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Biomedicines, Volume 11, Issue 3 (March 2023) – 346 articles

Cover Story (view full-size image): Sepsis and septic shock are among the deadliest diseases, responsible for an estimated annual global death toll of 11 million. Sepsis is a complex disorder involving a disbalance between inflammation and anti-inflammation, leading to the widespread unregulated release of inflammatory mediators, cytokines, and pathogen-related molecules, prominent in systemwide organ dysfunction. Unfortunately, rising antibiotic resistance among bacteria and a dwindling pipeline of newer antibiotics make its treatment difficult. To rise to this challenge, monoclonal antibodies as an alternative therapy have garnered substantial attention in recent years and may provide the solution to obliterate sepsis. View this paper
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11 pages, 502 KiB  
Article
Vitamin A Deficiency and Its Association with Visceral Adiposity in Women
by Érica Góes, Adryana Cordeiro, Claudia Bento and Andrea Ramalho
Biomedicines 2023, 11(3), 991; https://doi.org/10.3390/biomedicines11030991 - 22 Mar 2023
Cited by 2 | Viewed by 2274
Abstract
Body adiposity is associated with increased metabolic risk, and evidence indicates that vitamin A is important in regulating body fat. The aim of this study was to evaluate serum concentrations of vitamin A and its association with body adiposity in women with the [...] Read more.
Body adiposity is associated with increased metabolic risk, and evidence indicates that vitamin A is important in regulating body fat. The aim of this study was to evaluate serum concentrations of vitamin A and its association with body adiposity in women with the recommended intake of vitamin A. A cross-sectional study was designed with 200 women divided into four groups according to Body Mass Index (BMI): normal weight (NW), overweight (OW), class I obesity (OI), and class 2 obesity (OII). The cut-off points to assess inadequate participants were retinol < 1.05 µmol/L and β-carotene < 40 µg/dL. Body adiposity was assessed through different parameters and indexes, including waist circumference (WC), waist-to-height ratio (WHtR), hypertriglyceridemic waist (HW), lipid accumulation product (LAP), Visceral Adiposity Index (VAI), and Body Adiposity Index (BAI). It was observed that 55.5% of women had low serum concentrations of β-carotene (34.9 ± 13.8 µmol/L, p < 0.001) and 43.5% had low concentrations of retinol (0.71 ± 0.3 µmol/L, p < 0.001). Women classified as OI and OII had lower mean values of β-carotene (OI—35.9 ± 4.3 µg/dL: OII—32.0 ± 0.9 µg/dL [p < 0.001]). IAV showed significant negative correlation with retinol (r = −0.73, p < 0.001). Vitamin A deficiency is associated with excess body adiposity in women with the recommended intake of vitamin. Greater body adiposity, especially visceral, was correlated with reduced serum concentrations of vitamin A. Full article
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20 pages, 4181 KiB  
Review
Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis
by Annalisa L. E. Carli, Joshua M. Hardy, Hanadi Hoblos, Matthias Ernst, Isabelle S. Lucet and Michael Buchert
Biomedicines 2023, 11(3), 990; https://doi.org/10.3390/biomedicines11030990 - 22 Mar 2023
Viewed by 2040
Abstract
Doublecortin-like kinase 1 (DCLK1) is a functional serine/threonine (S/T)-kinase and a member of the doublecortin family of proteins which are characterized by their ability to bind to microtubules (MTs). DCLK1 is a proposed cancer driver gene, and its upregulation is associated with poor [...] Read more.
Doublecortin-like kinase 1 (DCLK1) is a functional serine/threonine (S/T)-kinase and a member of the doublecortin family of proteins which are characterized by their ability to bind to microtubules (MTs). DCLK1 is a proposed cancer driver gene, and its upregulation is associated with poor overall survival in several solid cancer types. However, how DCLK1 associates with MTs and how its kinase function contributes to pro-tumorigenic processes is poorly understood. This review builds on structural models to propose not only the specific functions of the domains but also attempts to predict the impact of individual somatic missense mutations on DCLK1 functions. Somatic missense mutations in DCLK1 are most frequently located within the N-terminal MT binding region and likely impact on the ability of DCLK1 to bind to αβ-tubulin and to polymerize and stabilize MTs. Moreover, the MT binding affinity of DCLK1 is negatively regulated by its auto-phosphorylation, and therefore mutations that affect kinase activity are predicted to indirectly alter MT dynamics. The emerging picture portrays DCLK1 as an MT-associated protein whose interactions with tubulin heterodimers and MTs are tightly controlled processes which, when disrupted, may confer pro-tumorigenic properties. Full article
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11 pages, 934 KiB  
Article
The Impact of BMI Changes on the Incidence of Glomerular Hematuria in Korean Adults: A Retrospective Study Based on the NHIS-HEALS Cohort
by Yu-Jin Kwon, Mina Kim, Hasung Kim and Jung Eun Lee
Biomedicines 2023, 11(3), 989; https://doi.org/10.3390/biomedicines11030989 - 22 Mar 2023
Viewed by 1327
Abstract
Obesity and recurrent hematuria are known risk factors for chronic kidney disease. However, there has been controversy on the association between obesity and glomerular hematuria. This study aimed to investigate the association between body mass index (BMI) and weight change and recurrent and [...] Read more.
Obesity and recurrent hematuria are known risk factors for chronic kidney disease. However, there has been controversy on the association between obesity and glomerular hematuria. This study aimed to investigate the association between body mass index (BMI) and weight change and recurrent and persistent hematuria in glomerular disease using a large-scale, population-based Korean cohort. Data were collected from the National Health Insurance Service-National Health Screening Cohort. Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrent and persistent hematuria in glomerular disease according to the BMI group. Compared with the BMI 23–25 kg/m2 group, the HR (95% CI) for incident recurrent and persistent hematuria in glomerular disease was 0.921 (0.831–1.021) in the BMI <23 kg/m2 group, 0.915 (0.823–1.018) in the BMI 25–30 kg/m2 group, and 1.151 (0.907–1.462) in the BMI ≥30 kg/m2 group. Compared with the stable weight group, the HRs (95% CIs) for incident recurrent and persistent hematuria in glomerular disease were 1.364 (1.029–1.808) and 0.985 (0.733–1.325) in the significant weight loss and gain groups, respectively. Despite adjusting for confounders, this result remained significant. Baseline BMI was not associated with the risk of incident recurrent and persistent hematuria in glomerular disease. Weight loss greater than 10% was associated with the incidence of recurrent and persistent hematuria in glomerular disease. Therefore, maintaining an individual’s weight could help prevent recurrent and persistent hematuria in glomerular disease in middle-aged and older Korean adults. Full article
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20 pages, 7325 KiB  
Case Report
Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration: Case Series
by Filomena Palmieri, Saad Younis, Walid Raslan and Lorenzo Fabozzi
Biomedicines 2023, 11(3), 988; https://doi.org/10.3390/biomedicines11030988 - 22 Mar 2023
Cited by 1 | Viewed by 1384
Abstract
Purpose: This study seeks to report the clinical and multimodal imaging findings of eight eyes of seven patients with neovascular age-related macular degeneration (nAMD) who developed bacillary layer detachment (BALAD). Setting/Venue: The patients were analysed at the Western Eye Hospital in London, UK. [...] Read more.
