Editorial

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Open AccessEditorial

Women’s Special Issue Series: Biomedicines

by Letizia Polito

Biomedicines 2024, 12(3), 471; https://doi.org/10.3390/biomedicines12030471 - 20 Feb 2024

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Following the invitation of Biomedicines, we decided to accept the project of this Special Issue because we believe that in many situations gender prejudices still exist and put women in a disadvantaged position for the dissemination of their research, preventing the scientific [...] Read more.

Following the invitation of Biomedicines, we decided to accept the project of this Special Issue because we believe that in many situations gender prejudices still exist and put women in a disadvantaged position for the dissemination of their research, preventing the scientific community from benefiting from a plurality of voices in the interpretation of scientific research [...] Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

Research

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10 pages, 492 KiB

Open AccessArticle

Clinical Implication of PD-L1 Expression in Patients with Endometrial Cancer

by Yeorae Kim, Ala Aiob, Hyojin Kim, Dong Hoon Suh, Kidong Kim, Yong Beom Kim and Jae Hong No

Biomedicines 2023, 11(10), 2691; https://doi.org/10.3390/biomedicines11102691 - 01 Oct 2023

Cited by 1 | Viewed by 1072

Abstract

This study investigated PD-L1 expression in endometrial cancer, its links with prognostic factors, and survival outcomes in 232 patients. Of these, 73 (31.5%) had PD-L1-positive tumors and 159 (68.5%) had PD-L1-negative tumors. PD-L1 expression significantly correlated with adverse prognostic factors. The PD-L1-positive group [...] Read more.

This study investigated PD-L1 expression in endometrial cancer, its links with prognostic factors, and survival outcomes in 232 patients. Of these, 73 (31.5%) had PD-L1-positive tumors and 159 (68.5%) had PD-L1-negative tumors. PD-L1 expression significantly correlated with adverse prognostic factors. The PD-L1-positive group had higher rates of high-grade tumors (37.0% vs. 19.1%, p = 0.004), deep myometrial invasion (35.6% vs. 24.4%, p = 0.004), lymphovascular space invasion (LVSI) (39.7% vs. 25.6%, p = 0.023), and lymph node metastasis (7.2% vs. 17.1%, p = 0.024) than the PD-L1-negative group. While 5-year progression-free survival (PFS) favored the PD-L1-negative group (94.1% vs. 86.3%), this difference lacked statistical significance (p = 0.139). No significant variations emerged in overall survival (OS) (p = 0.596) or recurrence rates between the groups. Although outcomes lack statistical significance, they suggest a plausible link between PD-L1 and established adverse prognostic factors, such as histological grade, myometrial invasion depth, LVSI, and lymph node metastasis in endometrial cancer. These insights hint at PD-L1’s potential as an informal prognostic indicator, potentially aiding in endometrial cancer patient management. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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20 pages, 4442 KiB

Open AccessArticle

Evaluation of Single Dose and Fractionated Dose of I-131 Radiolabeled Nanoparticles for Triple-Negative Breast Cancer Treatment

by Suphalak Khamruang Marshall, Nutnicha Kaewpradit, Tavadee Mudmarn, Jirassaya Buathong and Palmuk Sriwirote

Biomedicines 2023, 11(8), 2169; https://doi.org/10.3390/biomedicines11082169 - 01 Aug 2023

Cited by 2 | Viewed by 35837

Abstract

Combination chemotherapy is still the standard clinical care for triple-negative breast cancer (TNBC). However, sodium iodide symporter (NIS) uptake by TNBC has opened the potential of NIS as a molecular target for radioiodine theranostic treatments. Radiolabeled poly(lactic-co-glycolic) acid nanocarrier (NINP) was developed for [...] Read more.

