Life | May 2022 - Browse Articles

20 pages, 5268 KiB

Open AccessArticle

Ginseng^® Alleviates Malathion-Induced Hepatorenal Injury through Modulation of the Biochemical, Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Markers in Male Rats

by Heba I. Ghamry, Asmaa A. Aboushouk, Mohamed Mohamed Soliman, Sarah M. Albogami, Hossam G. Tohamy, Osama S. El Okle, Saed A. Althobaiti, Shaymaa Rezk, Foad Farrag, Azza I. Helal, Hanan A. Ghoneim and Mustafa Shukry

Life 2022, 12(5), 771; https://doi.org/10.3390/life12050771 - 23 May 2022

Cited by 5 | Viewed by 2550

Abstract

This study aims to see if Ginseng^® can reduce the hepatorenal damage caused by malathion. Four groups of forty male Wistar albino rats were alienated. Group 1 was a control group that got orally supplied corn oil (vehicle). Group 2 was intoxicated [...] Read more.

This study aims to see if Ginseng^® can reduce the hepatorenal damage caused by malathion. Four groups of forty male Wistar albino rats were alienated. Group 1 was a control group that got orally supplied corn oil (vehicle). Group 2 was intoxicated by malathion dissolved in corn oil orally at 135 mg/kg/day. Group 3 orally received both malathion + Panax Ginseng^® (300 mg/kg/day). Group 4 was orally given Panax Ginseng^® at a 300 mg/kg/day dose. Treatments were administered daily and continued for up to 30 consecutive days. Malathion’s toxic effect on both hepatic and renal tissues was revealed by a considerable loss in body weight and biochemically by a marked increase in liver enzymes, LDH, ACP, cholesterol, and functional renal markers with a marked decrease in serum TP, albumin, and TG levels with decreased AchE and Paraoxonase activity. Additionally, malondialdehydes, nitric oxide (nitrite), 8-hydroxy-2-deoxyguanosine, and TNFα with a significant drop in the antioxidant activities were reported in the malathion group. Malathion upregulated the inflammatory cytokines and apoptotic genes, while Nrf2, Bcl2, and HO-1 were downregulated. Ginseng^® and malathion co-treatment reduced malathion’s harmful effects by restoring metabolic indicators, enhancing antioxidant pursuit, lowering the inflammatory reaction, and alleviating pathological alterations. So, Ginseng^® may have protective effects against hepatic and renal malathion-induced toxicity on biochemical, antioxidant, molecular, and cell levels. Full article

(This article belongs to the Collection The Role of Bioactive Natural Compounds in the Treatment of Diseases)

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14 pages, 6129 KiB

Open AccessArticle

Smoothing the Undersampled Carpal Bone Model with Small Volume and Large Curvature: A Feasibility Study

by Chengcheng Ji, Jianzhang Li, Maximilian Praster, Björn Rath, Frank Hildebrand and Jörg Eschweiler

Life 2022, 12(5), 770; https://doi.org/10.3390/life12050770 - 23 May 2022

Cited by 3 | Viewed by 1575

Abstract

The carpal bones are eight small bones with irregularities and high curvature on their surfaces. The 3D model of the carpal bone serves as the foundation of further clinical applications, e.g., wrist kinematic behavior. However, due to the limitation of the Magnetic Resonance [...] Read more.

The carpal bones are eight small bones with irregularities and high curvature on their surfaces. The 3D model of the carpal bone serves as the foundation of further clinical applications, e.g., wrist kinematic behavior. However, due to the limitation of the Magnetic Resonance Imaging (MRI) technique, reconstructed carpal bone models are discretely undersampled, which has dramatic stair-step effects and leads to abnormal meshes on edges or surfaces, etc. Our study focuses on determining the viability of various smoothing techniques for a carpal model reconstructed by in vivo gathered MR images. Five algorithms, namely the Laplacian smoothing algorithm, the Laplacian smoothing algorithm with pre-dilation, the scale-dependent Laplacian algorithm, the curvature flow algorithm, and the inverse distance algorithm, were chosen for evaluation. The assessment took into account the Relative Volume Difference and the Hausdorff Distance as well as the surface quality and the preservation of morphological and morphometric properties. For the five algorithms, we analyzed the Relative Volume Difference and the Hausdorff Distance for all eight carpal bones. Among all the algorithms, the scale-dependent Laplacian method processed the best result regarding surface quality and the preservation of morphological and morphometric properties. Based on our extensive examinations, the scale-dependent Laplacian algorithm is suitable for the undersampled carpal bone model with small volume and large curvature. Full article

(This article belongs to the Section Medical Research)

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15 pages, 3046 KiB

Open AccessArticle

Translational Medicine in Uremic Vascular Calcification: Scavenging ROS Attenuates p-Cresyl Sulfate-Activated Caspase-1, NLRP3 Inflammasome and Eicosanoid Inflammation in Human Arterial Smooth Muscle Cells

by Jia-Feng Chang, Hsiao-Ling Kuo, Shih-Hao Liu, Chih-Yu Hsieh, Chih-Ping Hsu, Kuo-Chin Hung, Ting-Ming Wang, Chang-Chin Wu, Kuo-Cheng Lu, Wei-Ning Lin, Chi-Feng Hung and Wen-Chin Ko

Life 2022, 12(5), 769; https://doi.org/10.3390/life12050769 - 23 May 2022

Cited by 4 | Viewed by 2089

Abstract

We formerly proved that uremic vascular calcification (UVC) correlates tightly with oxidative elastic lamina (EL) injury and two cell fates (apoptosis and osteocytic conversion) in smooth muscle cells (SMC) of chronic kidney disease (CKD) patients and eliminating p-cresyl sulfate (PCS)-activated intracellular ROS ameliorates [...] Read more.

We formerly proved that uremic vascular calcification (UVC) correlates tightly with oxidative elastic lamina (EL) injury and two cell fates (apoptosis and osteocytic conversion) in smooth muscle cells (SMC) of chronic kidney disease (CKD) patients and eliminating p-cresyl sulfate (PCS)-activated intracellular ROS ameliorates the MAPK signaling pathway in a human arterial SMC (HASMC) model. Nonetheless, whether ROS scavenger attenuates PCS-triggered inflammasome activation and eicosanoid inflammation in the UVC process remains unknown. Patients with lower extremity amputation were categorized into CKD and normal control group according to renal function. We used immunohistochemistry stain to analyze UVC in arterial specimens, including oxidative injury (8-hydroxy-2′-deoxyguanosine (8-OHdG) and internal EL disruption), cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX2), interleukin-1 beta (IL-1β), caspase-1 and NLRP3. To simulate the patho-mechanism of human UVC, the therapeutic effects of ROS scavenger on PCS-triggered inflammatory pathways was explored in a HASMC model. We found CKD patients had higher circulating levels of PCS and an increase in medial arterial calcification than the control group. In CKD arteries, the severity of UVC corresponded with expressions of oxidative EL disruption and 8-OHdG. Furthermore, coupling expressions of cPLA2 and COX2 were accentuated in CKD arteries, indicative of eicosanoid inflammation. Notably, tissue expressions of IL-1β, caspase-1 and NLRP3 were enhanced in parallel with UVC severity, indicative of inflammasome activation. From bedside to bench, ROS scavenger attenuates PCS-activated expressions of cPLA2/COX2, pro-caspase-1 and NLRP3 in the HASMC model. UVC as an inevitable outcome is predictive of death in CKD patients. Nonetheless, UVC remain pharmacoresistant despite the evolution of treatment for mineral-parathyroid hormone-vitamin D axis. Beyond the mineral dysregulation, the stimulation of pro-oxidant PCS alone results in eicosanoid inflammation and inflammasome activation. Concerning the key role of Caspase-1 in pyroptosis, cell fates of HASMC in uremic milieu are not limited to apoptosis and osteogenesis. In view of this, reducing ROS and PCS may act as a therapeutic strategy for UVC-related cardiovascular events in CKD patients. Full article

(This article belongs to the Special Issue Frontiers in Vascular Biology)

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15 pages, 3321 KiB

Open AccessEditor’s ChoiceArticle

Role of SaPCR2 in Zn Uptake in the Root Elongation Zone of the Zn/Cd Hyperaccumulator Sedum alfredii

by Jun Ge, Jiayu Lin, Zhiying Wu, Kuan Xu, Jingyu Tao, Haizhong Lin, Shengke Tian and Lingli Lu

Life 2022, 12(5), 768; https://doi.org/10.3390/life12050768 - 23 May 2022

Viewed by 1554

Abstract

Zn pollution is a potential toxicant for agriculture and the environment. Sedum alfredii is a Zn/Cd hyperaccumulator found in China and has been proven as a useful resource for the phytoremediation of Zn-contaminated sites. However, the molecular mechanism of Zn uptake in S. [...] Read more.