Purpose: This study seeks to report the clinical and multimodal imaging findings of eight eyes of seven patients with neovascular age-related macular degeneration (nAMD) who developed bacillary layer detachment (BALAD). Setting/Venue: The patients were analysed at the Western Eye Hospital in London, UK. Methods: The approaches of this research include clinical examinations and multimodal imaging-based description of cases of nAMD with BALAD. Results: We report multimodal imaging findings of bacillary layer detachment (BALAD) in patients with nAMD. Conclusions: A bacillary layer detachment was detected in patients with neovascular age-related macular degeneration. This multimodal imaging finding is not commonly described in the literature for this disease. Full article
(This article belongs to the Special Issue Advanced Research in Age-Related Macular Degeneration (AMD))
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19 pages, 3844 KiB  
Article
Adipose-Derived Stromal Cells within a Gelatin Matrix Acquire Enhanced Regenerative and Angiogenic Properties: A Pre-Clinical Study for Application to Chronic Wounds
by Nicolo Costantino Brembilla, Ali Modarressi, Dominik André-Lévigne, Estelle Brioudes, Florian Lanza, Hubert Vuagnat, Stéphane Durual, Laurine Marger, Wolf-Henning Boehncke, Karl-Heinz Krause and Olivier Preynat-Seauve
Biomedicines 2023, 11(3), 987; https://doi.org/10.3390/biomedicines11030987 - 22 Mar 2023
Cited by 1 | Viewed by 1329
Abstract
This study evaluates the influence of a gelatin sponge on adipose-derived stromal cells (ASC). Transcriptomic data revealed that, compared to ASC in a monolayer, a cross-linked porcine gelatin sponge strongly influences the transcriptome of ASC. Wound healing genes were massively regulated, notably with [...] Read more.
This study evaluates the influence of a gelatin sponge on adipose-derived stromal cells (ASC). Transcriptomic data revealed that, compared to ASC in a monolayer, a cross-linked porcine gelatin sponge strongly influences the transcriptome of ASC. Wound healing genes were massively regulated, notably with the inflammatory and angiogenic factors. Proteomics on conditioned media showed that gelatin also acted as a concentrator and reservoir of the regenerative ASC secretome. This secretome promoted fibroblast survival and epithelialization, and significantly increased the migration and tubular assembly of endothelial cells within fibronectin. ASC in gelatin on a chick chorioallantoic membrane were more connected to vessels than an empty sponge, confirming an increased angiogenesis in vivo. No tumor formation was observed in immunodeficient nude mice to which an ASC gelatin sponge was transplanted subcutaneously. Finally, ASC in a gelatin sponge prepared from outbred rats accelerated closure and re-vascularization of ischemic wounds in the footpads of rats. In conclusion, we provide here preclinical evidence that a cross-linked porcine gelatin sponge is an optimal carrier to concentrate and increase the regenerative activity of ASC, notably angiogenic. This formulation of ASC represents an optimal, convenient and clinically compliant option for the delivery of ASC on ischemic wounds. Full article
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8 pages, 367 KiB  
Communication
High-Throughput and Automated Detection of HLA-B*27 Using the LabTurboTM AIO System
by Yung-Che Chou and Tze-Kiong Er
Biomedicines 2023, 11(3), 986; https://doi.org/10.3390/biomedicines11030986 - 22 Mar 2023
Cited by 1 | Viewed by 1247
Abstract
The adoption of an automated system can decrease the hands-on time requirements in a clinical laboratory setting. For the detection of HLA-B*27, implementing a high-throughput and fully automated system has several advantages over using manual methods. Therefore, this study aimed to evaluate automation [...] Read more.
The adoption of an automated system can decrease the hands-on time requirements in a clinical laboratory setting. For the detection of HLA-B*27, implementing a high-throughput and fully automated system has several advantages over using manual methods. Therefore, this study aimed to evaluate automation efficiency for the detection of HLA-B*27. Peripheral blood samples were obtained from 50 participants, and DNA was isolated from these samples. A Pharmigene PG27 detection kit was used for the qualitative detection of HLA-B*27. The performances of the semi-automated and fully automated LabTurboTM AIO systems in the detection of HLA-B*27 were compared. The mean absorbance (optical density) values for the MaelstromTM 8 and LabTurboTM AIO systems were found to be 1.88 and 1.9, respectively. The housekeeping gene was amplified and quantified using a real-time PCR assay across all DNA extracts to check the quality of the extracted human DNA. The results were expressed as the cycle threshold (Ct) values for all DNA extracts from both platforms. The mean Ct values for the Roche Cobas z480 and LabTurboTM AIO systems were found to be 22.7 and 20.4, respectively. This study demonstrated that the semi-automated method and the LabTurboTM AIO system yield consistent results for the detection of HLA-B*27. However, compared to the semi-automated method, the LabTurboTM AIO system provides standardized procedures, avoids manual handling, and improves turnaround time. Full article
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22 pages, 6934 KiB  
Article
Mixed-Culture Propagation of Uterine-Tissue-Resident Macrophages and Their Expression Properties of Steroidogenic Molecules
by Kazushige Ogawa and Takashi Tanida
Biomedicines 2023, 11(3), 985; https://doi.org/10.3390/biomedicines11030985 - 22 Mar 2023
Cited by 2 | Viewed by 1383
Abstract
Tissue-resident macrophages (Mø) play tissue/organ-specific roles, and the physiological/pathological implications of uterine Mø in fertility and infertility are not yet fully understood. Herein, we report a simple propagation method for tissue-resident Mø by mixed culture with the respective tissue/organ-residing cells as the niche. [...] Read more.
Tissue-resident macrophages (Mø) play tissue/organ-specific roles, and the physiological/pathological implications of uterine Mø in fertility and infertility are not yet fully understood. Herein, we report a simple propagation method for tissue-resident Mø by mixed culture with the respective tissue/organ-residing cells as the niche. We successfully propagated mouse uterine Mø by mixed culture with fibroblastic cells that exhibited properties of endometrial stromal cells. Propagated mouse uterine Mø were CD206- and arginase-1-positive; iNOS- and MHC-II-negative, indicating M2 polarization; and highly phagocytic, similar to endometrial Mø. Furthermore, uterine Mø were observed to express steroidogenic molecules including SRD5A1 and exhibited gap junction formation, likely with endometrial stromal cells. Accordingly, uterine Mø propagated by mixed culture may provide a new tool for studying immune–endocrine interactions related to fertility and infertility, particularly androgen’s intracrine actions in preparing the uterine tissue environment to support implantation and pregnancy as well as in the etiology of endometriosis. Full article
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease 4.0)
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6 pages, 1596 KiB  
Case Report
Surgical Management of Pterygium Colli with Significant Skin Laxity: A Case Report
by Charline Huttin, Patrick Ringenbach, Anastasia Durry, Mihai Hogas, Ionut Raducu Popescu, Alin Ciobica and Mihaela Elena Nastasa
Biomedicines 2023, 11(3), 984; https://doi.org/10.3390/biomedicines11030984 - 22 Mar 2023
Viewed by 2559
Abstract
Pterygium Colli or “palmate neck” is a congenital malformation that is most often part of a polimalformative syndrome. This deformity is a source of aesthetic and social embarrassment. Its correction is surgical. We present the case of a pterygium colli in a patient [...] Read more.
