Biomedicines

17 pages, 1952 KiB

Open AccessArticle

Subcortical Structures in Demented Schizophrenia Patients: A Comparative Study

by Juan Rivas, Santiago Gutierrez-Gomez, Juliana Villanueva-Congote, Jose Libreros, Joan Albert Camprodon and María Trujillo

Biomedicines 2023, 11(1), 233; https://doi.org/10.3390/biomedicines11010233 - 16 Jan 2023

Viewed by 1930

Abstract

There are few studies on dementia and schizophrenia in older patients looking for structural differences. This paper aims to describe relation between cognitive performance and brain volumes in older schizophrenia patients. Twenty schizophrenic outpatients —10 without-dementia (SND), 10 with dementia (SD)— and fifteen [...] Read more.

There are few studies on dementia and schizophrenia in older patients looking for structural differences. This paper aims to describe relation between cognitive performance and brain volumes in older schizophrenia patients. Twenty schizophrenic outpatients —10 without-dementia (SND), 10 with dementia (SD)— and fifteen healthy individuals —as the control group (CG)—, older than 50, were selected. Neuropsychological tests were used to examine cognitive domains. Brain volumes were calculated with magnetic resonance images. Cognitive performance was significantly better in CG than in schizophrenics. Cognitive performance was worst in SD than SND, except in semantic memory and visual attention. Hippocampal volumes showed significant differences between SD and CG, with predominance on the right side. Left thalamic volume was smaller in SD group than in SND. Structural differences were found in the hippocampus, amygdala, and thalamus; more evident in the amygdala and thalamus, which were mainly related to dementia. In conclusion, cognitive performance and structural changes allowed us to differentiate between schizophrenia patients and CG, with changes being more pronounced in SD than in SND. When comparing SND with SD, the functional alterations largely coincide, although sometimes in the opposite direction. Moreover, volume lost in the hippocampus, amygdala, and thalamus may be related to the possibility to develop dementia in schizophrenic patients. Full article

(This article belongs to the Section Neurobiology and Clinical Neuroscience)

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11 pages, 1471 KiB

Open AccessArticle

Artemisia annua L. Extracts Irreversibly Inhibit the Activity of CYP2B6 and CYP3A4 Enzymes

by Martin Kondža, Marta Mandić, Ivona Ivančić, Sanda Vladimir-Knežević and Ivica Brizić

Biomedicines 2023, 11(1), 232; https://doi.org/10.3390/biomedicines11010232 - 16 Jan 2023

Cited by 1 | Viewed by 2569

Abstract

Artemisia annua L. has long been known for its medicinal properties and isolation of ingredients whose derivatives are used for therapeutic purposes. The CYP2B6 and CYP3A4 enzymes belong to a large family of cytochrome P450 enzymes. These enzymes are involved in the metabolism [...] Read more.

Artemisia annua L. has long been known for its medicinal properties and isolation of ingredients whose derivatives are used for therapeutic purposes. The CYP2B6 and CYP3A4 enzymes belong to a large family of cytochrome P450 enzymes. These enzymes are involved in the metabolism of drugs and other xeonobiotics. It is known that various compounds can induce or inhibit the activity of these enzymes. The aim of this study was to investigate the nature of the inhibitory effect of Artemisia annua extract on CYP2B6 and CYP3A4 enzymes, as well as the type of inhibition, the presence of reversible or pseudo-irreversible inhibition, and the possible heme destruction. The methanolic extract of Artemisia annua showed an inhibitory effect on CYP2B6 (by almost 90%) and CYP3A4 enzymes (by almost 70%). A significant decrease in heme concentration by 46.8% and 38.2% was observed in different assays. These results clearly indicate that the studied plant extracts significantly inhibited the activity of CYP2B6 and CYP3A4 enzymes. Moreover, they showed irreversible inhibition, which is even more important for possible interactions with drugs and dietary supplements. Full article

(This article belongs to the Special Issue Cytochrome P450 (CYP) in Health and Disease)

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15 pages, 11359 KiB

Open AccessArticle

Hepatoprotective Efficacy of Cycloastragenol Alleviated the Progression of Liver Fibrosis in Carbon-Tetrachloride-Treated Mice

by Theerut Luangmonkong, Pittaya Puphancharoensuk, Varisara Tongsongsang, Peter Olinga and Warisara Parichatikanond

Biomedicines 2023, 11(1), 231; https://doi.org/10.3390/biomedicines11010231 - 16 Jan 2023

Viewed by 2040

Abstract

The continuous death of hepatocytes induced by various etiologies leads to an aberrant tissue healing process and promotes the progression of liver fibrosis and ultimately chronic liver diseases. To date, effective treatments to delay this harmful process remain an unmet clinical need. Cycloastragenol [...] Read more.

The continuous death of hepatocytes induced by various etiologies leads to an aberrant tissue healing process and promotes the progression of liver fibrosis and ultimately chronic liver diseases. To date, effective treatments to delay this harmful process remain an unmet clinical need. Cycloastragenol is an active phytochemical substance isolated from Astragalus membranaceus, a plant used in traditional Chinese medicine to protect the liver. Therefore, our study aimed to elucidate the efficacy of cycloastragenol on carbon-tetrachloride (CCl₄)-induced liver fibrosis in mice. We found that cycloastragenol at 200 mg/kg dosage exhibited anti-fibrotic efficacy as demonstrated by a decrease in collagen deposition, downregulation of mRNA expression of collagen type 1, and a reduction in the content of total collagens. In addition, cycloastragenol further augmented the levels of anti-fibrotic matrix metalloproteinases (Mmps), that is, Mmp8, proMmp9, and Mmp12, which play a pivotal role in fibrosis resolution. According to histological analysis and serum markers of hepatotoxicity, cycloastragenol protected the livers from damage and mitigated the increment of serum alanine aminotransferase and bilirubin implicating hepatoprotective efficacy against CCl₄. Moreover, cycloastragenol upregulated the mRNA expression of interleukin 6, a pleiotropic cytokine plays a vital role in the promotion of hepatocyte regeneration. In conclusion, cycloastragenol alleviated the progression of liver fibrosis in CCl₄-treated mice and its anti-fibrotic efficacy was mainly due to the hepatoprotective efficacy. Full article

(This article belongs to the Special Issue Biomedicines: 10th Anniversary)

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20 pages, 42160 KiB

Open AccessArticle

Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo

by Timur I. Fetisov, Anna A. Borunova, Alina S. Antipova, Elena E. Antoshina, Lubov S. Trukhanova, Tatyana G. Gorkova, Svetlana N. Zuevskaya, Alexei Maslov, Katerina Gurova, Andrei Gudkov, Ekaterina A. Lesovaya, Gennady A. Belitsky, Marianna G. Yakubovskaya and Kirill I. Kirsanov

Biomedicines 2023, 11(1), 230; https://doi.org/10.3390/biomedicines11010230 - 16 Jan 2023

Cited by 1 | Viewed by 2608

Abstract

The anticancer activity of Curaxin CBL0137, a DNA-binding small molecule with chromatin remodulating effect, has been demonstrated in different cancers. Herein, a comparative evaluation of CBL0137 activity was performed in respect to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia [...] Read more.