Zn pollution is a potential toxicant for agriculture and the environment. Sedum alfredii is a Zn/Cd hyperaccumulator found in China and has been proven as a useful resource for the phytoremediation of Zn-contaminated sites. However, the molecular mechanism of Zn uptake in S. alfredii is limited. In this study, the function of SaPCR2 on Zn uptake in S. alfredii was identified by gene expression analysis, yeast function assays, Zn accumulation and root morphology analysis in transgenic lines to further elucidate the mechanisms of uptake and translocation of Zn in S. alfredii. The results showed that SaPCR2 was highly expressed in the root elongation zone of the hyperaccumulating ecotype (HE) S. alfredii, and high Zn exposure downregulated the expression of SaPCR2 in the HE S. alfredii root. The heterologous expression of SaPCR2 in yeast suggested that SaPCR2 was responsible for Zn influx. The overexpression of SaPCR2 in the non-hyperaccumulating ecotype (NHE) S. alfredii significantly increased the root uptake of Zn, but did not influence Mn, Cu or Fe. SR-μ-XRF technology showed that more Zn was distributed in the vascular buddle tissues, as well as in the cortex and epidermis in the transgenic lines. Root morphology was also altered after SaPCR2 overexpression, and a severe inhibition was observed. In the transgenic lines, the meristematic and elongation zones of the root were lower compared to the WT, and Zn accumulation in meristem cells was also reduced. These results indicate that SaPCR2 is responsible for Zn uptake, and mainly functions in the root elongation zone. This research on SaPCR2 could provide a theoretical basis for the use of genetic engineering technology in the modification of crops for their safe production and biological enhancement. Full article

(This article belongs to the Special Issue Uptake, Translocation, and Metabolism of Trace Metals in Plants)

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18 pages, 3425 KiB

Open AccessArticle

Antiproliferative Effect of Phellodendron amurense Rupr. Based on Angiogenesis

by Ľudmila Balážová, Slavomír Kurhajec, Martin Kello, Zdenka Bedlovičová, Martina Zigová, Eva Petrovová, Katarína Beňová, Ján Mojžiš and Jarmila Eftimová

Life 2022, 12(5), 767; https://doi.org/10.3390/life12050767 - 21 May 2022

Cited by 8 | Viewed by 2166

Abstract

Phellodendron amurense Rupr. is medicinal plant used for supplemental therapy of various diseases based on their positive biological activities. The aim of this study was evaluated the main metabolite, safety of application and anticancer potential. Berberine was determined by HPLC as main alkaloid. [...] Read more.

Phellodendron amurense Rupr. is medicinal plant used for supplemental therapy of various diseases based on their positive biological activities. The aim of this study was evaluated the main metabolite, safety of application and anticancer potential. Berberine was determined by HPLC as main alkaloid. Harmful character was determined by irritation test in ovo. The potential cancerogenic effect was studied in vitro on a cellular level, in ovo by CAM assay and in vivo on whole organism Artemia franciscana. Extract from the bark of Phellodendron amurense showed antiproliferative and antiangiogenic effects. The results of our work showed promising anticancer effects based also on the inhibition of angiogenesis with minimum negative effects. Full article

(This article belongs to the Special Issue Natural Substances in Nutrition and Health of Animals)

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12 pages, 1709 KiB

Open AccessArticle

Pulmonary Artery Pressure-Guided Telemonitoring Reduced Pulmonary Artery Pressure but Did Not Result in Higher Doses of Guideline-Directed Medical Therapy–Observations from an Advanced Elderly German Heart Failure Cohort

by Ester J. Herrmann, Badrinarayanan Raghavan, Nina Eissing, Stephan Fichtlscherer, Christian W. Hamm and Birgit Assmus

Life 2022, 12(5), 766; https://doi.org/10.3390/life12050766 - 21 May 2022

Viewed by 1624

Abstract

Introduction: Remote pulmonary artery pressure (PAP)-guided heart failure (HF) therapy for NYHA class III patients has been shown to reduce hospitalizations and increase survival. We aimed to assess whether PAP monitoring allows for the increase in HF directed medication in an elderly German [...] Read more.

Introduction: Remote pulmonary artery pressure (PAP)-guided heart failure (HF) therapy for NYHA class III patients has been shown to reduce hospitalizations and increase survival. We aimed to assess whether PAP monitoring allows for the increase in HF directed medication in an elderly German cohort of advanced HF patients already receiving clinically optimized HF medication. Methods: We analyzed PAP and HF medication dosage, including diuretics, in 24 patients (mean age, 76 years) using implanted PAP-sensors during the first 12 months of PAP-guided HF care in an interdisciplinary HF unit. Results: During 12 months of PAP-guided HF therapy, PAP decreased significantly (△PAP systolic–6 ± 10, △PAP diastolic–4 ± 7, △PAP mean–4 ± 8 mm Hg, p < 0.01 for all). 16% of patients had an unplanned HF hospitalization. There was no significant change over time with respect to the dosage of RAAS inhibitors (ACE-I/ARB/ARNI), Beta blockers, or MRA treatments. In contrast, the dosage of loop diuretics increased significantly (2.1 ± 0.5-fold) over time. In the comparison of a “responder” (patients with PAP and diuretic dose decline) and “non-responder” (patients with PAP and diuretic dose increase) group, there were no significant differences between any of the baseline, medication, or HF hospitalization characteristics between the two groups. Conclusions: In elderly patients treated with clinically optimized HF medication, no further evidence-based medication increase could be achieved using PAP-guided HF care. However, by individual adjustment of diuretic dosage, a significant decline in PAP over time occurred, which could not be predicted by any of the baseline characteristics. Full article

(This article belongs to the Special Issue Pulmonary Hypertension: From Bench to Bedside)

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8 pages, 898 KiB

Open AccessArticle

The Pressure Dependence of the Stability of the G-quadruplex Formed by d(TGGGGT)

by Nabeel Tariq, Takuma Kume, Ujala N. Feroze and Robert B. Macgregor, Jr.

Life 2022, 12(5), 765; https://doi.org/10.3390/life12050765 - 21 May 2022

Cited by 1 | Viewed by 1584

Abstract

The G-quadruplex (GQ), a tetrahelix formed by guanine-rich nucleic acid sequences, is a potential drug target for several diseases. Monomolecular GQs are stabilized by guanine tetrads and non-guanine regions that form loops. Hydrostatic pressure destabilizes the folded, monomolecular GQ structures. In this communication, [...] Read more.