Pterygium Colli or “palmate neck” is a congenital malformation that is most often part of a polimalformative syndrome. This deformity is a source of aesthetic and social embarrassment. Its correction is surgical. We present the case of a pterygium colli in a patient with Noonan syndrome. He had a significant excess of skin with posterior skin laxity, causing significant social discomfort and imposing a vicious attitude, the head bent forward. We performed a posterolateral resection of this excess by resecting two posterior triangular flaps with a resulting t-shaped scar. The results were satisfactory; the excess skin was almost completely resorbed with minimal scarring. However, this technique did not correct the low lateral hairline implantation, and there were still two lateral flaps for which the patient did not wish to have a repeat surgery. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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11 pages, 3336 KiB  
Article
Identification of a Novel Protein-Based Prognostic Model in Gastric Cancers
by Zhijuan Xiong, Chutian Xing, Ping Zhang, Yunlian Diao, Chenxi Guang, Ying Ying and Wei Zhang
Biomedicines 2023, 11(3), 983; https://doi.org/10.3390/biomedicines11030983 - 22 Mar 2023
Viewed by 1372
Abstract
Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. However, there are still no reliable biomarkers for the prognosis of this disease. This study aims to construct a robust protein-based prognostic prediction model for GC patients. The protein expression data [...] Read more.
Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. However, there are still no reliable biomarkers for the prognosis of this disease. This study aims to construct a robust protein-based prognostic prediction model for GC patients. The protein expression data and clinical information of GC patients were downloaded from the TCPA and TCGA databases, and the expressions of 218 proteins in 352 GC patients were analyzed using bioinformatics methods. Additionally, Kaplan–Meier (KM) survival analysis and univariate and multivariate Cox regression analysis were applied to screen the prognosis-related proteins for establishing the prognostic prediction risk model. Finally, five proteins, including NDRG1_pT346, SYK, P90RSK, TIGAR, and XBP1, were related to the risk prognosis of gastric cancer and were selected for model construction. Furthermore, a significant trend toward worse survival was found in the high-risk group (p = 1.495 × 107). The time-dependent ROC analysis indicated that the model had better specificity and sensitivity compared to the clinical features at 1, 2, and 3 years (AUC = 0.685, 0.673, and 0.665, respectively). Notably, the independent prognostic analysis results revealed that the model was an independent prognostic factor for GC patients. In conclusion, the robust protein-based model based on five proteins was established, and its potential benefits in the prognostic prediction of GC patients were demonstrated. Full article
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12 pages, 2180 KiB  
Article
Immunohistochemical Evaluation of Candidate Biomarkers for Fluorescence-Guided Surgery of Myxofibrosarcoma Using an Objective Scoring Method
by Zeger Rijs, Esther Belt, Gijsbert M. Kalisvaart, Cornelis F. M. Sier, Peter J. K. Kuppen, Arjen H. G. Cleven, Alexander L. Vahrmeijer, Michiel A. J. van de Sande and Pieter B. A. A. van Driel
Biomedicines 2023, 11(3), 982; https://doi.org/10.3390/biomedicines11030982 - 22 Mar 2023
Cited by 3 | Viewed by 1524
Abstract
Introduction: Myxofibrosarcoma (MFS) is the most common soft-tissue sarcoma subtype in elderly patients. Local recurrence (LR) remains a major concern as the lack of intraoperative guidance and an infiltrative growth pattern with long, slender tails hamper surgeons’ ability to achieve adequate resection margins [...] Read more.
Introduction: Myxofibrosarcoma (MFS) is the most common soft-tissue sarcoma subtype in elderly patients. Local recurrence (LR) remains a major concern as the lack of intraoperative guidance and an infiltrative growth pattern with long, slender tails hamper surgeons’ ability to achieve adequate resection margins for MFS. Fluorescence-guided surgery (FGS) could overcome this concern by delineating tumor tissue during surgery. One of the most important steps to successful FGS is to define a tumor-specific biomarker that is highly overexpressed in tumor tissue while low or absent in adjacent healthy tissue. The aim of this study is to evaluate the expression of eight previously selected promising biomarkers for FGS in MFS tissue samples with adjacent healthy tissue using immunohistochemistry (IHC). Methods: The following eight biomarkers were stained in seventeen paraffin-embedded MFS samples: tumor endothelial marker-1 (TEM-1, also known as endosialin/CD248), vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1), vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Flk1), vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), platelet derived growth factor receptor-α (PDGFR-α), and cluster of differentiation 40 (CD40, also known as TNFRSF5). A pathologist specializing in sarcoma annotated the margin between the tumor and adjacent healthy tissue in each MFS tissue sample. Subsequently, we used an objective IHC scoring method to assess and compare the difference in staining intensity between the tumor and adjacent healthy tissue, which is crucial for the use of FGS. Results: TEM-1, VEGF-A, and PDGFR-α stained all MFS tumors, while the other biomarkers did not show expression in all MFS tumors. Ultimately, TEM-1 was identified as the most suitable biomarker for FGS in MFS based on higher tumor-to-background (TBR) staining intensity compared to VEGF-A and PDGFR-α, regardless of preoperative therapy. Conclusion: TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment. Full article
(This article belongs to the Special Issue Pathogenic Mechanisms and Novel Therapeutic Approaches for Sarcomas)
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22 pages, 703 KiB  
Article
Single Nucleotide Polymorphisms of the RAC1 Gene as Novel Susceptibility Markers for Neuropathy and Microvascular Complications in Type 2 Diabetes
by Iuliia Azarova, Elena Klyosova and Alexey Polonikov
Biomedicines 2023, 11(3), 981; https://doi.org/10.3390/biomedicines11030981 - 22 Mar 2023
Cited by 1 | Viewed by 1492
Abstract
Single nucleotide polymorphisms (SNP) in the RAC1 (Rac family small GTPase 1) gene have recently been linked to type 2 diabetes (T2D) and hyperglycemia due to their contribution to impaired redox homeostasis. The present study was designed to determine whether the common SNPs [...] Read more.