The anticancer activity of Curaxin CBL0137, a DNA-binding small molecule with chromatin remodulating effect, has been demonstrated in different cancers. Herein, a comparative evaluation of CBL0137 activity was performed in respect to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia and multiple myeloma (MM) cultured in vitro. MTT assay showed AML and MM higher sensitivity to CBL0137’s cytostatic effect comparatively to other hematological malignancy cells. Flow cytometry cell cycle analysis revealed an increase in subG1 and G2/M populations after CBL0137 cell treatment, but the prevalent type of arrest varied. Apoptosis activation by CBL0137 measured by Annexin-V/PI dual staining was more active in AML and MM cells. RT2 PCR array showed that changes caused by CBL0137 in signaling pathways involved in cancer pathogenesis were more intensive in AML and MM cells. On the murine model of AML WEHI-3, CBL0137 showed significant anticancer effects in vivo, which were evaluated by corresponding changes in spleen and liver. Thus, more pronounced anticancer effects of CBL0137 in vitro were observed in respect to AML and MM. Experiments in vivo also indicated the perspective of CBL0137 use for AML treatment. This in accordance with the frontline treatment approach in AML using epigenetic drugs. Full article

(This article belongs to the Special Issue Development of Small Molecules for Acute Myeloid Leukemia Therapy)

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19 pages, 1435 KiB

Open AccessReview

IGF2: A Role in Metastasis and Tumor Evasion from Immune Surveillance?

by Antonino Belfiore, Rosaria Valentina Rapicavoli, Rosario Le Moli, Rosamaria Lappano, Andrea Morrione, Ernestina Marianna De Francesco and Veronica Vella

Biomedicines 2023, 11(1), 229; https://doi.org/10.3390/biomedicines11010229 - 16 Jan 2023

Cited by 11 | Viewed by 3303

Abstract

Insulin-like growth factor 2 (IGF2) is upregulated in both childhood and adult malignancies. Its overexpression is associated with resistance to chemotherapy and worse prognosis. However, our understanding of its physiological and pathological role is lagging behind what we know about IGF1. Dysregulation of [...] Read more.

Insulin-like growth factor 2 (IGF2) is upregulated in both childhood and adult malignancies. Its overexpression is associated with resistance to chemotherapy and worse prognosis. However, our understanding of its physiological and pathological role is lagging behind what we know about IGF1. Dysregulation of the expression and function of IGF2 receptors, insulin receptor isoform A (IR-A), insulin growth factor receptor 1 (IGF1R), and their downstream signaling effectors drive cancer initiation and progression. The involvement of IGF2 in carcinogenesis depends on its ability to link high energy intake, increase cell proliferation, and suppress apoptosis to cancer risk, and this is likely the key mechanism bridging insulin resistance to cancer. New aspects are emerging regarding the role of IGF2 in promoting cancer metastasis by promoting evasion from immune destruction. This review provides a perspective on IGF2 and an update on recent research findings. Specifically, we focus on studies providing compelling evidence that IGF2 is not only a major factor in primary tumor development, but it also plays a crucial role in cancer spread, immune evasion, and resistance to therapies. Further studies are needed in order to find new therapeutic approaches to target IGF2 action. Full article

(This article belongs to the Special Issue The IGF2-Regulated Cellular- and Genetic Network in Physiology and Disease: A Call to Action)

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15 pages, 1946 KiB

Open AccessArticle

Neuroprotective Effects of Licochalcone D in Oxidative-Stress-Induced Primitive Neural Stem Cells from Parkinson’s Disease Patient-Derived iPSCs

by Minyoung Oh, Juhyeon Nam, Areum Baek, Ji-Hye Seo, Jung-Il Chae, Seo-Young Lee, Sun-Ku Chung, Byoung Chul Park, Sung Goo Park, Janghwan Kim and Young-Joo Jeon

Biomedicines 2023, 11(1), 228; https://doi.org/10.3390/biomedicines11010228 - 16 Jan 2023

Viewed by 2086

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to [...] Read more.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to be associated with abnormal aggregation of α-synuclein, elevation of oxidative stress, dysfunction of mitochondrial functions, and increased neuroinflammation. In this study, the effects of Licochalcone D (LCD) on MG132-induced neurotoxicity in primitive neural stem cells (pNSCs) derived from reprogrammed iPSCs were investigated. A cell viability assay showed that LCD had anti-apoptotic properties in MG132-induced oxidative-stressed pNSCs. It was confirmed that apoptosis was reduced in pNSCs treated with LCD through 7-AAD/Annexin Ⅴ staining and cleaved caspase3. These effects of LCD were mediated through an interaction with JunD and through the EGFR/AKT and JNK signaling pathways. These findings suggest that LCD could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD. Full article

(This article belongs to the Special Issue Parkinson’s Disease: From Pathophysiology to Novel Therapeutic Approaches)

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18 pages, 3093 KiB

Open AccessArticle

Potential Protective Effect of Dengue NS1 Human Monoclonal Antibodies against Dengue and Zika Virus Infections

by Rochanawan Sootichote, Wilarat Puangmanee, Surachet Benjathummarak, Siriporn Kowaboot, Atsushi Yamanaka, Korbporn Boonnak, Sumate Ampawong, Supawat Chatchen, Pongrama Ramasoota and Pannamthip Pitaksajjakul

Biomedicines 2023, 11(1), 227; https://doi.org/10.3390/biomedicines11010227 - 16 Jan 2023

Cited by 7 | Viewed by 2613

Abstract

Due to the lack of an effective therapeutic treatment to flavivirus, dengue virus (DENV) nonstructural protein 1 (NS1) has been considered to develop a vaccine owing to its lack of a role in antibody-dependent enhancement (ADE). However, both NS1 and its antibody have [...] Read more.

Due to the lack of an effective therapeutic treatment to flavivirus, dengue virus (DENV) nonstructural protein 1 (NS1) has been considered to develop a vaccine owing to its lack of a role in antibody-dependent enhancement (ADE). However, both NS1 and its antibody have shown cross-reactivity to host molecules and have stimulated anti-DENV NS1 antibody-mediated endothelial damage and platelet dysfunction. To overcome the pathogenic events and reactogenicity, human monoclonal antibodies (HuMAbs) against DENV NS1 were generated from DENV-infected patients. Herein, the four DENV NS1-specific HuMAbs revealed the therapeutic effects in viral neutralization, reduction of viral replication, and enhancement of cell cytolysis of DENV and zika virus (ZIKV) via complement pathway. Furthermore, we demonstrate that DENV and ZIKV NS1 trigger endothelial dysfunction, leading to vascular permeability in vitro. Nevertheless, the pathogenic effects from NS1 were impeded by 2 HuMAbs (D25-4D4C3 and D25-2B11E7) and also protected the massive cytokines stimulation (interleukin [IL-]-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-13, IL-17, eotaxin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, Inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1 α, MIP-1β, tumor necrosis factor-α, platelet-derived growth factor, and RANTES). Collectively, our findings suggest that the novel protective NS1 monoclonal antibodies generated from humans has multiple therapeutic benefits against DENV and ZIKV infections. Full article

(This article belongs to the Section Immunology and Immunotherapy)

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16 pages, 11528 KiB

Open AccessArticle

Network-Based Assessment of Minimal Change Disease Identifies Glomerular Response to IL-7 and IL-12 Pathways Activation as Innovative Treatment Target

by Øystein Eikrem, Bjørnar Lillefosse, Nicolas Delaleu, Philipp Strauss, Tarig Osman, Bjørn Egil Vikse, Hanna Debiec, Pierre Ronco, Miroslav Sekulic, Even Koch, Jessica Furriol, Sabine Maria Leh and Hans-Peter Marti

Biomedicines 2023, 11(1), 226; https://doi.org/10.3390/biomedicines11010226 - 16 Jan 2023

Cited by 1 | Viewed by 2275

Abstract

Background: Minimal change disease (MCD), a major cause of nephrotic syndrome, is usually treated by corticosteroid administration. MCD unresponsiveness to therapy and recurrences are nonetheless frequently observed, particularly in adults. To explore MCD-related pathogenetic mechanisms and to identify novel drug targets ultimately contributing [...] Read more.