The G-quadruplex (GQ), a tetrahelix formed by guanine-rich nucleic acid sequences, is a potential drug target for several diseases. Monomolecular GQs are stabilized by guanine tetrads and non-guanine regions that form loops. Hydrostatic pressure destabilizes the folded, monomolecular GQ structures. In this communication, we present data on the effect of pressure on the conformational stability of the tetramolecular GQ, d[5′-TGGGGT-3′]₄. This molecule does not have loops linking the tetrads; thus, its physical properties presumably reflect those of the tetrads alone. Understanding the properties of the tetrads will aid in understanding the contribution of the other structural components to the stability of GQ DNA. By measuring UV light absorption, we have studied the effect of hydrostatic pressure on the thermal stability of the tetramolecular d[5′-TGGGGT-3′]₄ in the presence of sodium ions. Our data show that, unlike monomolecular GQ, the temperature at which d[5′-TGGGGT-3′]₄ dissociates to form the constituent monomers is nearly independent of pressure up to 200 MPa. This implies that there is no net molar volume difference (∆V) between the GQ and the unfolded random-coil states. This finding further suggests that the large negative ∆V values for the unfolding of monomolecular GQ are due to the presence of the loop regions in those structures. Full article

(This article belongs to the Special Issue Biophysics of Nucleic Acids Celebrating the 75th Birthday of Professor Kenneth J. Breslauer)

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18 pages, 8013 KiB

Open AccessArticle

Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation

by Mohamed El-Sherbiny, Mohamed El-Shafey, Eman Said, Gehan Ahmed Shaker, Mohamed El-Dosoky, Hasnaa Ali Ebrahim, Sally Yussef Abed, Khalid M. Ibraheem, Ahmed Mohsen Faheem, Muntazar AlMutawa, Bayader Alatawi and Nehal M. Elsherbiny

Life 2022, 12(5), 764; https://doi.org/10.3390/life12050764 - 21 May 2022

Cited by 1 | Viewed by 2392

Abstract

In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium–glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as [...] Read more.

In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium–glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-κB and TNF-α expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune–histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury. Full article

(This article belongs to the Section Physiology and Pathology)

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11 pages, 618 KiB

Open AccessArticle

Circulating miRNA-195-5p and -451a in Patients with Acute Hemorrhagic Stroke in Emergency Department

by Mauro Giordano, Maria Consiglia Trotta, Tiziana Ciarambino, Michele D’Amico, Federico Schettini, Angela Di Sisto, Valentina D’Auria, Antonio Voza, Lorenzo Salvatore Malatino, Gianni Biolo, Filippo Mearelli, Francesco Franceschi, Giuseppe Paolisso and Luigi Elio Adinolfi

Life 2022, 12(5), 763; https://doi.org/10.3390/life12050763 - 21 May 2022

Cited by 3 | Viewed by 1915

Abstract

(1) Background: In our previous study, acute ischemic stroke (AIS) patients showed increased levels of circulating miRNAs (-195-5p and -451a) involved in vascular endothelial growth factor A (VEGF-A) regulation. Here, we evaluated, for the first time, both circulating miRNAs in acute intracerebral hemorrhagic [...] Read more.

(1) Background: In our previous study, acute ischemic stroke (AIS) patients showed increased levels of circulating miRNAs (-195-5p and -451a) involved in vascular endothelial growth factor A (VEGF-A) regulation. Here, we evaluated, for the first time, both circulating miRNAs in acute intracerebral hemorrhagic (ICH) patients. (2) Methods: Circulating miRNAs and serum VEGF-A were assessed by real-time PCR and ELISA in 20 acute ICH, 21 AIS patients, and 21 controls. These were evaluated at hospital admission (T0) and after 96 h (T96) from admission. (3) Results: At T0, circulating miRNAs were five-times up-regulated in AIS patients, tending to decrease at T96. By contrast, in the acute ICH group, circulating miRNAs were significantly increased at both T0 and T96. Moreover, a significant decrease was observed in serum VEGF-A levels at T0 in AIS patients, tending to increase at T96. Conversely, in acute ICH patients, the levels of VEGF-A were significantly decreased at both T0 and T96. (4) Conclusions: The absence of a reduction in circulating miRNAs (195-5p and -451a), reported in acute ICH subjects after 96 h from hospital admission, together with the absence of increment of serum VEGF-A, may represent useful biomarkers indicating the severe brain damage status that characterizes acute ICH patients. Full article

(This article belongs to the Special Issue Ischemic Stroke: From Pathophysiology to Novel Therapeutic Approaches)

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11 pages, 1826 KiB

Open AccessArticle

CD103 Expression on Regulatory and Follicular T Cells in Lymph Nodes, Bronchoalveolar Lavage Fluid and Peripheral Blood of Sarcoidosis Patients

by Miriana d’Alessandro, Sara Gangi, Dalila Cavallaro, Laura Bergantini, Fabrizio Mezzasalma, Stefano Cattelan, Stefano Baglioni, Marta Abbritti, Paolo Cameli and Elena Bargagli

Life 2022, 12(5), 762; https://doi.org/10.3390/life12050762 - 20 May 2022

Cited by 7 | Viewed by 1987

Abstract

(1) Background: Sarcoidosis is a chronic multisystem disorder of unknown aetiology, driven by a T-cell mechanism allowing T-cell attachment and transmigration through the endothelium, and endorsed by the expression of an integrin alpha-E beta-7 (CD103). This study aimed to analyse the different distribution [...] Read more.

(1) Background: Sarcoidosis is a chronic multisystem disorder of unknown aetiology, driven by a T-cell mechanism allowing T-cell attachment and transmigration through the endothelium, and endorsed by the expression of an integrin alpha-E beta-7 (CD103). This study aimed to analyse the different distribution and compartmentalisation of CD103 expression on T cell subsets in BAL, peripheral blood mononuclear cells (PBMC) and lymph nodes (LLN) from sarcoidosis patients. (2) Patients: We consecutively and prospectively enrolled 14 sarcoidosis patients. We collected PBMC, LLN and BAL at the same time from all patients. Through flow cytometric analysis, we analysed the expression of CD103 on regulatory and follicular T cell subsets. (3) Results: All patients were in radiological Scadding stage II. The multivariate analysis found that the variables which most influenced the peripheral blood compartment were high CD8⁺ and low ThReg, CD8⁺CD103⁺ and Tfh cell percentages. A principal component analysis plot performed to distinguish LLN, BAL and PBMC showed that they separated on the basis of CD4⁺, CD4⁺CD103⁺, CD8⁺, CD8⁺CD103⁺, TcEffector, TcNaive, ThNaive, ThEffector, Threg, ThregCD103⁺, Tfh, TcfCXC5⁺ and CD4⁺CD103⁺/CD4⁺ with 65.96% of the total variance. (4) Conclusions: Our study is the first to report a link between the imbalance in circulating, alveolar and lymph node CD8⁺ and CD8⁺CD103⁺ T cells, ThReg, Tfh and ThNaive and the CD103⁺CD4⁺/CD4⁺ T cell ratio in the development of sarcoidosis. These findings shine a spotlight on the pathogenesis of sarcoidosis and may offer new predictors for diagnosis. Our study provides additional understanding for a personalised, and hopefully more effective treatment of sarcoidosis. Full article

(This article belongs to the Section Medical Research)

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13 pages, 4881 KiB

Open AccessArticle

Histomorphometry of Ossification in Functionalised Ceramics with Tripeptide Arg-Gly-Asp (RGD): An In Vivo Study

by Filippo Migliorini, Hanno Schenker, Nicola Maffulli, Frank Hildebrand and Jörg Eschweiler

Life 2022, 12(5), 761; https://doi.org/10.3390/life12050761 - 20 May 2022

Cited by 6 | Viewed by 1637

Abstract

The present study investigated the osseointegration promoted by functionalised ceramics with peptide Arg-Gly-Asp (RGD) in a rabbit model in vivo. Histomorphometry of the RGD functionalised ceramic implants was conducted by a trained pathologist to quantify the amount of mature and immature ossification at [...] Read more.