Combination chemotherapy is still the standard clinical care for triple-negative breast cancer (TNBC). However, sodium iodide symporter (NIS) uptake by TNBC has opened the potential of NIS as a molecular target for radioiodine theranostic treatments. Radiolabeled poly(lactic-co-glycolic) acid nanocarrier (NINP) was developed for NIS targeted delivery of I-131 to MDA-MB-231 cells to overcome I-131 low uptake in cancer cells and rapid clearance. The NINP diameter of 237 nm has good particle size uniformity and excellent particle stability. Radiochemical purity, radioactive stability, and radiolabeling yield of NINPs over 72 h were >95%. Cytotoxicity confirmed fractionated NINPs over 72 h to be more effective in cell death than single-dose NINP and both single and fractionated Na¹³¹I. Cellular uptake in a three-dimensional spheroid confirmed that NINP fractionated-dose achieved ~4.8-fold-higher mean fluorescent intensity than Na¹³¹I and ~2.7-fold greater reduction in cell viability compared to single-dose. The NINP fractionated-dose initiated greater cellular DNA damage to cells than single-dose NINP, resulting in inhibition of cell cycle progression, resulting in cell cycle progression being inhibited by cyclin-dependent kinases, which play a vital role in the control of MDA-MB-231 cell cycle. NINPs are biocompatible with blood, and were found to have no negative impact on red blood cells. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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14 pages, 4842 KiB

Open AccessArticle

New Insights on Saporin Resistance to Chemical Derivatization with Heterobifunctional Reagents

by Massimo Bortolotti, Francesco Biscotti, Andrea Zanello, Andrea Bolognesi and Letizia Polito

Biomedicines 2023, 11(4), 1214; https://doi.org/10.3390/biomedicines11041214 - 19 Apr 2023

Cited by 2 | Viewed by 1580

Abstract

Saporin is a type 1 ribosome-inactivating protein widely used as toxic payload in the construction of targeted toxins, chimeric molecules formed by a toxic portion linked to a carrier moiety. Among the most used carriers, there are large molecules (mainly antibodies) and small [...] Read more.

Saporin is a type 1 ribosome-inactivating protein widely used as toxic payload in the construction of targeted toxins, chimeric molecules formed by a toxic portion linked to a carrier moiety. Among the most used carriers, there are large molecules (mainly antibodies) and small molecules (such as neurotransmitters, growth factors and peptides). Some saporin-containing targeted toxins have been used for the experimental treatment of several diseases, giving very promising results. In this context, one of the reasons for the successful use of saporin lies in its resistance to proteolytic enzymes and to conjugation procedures. In this paper, we evaluated the influence of derivatization on saporin using three heterobifunctional reagents, namely 2-iminothiolane (2-IT), N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) and 4-succinimidyloxycarbonyl-α-methyl-α-[2-pyridyldithio]toluene (SMPT). In order to obtain the highest number of inserted -SH groups with the lowest reduction of saporin biological activities, we assessed the residual ability of saporin to inhibit protein synthesis, to depurinate DNA and to induce cytotoxicity after derivatization. Our results demonstrate that saporin maintains an excellent resistance to derivatization processes, especially with SPDP, and permit us to define reaction conditions, in which saporin biological properties may not be altered. Therefore, these findings provide useful information for the construction of saporin-based targeted toxins, especially with small carriers. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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12 pages, 5135 KiB

Open AccessArticle

Urolithin A’s Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats

by Shahid Karim, Batoul Madani, Abdulhadi S. Burzangi, Mohammed Alsieni, Mohammed A. Bazuhair, Maha Jamal, Hussam Daghistani, Mohammed O. Barasheed, Huda Alkreathy, Mohammad Ahmed Khan and Lateef M. Khan

Biomedicines 2023, 11(4), 1125; https://doi.org/10.3390/biomedicines11041125 - 07 Apr 2023

Cited by 6 | Viewed by 2275

Abstract

Human colon microbiota produce a metabolite called urolithin A (URO A) from ellagic acid and linked compounds, and this metabolite has been demonstrated to have antioxidant, anti-inflammatory, and antiapoptotic activities. The current work examines the various mechanisms through which URO A protects against [...] Read more.