Background: Minimal change disease (MCD), a major cause of nephrotic syndrome, is usually treated by corticosteroid administration. MCD unresponsiveness to therapy and recurrences are nonetheless frequently observed, particularly in adults. To explore MCD-related pathogenetic mechanisms and to identify novel drug targets ultimately contributing to novel therapeutic avenues with a certain specificity for MCD, we compared glomerular transcriptomes from MCD with membranous nephropathy (MN) patients and healthy controls. Methods: Renal biopsies from adult patients with MCD (n = 14) or MN (n = 12), and non-diseased controls (n = 8) were selected from the Norwegian Kidney Biopsy Registry. RNA for 75 base-pair paired-end RNASeq were obtained from laser capture micro-dissected (LCM) glomeruli from FFPE sections. Transcriptional landscapes were computed by combining pathway-centered analyses and network science methodologies that integrate multiple bioinformatics resources. Results: Compared to normal glomeruli, cells from MCD displayed an inflammatory signature apparently governed by the IL1 and IL7 systems. While enrichment of IL1 production and secretion was a shared feature of MCD and MN compared to normal tissue, responses involving IL7 pathway activation were unique to MCD. Indeed, IL7R expressed by glomeruli was the most upregulated gene of the interleukin family in MCD versus normal controls. IL7 pathway activation was paralleled by significant enrichment in adaptive immune system processes and transcriptional regulation and depletion in pathways related to energy metabolism and transcription. Downregulation of these organ function-related themes again occurred predominately in MCD and was significantly less pronounced in MN. Immunofluorescence and immunohistochemistry, respectively, confirmed the expression of phosphorylated IL-7 receptor alpha (IL7RA, CD127) and IL12 receptor beta 1 (IL12RB1) proteins. Conclusions: Gene expression profiling of archival FFPE-biopsies identifies MCD-specific signatures with IL7RA and IL12RB1 as novel targets for MCD treatment. Full article

(This article belongs to the Special Issue Progress in the Pathogenesis, Diagnosis and Treatment of Chronic Kidney Disease)

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13 pages, 2360 KiB

Open AccessArticle

Expression of E4 Protein and HPV Major Capsid Protein (L1) as A Novel Combination in Squamous Intraepithelial Lesions

by Marcin Przybylski, Dominik Pruski, Sonja Millert-Kalińska, Monika Krzyżaniak, Mateusz de Mezer, Magdalena Frydrychowicz, Robert Jach and Jakub Żurawski

Biomedicines 2023, 11(1), 225; https://doi.org/10.3390/biomedicines11010225 - 16 Jan 2023

Cited by 1 | Viewed by 1953

Abstract

We aim to describe the relationship between the immunohistochemical expression patterns of HPV E4 markers and the presence of HPV major capsid protein (L1) in cervical tissues obtained by biopsy of patients with abnormal liquid-based cytology (LBC) results, HR HPV infections, or clinically [...] Read more.

We aim to describe the relationship between the immunohistochemical expression patterns of HPV E4 markers and the presence of HPV major capsid protein (L1) in cervical tissues obtained by biopsy of patients with abnormal liquid-based cytology (LBC) results, HR HPV infections, or clinically suspicious cervix. A novel HPV-encoded marker, SILgrade-E4 (XR-E4-1), and an HPV (clone K1H8) antibody were used to demonstrate the expression in terminally differentiated epithelial cells with a productive HPV infection in the material. A semiquantitative analysis was performed based on light microscope images. The level of E4 protein decreased with the disease severity. Patients with LSIL-CIN 1 and HSIL-CIN 2 diagnoses had significantly lower levels of HPV major capsid protein (L1) than those without confirmed cervical lesions. Our analysis confirms a higher incidence of L1 in patients with molecularly diagnosed HPV infections and excluded lesions of LSIL-CIN 1 and HSIL-CIN 2. Further studies on the novel biomarkers might help assess the chances of the remission of lesions such as LSIL-CIN 1 and HSIL-CIN 2. Higher levels of E4 protein and L1 may confirm a greater probability of the remission of lesions and incidental infections. In the cytological verification or HPV-dependent screening model, testing for E4 protein and L1 expression may indicate a group with a lower risk of progression of histopathologically diagnosed lesions. Full article

(This article belongs to the Special Issue Advanced Research in Molecular Biology and Immunology of Gynecological Cancers)

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18 pages, 3589 KiB

Open AccessReview

An Overview of Potential Natural Photosensitizers in Cancer Photodynamic Therapy

by Bushra Aziz, Iffat Aziz, Ahmat Khurshid, Ehsan Raoufi, Fahime Nasr Esfahani, Zahra Jalilian, M. R. Mozafari, Elham Taghavi and Masroor Ikram

Biomedicines 2023, 11(1), 224; https://doi.org/10.3390/biomedicines11010224 - 16 Jan 2023

Cited by 19 | Viewed by 3505

Abstract

Cancer is one of the main causes of death worldwide. There are several different types of cancer recognized thus far, which can be treated by different approaches including surgery, radiotherapy, chemotherapy or a combination thereof. However, these approaches have certain drawbacks and limitations. [...] Read more.

Cancer is one of the main causes of death worldwide. There are several different types of cancer recognized thus far, which can be treated by different approaches including surgery, radiotherapy, chemotherapy or a combination thereof. However, these approaches have certain drawbacks and limitations. Photodynamic therapy (PDT) is regarded as an alternative noninvasive approach for cancer treatment based on the generation of toxic oxygen (known as reactive oxygen species (ROS)) at the treatment site. PDT requires photoactivation by a photosensitizer (PS) at a specific wavelength (λ) of light in the vicinity of molecular oxygen (singlet oxygen). The cell death mechanisms adopted in PDT upon PS photoactivation are necrosis, apoptosis and stimulation of the immune system. Over the past few decades, the use of natural compounds as a photoactive agent for the selective eradication of neoplastic lesions has attracted researchers’ attention. Many reviews have focused on the PS cell death mode of action and photonanomedicine approaches for PDT, while limited attention has been paid to the photoactivation of phytocompounds. Photoactivation is ever-present in nature and also found in natural plant compounds. The availability of various laser light setups can play a vital role in the discovery of photoactive phytocompounds that can be used as a natural PS. Exploring phytocompounds for their photoactive properties could reveal novel natural compounds that can be used as a PS in future pharmaceutical research. In this review, we highlight the current research regarding several photoactive phytocompound classes (furanocoumarins, alkaloids, poly-acetylenes and thiophenes, curcumins, flavonoids, anthraquinones, and natural extracts) and their photoactive potential to encourage researchers to focus on studies of natural agents and their use as a potent PS to enhance the efficiency of PDT. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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16 pages, 1326 KiB

Open AccessArticle

Acute Spontaneous Lobar Cerebral Hemorrhages Present a Different Clinical Profile and a More Severe Early Prognosis than Deep Subcortical Intracerebral Hemorrhages—A Hospital-Based Stroke Registry Study

by Joana Maria Flaquer-Pérez de Mendiola, Adrià Arboix, Luís García-Eroles and Maria José Sánchez-López

Biomedicines 2023, 11(1), 223; https://doi.org/10.3390/biomedicines11010223 - 16 Jan 2023

Cited by 6 | Viewed by 2956

Abstract

Acute spontaneous intracerebral hemorrhage (ICH) is the most severe stroke subtype, with a high risk of death, dependence, and dementia. Knowledge about the clinical profile and early outcomes of ICH patients with lobar versus deep subcortical brain topography remains limited. In this study, [...] Read more.