The present study investigated the osseointegration promoted by functionalised ceramics with peptide Arg-Gly-Asp (RGD) in a rabbit model in vivo. Histomorphometry of the RGD functionalised ceramic implants was conducted by a trained pathologist to quantify the amount of mature and immature ossification at the bone interface, and then compared to titanium alloy implants. The region of interest was the area surrounding the implant. The percentage of ROI covered by osteoid implant contact and mature bone implant contact were assessed. The presence of bone resorption, necrosis, and/or inflammation in the areas around the implant were quantitatively investigated. All 36 rabbits survived the experimental period of 6 and 12 weeks. All implants remained in situ. No necrosis, bone resorption, or inflammation were identified. At 12 weeks follow-up, the overall mean bone implant contact (p = 0.003) and immature osteoid contact (p = 0.03) were improved compared to the mean values evidenced at 6 weeks. At 6 weeks follow-up, the overall osteoid implant contact was greater in the RGD enhanced group compared to the titanium implant (p = 0.01). The other endpoints of interest were similar between the two implants at all follow-up points (p ≥ 0.05). Functionalised ceramics with peptide RGD promoted ossification in vivo. The overall osteoid and bone implant contact improved significantly from 6 to 12 weeks. Finally, RGD enhanced ceramic promoted faster osteoid implant contact in vivo than titanium implants. Overall, the amount of ossification at 12 weeks is comparable with the titanium implants. No necrosis, bone resorption, or inflammation were observed in any sample. Full article

(This article belongs to the Special Issue Advances in Wrist Arthroplasty: From Biomechanics to Clinical Application)

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14 pages, 703 KiB

Open AccessEditor’s ChoiceReview

Regulatory Effects of Statins on SIRT1 and Other Sirtuins in Cardiovascular Diseases

by Danial Khayatan, Seyed Mehrad Razavi, Zahra Najafi Arab, Maryam Khanahmadi, Saeideh Momtaz, Alexandra E. Butler, Fabrizio Montecucco, Yuliya V. Markina, Amir Hossein Abdolghaffari and Amirhossein Sahebkar

Life 2022, 12(5), 760; https://doi.org/10.3390/life12050760 - 20 May 2022

Cited by 5 | Viewed by 5237

Abstract

Adverse cardiovascular disease (CVD) outcomes, such as sudden cardiac death, acute myocardial infarction, and stroke, are often catastrophic. Statins are frequently used to attenuate the risk of CVD-associated morbidity and mortality through their impact on lipids and they may also have anti-inflammatory and [...] Read more.

Adverse cardiovascular disease (CVD) outcomes, such as sudden cardiac death, acute myocardial infarction, and stroke, are often catastrophic. Statins are frequently used to attenuate the risk of CVD-associated morbidity and mortality through their impact on lipids and they may also have anti-inflammatory and other plaque-stabilization effects via different signaling pathways. Different statins, including atorvastatin, rosuvastatin, pravastatin, pitavastatin, and simvastatin, are administered to manage circulatory lipid levels. In addition, statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase via modulating sirtuins (SIRTs). During the last two decades, SIRTs have been investigated in mammals and categorized as a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs) with significant oxidative stress regulatory function in cells—a key factor in extending cell lifespan. Recent work has demonstrated that statins upregulate SIRT1 and SIRT2 and downregulate SIRT6 in both in vitro and in vivo experiments and clinical trials. As statins show modulatory properties, especially in CVDs, future investigations are needed to delineate the role of SIRT family members in disease and to expand knowledge about the effects of statins on SIRTs. Here, we review what is currently known about the impact of statins on SIRTs and how these changes correlate with disease, particularly CVDs. Full article

(This article belongs to the Section Pharmaceutical Science)

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16 pages, 6846 KiB

Open AccessArticle

Revisiting DNA Sequence-Dependent Deformability in High-Resolution Structures: Effects of Flanking Base Pairs on Dinucleotide Morphology and Global Chain Configuration

by Robert T. Young, Luke Czapla, Zoe O. Wefers, Benjamin M. Cohen and Wilma K. Olson

Life 2022, 12(5), 759; https://doi.org/10.3390/life12050759 - 20 May 2022

Cited by 5 | Viewed by 2798

Abstract

DNA carries more than the list of biochemical ingredients that drive the basic functions of living systems. The sequence of base pairs includes a multitude of structural and energetic signals, which determine the degree to which the long, threadlike molecule moves and how [...] Read more.

DNA carries more than the list of biochemical ingredients that drive the basic functions of living systems. The sequence of base pairs includes a multitude of structural and energetic signals, which determine the degree to which the long, threadlike molecule moves and how it responds to proteins and other molecules that control its processing and govern its packaging. The chemical composition of base pairs directs the spatial disposition and fluctuations of successive residues. The observed arrangements of these moieties in high-resolution protein–DNA crystal structures provide one of the best available estimates of the natural, sequence-dependent structure and deformability of the double-helical molecule. Here, we update the set of knowledge-based elastic potentials designed to describe the observed equilibrium structures and configurational fluctuations of the ten unique base-pair steps. The large number of currently available structures makes it possible to characterize the configurational preferences of the DNA base-pair steps within the context of their immediate neighbors, i.e., tetrameric context. Use of these knowledge-based potentials shows promise in accounting for known effects of sequence in long chain molecules, e.g., the degree of curvature reported in classic gel mobility studies and the recently reported sequence-dependent responses of supercoiled minicircles to nuclease cleavage. Full article

(This article belongs to the Special Issue Biophysics of Nucleic Acids Celebrating the 75th Birthday of Professor Kenneth J. Breslauer)

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10 pages, 732 KiB

Open AccessArticle

The Effectiveness of Shoulder Mobility and Strength Programs in Competitive Water-Polo Players

by Isaac López-Laval, Sebastian Sitko, Jaime Cantonero, Francisco Corbi and Rafel Cirer-Sastre

Life 2022, 12(5), 758; https://doi.org/10.3390/life12050758 - 20 May 2022

Viewed by 2377

Abstract

Background: Water-polo is the water sport with the highest incidence of injuries, with shoulder pain being the most common one. The understanding of risk factors and guidance on preventive measures is essential in this sport discipline. The aim of this study was to [...] Read more.

Background: Water-polo is the water sport with the highest incidence of injuries, with shoulder pain being the most common one. The understanding of risk factors and guidance on preventive measures is essential in this sport discipline. The aim of this study was to determine the effects of a specific 6-week training plan on range of motion (ROM) and joint strength levels in a group of professional water-polo players. Methods: Quasi-experimental study with a sample of 28 participants (age: 20.1 ± 2.5 years; height: 176.9 ± 6.2 cm; body mass: 74.6 ± 8.1 kg). Three study groups, which consisted of one control group and two experimental groups, were established. Two repeated measurements, pre and post intervention, were performed. During these measurements, ROM of the glenohumeral joint was analyzed both in external (ER) and internal (IR) rotation, as well as the maximal isometric strength. Conclusions: The application of a training program improved glenohumeral joint ROM. ER and IR evolve differently in both shoulders. ER improved only in the throwing arm only in the group undergoing intervention but for the non-dominant side, improvements were observed in both ER and IR, regardless of whether or not they had followed the intervention plan. No improvements were observed in either the isometric strength or contralateral asymmetries. Full article

(This article belongs to the Collection Advances in Exercise Biomechanics and Physiology)

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17 pages, 1436 KiB

Open AccessReview

Functional Properties of Cancer Epithelium and Stroma-Derived Exosomes in Head and Neck Squamous Cell Carcinoma

by Yang Li, Shengtao Gao, Qi Hu and Fanglong Wu

Life 2022, 12(5), 757; https://doi.org/10.3390/life12050757 - 20 May 2022

Cited by 6 | Viewed by 2159

Abstract

Stroma–cancer cell crosstalk involves a complex signaling network that contributes to tumor progression, including carcinogenesis, angiogenesis, migration, invasion, and therapy resistance in cancers. Exosomes, as extracellular membranous nanovesicles released by almost all types of cells, including tumor cells and stromal cells, play a [...] Read more.