Human colon microbiota produce a metabolite called urolithin A (URO A) from ellagic acid and linked compounds, and this metabolite has been demonstrated to have antioxidant, anti-inflammatory, and antiapoptotic activities. The current work examines the various mechanisms through which URO A protects against doxorubicin (DOX)-induced liver injury in Wistar rats. In this experiment, Wistar rats were administered DOX intraperitoneally (20 mg kg⁻¹) on day 7 while given URO A intraperitoneally (2.5 or 5 mg kg⁻¹ d⁻¹) for 14 days. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) were measured. Hematoxylin and eosin (HE) staining was used to evaluate histopathological characteristics, and then antioxidant and anti-inflammatory properties were evaluated in tissue and serum, respectively. We also looked at how active caspase 3 and cytochrome c oxidase were in the liver. The findings demonstrated that supplementary URO A therapy clearly mitigated DOX-induced liver damage. The antioxidant enzymes SOD and CAT were elevated in the liver, and the levels of inflammatory cytokines, such as TNF-α, NF-kB, and IL-6, in the tissue were significantly attenuated, all of which complemented the beneficial effects of URO A in DOX-induced liver injury. In addition, URO A was able to alter the expression of caspase 3 and cytochrome c oxidase in the livers of rats that were subjected to DOX stress. These results showed that URO A reduced DOX-induced liver injury by reducing oxidative stress, inflammation, and apoptosis. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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14 pages, 5758 KiB

Open AccessArticle

Biochemical, Histological, and Ultrastructural Studies of the Protective Role of Vitamin E on Cyclophosphamide-Induced Cardiotoxicity in Male Rats

by Azza A. Attia, Jehan M. Sorour, Neama A. Mohamed, Tagreed T. Mansour, Rasha A. Al-Eisa and Nahla S. El-Shenawy

Biomedicines 2023, 11(2), 390; https://doi.org/10.3390/biomedicines11020390 - 28 Jan 2023

Cited by 5 | Viewed by 2025

Abstract

Background: Cyclophosphamide (CP) (Cytoxan or Endoxan) is an efficient anti-tumor agent, widely used for the treatment of various neoplastic diseases. The study aimed to investigate the protective role of vitamin E (vit E) in improving cardiotoxicity in rats induced by CP. Materials and [...] Read more.

Background: Cyclophosphamide (CP) (Cytoxan or Endoxan) is an efficient anti-tumor agent, widely used for the treatment of various neoplastic diseases. The study aimed to investigate the protective role of vitamin E (vit E) in improving cardiotoxicity in rats induced by CP. Materials and methods: Forty male Wistar rats were divided randomly into four experimental groups (each consisting of ten rats); the control group was treated with saline. The other three groups were treated with vit E, CP, and the combination of vit E and CP. Serum lipid profiles, enzyme cardiac biomarkers, and cardiac tissue antioxidants were evaluated, as well as histological and ultrastructure investigations. Results: CP-treated rats showed a significant increase in serum levels of cardiac markers (troponin, CK, LDH, AST, and ALT), lipid profiles, a reduction in the antioxidant enzyme activities (CAT, SOD, and GPx), and an elevation in the level of lipid peroxidation (LPO). The increase in the levels of troponin, LDH, AST, ALP, and triglycerides is a predominant indicator of cardiac damage due to the toxic effect of CP. The biochemical changes parallel cardiac injuries such as myocardial infarction, myocarditis, and heart failure. Vitamin E played a pivotal role, as it attenuated most of these changes because of its ability to scavenge free radicals and reduce LPO. In addition, vit E was found to improve the histopathological alterations caused by CP where no evidence of damage was observed in the cardiac architecture, and the cardiac fibers had regained their normal structure with minimal hemorrhage. Conclusions: As a result of its antioxidant activity and its stabilizing impact on the cardiomyocyte membranes, vit E is recommended as a potential candidate in decreasing the damaging effects of CP. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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11 pages, 1987 KiB

Open AccessArticle

Lower Extremity Arterial Disease in Type 2 Diabetes Mellitus: Metformin Inhibits Femoral Artery Ultrastructural Alterations as well as Vascular Tissue Levels of AGEs/ET-1 Axis-Mediated Inflammation and Modulation of Vascular iNOS and eNOS Expression

by Ayed A. Shati, Amro Maarouf, Amal F. Dawood, Nervana M. Bayoumy, Youssef A. Alqahtani, Refaat A. Eid, Saeed M. Alqahtani, Mohamed Abd Ellatif, Bahjat Al-Ani and Alia Albawardi

Biomedicines 2023, 11(2), 361; https://doi.org/10.3390/biomedicines11020361 - 26 Jan 2023

Cited by 2 | Viewed by 1613

Abstract

Lower extremity arterial disease (LEAD) is a major risk factor for amputation in diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 (ET-1)/nitric oxide synthase (NOS) axis-mediated femoral artery injury with and without metformin has not been previously investigated. Type 2 diabetes mellitus (T2DM) [...] Read more.