Acute spontaneous intracerebral hemorrhage (ICH) is the most severe stroke subtype, with a high risk of death, dependence, and dementia. Knowledge about the clinical profile and early outcomes of ICH patients with lobar versus deep subcortical brain topography remains limited. In this study, we investigated the effects of ICH topography on demographics, cerebrovascular risk factors, clinical characteristics, and early outcomes in a sample of 298 consecutive acute ICH patients (165 with lobar and 133 with subcortical hemorrhagic stroke) available in a single-center-based stroke registry over 24 years. The multiple logistic regression analysis shows that variables independently associated with lobar ICH were early seizures (OR 6.81, CI 95% 1.27–5.15), chronic liver disease (OR 4.55, 95% CI 1.03–20.15), hemianopia (OR 2.55, 95% CI 1.26–5.15), headaches (OR 1.90, 95% CI 1.90, 95% IC 1.06–3.41), alcohol abuse (>80 gr/day) (OR 0–10, 95% CI 0.02–0,53), hypertension (OR 0,41, 95% CI 0.23–0–70), sensory deficit (OR 0.43, 95% CI 0.25–0.75), and limb weakness (OR: 0.47, 95% CI 0.24–0.93). The in-hospital mortality was 26.7% for lobar and 16.5% for subcortical ICH. The study confirmed that the clinical spectrum, prognosis, and early mortality of patients with ICH depend on the site of bleeding, with a more severe early prognosis in lobar intracerebral hemorrhage. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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19 pages, 4099 KiB

Open AccessArticle

Noradrenergic Modulation of Learned and Innate Behaviors in Dopamine Transporter Knockout Rats by Guanfacine

by Anna Volnova, Natalia Kurzina, Anastasia Belskaya, Arina Gromova, Arseniy Pelevin, Maria Ptukha, Zoia Fesenko, Alla Ignashchenkova and Raul R. Gainetdinov

Biomedicines 2023, 11(1), 222; https://doi.org/10.3390/biomedicines11010222 - 15 Jan 2023

Cited by 3 | Viewed by 2205

Abstract

Investigation of the precise mechanisms of attention deficit and hyperactivity disorder (ADHD) and other dopamine-associated conditions is crucial for the development of new treatment approaches. In this study, we assessed the effects of repeated and acute administration of α2A-adrenoceptor agonist guanfacine on innate [...] Read more.

Investigation of the precise mechanisms of attention deficit and hyperactivity disorder (ADHD) and other dopamine-associated conditions is crucial for the development of new treatment approaches. In this study, we assessed the effects of repeated and acute administration of α2A-adrenoceptor agonist guanfacine on innate and learned forms of behavior of dopamine transporter knockout (DAT-KO) rats to evaluate the possible noradrenergic modulation of behavioral deficits. DAT-KO and wild type rats were trained in the Hebb–Williams maze to perform spatial working memory tasks. Innate behavior was evaluated via pre pulse inhibition (PPI). Brain activity of the prefrontal cortex and the striatum was assessed. Repeated administration of GF improved the spatial working memory task fulfillment and PPI in DAT-KO rats, and led to specific changes in the power spectra and coherence of brain activity. Our data indicate that both repeated and acute treatment with a non-stimulant noradrenergic drug lead to improvements in the behavior of DAT-KO rats. This study further supports the role of the intricate balance of norepinephrine and dopamine in the regulation of attention. The observed compensatory effect of guanfacine on the behavior of hyperdopaminergic rats may be used in the development of combined treatments to support the dopamine–norepinephrine balance. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Translational Laboratory and Experimental Medicine for the Sake of Neurological Diseases and Mental Illness)

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16 pages, 1129 KiB

Open AccessReview

Resveratrol and Its Role in the Management of B-Cell Malignancies—A Recent Update

by Dhruv Sanjay Gupta, Vaishnavi Gadi, Ginpreet Kaur, Meena Chintamaneni, Hardeep Singh Tuli, Seema Ramniwas and Gautam Sethi

Biomedicines 2023, 11(1), 221; https://doi.org/10.3390/biomedicines11010221 - 15 Jan 2023

Cited by 6 | Viewed by 2280

Abstract

The growing incidence of B cell malignancies globally has prompted research on the pharmacological properties of phytoconstituents in cancer management. Resveratrol, a polyphenolic stilbenoid widely found in nature, has been explored for its anti-inflammatory and antioxidant properties, and promising results from different pre-clinical [...] Read more.

The growing incidence of B cell malignancies globally has prompted research on the pharmacological properties of phytoconstituents in cancer management. Resveratrol, a polyphenolic stilbenoid widely found in nature, has been explored for its anti-inflammatory and antioxidant properties, and promising results from different pre-clinical studies have indicated its potential for management of B cell malignancies. However, these claims must be substantiated by a greater number of clinical trials in diverse populations, in order to establish its safety and efficacy profile. In addition to this, there is a need to explore nanodelivery of this agent, owing to its poor solubility, which in turn may impact its bioavailability. This review aims to offer an overview of the occurrence and pathogenesis of B cell malignancies with a special focus on the inflammatory pathways involved, the mechanism of actions of resveratrol and its pharmacokinetic profile, results from pre-clinical and clinical studies, as well as an overview of the marketed formulations. The authors have also presented their opinion on the various challenges associated with the clinical development of resveratrol and future perspectives regarding therapeutic applications of this agent. Full article

(This article belongs to the Special Issue Molecular Pathogenesis of B-cell Malignancies)

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18 pages, 898 KiB

Open AccessReview

Early Saphenous Vein Graft Aneurysm Rupture: A Not So-Late Complication. Case Report and Comprehensive Literature Review

by Eleonora Mezzetti, Aniello Maiese, Federica Spina, Fabio Del Duca, Alessandra De Matteis, Marco Di Paolo, Raffaele La Russa, Emanuela Turillazzi and Vittorio Fineschi

Biomedicines 2023, 11(1), 220; https://doi.org/10.3390/biomedicines11010220 - 14 Jan 2023

Cited by 1 | Viewed by 1359

Abstract

Background and Objectives: Saphenous vein graft (SVG) is a cardiac surgical practice used to create a cardiac bypass in cases of coronary artery obstruction. It consists of a surgical procedure that involves the creation of an aorto-coronary communication by a venous conduit (saphenous [...] Read more.

Background and Objectives: Saphenous vein graft (SVG) is a cardiac surgical practice used to create a cardiac bypass in cases of coronary artery obstruction. It consists of a surgical procedure that involves the creation of an aorto-coronary communication by a venous conduit (saphenous vein) to bypass coronary stenosis and allow cardiac revascularization. This practice can be affected by early and late complications. The most feared complication is graft aneurysm or pseudoaneurysm degeneration and rupture which are considered late complications. This paper presents a rare case of SVG aneurysmal rupture that occurred 24 h after surgery and a review of the literature to provide a general look at the state of knowledge. Materials and Methods: The systematic review was carried out using the guidelines according to the PRISMA method. Results: Cases of aneurysmal rupture have never been described prior to one month after surgery. The male sex and subjects under 45 are the most affected by this complication. Death occurs in less than half of the cases, being more frequent in young people. Performing a CT or angio-CT examination led to the diagnosis. Conclusions: It is impossible to estimate the implanted vessel’s quality, so postoperative follow-up is fundamental. Transesophageal ultrasound can be useful, and hematochemical tests are valuable early diagnostic tools, whrease CT and angio-CT can be useful even months after surgery. Forensic analysis should always perform an autopsy and graft histological examination. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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11 pages, 595 KiB

Open AccessArticle

Antiparasitic Activity of Fluorophenyl-Substituted Pyrimido[1,2-a]benzimidazoles

by Ibrahim S. Al Nasr, Waleed S. Koko, Tariq A. Khan, Rainer Schobert and Bernhard Biersack

Biomedicines 2023, 11(1), 219; https://doi.org/10.3390/biomedicines11010219 - 14 Jan 2023

Cited by 2 | Viewed by 1726

Abstract

A series of fourteen pyrimido[1,2-a]benzimidazole compounds was prepared by straightforward heterocyclic chemistry and oxidation methods. The new pyrimidobenzimidazole derivative 2a with a 3-fluorophenyl substituent was identified as a new antiparasitic compound showing excellent activities against Leishmania major parasites. 2a was highly [...] Read more.