Stroma–cancer cell crosstalk involves a complex signaling network that contributes to tumor progression, including carcinogenesis, angiogenesis, migration, invasion, and therapy resistance in cancers. Exosomes, as extracellular membranous nanovesicles released by almost all types of cells, including tumor cells and stromal cells, play a critical role in signal delivery and material communication, in which the characteristics of their parent cells are reflected. The tumor or stroma-derived exosomes mediate cell–cell communication in the tumor microenvironment by transporting DNA, RNA, proteins, lipids, and metabolites. Recent studies on head and neck squamous cell carcinoma (HNSCC) have demonstrated that tumor-derived exosomes support various tumor biological behaviors, whereas the functional roles of stroma-derived exosomes remain largely unknown. Although these exosomes are emerging as promising targets in early diagnosis, prognostic prediction, and pharmaceutical carriers for antitumor therapy, there are still multiple hurdles to be overcome before they can be used in clinical applications. Herein, we systematically summarize the promotive roles of the epithelium and stroma-derived exosomes in HNSCC and highlight the potential clinical applications of exosomes in the treatment of HNSCC. Full article

(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)

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15 pages, 4751 KiB

Open AccessArticle

Human Amniotic Mesenchymal Stem Cells and Fibroblasts Accelerate Wound Repair of Cystic Fibrosis Epithelium

by Elisa Beccia, Valeria Daniello, Onofrio Laselva, Giorgia Leccese, Michele Mangiacotti, Sante Di Gioia, Gianfranco La Bella, Lorenzo Guerra, Maria Matteo, Antonella Angiolillo and Massimo Conese

Life 2022, 12(5), 756; https://doi.org/10.3390/life12050756 - 19 May 2022

Cited by 2 | Viewed by 1775

Abstract

Cystic fibrosis (CF) airways are affected by a deranged repair of the damaged epithelium resulting in altered regeneration and differentiation. Previously, we showed that human amniotic mesenchymal stem cells (hAMSCs) corrected base defects of CF airway epithelial cells via connexin (CX)43-intercellular gap junction [...] Read more.

Cystic fibrosis (CF) airways are affected by a deranged repair of the damaged epithelium resulting in altered regeneration and differentiation. Previously, we showed that human amniotic mesenchymal stem cells (hAMSCs) corrected base defects of CF airway epithelial cells via connexin (CX)43-intercellular gap junction formation. In this scenario, it is unknown whether hAMSCs, or fibroblasts sharing some common characteristics with MSCs, can operate a faster repair of a damaged airway epithelium. A tip-based scratch assay was employed to study wound repair in monolayers of CFBE14o- cells (CFBE, homozygous for the F508del mutation). hAMSCs were either co-cultured with CFBE cells before the wound or added to the wounded monolayers. NIH-3T3 fibroblasts (CX43+) were added to wounded cells. HeLa cells (CX43-) were used as controls. γ-irradiation was optimized to block CFBE cell proliferation. A specific siRNA was employed to downregulate CX43 expression in CFBE cells. CFBE cells showed a delayed repair as compared with wt-CFTR cells (16HBE41o-). hAMSCs enhanced the wound repair rate of wounded CFBE cell monolayers, especially when added post wounding. hAMSCs and NIH-3T3 fibroblasts, but not HeLa cells, increased wound closure of irradiated CFBE monolayers. CX43 downregulation accelerated CFBE wound repair rate without affecting cell proliferation. We conclude that hAMSCs and fibroblasts enhance the repair of a wounded CF airway epithelium, likely through a CX43-mediated mechanism mainly involving cell migration. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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Graphical abstract

9 pages, 442 KiB

Open AccessCommunication

Increased Levels of Beta-Endorphin and Noradrenaline after a Brief High-Impact Multidimensional Rehabilitation Program in Multiple Sclerosis

by Alessia d’Arma, Marina Saresella, Valentina Rossi, Ivana Marventano, Federica Piancone, Francesca La Rosa, Mario Clerici and Laura Mendozzi

Life 2022, 12(5), 755; https://doi.org/10.3390/life12050755 - 19 May 2022

Cited by 3 | Viewed by 1457

Abstract

Finding new solutions for the management of multiple sclerosis (MS) is crucial: further research is needed to study the effect of non-pharmacological interventions on the symptoms and the course of the disease, especially on lifestyle. Benefits from a proper lifestyle are evident not [...] Read more.

Finding new solutions for the management of multiple sclerosis (MS) is crucial: further research is needed to study the effect of non-pharmacological interventions on the symptoms and the course of the disease, especially on lifestyle. Benefits from a proper lifestyle are evident not only on a clinical level but also on immune and neuro-endocrine systems. A brief high-impact multidimensional rehabilitation program (b-HIPE) was proposed for a sample of people with MS (pwMS) with a medium level of disease disability. We tested the change on clinical parameters and quality of life (QoL) after participation in B-HIPE. We furthermore decided to measure beta-endorphin and catecholamines concentrations pre- and post-participation in the b-HIPE program, due to the relationship between these hormones and the immune system in neurodegenerative diseases. Our results showed that after the b-HIPE program, an improvement of clinical parameters and QoL occurred. Moreover, we found higher levels of beta-endorphin and noradrenaline after participation in the program. These findings highlight the importance of implementing lifestyle interventions in the clinical management of MS. Furthermore, we hypothesize that the B-HIPE program increased beta-endorphin and noradrenaline levels, helping to reduce the inflammation related to MS disease. Full article

(This article belongs to the Section Physiology and Pathology)

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20 pages, 1087 KiB

Open AccessCommunication

Prevention and Treatment of Life-Threatening COVID-19 May Be Possible with Oxygen Treatment

by Jukka Ylikoski, Jarmo Lehtimäki, Rauno Pääkkönen and Antti Mäkitie

Life 2022, 12(5), 754; https://doi.org/10.3390/life12050754 - 19 May 2022

Cited by 3 | Viewed by 3044

Abstract

Most SARS CoV-2 infections probably occur unnoticed or cause only cause a mild common cold that does not require medical intervention. A significant proportion of more severe cases is characterized by early neurological symptoms such as headache, fatigue, and impaired consciousness, including respiratory [...] Read more.

Most SARS CoV-2 infections probably occur unnoticed or cause only cause a mild common cold that does not require medical intervention. A significant proportion of more severe cases is characterized by early neurological symptoms such as headache, fatigue, and impaired consciousness, including respiratory distress. These symptoms suggest hypoxia, specifically affecting the brain. The condition is best explained by primary replication of the virus in the nasal respiratory and/or the olfactory epithelia, followed by an invasion of the virus into the central nervous system, including the respiratory centers, either along a transneural route, through disruption of the blood-brain barrier, or both. In patients, presenting with early dyspnea, the primary goal of therapy should be the reversal of brain hypoxia as efficiently as possible. The first approach should be intermittent treatment with 100% oxygen using a tight oronasal mask or a hood. If this does not help within a few hours, an enclosure is needed to increase the ambient pressure. This management approach is well established in the hypoxia-related diseases in diving and aerospace medicine and preserves the patient’s spontaneous breathing. Preliminary research evidence indicates that even a small elevation of the ambient pressure might be lifesaving. Other neurological symptoms, presenting particularly in long COVID-19, suggest imbalance of the autonomous nervous system, i.e., dysautonomia. These patients could benefit from vagal nerve stimulation. Full article

(This article belongs to the Special Issue COVID-19 Prevention and Treatment)

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17 pages, 1398 KiB

Open AccessEditor’s ChoiceArticle

SIRT1: Genetic Variants and Serum Levels in Age-Related Macular Degeneration

by Kriste Kaikaryte, Greta Gedvilaite, Alvita Vilkeviciute, Loresa Kriauciuniene, Ruta Mockute, Dzastina Cebatoriene, Reda Zemaitiene, Vilma Jurate Balciuniene and Rasa Liutkeviciene

Life 2022, 12(5), 753; https://doi.org/10.3390/life12050753 - 19 May 2022

Viewed by 1762

Abstract

Background: The aim of this paper was to determine the frequency of SIRT1 rs3818292, rs3758391, rs7895833 single nucleotide polymorphism genotypes and SIRT1 serum levels associated with age-related macular degeneration (AMD) in the Lithuanian population. Methods: Genotyping of SIRT1 rs3818292, rs3758391 and rs7895833 was [...] Read more.