Lower extremity arterial disease (LEAD) is a major risk factor for amputation in diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 (ET-1)/nitric oxide synthase (NOS) axis-mediated femoral artery injury with and without metformin has not been previously investigated. Type 2 diabetes mellitus (T2DM) was established in rats, with another group of rats treated for two weeks with 200 mg/kg metformin, before being induced with T2DM. The latter cohort were continued on metformin until they were sacrificed at week 12. Femoral artery injury was established in the diabetic group as demonstrated by substantial alterations to the femoral artery ultrastructure, which importantly were ameliorated by metformin. In addition, diabetes caused a significant (p < 0.0001) upregulation of vascular tissue levels of AGEs, ET-1, and iNOS, as well as high blood levels of glycated haemoglobin, TNF-α, and dyslipidemia. All of these parameters were also significantly inhibited by metformin. Moreover, metformin treatment augmented arterial eNOS expression which had been inhibited by diabetes progression. Furthermore, a significant correlation was observed between femoral artery endothelial tissue damage and glycemia, AGEs, ET-1, TNF-α, and dyslipidemia. Thus, in a rat model of T2DM-induced LEAD, an association between femoral artery tissue damage and the AGEs/ET-1/inflammation/NOS/dyslipidemia axis was demonstrated, with metformin treatment demonstrating beneficial vascular protective effects. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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14 pages, 2568 KiB

Open AccessArticle

Epithelial Cell Adhesion Molecule (EpCAM) Expression Can Be Modulated via NFκB

by Saadiya Zia, Komal Tehreem, Sidra Batool, Mehreen Ishfaq, Shaher Bano Mirza, Shahrukh Khan, Majed N. Almashjary, Mohannad S. Hazzazi, Husam Qanash, Ahmad Shaikh, Roua S. Baty, Ibrahim Jafri, Nouf H. Alsubhi, Ghadeer I. Alrefaei, Rokayya Sami and Ramla Shahid

Biomedicines 2022, 10(11), 2985; https://doi.org/10.3390/biomedicines10112985 - 20 Nov 2022

Cited by 3 | Viewed by 2361

Abstract

The epithelial cell adhesion molecule (EpCAM) is considered an essential proliferation signature in cancer. In the current research study, qPCR induced expression of EpCAM was noted in acute lymphoblastic leukemia (ALL) cases. Costunolide, a sesquiterpene lactone found in crepe ginger and lettuce, is [...] Read more.

The epithelial cell adhesion molecule (EpCAM) is considered an essential proliferation signature in cancer. In the current research study, qPCR induced expression of EpCAM was noted in acute lymphoblastic leukemia (ALL) cases. Costunolide, a sesquiterpene lactone found in crepe ginger and lettuce, is a medicinal herb with anticancer properties. Expression of EpCAM and its downstream target genes (Myc and TERT) wasdownregulated upon treatment with costunolide in Jurkat cells. A significant change in the telomere length of Jurkat cells was not noted at 72 h of costunolide treatment. An in silico study revealed hydrophobic interactions between EpCAM extracellular domain and Myc bHLH with costunolide. Reduced expression of NFκB, a transcription factor of EpCAM, Myc, and TERT in costunolide-treated Jurkat cells, suggested that costunolide inhibits gene expression by targeting NFκB and its downstream targets. Overall, the study proposes that costunolide could be a promising therapeutic biomolecule for leukemia. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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Review

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18 pages, 1527 KiB

Open AccessReview

Oncogenic Long Noncoding RNAs in Prostate Cancer, Osteosarcoma, and Metastasis

by Aishah Al-Shehri and Sherin Bakhashab

Biomedicines 2023, 11(2), 633; https://doi.org/10.3390/biomedicines11020633 - 20 Feb 2023

Cited by 1 | Viewed by 1867

Abstract

Prostate cancer (PC) is a common malignancy and is one of the leading causes of cancer-related death in men worldwide. Osteosarcoma (OS) is the most common bone cancer, representing 20–40% of all bone malignancy cases. Cancer metastasis is a process by which malignant [...] Read more.