A series of fourteen pyrimido[1,2-a]benzimidazole compounds was prepared by straightforward heterocyclic chemistry and oxidation methods. The new pyrimidobenzimidazole derivative 2a with a 3-fluorophenyl substituent was identified as a new antiparasitic compound showing excellent activities against Leishmania major parasites. 2a was highly active against L. major promastigotes and amastigotes with EC₅₀ values in the nanomolar concentration range. Compound 3b was less active than 2a against L. major, but more active against Toxoplasma gondii with considerable selectivity. Hence, two promising and selective antiparasitic drug candidates 2a and 3b for the treatment of two parasitic diseases were identified, which can be prepared by green chemistry methods using simple one-pot reactions and oxidation procedures, respectively. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series in Drug Discovery)

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7 pages, 446 KiB

Open AccessCase Report

Mesenchymal Stromal Cell Therapy Reverses Detrusor Hypoactivity in a Chronic Kidney Patient

by Henrique Rodrigues Scherer Coelho, Silvia Cordeiro das Neves, Jovino Nogueira da Silva Menezes, Andréia Conceição Milan Brochado Antoniolli-Silva and Rodrigo Juliano Oliveira

Biomedicines 2023, 11(1), 218; https://doi.org/10.3390/biomedicines11010218 - 14 Jan 2023

Cited by 1 | Viewed by 1362

Abstract

Detrusor hypoactivity (DH) is characterized by low detrusor pressure or a short contraction associated with low urinary flow. This condition can progress to chronic renal failure (CRF) and result in the need for dialysis. The present case report demonstrates that a patient diagnosed [...] Read more.

Detrusor hypoactivity (DH) is characterized by low detrusor pressure or a short contraction associated with low urinary flow. This condition can progress to chronic renal failure (CRF) and result in the need for dialysis. The present case report demonstrates that a patient diagnosed with DH and CRF who received two transplants with 2 × 10⁶ autologous mesenchymal stromal cells at an interval of 30 days recovered the contractile strength of the bladder and normalized his renal function. The patient had a score of 19 on the ICIQ-SF before cell therapy, and that score was reduced to 1 after transplantation. These results demonstrate that there was an improvement in his voiding function, urinary stream and urine volume as evaluated by urofluxometry. In addition, a urodynamic study carried out after treatment showed an increase in the maximum flow from 2 mL/s to 23 mL/s, the detrusor pressure in the maximum flow from 21 cm H₂O to 46 cm H₂O and a BCI that went from 31 to 161, characterizing good detrusor contraction. Thus, in the present case, the transplantation of autologous mesenchymal stromal cells proved to be a viable therapeutic option to allow the patient to recover the contractile strength of the bladder, and reversed the CRF. Full article

(This article belongs to the Special Issue Mesenchymal Stromal (Stem) Cells)

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18 pages, 4405 KiB

Open AccessArticle

Green Synthesized Silver Nanoparticle-Loaded Liposome-Based Nanoarchitectonics for Cancer Management: In Vitro Drug Release Analysis

by Priyanka Jayachandran, Suganya Ilango, Vivekananthan Suseela, Ramalingam Nirmaladevi, Mohammed Rafi Shaik, Mujeeb Khan, Merajuddin Khan and Baji Shaik

Biomedicines 2023, 11(1), 217; https://doi.org/10.3390/biomedicines11010217 - 14 Jan 2023

Cited by 20 | Viewed by 3578

Abstract

Silver nanoparticles act as antitumor agents because of their antiproliferative and apoptosis-inducing properties. The present study aims to develop silver nanoparticle-loaded liposomes for the effective management of cancer. Silver nanoparticle-encapsulated liposomes were prepared using the thin-film hydration method coupled with sonication. The prepared [...] Read more.

Silver nanoparticles act as antitumor agents because of their antiproliferative and apoptosis-inducing properties. The present study aims to develop silver nanoparticle-loaded liposomes for the effective management of cancer. Silver nanoparticle-encapsulated liposomes were prepared using the thin-film hydration method coupled with sonication. The prepared liposomes were characterized by DLS (Dynamic Light Scattering analysis), FESEM (Field Emission Scanning Electron Microscope), and FTIR (Fourier Transform Infrared spectroscopy). The in vitro drug release profile of the silver nanoparticle-loaded liposomes was carried out using the dialysis bag method and the drug release profile was validated using various mathematical models. A high encapsulation efficiency of silver nanoparticle-loaded liposome was observed (82.25%). A particle size and polydispersity index of 172.1 nm and 0.381, respectively, and the zeta potential of −21.5 mV were recorded. FESEM analysis revealed spherical-shaped nanoparticles in the size range of 80–97 nm. The in vitro drug release profile of the silver nanoparticle-loaded liposomes was carried out using the dialysis bag method in three different pHs: pH 5.5, pH 6.8, and pH 7.4. A high silver nanoparticle release was observed in pH 5.5 which corresponds to the mature endosomes of tumor cells; 73.32 ± 0.68% nanoparticle was released at 72 h in pH 5.5. Among the various mathematical models analyzed, the Higuchi model was the best-fitted model as there is the highest value of the correlation coefficient which confirms that the drug release follows the diffusion-controlled process. From the Korsmeyer–Peppas model, it was confirmed that the drug release is based on anomalous non-Fickian diffusion. The results indicate that the silver nanoparticle-loaded liposomes can be used as an efficient drug delivery carrier to target cancer cells of various types. Full article

(This article belongs to the Special Issue Nanomedicine in Cancer: Therapy and Drug Discovery)

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11 pages, 1763 KiB

Open AccessArticle

The Regional Burden and Disability-Adjusted Life Years of Knee Osteoarthritis in Kazakhstan 2014–2020

by Gulnur Zhakhina, Arnur Gusmanov, Yesbolat Sakko, Sauran Yerdessov, Yuliya Semenova, Dina Saginova, Arman Batpen and Abduzhappar Gaipov

Biomedicines 2023, 11(1), 216; https://doi.org/10.3390/biomedicines11010216 - 14 Jan 2023

Cited by 3 | Viewed by 2019

Abstract

A Global Burden of Disease (GBD) study reported that 9.6 million years lived with disability (YLDs) were lost due to hip and knee osteoarthritis (KOA) in 2017. Although the GBD study presents the disease burden at the global level, there is no information [...] Read more.