Background: The aim of this paper was to determine the frequency of SIRT1 rs3818292, rs3758391, rs7895833 single nucleotide polymorphism genotypes and SIRT1 serum levels associated with age-related macular degeneration (AMD) in the Lithuanian population. Methods: Genotyping of SIRT1 rs3818292, rs3758391 and rs7895833 was performed using RT-PCR. SIRT1 serum level was determined using the ELISA method. Results: We found that rs3818292 and rs7895833 were associated with an increased risk of developing exudative AMD. Additional sex-differentiated analysis revealed only rs7895833 was associated with an increased risk of developing exudative AMD in women after strict Bonferroni correction. The analysis also revealed that individuals carrying rs3818292, rs3758391 and rs7895833 haplotype G-T-G are associated with increased odds of exudative AMD. Still, the rare haplotypes were associated with the decreased odds of exudative AMD. After performing an analysis of serum SIRT1 levels and SIRT1 genetic variant, we found that carriers of the SIRT1 rs3818292 minor allele G had higher serum SIRT1 levels than the AA genotype. In addition, individuals carrying at least one SIRT1 rs3758391 T allele also had elevated serum SIRT1 levels compared with individuals with the wild-type CC genotype. Conclusions: Our study showed that the SIRT1 polymorphisms rs3818292 and rs7895833 and rs3818292-rs3758391-rs7895833 haplotype G-T-G could be associated with the development of exudative AMD. Also, two SNPs (rs3818292 and rs3758391) are associated with elevated SIRT1 levels. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration: From Mechanisms to Therapy)

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13 pages, 3638 KiB

Open AccessArticle

Differential Activation of pERK1/2 and c-Fos Following Injury to Different Regions of Primary Sensory Neuron

by Bei Miao, Hongyu Yao, Peng Chen and Xue-Jun Song

Life 2022, 12(5), 752; https://doi.org/10.3390/life12050752 - 19 May 2022

Cited by 2 | Viewed by 2291

Abstract

Nerve injury causes hyperexcitability of the dorsal root ganglion (DRG) and spinal dorsal horn (DH) neurons, which results in neuropathic pain. We have previously demonstrated that partial dorsal rhizotomy (PDR) produced less severe pain-like behavior than chronic constriction injury (CCI) or chronic compression [...] Read more.

Nerve injury causes hyperexcitability of the dorsal root ganglion (DRG) and spinal dorsal horn (DH) neurons, which results in neuropathic pain. We have previously demonstrated that partial dorsal rhizotomy (PDR) produced less severe pain-like behavior than chronic constriction injury (CCI) or chronic compression of DRG (CCD) and did not enhance DRG neuronal excitability. However, the mechanisms underlying such discrepancy remain unclear. This study was designed to compare the activation of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) in DRG and DH, and c-Fos in DH following treatments of CCI, CCD, and PDR. We confirmed that thermal hyperalgesia produced by PDR was less severe than that produced by CCI or CCD. We showed that pERK1/2 in DRG and DH was greatly activated by CCI or CCD, whereas PDR produced only transient and mild pERK1/2 activation. CCI, CCD, and PDR induced robust c-Fos expression in DH; nevertheless, c-Fos⁺ neurons following PDR were much fewer than that following CCI or CCD. Blocking retrograde axonal transport by colchicine proximal to the CCI injury site diminished thermal hyperalgesia and inhibited pERK1/2 and c-Fos activation. These findings demonstrate that less severe pain-like behavior produced by PDR than CCI or CCD attributes to less activation of pERK1/2 and c-Fos. Such neurochemical activation partially relies on retrograde axonal transport of certain “injury signals” from the peripheral injured site to DRG somata. Full article

(This article belongs to the Special Issue Neurological Diseases: From Molecular Mechanisms to Therapy)

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13 pages, 1029 KiB

Open AccessArticle

Expression Analysis of Genes Involved in Transport Processes in Mice with MPTP-Induced Model of Parkinson’s Disease

by Margarita M. Rudenok, Maria I. Shadrina, Elena V. Filatova, Ivan N. Rybolovlev, Maxim S. Nesterov, Denis A. Abaimov, Ruslan A. Ageldinov, Anna A. Kolacheva, Michael V. Ugrumov, Petr A. Slominsky and Anelya Kh. Alieva

Life 2022, 12(5), 751; https://doi.org/10.3390/life12050751 - 19 May 2022

Cited by 5 | Viewed by 2105

Abstract

Processes of intracellular and extracellular transport play one of the most important roles in the functioning of cells. Changes to transport mechanisms in a neuron can lead to the disruption of many cellular processes and even to cell death. It was shown that [...] Read more.

Processes of intracellular and extracellular transport play one of the most important roles in the functioning of cells. Changes to transport mechanisms in a neuron can lead to the disruption of many cellular processes and even to cell death. It was shown that disruption of the processes of vesicular, axonal, and synaptic transport can lead to a number of diseases of the central nervous system, including Parkinson’s disease (PD). Here, we studied changes in the expression of genes whose protein products are involved in the transport processes (Snca, Drd2, Rab5a, Anxa2, and Nsf) in the brain tissues and peripheral blood of mice with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced models of PD. We detected changes in the expressions of Drd2, Anxa2, and Nsf at the earliest modeling stages. Additionally, we have identified conspicuous changes in the expression level of Anxa2 in the striatum and substantia nigra of mice with MPTP-induced models of PD in its early stages. These data clearly suggest the involvement of protein products in these genes in the earliest stages of the pathogenesis of PD. Full article

(This article belongs to the Special Issue Neurological Diseases: From Molecular Mechanisms to Therapy)

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16 pages, 991 KiB

Open AccessReview

Nanoparticles: Synthesis and Their Role as Potential Drug Candidates for the Treatment of Parasitic Diseases

by Hammad Ur Rehman Bajwa, Muhammad Kasib Khan, Zaheer Abbas, Roshan Riaz, Tauseef ur Rehman, Rao Zahid Abbas, Muhammad Tahir Aleem, Asghar Abbas, Mashal M. Almutairi, Fahdah Ayed Alshammari, Yasser Alraey and Abdulaziz Alouffi

Life 2022, 12(5), 750; https://doi.org/10.3390/life12050750 - 18 May 2022

Cited by 23 | Viewed by 3827

Abstract

Protozoa, helminths and ectoparasites are the major groups of parasites distributed worldwide. Currently, these parasites are treated with chemotherapeutic antiprotozoal drugs, anti-helminthic and anti-ectoparasitic agents, but, with the passage of time, resistance to these drugs has developed due to overuse. In this scenario, [...] Read more.