Single nucleotide polymorphisms (SNP) in the RAC1 (Rac family small GTPase 1) gene have recently been linked to type 2 diabetes (T2D) and hyperglycemia due to their contribution to impaired redox homeostasis. The present study was designed to determine whether the common SNPs of the RAC1 gene are associated with diabetic complications such as neuropathy (DN), retinopathy (DR), nephropathy, angiopathy of the lower extremities (DA), and diabetic foot syndrome. A total of 1470 DNA samples from T2D patients were genotyped for six common SNPs by the MassArray Analyzer-4 system. The genotype rs7784465-T/C of RAC1 was associated with an increased risk of DR (p = 0.016) and DA (p = 0.03) in males, as well as with DR in females (p = 0.01). Furthermore, the SNP rs836478 showed an association with DR (p = 0.005) and DN (p = 0.025) in males, whereas the SNP rs10238136 was associated with DA in females (p = 0.002). In total, three RAC1 haplotypes showed significant associations (FDR < 0.05) with T2D complications in a sex-specific manner. The study’s findings demonstrate, for the first time, that the RAC1 gene’s polymorphisms represent novel and sex-specific markers of neuropathy and microvascular complications in type 2 diabetes, and that the gene could be a new target for the pharmacological inhibition of oxidative stress as a means of preventing diabetic complications. Full article
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9 pages, 1000 KiB  
Brief Report
The Role of the Left Inferior Parietal Cortex in Gilles de la Tourette Syndrome—An rTMS Study
by Theresa Paulus, Lynn Wernecke, Annik Lundie, Julia Friedrich, Julius Verrel, Tina Rawish, Anne Weissbach, Christian Frings, Christian Beste, Tobias Bäumer and Alexander Münchau
Biomedicines 2023, 11(3), 980; https://doi.org/10.3390/biomedicines11030980 - 22 Mar 2023
Cited by 1 | Viewed by 1639
Abstract
Increased activity in the left inferior parietal cortex (BA40) plays a role in the generation of tics in the Gilles de la Tourette syndrome (GTS). Thus, inhibitory repetitive transcranial magnetic stimulation (rTMS) applied to BA40 was hypothesized to alleviate symptoms in GTS. We [...] Read more.
Increased activity in the left inferior parietal cortex (BA40) plays a role in the generation of tics in the Gilles de la Tourette syndrome (GTS). Thus, inhibitory repetitive transcranial magnetic stimulation (rTMS) applied to BA40 was hypothesized to alleviate symptoms in GTS. We investigated the immediate effects of single-session 1 Hz rTMS and sham stimulation delivered to the left BA40 on tics assessed with the Rush video protocol in 29 adults with GTS. There were no significant effects on tic symptoms following rTMS or sham stimulation. Moreover, there was no difference when comparing the effects of both stimulation conditions. Bayesian statistics indicated substantial evidence against an intervention effect. The left BA40 appears not to be a useful target for 1 Hz rTMS to modulate tic symptoms in GTS patients. Full article
(This article belongs to the Special Issue The Neurobiology of Tourette Syndrome along the Lifespan)
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10 pages, 384 KiB  
Article
Optimal Timing of Coronary Artery Bypass Grafting in Haemodynamically Stable Patients after Myocardial Infarction
by Chloé Bernard, Marie Catherine Morgant, Aline Jazayeri, Thomas Perrin, Ghislain Malapert, Saed Jazayeri, Alain Bernard and Olivier Bouchot
Biomedicines 2023, 11(3), 979; https://doi.org/10.3390/biomedicines11030979 - 22 Mar 2023
Cited by 1 | Viewed by 1678
Abstract
During the acute phase of myocardial infarction, the culprit artery must be revascularized quickly with angioplasty. Surgery then completes the procedure in a second stage. If emergency surgery is performed, the resulting death rate is high; 15–20% of patients are operated on within [...] Read more.
During the acute phase of myocardial infarction, the culprit artery must be revascularized quickly with angioplasty. Surgery then completes the procedure in a second stage. If emergency surgery is performed, the resulting death rate is high; 15–20% of patients are operated on within the first 48 h after the myocardial infarction. The timing of surgical revascularization and the patient’s preoperative state influence the mortality rate. We aimed to evaluate the impact of surgery delay on morbimortality. Between 2007 and 2017, a retrospective monocentric study was conducted including 477 haemodynamically stable patients after myocardial infarction who underwent an urgent coronary bypass. Three groups were described, depending on the timing of the surgery: during the first 4 days (Group 1, n = 111, 23%), 5 to 10 days (Group 2, n = 242, 51%) and after 11 days (Group 3, n = 124, 26%). The overall thirty-day mortality was 7.1% (n = 34). The death rate was significantly higher in Group 1 (n = 16; 14% vs. n = 10; 4.0% vs. n = 8; 6%, p < 0.01). The mortality risk factors identified were age (OR: 1.08; CI 95%: 1.04–1.12; p < 0.001), peripheral arteriopathy (OR: 3.31; CI 95%: 1.16–9.43; p = 0.024), preoperative renal failure (OR: 6.39; CI 95%: 2.49–15.6; p < 0.001) and preoperative ischemic recurrence (OR: 3.47; CI 95%: 1.59–7.48; p < 0.01). Ninety-two patients presented with preoperative ischemic recurrence (19%), with no difference between the groups. The optimal timing for the surgical revascularization of MI seems to be after Day 4 in stable patients. However, timing is not the only factor influencing the death rate: the patient’s health condition and disease severity must be considered in the individual management strategy. Full article
(This article belongs to the Special Issue Recent Developments in Coronary Artery Disease)
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23 pages, 2516 KiB  
Review
Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement
by Nicolas Monnin, Anne Julie Fattet and Isabelle Koscinski
Biomedicines 2023, 11(3), 978; https://doi.org/10.3390/biomedicines11030978 - 22 Mar 2023
Cited by 11 | Viewed by 4590
Abstract
Endometriosis is a chronic disease caused by ectopic endometrial tissue. Endometriotic implants induce inflammation, leading to chronic pain and impaired fertility. Characterized by their dependence on estradiol (via estrogen receptor β (ESRβ)) and their resistance to progesterone, endometriotic implants produce their own source [...] Read more.
Endometriosis is a chronic disease caused by ectopic endometrial tissue. Endometriotic implants induce inflammation, leading to chronic pain and impaired fertility. Characterized by their dependence on estradiol (via estrogen receptor β (ESRβ)) and their resistance to progesterone, endometriotic implants produce their own source of estradiol through active aromatase. Steroidogenic factor-1 (SF1) is a key transcription factor that promotes aromatase synthesis. The expression of SF1 and ESRβ is enhanced by the demethylation of their promoter in progenitor cells of the female reproductive system. High local concentrations of estrogen are involved in the chronic inflammatory environment favoring the implantation and development of endometriotic implants. Similar local conditions can promote, directly and indirectly, the appearance and development of genital cancer. Recently, certain components of the microbiota have been identified as potentially promoting a high level of estrogen in the blood. Many environmental factors are also suspected of increasing the estrogen concentration, especially prenatal exposure to estrogen-like endocrine disruptors such as DES and bisphenol A. Phthalates are also suspected of promoting endometriosis but throughmeans other than binding to estradiol receptors. The impact of dioxin or tobacco seems to be more controversial. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
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3 pages, 181 KiB  
Editorial
Chronic Kidney Disease—How Does It Go, and What Can We Do and Expect?
by Li-Yun Chang and Jer-Ming Chang
Biomedicines 2023, 11(3), 977; https://doi.org/10.3390/biomedicines11030977 - 22 Mar 2023
Viewed by 1067
Abstract
Chronic kidney disease (CKD), as a worldwide threat to public health, is a key determinant of poor health outcomes, but the severity of the problem is probably not fully appreciated [...] Full article
(This article belongs to the Special Issue Pathogenesis and Treatment Progress of Chronic Kidney Diseases)
20 pages, 1595 KiB  
Article
Canine Coronavirus Infection Modulates the Biogenesis and Composition of Cell-Derived Extracellular Vesicles
by Rachana Pandit, Ayodeji O. Ipinmoroti, Brennetta J. Crenshaw, Ting Li and Qiana L. Matthews
Biomedicines 2023, 11(3), 976; https://doi.org/10.3390/biomedicines11030976 - 21 Mar 2023
Cited by 1 | Viewed by 1897
Abstract
Coronavirus (CoV) has persistently become a global health concern causing various diseases in a wide variety of hosts, including humans, birds, and companion animals. However, the virus-mediated responses in animal hosts have not been studied extensively due to pathogenesis complexity and disease developments. [...] Read more.