A Global Burden of Disease (GBD) study reported that 9.6 million years lived with disability (YLDs) were lost due to hip and knee osteoarthritis (KOA) in 2017. Although the GBD study presents the disease burden at the global level, there is no information on any Central Asian country. This study aims to investigate the epidemiology of knee osteoarthritis in Kazakhstan. The data of 56,895 people with KOA between 2014–2020 was derived from the Unified National Electronic Health System of Kazakhstan and retrospectively analyzed. The majority of the cohort (76%) were women, of Kazakh ethnicity (66%), and older than 50 years of age (87%). The risk of gonarthrosis escalated for women after 50 years and peaked at 75 years with a rate of 3062 females admitted to hospital per 100,000 women in the population. This observation is approximately three times higher than for men of the same age group. A geographical analysis showed that the Jambyl oblast, West Kazakhstan, North Kazakhstan, and the Akmola oblast have the highest burden of disease. During the observation period, 127,077 age-adjusted YLDs were lost due to knee osteoarthritis. This is the first study in Kazakhstan to investigate the burden of knee osteoarthritis. This research recognizes age and sex-based differences, and regional disparities in the incidence of knee osteoarthritis. This knowledge can lead to the development of more specific diagnostic approaches and gender-personalized therapy protocols for patients. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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15 pages, 13286 KiB

Open AccessArticle

Biofilms on Indwelling Artificial Urinary Sphincter Devices Harbor Complex Microbe–Metabolite Interaction Networks and Reconstitute Differentially In Vitro by Material Type

by Glenn T. Werneburg, Daniel Hettel, Ava Adler, Sromona D. Mukherjee, Scott D. Lundy, Kenneth W. Angermeier, Hadley M. Wood, Bradley C. Gill, Sandip P. Vasavada, Howard B. Goldman, Raymond R. Rackley, Daniel A. Shoskes and Aaron W. Miller

Biomedicines 2023, 11(1), 215; https://doi.org/10.3390/biomedicines11010215 - 14 Jan 2023

Cited by 2 | Viewed by 2011

Abstract

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. [...] Read more.

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe–metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection. Full article

(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)

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19 pages, 3799 KiB

Open AccessArticle

TGF-Beta Modulates the Integrity of the Blood Brain Barrier In Vitro, and Is Associated with Metabolic Alterations in Pericytes

by Leonie Schumacher, Rédouane Slimani, Laimdota Zizmare, Jakob Ehlers, Felix Kleine Borgmann, Julia C. Fitzgerald, Petra Fallier-Becker, Anja Beckmann, Alexander Grißmer, Carola Meier, Ali El-Ayoubi, Kavi Devraj, Michel Mittelbronn, Christoph Trautwein and Ulrike Naumann

Biomedicines 2023, 11(1), 214; https://doi.org/10.3390/biomedicines11010214 - 14 Jan 2023

Cited by 2 | Viewed by 2696

Abstract

The blood–brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important [...] Read more.

The blood–brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintaining BBB integrity, can be functionally modified by GBM cells which induce proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors. We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as an in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, leading to the disruption of a so far intact and tight BBB. TGF-β notably changed the metabolic behavior of pericytes, by shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by modulating pathways that are necessary for the biosynthesis of molecules used for proliferation and cell division. Combined metabolomic and transcriptomic analyses further underscored that the observed functional and metabolic changes of TGF-β-treated pericytes are closely connected with their role as important supporting cells during angiogenic processes. Full article

(This article belongs to the Special Issue Angiogenesis and Anti-angiogenesis in Health and Diseases 2.0)

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21 pages, 987 KiB

Open AccessReview

The Biology of Lysosomes: From Order to Disorder

by Olga Amaral, Mariana Martins, Ana Rita Oliveira, Ana Joana Duarte, Inês Mondragão-Rodrigues and M. Fátima Macedo

Biomedicines 2023, 11(1), 213; https://doi.org/10.3390/biomedicines11010213 - 14 Jan 2023

Cited by 5 | Viewed by 4625

Abstract

Since its discovery in 1955, the understanding of the lysosome has continuously increased. Once considered a mere waste removal system, the lysosome is now recognised as a highly crucial cellular component for signalling and energy metabolism. This notable evolution raises the need for [...] Read more.

Since its discovery in 1955, the understanding of the lysosome has continuously increased. Once considered a mere waste removal system, the lysosome is now recognised as a highly crucial cellular component for signalling and energy metabolism. This notable evolution raises the need for a summarized review of the lysosome’s biology. As such, throughout this article, we will be compiling the current knowledge regarding the lysosome’s biogenesis and functions. The comprehension of this organelle’s inner mechanisms is crucial to perceive how its impairment can give rise to lysosomal disease (LD). In this review, we highlight some examples of LD fine-tuned mechanisms that are already established, as well as others, which are still under investigation. Even though the understanding of the lysosome and its pathologies has expanded through the years, some of its intrinsic molecular aspects remain unknown. In order to illustrate the complexity of the lysosomal diseases we provide a few examples that have challenged the established single gene—single genetic disorder model. As such, we believe there is a strong need for further investigation of the exact abnormalities in the pathological pathways in lysosomal disease. Full article

(This article belongs to the Special Issue Inherited Metabolic Disorders: From Bench to Bedside)

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6 pages, 221 KiB

Open AccessCommunication

Longitudinal Measurement of Histidine-Rich Glycoprotein Levels in Bronchopulmonary Dysplasia: A Pilot Study

by Daisaku Morimoto, Yosuke Washio, Kei Tamai, Takeshi Sato, Tomoka Okamura, Hirokazu Watanabe, Yu Fukushima, Junko Yoshimoto, Misao Kageyama, Kenji Baba and Hirokazu Tsukahara

Biomedicines 2023, 11(1), 212; https://doi.org/10.3390/biomedicines11010212 - 14 Jan 2023

Viewed by 1125

Abstract

Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether [...] Read more.

Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 µg/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants. Full article

(This article belongs to the Special Issue Prematurity-Related Morbidities in Neonates: From Pathophysiology to Novel Therapeutic Approaches)

12 pages, 1926 KiB

Open AccessArticle

Biomechanical Properties of the Aortic Wall: Changes during Vascular Calcification

by Jinwen Zhou, Manasa Reddy Gummi, Anna Greco, Milen Babic, Jaqueline Herrmann, Farid I. Kandil, Markus van der Giet, Markus Tölle and Mirjam Schuchardt

Biomedicines 2023, 11(1), 211; https://doi.org/10.3390/biomedicines11010211 - 14 Jan 2023

Viewed by 1610

Abstract

Medial vascular calcification (MAC) is characterized by the deposition of hydroxyapatite (HAP) in the medial layer of the vessel wall, leading to disruption of vessel integrity and vascular stiffness. Because currently no direct therapeutic interventions for MAC are available, studying the MAC pathogenesis [...] Read more.

Medial vascular calcification (MAC) is characterized by the deposition of hydroxyapatite (HAP) in the medial layer of the vessel wall, leading to disruption of vessel integrity and vascular stiffness. Because currently no direct therapeutic interventions for MAC are available, studying the MAC pathogenesis is of high research interest. Several methods exist to measure and describe the pathophysiological processes in the vessel wall, such as histological staining and gene expression. However, no method describing the physiological properties of the arterial wall is currently available. This study aims to close that gap and validate a method to measure the biomechanical properties of the arterial wall during vascular calcification. Therefore, a stress–stretch curve is monitored using small-vessel-myography upon ex vivo calcification of rat aortic tissue. The measurement of biomechanical properties could help to gain further insights into vessel integrity during calcification progression. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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19 pages, 5441 KiB

Open AccessArticle

Inflammatory Cytokine-Induced HIF-1 Activation Promotes Epithelial–Mesenchymal Transition in Endometrial Epithelial Cells

by Yoshiko Hashimoto, Tomoko Tsuzuki-Nakao, Naoko Kida, Yoshiyuki Matsuo, Tetsuo Maruyama, Hidetaka Okada and Kiichi Hirota

Biomedicines 2023, 11(1), 210; https://doi.org/10.3390/biomedicines11010210 - 14 Jan 2023

Cited by 4 | Viewed by 1794

Abstract

The endometrium undergoes repeated proliferation and shedding during the menstrual cycle. Significant changes to this environment include fluctuations in the partial pressure of oxygen, exposure to a high-cytokine environment associated with intrauterine infection, and inflammation. Chronic endometritis is a condition wherein mild inflammation [...] Read more.