Protozoa, helminths and ectoparasites are the major groups of parasites distributed worldwide. Currently, these parasites are treated with chemotherapeutic antiprotozoal drugs, anti-helminthic and anti-ectoparasitic agents, but, with the passage of time, resistance to these drugs has developed due to overuse. In this scenario, nanoparticles are proving to be a major breakthrough in the treatment and control of parasitic diseases. In the last decade, there has been enormous development in the field of nanomedicine for parasitic control. Gold and silver nanoparticles have shown promising results in the treatments of various types of parasitic infections. These nanoparticles are synthesized through the use of various conventional and molecular technologies and have shown great efficacy. They work in different ways, that include damaging the parasite membrane, DNA (Deoxyribonucleic acid) disruption, protein synthesis inhibition and free-radical formation. These agents are effective against intracellular parasites as well. Other nanoparticles, such as iron, nickel, zinc and platinum, have also shown good results in the treatment and control of parasitic infections. It is hoped that this research subject will become the future of modern drug development. This review summarizes the methods that are used to synthesize nanoparticles and their possible mechanisms of action against parasites. Full article

(This article belongs to the Special Issue Advances in Livestock and Human Parasites)

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18 pages, 2004 KiB

Open AccessArticle

Structured, Harmonized, and Interoperable Integration of Clinical Routine Data to Compute Heart Failure Risk Scores

by Kim K. Sommer, Ali Amr, Udo Bavendiek, Felix Beierle, Peter Brunecker, Henning Dathe, Jürgen Eils, Maximilian Ertl, Georg Fette, Matthias Gietzelt, Bettina Heidecker, Kristian Hellenkamp, Peter Heuschmann, Jennifer D. E. Hoos, Tibor Kesztyüs, Fabian Kerwagen, Aljoscha Kindermann, Dagmar Krefting, Ulf Landmesser, Michael Marschollek, Benjamin Meder, Angela Merzweiler, Fabian Prasser, Rüdiger Pryss, Jendrik Richter, Philipp Schneider, Stefan Störk and Christoph Dieterich Show full author list Hide full author list

Life 2022, 12(5), 749; https://doi.org/10.3390/life12050749 - 18 May 2022

Viewed by 2626

Abstract

Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the [...] Read more.

Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the risk of mortality and HF hospitalizations. However, these scores are poorly implemented into routine care, predominantly because their calculation requires considerable efforts in practice and necessary data often are not available in an interoperable format. In this work, we demonstrate the feasibility of a multi-site solution to derive and calculate two exemplary HF scores from clinical routine data (MAGGIC score with six continuous and eight categorical variables; Barcelona Bio-HF score with five continuous and six categorical variables). Within HiGHmed, a German Medical Informatics Initiative consortium, we implemented an interoperable solution, collecting a harmonized HF-phenotypic core data set (CDS) within the openEHR framework. Our approach minimizes the need for manual data entry by automatically retrieving data from primary systems. We show, across five participating medical centers, that the implemented structures to execute dedicated data queries, followed by harmonized data processing and score calculation, work well in practice. In summary, we demonstrated the feasibility of clinical routine data usage across multiple partner sites to compute HF risk scores. This solution can be extended to a large spectrum of applications in clinical care. Full article

(This article belongs to the Special Issue Computational Analysis of Biomedical Data)

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13 pages, 6581 KiB

Open AccessEditor’s ChoiceArticle

Diffusion Tensor Imaging of a Median Nerve by Magnetic Resonance: A Pilot Study

by Kanza Awais, Žiga Snoj, Erika Cvetko and Igor Serša

Life 2022, 12(5), 748; https://doi.org/10.3390/life12050748 - 18 May 2022

Cited by 2 | Viewed by 1853

Abstract

The magnetic resonance Diffusion Tensor Imaging (DTI) is a powerful extension of Diffusion Weighted Imaging (DWI) utilizing multiple bipolar gradients, allowing for the evaluation of the microstructural environment of the highly anisotropic tissues. DTI was predominantly used for the assessment of the central [...] Read more.

The magnetic resonance Diffusion Tensor Imaging (DTI) is a powerful extension of Diffusion Weighted Imaging (DWI) utilizing multiple bipolar gradients, allowing for the evaluation of the microstructural environment of the highly anisotropic tissues. DTI was predominantly used for the assessment of the central nervous system (CNS), but with the advancement in magnetic resonance (MR) hardware and software, it has now become possible to image the peripheral nerves which were difficult to evaluate previously because of their small caliber. This study focuses on the assessment of the human median peripheral nerve ex vivo by DTI microscopy at 9.4 T magnetic field which allowed the evaluation of diffusion eigenvalues, the mean diffusivity and the fractional anisotropy at 35 μm in-plane resolution. The resolution was sufficient for clear depiction of all nerve anatomical structures and therefore further image analysis allowed the obtaining of average values for DT parameters in nerve fascicles (intrafascicular region and perineurium) as well as in the surrounding epineurium. The results confirmed the highest fractional anisotropy of 0.33 and principal diffusion eigenvalue of 1.0 × 10⁻⁹ m²/s in the intrafascicular region, somewhat lower values of 0.27 and 0.95 × 10⁻⁹ m²/s in the perineurium region and close to isotropic with very slow diffusion (0.15 and 0.05 × 10⁻⁹ m²/s) in the epineurium region. Full article

(This article belongs to the Special Issue Imaging in Neurosurgery: State of the Art)

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12 pages, 2789 KiB

Open AccessArticle

Chromatographic Fractionation of Penicillium polonicum Fermentation Metabolites in Search of the Nephrotoxin(s) for Rats

by Ana Miljkovic and Peter Mantle

Life 2022, 12(5), 747; https://doi.org/10.3390/life12050747 - 18 May 2022

Cited by 3 | Viewed by 1612

Abstract

Complex renal histopathological changes in rats, in silent response to dietary contamination with wheat moulded by a common Penicillium from the Balkans, have long eluded attribution of a causal toxin. So far, water-soluble amphoteric glyco-peptides seem responsible, at least for the nuclear pyknoses [...] Read more.

Complex renal histopathological changes in rats, in silent response to dietary contamination with wheat moulded by a common Penicillium from the Balkans, have long eluded attribution of a causal toxin. So far, water-soluble amphoteric glyco-peptides seem responsible, at least for the nuclear pyknoses in nephron epithelia after several days of dietary exposure. Recently, refined histology analysis has diagnosed pyknosis as apoptosis, and followed the finding through application of medium-pressure liquid chromatography, anion exchange and silica layer chromatography to fractionate a water/alcohol-soluble extract of a fungal fermentation on wheat. Proline was revealed, with other amino acids, in acid hydrolysate of the fermentation extract. Application of mass spectrometry has recognized prominent ions (m/z 550 and 564) correlated with fragmentations consistent with a terminal proline moiety for the putative toxins, coupled with other structural fragments and correlated with apoptosis. Use of ¹⁴C-proline in probing Penicillium polonicum fermentation to aid isolation of the new potential toxins, along with application of gel electrophoresis, may further aid characterization of the apoptosis toxin(s). The present focus on proline peptides in mycotoxicosis fits easily with their increasingly recognised pharmacological activity associated with proline’s rigid secondary amine structure, which causes conformational contortion in peptides. Nevertheless, there remains the striking rat renal karyocytomegaly by P. polonicum, for which there is yet no causative mycotoxin. Full article

(This article belongs to the Special Issue Spectroscopy in Biology and Medicine)

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20 pages, 6423 KiB

Open AccessArticle

Consensus Enolase of Trypanosoma Cruzi: Evaluation of Their Immunogenic Properties Using a Bioinformatics Approach

by Alejandro Diaz-Hernandez, Maria Cristina Gonzalez-Vazquez, Minerva Arce-Fonseca, Olivia Rodríguez-Morales, Maria Lilia Cedillo-Ramirez and Alejandro Carabarin-Lima

Life 2022, 12(5), 746; https://doi.org/10.3390/life12050746 - 18 May 2022

Cited by 3 | Viewed by 2458

Abstract

There is currently no vaccine against American trypanosomiasis, caused by the parasite Trypanosoma cruzi. This is due to the genomic variation observed in the six DTUs of T. cruzi. This work aims to propose a consensus sequence of the enolase protein [...] Read more.