Coronavirus (CoV) has persistently become a global health concern causing various diseases in a wide variety of hosts, including humans, birds, and companion animals. However, the virus-mediated responses in animal hosts have not been studied extensively due to pathogenesis complexity and disease developments. Extracellular vesicles (EVs) are widely explored in viral infections for their intercellular communication, nanocarrier, and immunomodulatory properties. We proposed that coronavirus hijacks the host exosomal pathway and modulates the EV biogenesis, composition, and protein trafficking in the host. In the present study, Crandell–Rees feline kidney (CRFK) cells were infected with canine coronavirus (CCoV) in an exosome-free medium at the multiplicity of infection (MOI) of 400 infectious units (IFU) at various time points. The cell viability was significantly decreased over time, as determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Post-infection EVs were isolated, and transmission electron microscopy (TEM) showed the presence of small EVs (sEVs) after infection. NanoSight particle tracking analysis (NTA) revealed that EV sizes averaged between 100 and 200 nm at both incubation times; however, the mean size of infection-derived EVs was significantly decreased at 48 h when compared to uninfected control EVs. Quantitative analysis of protein levels performed by dot blot scanning showed that the expression levels of ACE-2, annexin-V, flotillin-1, TLR-7, LAMP, TNF-α, caspase-1, caspase-8, and others were altered in EVs after infection. Our findings suggested that coronavirus infection impacts cell viability, modulates EV biogenesis, and alters cargo composition and protein trafficking in the host, which could impact viral progression and disease development. Future experiments with different animal CoVs will provide a detailed understanding of host EV biology in infection pathogenesis and progression. Hence, EVs could offer a diagnostic and therapeutic tool to study virus-mediated host responses that could be extended to study the interspecies jump of animal CoVs to cause infection in humans. Full article
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13 pages, 491 KiB  
Review
Thyroid Hormone and Heart Failure: Charting Known Pathways for Cardiac Repair/Regeneration
by Polyxeni Mantzouratou, Eleftheria Malaxianaki, Domenico Cerullo, Angelo Michele Lavecchia, Constantinos Pantos, Christodoulos Xinaris and Iordanis Mourouzis
Biomedicines 2023, 11(3), 975; https://doi.org/10.3390/biomedicines11030975 - 21 Mar 2023
Cited by 1 | Viewed by 2299
Abstract
Heart failure affects more than 64 million people worldwide, having a serious impact on their survival and quality of life. Exploring its pathophysiology and molecular bases is an urgent need in order to develop new therapeutic approaches. Thyroid hormone signaling, evolutionarily conserved, controls [...] Read more.
Heart failure affects more than 64 million people worldwide, having a serious impact on their survival and quality of life. Exploring its pathophysiology and molecular bases is an urgent need in order to develop new therapeutic approaches. Thyroid hormone signaling, evolutionarily conserved, controls fundamental biological processes and has a crucial role in development and metabolism. Its active form is L-triiodothyronine, which not only regulates important gene expression by binding to its nuclear receptors, but also has nongenomic actions, controlling crucial intracellular signalings. Stressful stimuli, such as acute myocardial infarction, lead to changes in thyroid hormone signaling, and especially in the relation of the thyroid hormone and its nuclear receptor, which are associated with the reactivation of fetal development programmes, with structural remodeling and phenotypical changes in the cardiomyocytes. The recapitulation of fetal-like features of the signaling may be partially an incomplete effort of the myocardium to recapitulate its developmental program and enable cardiomyocytes to proliferate and finally to regenerate. In this review, we will discuss the experimental and clinical evidence about the role of the thyroid hormone in the recovery of the myocardium in the setting of heart failure with reduced and preserved ejection fraction and its future therapeutic implications. Full article
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10 pages, 289 KiB  
Article
Subclinical Carotid Atherosclerosis in Patients with Rheumatoid Arthritis at Low Cardiovascular Risk
by Elena V. Gerasimova, Tatiana V. Popkova, Daria A. Gerasimova, Yuliya V. Markina and Tatiana V. Kirichenko
Biomedicines 2023, 11(3), 974; https://doi.org/10.3390/biomedicines11030974 - 21 Mar 2023
Cited by 4 | Viewed by 1320
Abstract
Objective: To evaluate the rate of subclinical carotid atherosclerosis and clinical significance of immunoinflammatory markers in patients with rheumatoid arthritis (RA) at low cardiovascular risk. Materials and Methods: The study included 275 RA patients and a control group of 100 participants without autoimmune [...] Read more.
Objective: To evaluate the rate of subclinical carotid atherosclerosis and clinical significance of immunoinflammatory markers in patients with rheumatoid arthritis (RA) at low cardiovascular risk. Materials and Methods: The study included 275 RA patients and a control group of 100 participants without autoimmune diseases. All study participants were at low cardiovascular risk, calculated by the QRISK3 scale (<20%), and free of cardiovascular disease. Ultrasound examination of carotid arteries was performed to measure cIMT and to detect atherosclerotic plaques (ASP) in carotid arteries. sIСАМ-1, sVСАМ, and sCD40L levels were determined by enzyme immunoassay. Results: Carotid ASP was observed more frequently in RA patients (27%) than in the control group (17%), p = 0.03. The frequency of ASP in RA patients did not depend on the disease’s stage or activity. There was a significant correlation between cIMT and age, cardiovascular risk determined by QRISK3, level of total cholesterol, LDL, and blood pressure in RA patients, p < 0.05 in all cases. No correlation between cIMT and blood levels of sCD40L, sVCAM, and sICAM was found. In RA patients, a higher concentration of sVCAM was detected in the carotid ASP group compared to the non-atherosclerotic group. sCD40L was associated with cIMT and total cholesterol in the ASP group and with total cholesterol and blood pressure in non-atherosclerotic patients. Conclusions: Subclinical atherosclerotic lesions of the carotid arteries were observed significantly more frequently in RA patients with low cardiovascular risk than in the control group. The results of the study demonstrate the association between cIMT, traditional cardiovascular risk factors, and immunoinflammatory markers in RA patients. Full article
(This article belongs to the Special Issue Atherosclerosis: Pathophysiology and Associations with Other Diseases)
20 pages, 4717 KiB  
Article
PPARα Inhibits Astrocyte Inflammation Activation by Restoring Autophagic Flux after Transient Brain Ischemia
by Doudou Luo, Wenxuan Ye, Ling Chen, Xiaoqian Yuan, Yali Zhang, Caixia Chen, Xin Jin and Yu Zhou
Biomedicines 2023, 11(3), 973; https://doi.org/10.3390/biomedicines11030973 - 21 Mar 2023
Cited by 3 | Viewed by 1516
Abstract
Astrocyte inflammation activation is an important cause that hinders the recovery of motor function after cerebral ischemia. However, its molecular mechanism has not yet been clearly clarified. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated nuclear transcriptional factor. This study aims to [...] Read more.