The endometrium undergoes repeated proliferation and shedding during the menstrual cycle. Significant changes to this environment include fluctuations in the partial pressure of oxygen, exposure to a high-cytokine environment associated with intrauterine infection, and inflammation. Chronic endometritis is a condition wherein mild inflammation persists in the endometrium and is one of the causes of implantation failure and miscarriage in early pregnancy. It is thought that the invasion of embryos into the endometrium requires epithelial–mesenchymal transition (EMT)-associated changes in the endometrial epithelium. However, the effects of inflammation on the endometrium remain poorly understood. In this study, we investigated the effects of the intrauterine oxygen environment, hypoxia-inducible factor (HIF), and inflammation on the differentiation and function of endometrial epithelial cells. We elucidated the ways in which inflammatory cytokines affect HIF activity and EMT in an immortalized cell line (EM-E6/E7/TERT) derived from endometrial epithelium. Pro-inflammatory cytokines caused significant accumulation of HIF-1α protein, increased HIF-1α mRNA levels, and enhanced hypoxia-induced accumulation of HIF-1α protein. The combined effect of inflammatory cytokines and hypoxia increased the expression of EMT-inducing factors and upregulated cell migration. Our findings indicate that pro-inflammatory factors, including cytokines and LPS, work synergistically with hypoxia to activate HIF-1 and promote EMT in endometrial epithelial cells. Full article

(This article belongs to the Special Issue Molecular and Cellular Biology in Reproductive Medicine)

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11 pages, 2796 KiB

Open AccessArticle

by Suman Chowdhury, Gusheng Wu, Zi-Hua Lu, Ranjeet Kumar and Robert Ledeen

Biomedicines 2023, 11(1), 209; https://doi.org/10.3390/biomedicines11010209 - 14 Jan 2023

Cited by 5 | Viewed by 1450

Abstract

The purpose of this study was to determine whether the age-related decline in a-series gangliosides (especially GM1), shown to be a factor in the brain-related etiology of Parkinson’s disease (PD), also pertains to the peripheral nervous system (PNS) and aspects of PD unrelated [...] Read more.

The purpose of this study was to determine whether the age-related decline in a-series gangliosides (especially GM1), shown to be a factor in the brain-related etiology of Parkinson’s disease (PD), also pertains to the peripheral nervous system (PNS) and aspects of PD unrelated to the central nervous system (CNS). Following Svennerholm’s demonstration of the age-dependent decline in a-series gangliosides (both GM1 and GD1a) in the human brain, we previously demonstrated a similar decline in the normal mouse brain. The present study seeks to determine whether a similar a-series decline occurs in the periphery of normal mice as a possible prelude to the non-CNS symptoms of PD. We used mice of increasing age to measure a-series gangliosides in three peripheral tissues closely associated with PD pathology. Employing high-performance thin-layer chromatography (HPTLC), we found a substantial decrease in both GM1 and GD1a in all three tissues from 191 days of age. Motor and cognitive dysfunction were also shown to worsen, as expected, in synchrony with the decrease in GM1. Based on the previously demonstrated parallel between mice and humans concerning age-related a-series ganglioside decline in the brain, we propose the present findings to suggest a similar a-series decline in human peripheral tissues as the primary contributor to non-CNS pathologies of PD. An onset of sporadic PD would thus be seen as occurring simultaneously throughout the brain and body, albeit at varying rates, in association with the decline in a-series gangliosides. This would obviate the need to postulate the transfer of aggregated α-synuclein between brain and body or to debate brain vs. body as the origin of PD. Full article

(This article belongs to the Special Issue Sphingolipid Metabolism and Signaling in Health and Diseases)

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27 pages, 2297 KiB

Open AccessReview

Exploring the Use of Cold Atmospheric Plasma to Overcome Drug Resistance in Cancer

by Dzohara Murillo, Carmen Huergo, Borja Gallego, René Rodríguez and Juan Tornín

Biomedicines 2023, 11(1), 208; https://doi.org/10.3390/biomedicines11010208 - 14 Jan 2023

Cited by 15 | Viewed by 5512

Abstract

Drug resistance is a major problem in cancer treatment, as it limits the effectiveness of pharmacological agents and can lead to disease progression. Cold atmospheric plasma (CAP) is a technology that uses ionized gas (plasma) to generate reactive oxygen and nitrogen species (RONS) [...] Read more.

Drug resistance is a major problem in cancer treatment, as it limits the effectiveness of pharmacological agents and can lead to disease progression. Cold atmospheric plasma (CAP) is a technology that uses ionized gas (plasma) to generate reactive oxygen and nitrogen species (RONS) that can kill cancer cells. CAP is a novel approach for overcoming drug resistance in cancer. In recent years, there has been a growing interest in using CAP to enhance the effectiveness of chemotherapy drugs. In this review, we discuss the mechanisms behind this phenomenon and explore its potential applications in cancer treatment. Going through the existing literature on CAP and drug resistance in cancer, we highlight the challenges and opportunities for further research in this field. Our review suggests that CAP could be a promising option for overcoming drug resistance in cancer and warrants further investigation. Full article

(This article belongs to the Special Issue Cold Atmospheric Plasma Applications in Cancer)

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16 pages, 1492 KiB

Open AccessArticle

Clinical and Personal Predictors of Helmet-CPAP Use and Failure in Patients Firstly Admitted to Regular Medical Wards with COVID-19-Related Acute Respiratory Distress Syndrome (hCPAP-f Study)

by Francesco Cei, Ludia Chiarugi, Simona Brancati, Silvia Dolenti, Maria Silvia Montini, Matteo Rosselli, Mario Filippelli, Chiara Ciacci, Irene Sellerio, Marco Maria Gucci, Giulia Vannini, Rinaldo Lavecchia, Loredana Staglianò, Daniele di Stefano, Tiziana Gurrera, Mario Romagnoli, Valentina Francolini, Francesca Dainelli, Grazia Panigada, Giancarlo Landini, Gianluigi Mazzoccoli and Roberto Tarquini Show full author list Hide full author list

Biomedicines 2023, 11(1), 207; https://doi.org/10.3390/biomedicines11010207 - 13 Jan 2023

Cited by 1 | Viewed by 1936

Abstract

Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19 is substantially different from ARDS caused by other diseases and its treatment is dissimilar and challenging. As many studies showed conflicting results regarding the use of Non-invasive ventilation in COVID-19-associated ARDS, no unquestionable indications by [...] Read more.

Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19 is substantially different from ARDS caused by other diseases and its treatment is dissimilar and challenging. As many studies showed conflicting results regarding the use of Non-invasive ventilation in COVID-19-associated ARDS, no unquestionable indications by operational guidelines were reported. The aim of this study was to estimate the use and success rate of Helmet (h) Continuous Positive Airway Pressure (CPAP) in COVID-19-associated ARDS in medical regular wards patients and describe the predictive risk factors for its use and failure. In our monocentric retrospective observational study, we included patients admitted for COVID-19 in medical regular wards. hCPAP was delivered when supplemental conventional or high-flow nasal oxygen failed to achieve respiratory targets. The primary outcomes were hCPAP use and failure rate (including the need to use Bilevel (BL) PAP or oro-tracheal intubation (OTI) and death during ventilation). The secondary outcome was the rate of in-hospital death and OTI. We computed a score derived from the factors independently associated with hCPAP failure. Out of 701 patients admitted with COVID-19 symptoms, 295 were diagnosed with ARDS caused by COVID-19 and treated with hCPAP. Factors associated with the need for hCPAP use were the PaO₂/FiO₂ ratio < 270, IL-6 serum levels over 46 pg/mL, AST > 33 U/L, and LDH > 570 U/L; age > 78 years and neuropsychiatric conditions were associated with lower use of hCPAP. Failure of hCPAP occurred in 125 patients and was associated with male sex, polypharmacotherapy (at least three medications), platelet count < 180 × 10⁹/L, and PaO₂/FiO₂ ratio < 240. The computed hCPAP-f Score, ranging from 0 to 11.5 points, had an AUC of 0.74 in predicting hCPAP failure (significantly superior to Call Score), and 0.73 for the secondary outcome (non-inferior to IL-6 serum levels). In conclusion, hCPAP was widely used in patients with COVID-19 symptoms admitted to medical regular wards and developing ARDS, with a low OTI rate. A score computed combining male sex, multi-pharmacotherapy, low platelet count, and low PaO₂/FiO₂ was able to predict hCPAP failure in hospitalized patients with ARDS caused by COVID-19. Full article