There is currently no vaccine against American trypanosomiasis, caused by the parasite Trypanosoma cruzi. This is due to the genomic variation observed in the six DTUs of T. cruzi. This work aims to propose a consensus sequence of the enolase protein from different strains of T. cruzi and mainly evaluate its immunogenic properties at the bioinformatic level. From specialized databases, 15 sequences of the enolase gene were aligned to obtain a consensus sequence, where this sequence was modeled and then evaluated and validated through different bioinformatic programs to learn their immunogenic potential. Finally, chimeric peptides were designed with the most representative epitopes. The results showed high immunogenic potential with six epitopes for MHC-I, and seven epitopes for MHC-II, all of which were highly representative of the enolase present in strains from the American continent as well as five epitopes for B cells. Regarding the computational modeling, molecular docking with Toll-like receptors showed a high affinity and low constant of dissociation, which could lead to an innate-type immune response that helps to eliminate the parasite. In conclusion, the consensus sequence proposed for enolase is capable of providing an ideal immune response; however, the experimental evaluation of this enolase consensus and their chimeric peptides should be a high priority to develop a vaccine against Chagas disease. Full article

(This article belongs to the Section Medical Research)

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12 pages, 768 KiB

Open AccessArticle

Altitude Effect on Cutaneous Melanoma Epidemiology in the Veneto Region (Northern Italy): A Pilot Study

by Paolo Del Fiore, Irene Russo, Alessandro Dal Monico, Jacopo Tartaglia, Beatrice Ferrazzi, Marcodomenico Mazza, Francesco Cavallin, Saveria Tropea, Alessandra Buja, Rocco Cappellesso, Lorenzo Nicolè, Vanna Chiarion-Sileni, Chiara Menin, Antonella Vecchiato, Angelo Paolo Dei Tos, Mauro Alaibac and Simone Mocellin

Life 2022, 12(5), 745; https://doi.org/10.3390/life12050745 - 17 May 2022

Viewed by 2051

Abstract

The incidence of cutaneous melanoma has been increasing in the last decades among the fair-skinned population. Despite its complex and multifactorial etiology, the exposure to ultraviolet radiation (UVR) is the most consistent modifiable risk factor for melanoma. Several factors influence the amount of [...] Read more.

The incidence of cutaneous melanoma has been increasing in the last decades among the fair-skinned population. Despite its complex and multifactorial etiology, the exposure to ultraviolet radiation (UVR) is the most consistent modifiable risk factor for melanoma. Several factors influence the amount of UVR reaching the Earth’s surface. Our study aimed to explore the relationship between melanoma and altitude in an area with mixed geographic morphology, such as the Veneto region (Italy). We included 2752 melanoma patients who were referred to our centers between 1998 and 2014. Demographics, histological and clinical data, and survival information were extracted from a prospectively maintained local database. Head/neck and acral melanoma were more common in patients from the hills and the mountains, while limb and trunk melanoma were more common in patients living in plain and coastal areas. Breslow thickness, ulceration and mitotic rate impaired with increased altitude. However, the geographical area of origin was not associated with overall or disease-free survival. The geographical area of origin of melanoma patients and the “coast-plain-hill gradient” could help to estimate the influence of different sun exposure and to explain the importance of vitamin D levels in skin-cancer control. Full article

(This article belongs to the Special Issue Primitive and Metastatic Tumors of the Skin)

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1 pages, 156 KiB

Open AccessCorrection

Correction: Hansma, H.G. Potassium at the Origins of Life: Did Biology Emerge from Biotite in Micaceous Clay? Life 2022, 12, 301

by Helen Greenwood Hansma

Life 2022, 12(5), 744; https://doi.org/10.3390/life12050744 - 17 May 2022

Cited by 3 | Viewed by 1026

Abstract

The author wishes to make the following correction to this paper [...] Full article

(This article belongs to the Collection Feature Review Papers for Life)

19 pages, 3705 KiB

Open AccessReview

Molecular Mechanisms Underlying the Pain-Relieving Effects of Extracorporeal Shock Wave Therapy: A Focus on Fascia Nociceptors

by Larisa Ryskalin, Gabriele Morucci, Gianfranco Natale, Paola Soldani and Marco Gesi

Life 2022, 12(5), 743; https://doi.org/10.3390/life12050743 - 17 May 2022

Cited by 14 | Viewed by 4860

Abstract

In recent years, extracorporeal shock wave therapy (ESWT) has received increasing attention for its potential beneficial effects on various bone and soft-tissue pathologies, yielding promising outcomes for pain relief and functional recovery. In fact, ESWT has emerged as an alternative, non-invasive, and safe [...] Read more.

In recent years, extracorporeal shock wave therapy (ESWT) has received increasing attention for its potential beneficial effects on various bone and soft-tissue pathologies, yielding promising outcomes for pain relief and functional recovery. In fact, ESWT has emerged as an alternative, non-invasive, and safe treatment for the management of numerous musculoskeletal disorders, including myofascial pain syndrome (MPS). In particular, MPS is a common chronic painful condition, accounting for the largest proportion of patients affected by musculoskeletal problems. Remarkably, sensory innervation and nociceptors of the fascial system are emerging to play a pivotal role as pain generators in MPS. At the same time, increasing evidence demonstrates that application of ESWT results in selective loss of sensory unmyelinated nerve fibers, thereby inducing long-lasting analgesia. The findings discussed in the present review are supposed to add novel viewpoints that may further enrich our knowledge on the complex interactions occurring between disorders of the deep fascia including changes in innervation, sensitization of fascial nociceptors, the pathophysiology of chronic musculoskeletal pain of MPS, and EWST-induced analgesia. Moreover, gaining mechanistic insights into the molecular mechanisms of pain-alleviating effects of ESWT may broaden the fields of shock waves clinical practice far beyond the musculoskeletal system or its original application for lithotripsy. Full article

(This article belongs to the Special Issue Fasciae from a Molecular and Biomechanical Perspective)

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8 pages, 1076 KiB

Open AccessArticle

Possible Antagonism between Cladosporium cladosporioides and Microcystis aeruginosa in a Freshwater Lake during Bloom Seasons

by Larry Wymer, Stephen Vesper, Ian Struewing, Joel Allen and Jingrang Lu

Life 2022, 12(5), 742; https://doi.org/10.3390/life12050742 - 17 May 2022

Viewed by 1482

Abstract

To ensure drinking-water safety, it is necessary to understand the factors that regulate harmful cyanobacterial blooms (HCBs) and the toxins they produce. One controlling factor might be any relationship between fungi and the cyanobacteria. To test this possibility, water samples were obtained from [...] Read more.

To ensure drinking-water safety, it is necessary to understand the factors that regulate harmful cyanobacterial blooms (HCBs) and the toxins they produce. One controlling factor might be any relationship between fungi and the cyanobacteria. To test this possibility, water samples were obtained from Harsha Lake in southwestern Ohio during the 2015, 2016, and 2017 bloom seasons, i.e., late May through September. In each water sample, the concentration of the filamentous fungus Cladosporium cladosporioides was determined by quantitative PCR (qPCR) assay, and Microcystis aeruginosa microcystin-gene transcript copy number (McyG TCN) was quantified by reverse-transcriptase qPCR (RT-qPCR) analyses. The results showed that during each bloom season, the C. cladosporioides concentration and McyG TCN appeared to be interrelated. Therefore, C. cladosporioides concentrations were statistically evaluated via regression on McyG TCN in the water samples for lag times of 1 to 7 days. The regression equation developed to model the relationship demonstrated that a change in the C. cladosporioides concentration resulted in an opposing change in McyG TCN over an approximately 7-day interval. Although the interaction between C. cladosporioides and McyG TCN was observed in each bloom season, the magnitude of each component varied yearly. To better understand this possible interaction, outdoor Cladosporium spore-count data for the Harsha Lake region were obtained for late May through September of each year from the South West Ohio Air Quality Agency. The average Cladosporium spore count in the outdoor air samples was significantly greater in 2016 than in either 2015 or 2017, and the M. aeruginosa McyG TCN was significantly lower in Harsha Lake water samples in 2016 compared to 2015 or 2017. These results suggest that there might be a “balanced antagonism” between C. cladosporioides and M. aeruginosa during the bloom season. Full article

(This article belongs to the Special Issue The Environmental Microbiome and Its Interactions)

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Life, Volume 12, Issue 5 (May 2022) – 166 articles

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