created Clin-MIP polyurethane nanofibrous scaffold. This innovative approach offers insight into creating materials with several uses for treating infectious wounds caused by acne. Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Drug Delivery)
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15 pages, 4599 KiB  
Article
Hirsutonosema embarrassi n. gen. n. sp. (Phylum Microsporidia) in the Ovary of Mucket (Actinonaias ligamentina), Plain Pocketbook (Lampsilis cardium), and Fatmucket (Lampsilis siliquoidea) (Unionidae) from the Embarrass River, Wisconsin, USA
by Susan Knowles, Eric M. Leis, Jordan C. Richard, Isaac F. Standish, Jamie Bojko, Jesse Weinzinger and Diane L. Waller
Parasitologia 2024, 4(2), 184-198; https://doi.org/10.3390/parasitologia4020016 - 7 Jun 2024
Viewed by 1500
Abstract
During an epidemiological survey following a mortality event of freshwater mussels in 2018 in the Embarrass River, Wisconsin, USA, we identified a novel microsporidian parasite in the ovaries of mucket (Actinonaias ligamentina), plain pocketbook (Lampsilis cardium), and fatmucket ( [...] Read more.
During an epidemiological survey following a mortality event of freshwater mussels in 2018 in the Embarrass River, Wisconsin, USA, we identified a novel microsporidian parasite in the ovaries of mucket (Actinonaias ligamentina), plain pocketbook (Lampsilis cardium), and fatmucket (Lampsilis siliquoidea) (Unionidae). Histopathology showed round-to-oval microsporidian spores in the cytoplasm of oocytes in 60% (3/5) of female mucket, 100% (4/4) of female plain pocketbook, and 50% (1/2) of female fatmucket. Using transmission electron microscopy, we found that mature spores were round-to-oval and measured 4.13 ± 0.64 µm (3.14–5.31) long by 2.88 ± 0.37 µm (2.36–3.68) wide. The spores had a thin electron-dense exospore with a spiky “hairy” coat, a thick electron lucent endospore, diplokaryotic nuclei, a polar vacuole, and 27–28 polar filaments arranged in 1–3 rows. Sequencing of the small subunit rRNA produced a 1356 bp sequence most similar to that of Pseudonosema cristatellae (92%), and phylogenetic analysis grouped it within the freshwater Neopereziida. Genetic, morphological, and ultrastructural characteristics did not closely match those of other Pseudonosema spp., and a new genus and species, Hirsutonosema embarrassi n. gen. n. sp., were designated. Additional studies could evaluate host susceptibility, distribution, seasonality, transmission, and lethal or sub-lethal effects of this parasite on freshwater mussels. Full article
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