Astrocyte inflammation activation is an important cause that hinders the recovery of motor function after cerebral ischemia. However, its molecular mechanism has not yet been clearly clarified. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated nuclear transcriptional factor. This study aims to further clarify the role of PPARα in astrocyte inflammation activation after cerebral ischemia and to explore the underlying mechanism. Astrocyte activation was induced in an in vivo model by transient middle cerebral artery occlusion (tMCAO) in mice. The in vitro model was induced by an oxygen-glucose deprivation/reoxygenation (OGD/R) in a primary culture of mouse astrocyte. PPARα-deficient mice were used to observe the effects of PPARα on astrocyte activation and autophagic flux. Our results showed that PPARα was mainly expressed in activated astrocytes during the chronic phase of brain ischemia and PPARα dysfunction promoted astrocyte inflammatory activation. After cerebral ischemia, the expressions of LC3-II/I and p62 both increased. Autophagic vesicle accumulation was observed by electron microscopy in astrocytes, and the block of autophagic flux was indicated by an mRFP-GFP-LC3 adenovirus infection assay. A PPARα deficit aggravated the autophagic flux block, while PPARα activation preserved the lysosome function and restored autophagic flux in astrocytes after OGD/R. The autophagic flux blocker bafilomycin A1 and chloroquine antagonized the effect of the PPARα agonist on astrocyte activation inhibition. This study identifies a potentially novel function of PPARα in astrocyte autophagic flux and suggests a therapeutic target for the prevention and treatment of chronic brain ischemic injury. Full article
(This article belongs to the Special Issue PPARs in Health and Disease)
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13 pages, 1347 KiB  
Article
Anaemia and Congestion in Heart Failure: Correlations and Prognostic Role
by Pietro Scicchitano, Massimo Iacoviello, Antonio Massari, Micaela De Palo, Angela Potenza, Raffaella Landriscina, Silvia Abruzzese, Maria Tangorra, Piero Guida, Marco Matteo Ciccone, Pasquale Caldarola and Francesco Massari
Biomedicines 2023, 11(3), 972; https://doi.org/10.3390/biomedicines11030972 - 21 Mar 2023
Cited by 5 | Viewed by 1217
Abstract
The aim of this study was to evaluate the relationship between anaemia and biomarkers of central/peripheral congestion in heart failure (HF) and the impact on mortality. We retrospectively evaluated 434 acute/chronic HF (AHF/CHF) patients. Anaemia was defined as haemoglobin levels <12 g/dL (women) [...] Read more.
The aim of this study was to evaluate the relationship between anaemia and biomarkers of central/peripheral congestion in heart failure (HF) and the impact on mortality. We retrospectively evaluated 434 acute/chronic HF (AHF/CHF) patients. Anaemia was defined as haemoglobin levels <12 g/dL (women) or <13 g/dL (men). The brain natriuretic peptide (BNP) and hydration index (HI) were measured. The endpoint of the study was all-cause mortality. Anaemia occurred in 59% of patients with AHF and in 35% with CHF (p < 0.001) and showed a significant correlation with the NYHA functional class and renal function. BNP and HI were significantly higher in patients with anaemia than in those without anaemia. Independent predictors of anaemia included BNP, estimated creatinine clearance (eCrCL), and HI. The all-cause mortality rate was 21%, which was significantly higher in patients with anaemia than in those without anaemia (30% vs. 14%, p < 0.001; hazard ratio: 2.6). At multivariate Cox regression analysis, BNP, eCrCL, and HI were independent predictors for mortality (Hazard ratios: 1.0002, 0.97, and 1.05, respectively), while anaemia was not. Anaemia correlates with HF status, functional class, renal function, BNP, and HI. Anaemia was not an independent predictor for mortality, acting as a disease severity marker in congestive patients rather than as a predictor of death. Full article
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18 pages, 1880 KiB  
Review
Insight on Infections in Diabetic Setting
by Bianca Pari, Matteo Gallucci, Alberto Ghigo and Maria Felice Brizzi
Biomedicines 2023, 11(3), 971; https://doi.org/10.3390/biomedicines11030971 - 21 Mar 2023
Cited by 2 | Viewed by 1809
Abstract
The correlation between diabetes mellitus and infectious diseases is widely recognized. DM patients are characterized by the impaired function of the immune system. This translates into the occurrence of a variety of infections, including urinary tract, skin and surgical site infections, pneumonia, tuberculosis, [...] Read more.
The correlation between diabetes mellitus and infectious diseases is widely recognized. DM patients are characterized by the impaired function of the immune system. This translates into the occurrence of a variety of infections, including urinary tract, skin and surgical site infections, pneumonia, tuberculosis, and, more recently, SARS-CoV-2. Hyperglycemia has been identified as a relevant factor contributing to unfavorable outcomes in hospitalized patients including SARS-CoV-2 patients. Several studies have been performed proving that to maintain the proper and stringent monitoring of glycemia, a balanced diet and physical activity is mandatory to reduce the risk of infections and their associated complications. This review is focused on the mechanisms accounting for the increased susceptibility of DM patients to infections, with particular attention to the impact of newly introduced hypoglycemic drugs in sepsis management. Full article
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15 pages, 2966 KiB  
Article
Transcriptional and Epigenetic Alterations in the Progression of Non-Alcoholic Fatty Liver Disease and Biomarkers Helping to Diagnose Non-Alcoholic Steatohepatitis
by Yalan Zhu, He Zhang, Pengjun Jiang, Chengxia Xie, Yao Luo and Jie Chen
Biomedicines 2023, 11(3), 970; https://doi.org/10.3390/biomedicines11030970 - 21 Mar 2023
Cited by 4 | Viewed by 1596
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions from simple steatosis (non-alcoholic fatty liver (NAFL)) to non-alcoholic steatohepatitis (NASH), and its global prevalence continues to rise. NASH, the progressive form of NAFLD, has higher risks of liver and non-liver related [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions from simple steatosis (non-alcoholic fatty liver (NAFL)) to non-alcoholic steatohepatitis (NASH), and its global prevalence continues to rise. NASH, the progressive form of NAFLD, has higher risks of liver and non-liver related adverse outcomes compared with those patients with NAFL alone. Therefore, the present study aimed to explore the mechanisms in the progression of NAFLD and to develop a model to diagnose NASH based on the transcriptome and epigenome. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) among the three groups (normal, NAFL, and NASH) were identified, and the functional analysis revealed that the development of NAFLD was primarily related to the oxidoreductase-related activity, PPAR signaling pathway, tight junction, and pathogenic Escherichia coli infection. The logistic regression (LR) model, consisting of ApoF, THOP1, and BICC1, outperformed the other five models. With the highest AUC (0.8819, 95%CI: 0.8128–0.9511) and a sensitivity of 97.87%, as well as a specificity of 64.71%, the LR model was determined as the diagnostic model, which can differentiate NASH from NAFL. In conclusion, several potential mechanisms were screened out based on the transcriptome and epigenome, and a diagnostic model was built to help patient stratification for NAFLD populations. Full article
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29 pages, 4972 KiB  
Review
G-Quadruplexes in c-MYC Promoter as Targets for Cancer Therapy
by Bárbara Bahls, Israa M. Aljnadi, Rita Emídio, Eduarda Mendes and Alexandra Paulo
Biomedicines 2023, 11(3), 969; https://doi.org/10.3390/biomedicines11030969 - 21 Mar 2023
Cited by 12 | Viewed by 2669
Abstract
Cancer is a societal burden demanding innovative approaches. A major problem with the conventional chemotherapeutic agents is their strong toxicity and other side effects due to their poor selectivity. Uncontrolled proliferation of cancer cells is due to mutations, deletions, or amplifications in genes [...] Read more.