(This article belongs to the Special Issue Emerging Trends in Complications Associated with SARS-CoV-2 Infection)

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18 pages, 1680 KiB

Open AccessArticle

The Vastus Lateralis Muscle Interstitium Proteome Changes after an Acute Nociception in Patients with Fibromyalgia Compared to Healthy Subjects—A Microdialysis Study

by Bijar Ghafouri, Daria Matikhan, Nikolaos Christidis, Malin Ernberg, Eva Kosek, Kaisa Mannerkorpi, Björn Gerdle and Karin Wåhlén

Biomedicines 2023, 11(1), 206; https://doi.org/10.3390/biomedicines11010206 - 13 Jan 2023

Viewed by 1774

Abstract

Fibromyalgia (FM) is a complex disorder and a clinical challenge to diagnose and treat. Microdialysis is a valuable tool that has been used to investigate the interstitial proteins and metabolites of muscle in patients with fibromyalgia. The implantation of the catheter in the [...] Read more.

Fibromyalgia (FM) is a complex disorder and a clinical challenge to diagnose and treat. Microdialysis is a valuable tool that has been used to investigate the interstitial proteins and metabolites of muscle in patients with fibromyalgia. The implantation of the catheter in the muscle causes acute tissue trauma and nociception. The aim of this study was to investigate acute proteome changes in the vastus lateralis muscle in women fibromyalgia patients (FM) and healthy subjects (CON). A further aim was to study if a 15-week resistance exercise program in FM had any influence on how chronic painful muscle responds to acute nociception. Twenty-six women patients with FM and twenty-eight CON were included in this study. A microdialysis catheter (100 kilo Dalton cut off, membrane 30 mm) was inserted in the vastus lateralis muscle, and samples were collected every 20 min. Subjects rated pain before catheter insertion, directly after, and every 20 min of sample collection. Dialysate samples from time points 0–120 were pooled and considered trauma samples due to the catheter insertion. The samples were analyzed with nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). Advanced multivariate data analysis was used to investigate protein profile changes between the groups. Multivariate data analysis showed significant (CV-ANOVA p = 0.036) discrimination between FM and CON based on changes in 26 proteins. After the 15-week exercise intervention, the expression levels of the 15 proteins involved in muscle contraction, response to stimulus, stress, and immune system were increased to the same expression levels as in CON. In conclusion, this study shows that microdialysis, in combination with proteomics, can provide new insights into the interstitial proteome in the muscle of FM. In response to acute nociception, exercise may alter the innate reactivity in FM. Exercise may also modulate peripheral muscle proteins related to muscle contraction, stress, and immune response in patients with FM. Full article

(This article belongs to the Collection Neurogenic Neuroinflammation in Fibromyalgia)

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14 pages, 3324 KiB

Open AccessReview

METCAM Is a Potential Biomarker for Predicting the Malignant Propensity of and as a Therapeutic Target for Prostate Cancer

by Jui-Chuang Wu and Guang-Jer Wu

Biomedicines 2023, 11(1), 205; https://doi.org/10.3390/biomedicines11010205 - 13 Jan 2023

Cited by 2 | Viewed by 1760

Abstract

Prostate cancer is the second leading cause of cancer-related death worldwide. This is because it is still unknown why indolent prostate cancer becomes an aggressive one, though many risk factors for this type of cancer have been suggested. Currently, many diagnostic markers have [...] Read more.

Prostate cancer is the second leading cause of cancer-related death worldwide. This is because it is still unknown why indolent prostate cancer becomes an aggressive one, though many risk factors for this type of cancer have been suggested. Currently, many diagnostic markers have been suggested for predicting malignant prostatic carcinoma cancer; however, only a few, such as PSA (prostate-specific antigen), Prostate Health Index (PHI), and PCA3, have been approved by the FDA. However, each biomarker has its merits as well as shortcomings. The serum PSA test is incapable of differentiating prostate cancer from BPH and also has an about 25% false-positive prediction rate for the malignant status of cancer. The PHI test has the potential to replace the PSA test for the discrimination of BPH from prostate cancer and for the prediction of high-grade cancer avoiding unnecessary biopsies; however, the free form of PSA is unstable and expensive. PCA3 is not associated with locally advanced disease and is limited in terms of its prediction of aggressive cancer. Currently, several urine biomarkers have shown high potential in terms of being used to replace circulating biomarkers, which require a more invasive method of sample collection, such as via serum. Currently, the combined multiple tumor biomarkers may turn out to be a major trend in the diagnosis and assessment of the treatment effectiveness of prostate cancer. Thus, there is still a need to search for more novel biomarkers to develop a perfect cocktail, which consists of multiple biomarkers, in order to predict malignant prostate cancer and follow the efficacy of the treatment. We have discovered that METCAM, a cell adhesion molecule in the Ig-like superfamily, has great potential regarding its use as a biomarker for differentiating prostate cancer from BPH, predicting the malignant propensity of prostate cancer at the early premalignant stage, and differentiating indolent prostate cancers from aggressive cancers. Since METCAM has also been shown to be able to initiate the spread of prostate cancer cell lines to multiple organs, we suggest that it may be used as a therapeutic target for the clinical treatment of patients with malignant prostate cancer. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)

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14 pages, 961 KiB

Open AccessReview

Current Approaches in Surgical and Immunotherapy-Based Management of Renal Cell Carcinoma with Tumor Thrombus

by Marina M. Tabbara, Javier González, Melanie Martucci and Gaetano Ciancio

Biomedicines 2023, 11(1), 204; https://doi.org/10.3390/biomedicines11010204 - 13 Jan 2023

Cited by 7 | Viewed by 2408

Abstract

Renal cell carcinoma (RCC) accounts for 2–3% of all malignant disease in adults, with 30% of RCC diagnosed at locally advanced or metastatic stages of disease. A form of locally advanced disease is the tumor thrombus (TT), which commonly grows from the intrarenal [...] Read more.

Renal cell carcinoma (RCC) accounts for 2–3% of all malignant disease in adults, with 30% of RCC diagnosed at locally advanced or metastatic stages of disease. A form of locally advanced disease is the tumor thrombus (TT), which commonly grows from the intrarenal veins, through the main renal vein, and up the inferior vena cava (IVC), and rarely, into the right cardiac chambers. Advances in all areas of medicine have allowed increased understanding of the underlying biology of these tumors and improved preoperative staging. Although the development of several novel system agents, including several clinical trials utilizing immune checkpoint inhibitors and combination therapies, has been shown to lower perioperative morbidity and increase post-operative recurrence-free and progression-free survival, surgery remains the mainstay of therapy to achieve a cure. In this review, we provide a description of specific surgical approaches and techniques used to minimize intra- and post-operative complications during radical nephrectomy and tumor thrombectomy of RCC with TT extension of various levels. Additionally, we provide an in-depth review of the major developments in neoadjuvant and adjuvant immunotherapy-based treatment and the impact of ongoing and recently completed clinical trials on the surgical treatment of advanced RCC. Full article

(This article belongs to the Special Issue Renal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches 2.0)

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Biomedicines, Volume 11, Issue 1 (January 2023) – 233 articles

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