Prostate cancer (PC) is a common malignancy and is one of the leading causes of cancer-related death in men worldwide. Osteosarcoma (OS) is the most common bone cancer, representing 20–40% of all bone malignancy cases. Cancer metastasis is a process by which malignant tumor cells detach from the primary tumor site via a cascade of processes and migrate to secondary sites through the blood circulation or lymphatic system to colonize and form secondary tumors. PC has a specific affinity to the bone based on the “seed and soil” theory; once PC reach the bone, it becomes incurable. Several studies have identified long noncoding RNAs (lncRNAs) as potential targets for cancer therapy or as diagnostic and prognostic biomarkers. The dysregulation of various lncRNAs has been found in various cancer types, including PC, OS, and metastasis. However, the mechanisms underlying lncRNA oncogenic activity in tumor progression and metastasis are extremely complex and remain incompletely understood. Therefore, understanding oncogenic lncRNAs and their role in OS, PC, and metastasis and the underlying mechanism may help better manage and treat this malignancy. The aim of this review is to summarize current knowledge of oncogenic lncRNAs and their involvement in PC, OS, and bone metastasis. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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Other

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11 pages, 674 KiB

Open AccessSystematic Review

Lactated Ringer’s Solution Reduces Severity, Mortality, Systemic and Local Complications in Acute Pancreatitis: A Systematic Review and Meta-Analysis

by Klementina Ocskay, Péter Mátrai, Péter Hegyi and Andrea Párniczky

Biomedicines 2023, 11(2), 321; https://doi.org/10.3390/biomedicines11020321 - 23 Jan 2023

Cited by 4 | Viewed by 2430

Abstract

Fluid therapy is the cornerstone of early supportive therapy in acute pancreatitis (AP). Regrettably, the type of fluid is still debated among clinicians, despite recent evidence from randomized controlled trials (RCTs). We aimed to incorporate all evidence from RCTs comparing lactated Ringer’s solution [...] Read more.

Fluid therapy is the cornerstone of early supportive therapy in acute pancreatitis (AP). Regrettably, the type of fluid is still debated among clinicians, despite recent evidence from randomized controlled trials (RCTs). We aimed to incorporate all evidence from RCTs comparing lactated Ringer’s solution (LR) with normal saline (NS) in adult and pediatric AP patients, with particular emphasis on clinically relevant outcomes. We evaluated RCTs comparing intravenous fluid resuscitation with LR to NS in adult or pediatric AP patients according to a prospectively registered protocol (CRD42021224542). Moderate-to-severe AP (MSAP), mortality, length of hospitalization (LoH), need for intensive care, the incidence of systemic (organ failure, OF) and local complications (in total), necrosis and pseudocyst formation were analyzed separately. Risk ratio (RR) and median difference (MD) were calculated with 95% confidence intervals (CI) using a random effect model. Risk of bias and quality of evidence were assessed. Altogether, 8 eligible RCTs were found, including 557 patients (LR: 278; NS: 279). LR reduced the risk of MSAP by 31% (RR: 0.59, 95% CI: 0.36–0.97, high quality) and the risk of death by 62% (RR: 0.48; 95% CI: 0.24–0.98, very low quality). LR was associated with a significantly lower risk of need for intensive care (RR: 0.50, 95% CI: 0.33–0.77), OF (RR: 0.78, 95% CI: 0.61–0.99) and local complications (RR: 0.64, 95% CI: 0.46–0.89). No significant risk reduction was observed for LoH (MD: −0.57 days, CI: −1.33–0.19), necrosis, pseudocyst and inflammatory parameters by LR compared to NS. LR reduces severity, mortality, need of intensive care and systemic and local complications in AP. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Biomedicines)

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