Cancer is a societal burden demanding innovative approaches. A major problem with the conventional chemotherapeutic agents is their strong toxicity and other side effects due to their poor selectivity. Uncontrolled proliferation of cancer cells is due to mutations, deletions, or amplifications in genes (oncogenes) encoding for proteins that regulate cell growth and division, such as transcription factors, for example, c-MYC. The direct targeting of the c-MYC protein has been attempted but so far unsuccessfully, as it lacks a definite binding site for the modulators. Meanwhile, another approach has been explored since the discovery that G-quadruplex secondary DNA structures formed in the guanine-rich sequences of the c-MYC promoter region can downregulate the transcription of this oncogene. Here, we will overview the major achievements made in the last decades towards the discovery of a new class of anticancer drugs targeting G-quadruplexes in the c-MYC promoter of cancer cells. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series in Drug Discovery)
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13 pages, 3068 KiB  
Review
Updates on Lymphovascular Invasion in Breast Cancer
by Elisabetta Kuhn, Donatella Gambini, Luca Despini, Dario Asnaghi, Letterio Runza and Stefano Ferrero
Biomedicines 2023, 11(3), 968; https://doi.org/10.3390/biomedicines11030968 - 21 Mar 2023
Cited by 8 | Viewed by 7647
Abstract
Traditionally, lymphovascular invasion (LVI) has represented one of the foremost pathological features of malignancy and has been associated with a worse prognosis in different cancers, including breast carcinoma. According to the most updated reporting protocols, the assessment of LVI is required in the [...] Read more.
Traditionally, lymphovascular invasion (LVI) has represented one of the foremost pathological features of malignancy and has been associated with a worse prognosis in different cancers, including breast carcinoma. According to the most updated reporting protocols, the assessment of LVI is required in the pathology report of breast cancer surgical specimens. Importantly, strict histological criteria should be followed for LVI assessment, which nevertheless is encumbered by inconsistency in interpretation among pathologists, leading to significant interobserver variability and scarce reproducibility. Current guidelines for breast cancer indicate biological factors as the main determinants of oncological and radiation therapy, together with TNM staging and age. In clinical practice, the widespread use of genomic assays as a decision-making tool for hormone receptor-positive, HER2-negative breast cancer and the subsequent availability of a reliable prognostic predictor have likely scaled back interest in LVI’s predictive value. However, in selected cases, the presence of LVI impacts adjuvant therapy. This review summarizes current knowledge on LVI in breast cancer with regard to definition, histopathological assessment, its biological understanding, clinicopathological association, and therapeutic implications. Full article
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19 pages, 27178 KiB  
Review
Recent Biomedical Applications of Coupling Nanocomposite Polymeric Materials Reinforced with Variable Carbon Nanofillers
by Abeer M. Alosaimi, Randa O. Alorabi, Dina F. Katowah, Zahrah T. Al-Thagafi, Eman S. Alsolami, Mahmoud A. Hussein, Mohammad Qutob and Mohd Rafatullah
Biomedicines 2023, 11(3), 967; https://doi.org/10.3390/biomedicines11030967 - 21 Mar 2023
Cited by 4 | Viewed by 1541
Abstract
The hybridization between polymers and carbon materials is one of the most recent and crucial study areas which abstracted more concern from scientists in the past few years. Polymers could be classified into two classes according to the source materials synthetic and natural. [...] Read more.
The hybridization between polymers and carbon materials is one of the most recent and crucial study areas which abstracted more concern from scientists in the past few years. Polymers could be classified into two classes according to the source materials synthetic and natural. Synthetic polymeric materials have been applied over a floppy zone of industrial fields including the field of biomedicine. Carbon nanomaterials including (fullerene, carbon nanotubes, and graphene) classified as one of the most significant sources of hybrid materials. Nanocarbons are improving significantly mechanical properties of polymers in nanocomposites in addition to physical and chemical properties of the new materials. In all varieties of proposed bio-nanocomposites, a considerable improvement in the microbiological performance of the materials has been explored. Various polymeric materials and carbon-course nanofillers were present, along with antibacterial, antifungal, and anticancer products. This review spots the light on the types of synthetic polymers-based carbon materials and presented state-of-art examples on their application in the area of biomedicine. Full article
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17 pages, 2884 KiB  
Article
Skin Microbiota: Setting up a Protocol to Evaluate a Correlation between the Microbial Flora and Skin Parameters
by Paola Perugini, Camilla Grignani, Giorgia Condrò, Harald van der Hoeven, Annamaria Ratti, Antonella Mondelli, Antonio Colpani and Mariella Bleve
Biomedicines 2023, 11(3), 966; https://doi.org/10.3390/biomedicines11030966 - 21 Mar 2023
Cited by 3 | Viewed by 2488
Abstract
The concept of skin microbiota is not really clear and more accurate approaches are necessary to explain how microbial flora can influence skin biophysical parameters in healthy individuals and in pathology patients with non-infectious skin disease. The aim of this work is to [...] Read more.
The concept of skin microbiota is not really clear and more accurate approaches are necessary to explain how microbial flora can influence skin biophysical parameters in healthy individuals and in pathology patients with non-infectious skin disease. The aim of this work is to provide a suitable, fast and reproducible protocol to correlate skin parameters with the composition of skin microbiota. For this purpose, the work was split into two main phases. The first phase was focused on the selection of volunteers by the administration of a specific questionnaire. The skin microbiota was then collected from the forehead of selected volunteers as a test area and from the shoulder as control area. On the same skin area, the biophysical parameters, such as trans-epidermal water loss (TEWL), sebum level (SL), porphyrin intensity, keratin content and stratum corneum water content were taken. All parameters were taken at t0 and after 15 days without changes in the volunteers’ lifestyle. A strong correlation was found between forehead and shoulder area for porphyrin intensity, pH and TEWL parameters, and between Cutibacterium acnes and some biophysical parameters both in the forehead and the shoulder area. The procedural setup in this work represents the starting point for evaluating problematic skins and the efficacy of cosmetic products or treatment against skin dysbiosis. Full article
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18 pages, 1198 KiB  
Review
Circulating miRNA as a Biomarker in Oral Cancer Liquid Biopsy
by Alexandra Roi, Simina Boia, Laura-Cristina Rusu, Ciprian Ioan Roi, Eugen Radu Boia and Mircea Riviș
Biomedicines 2023, 11(3), 965; https://doi.org/10.3390/biomedicines11030965 - 21 Mar 2023
Cited by 4 | Viewed by 1980
Abstract
Oral cancer is currently challenging the healthcare system, with a high incidence among the population and a poor survival rate. One of the main focuses related to this malignancy is the urge to implement a viable approach for improving its early diagnosis. By [...] Read more.
Oral cancer is currently challenging the healthcare system, with a high incidence among the population and a poor survival rate. One of the main focuses related to this malignancy is the urge to implement a viable approach for improving its early diagnosis. By introducing the use of liquid biopsy and the identification of potential biomarkers, aiming for a noninvasive approach, new advancements offer promising perspectives in the diagnosis of oral cancer. The present review discusses the potential of circulating miRNAs as oral cancer biomarkers identified in body fluids such as serum, plasma, and saliva samples of oral cancer patients. Existing results reveal an important implication of different miRNA expressions involved in the initiation, development, progression, and metastasis rate of oral malignancy. Liquid biomarkers can play a crucial role in the development of the concept of personalized medicine, providing a wide range of clinical applications and future targeted therapies. Full article
(This article belongs to the Special Issue Cell Biology in Dentistry)
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11 pages, 263 KiB  
Article
Calculated Whole Blood Viscosity and Albumin/Fibrinogen Ratio in Patients with a New Diagnosis of Multiple Myeloma: Relationships with Some Prognostic Predictors
by Melania Carlisi, Rosalia Lo Presti, Salvatrice Mancuso, Sergio Siragusa and Gregorio Caimi
Biomedicines 2023, 11(3), 964; https://doi.org/10.3390/biomedicines11030964 - 21 Mar 2023
Cited by 1 | Viewed by 1098
Abstract
Background: In this single center study, we retrospectively evaluated the calculated hemorheological profile in patients with a new diagnosis of multiple myeloma, with the aim to evaluate possible relationships with some prognostic predictors, such as ISS, albumin levels, beta2-microglobulin, red cell distribution width, [...] Read more.
Background: In this single center study, we retrospectively evaluated the calculated hemorheological profile in patients with a new diagnosis of multiple myeloma, with the aim to evaluate possible relationships with some prognostic predictors, such as ISS, albumin levels, beta2-microglobulin, red cell distribution width, and bone marrow plasma cell infiltration. Methods: In a cohort of 190 patients, we examined the calculated blood viscosity using the de Simone formula, and the albumin/fibrinogen ratio as a surrogate of erythrocyte aggregation, and then we related these parameters to prognostic factors, using the Kruskal–Wallis and the Mann–Whitney tests, respectively. Results: From our analysis, it emerged that the evaluated hemorheological pattern differed in the three isotypes of multiple myeloma, and the whole blood viscosity was higher in IgA and IgG isotypes with respect to the light chain multiple myeloma (p < 0.001). Moreover, we observed that, as the ISS stage progressed, the albumin/fibrinogen ratio was reduced, and the same hemorheological trend was traced in subgroups with lower albumin levels, higher beta2-microglobulin and red cell distribution width RDW values, and in the presence of a greater bone marrow plasma cell infiltrate. Conclusions: Through the changes in blood viscosity in relation to different prognostic factors, this analysis might underline the role of the hemorheological pattern in multiple myeloma. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
17 pages, 6196 KiB  
Article
Mechanical Characterization of 3D-Printed Patterned Membranes for Cardiac Tissue Engineering: An Experimental and Numerical Study
by Aurelia Poerio, Bertrand Guibert, Mélanie M. Leroux, João F. Mano, Franck Cleymand and Jean-Philippe Jehl
Biomedicines 2023, 11(3), 963; https://doi.org/10.3390/biomedicines11030963 - 21 Mar 2023
Cited by 2 | Viewed by 1352
Abstract
A myocardial infarction can cause irreversible damage to the heart muscle. A promising approach for the treatment of myocardial infarction and prevention of severe complications is the application of cardiac patches or epicardial restraint devices. The challenge for the fabrication of cardiac patches [...] Read more.
A myocardial infarction can cause irreversible damage to the heart muscle. A promising approach for the treatment of myocardial infarction and prevention of severe complications is the application of cardiac patches or epicardial restraint devices. The challenge for the fabrication of cardiac patches is the replication of the fibrillar structure of the myocardium, in particular its anisotropy and local elasticity. In this study, we developed a chitosan–gelatin–guar gum-based biomaterial ink that was fabricated using 3D printing to create patterned anisotropic membranes. The experimental results were then used to develop a numerical model able to predict the elastic properties of additional geometries with tunable elasticity that could easily match the mechanical properties of the heart tissue (particularly the myocardium). Full article
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11 pages, 2688 KiB  
Article
Effectiveness and Safety of Belimumab in Chinese Lupus Patients: A Multicenter, Real-World Observational Study
by Fangfang Sun, Huaxiang Wu, Zitao Wang, Tong Wu, Xue Wu, Jie Chen, Danting Zhang, Chunde Bao, Nan Shen, Lijun Wu, Jing Zhu and Shuang Ye
Biomedicines 2023, 11(3), 962; https://doi.org/10.3390/biomedicines11030962 - 21 Mar 2023
Cited by 2 | Viewed by 2547
Abstract
Objective: The effectiveness and safety of belimumab in Chinese lupus patients with different disease activities were investigated in a real-world setting. Method: Patients who received 10 mg/kg belimumab intravenously on weeks 0, 2, and 4, and then every 4 weeks on [...] Read more.
Objective: The effectiveness and safety of belimumab in Chinese lupus patients with different disease activities were investigated in a real-world setting. Method: Patients who received 10 mg/kg belimumab intravenously on weeks 0, 2, and 4, and then every 4 weeks on a background of standard-of-care (SoC) therapy and had a follow-up of more than 6 months were enrolled from four centers in China. They were stratified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score at baseline as the moderate/severe (SELENA-SLEDAI > 6) or mild subgroups (SELENA-SLEDAI ≤ 6). Attainment of the Lupus Low Disease Activity State (LLDAS) or remission on treatment was analyzed in all patients. The SLE Responder Index 4 (SRI-4) and SELENA-SLEDAI Flare Index (SFI) were evaluated for patients with moderate/severe disease and mild disease, respectively. Patients in the control arm with SoC alone from previous metformin lupus trials were selected by propensity score matching (PSM) as the reference group. Results: 224 SLE patients with a mean follow-up of 11.7 months receiving belimumab were enrolled in this observational study, of which 126 and 98 were in the moderate/severe and mild subgroup, respectively. At 12 months, 54.76% of the patients attained LLDAS and 28.57% attained remission. Lower daily prednisone at baseline were independently associated with 12-month LLDAS. Further, 87% of the subgroup with moderate/severe disease achieved SRI-4 at 12 months and a high SLEDAI at baseline was its predictive factor. For the mild subgroup, a reduced flare rate was observed compared with PSM reference (17.5%, vs. 38.6%, p = 0.021). Infection events, particularly viral infections and pneumonia were recorded in 7 and 6 patients, respectively. Conclusion: Our real-world data supported the effectiveness and safety of belimumab in Chinese lupus patients. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Chronic Pain and New Therapeutic Strategies)
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