Irreversible Tissue Research Articles

Measurement and Prediction of Sawing Characteristics Using Dental Reciprocating Saws: A Pilot Study on Fresh Bovine Scapula

Bone sawing is one of the most common operations during traditional dental and cranio-maxillofacial surgery and training systems based on virtual reality technology. It is necessary to predict and update conditions (including the sawing force, temperature and tool wear) in real time during VR surgical training and surgical simulation. All the specimens used in this study were fresh bovine scapula. The forces and temperatures were measured during the sawing process. Additionally, the thermal conductivity was measured via a laser flash instrument. Response surface methodology (RSM) was adopted to analyze and model the sawing force and sawing temperature. Meanwhile, tool wear was observed using a scanning electron microscope. The regression models of the sawing force and temperature rise under different experimental conditions were acquired. To obtain the minimum force within the recommended parameter ranges of commonly used medical reference parameters for bone sawing, a higher rotational speed combined with a lower feed rate were recommended. When considering the sawing force and temperature rise comprehensively, the rotational speed should not be extremely high (about 13,000 rpm is recommended). Meanwhile, abrasive wear is the main wear mode of saw blades. In order to avoid surgery failure, it is necessary to replace the saw blade in time. The experimental data were confirmed to be scientific and accurate for the predicted models of sawing conditions. To minimize the main cutting force, a feed rate of 40 mm/min combined with a rotational speed of 13,700 rpm is recommended. High cutting temperatures have the potential to cause irreversible tissue damage, so surgeons using dental reciprocating saws need to avoid excessively high-speed gears.

Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children

Background and purposeIron overload in the body is associated with serious and irreversible tissue damage. This study aimed to investigate the iron‐chelating, antioxidant, anti-inflammatory, and hepatoprotective activities of grape seed extract (GSE) supplement as well as its safety in β‐thalassemia major (β‐TM) pediatric patients receiving deferasirox as a standard iron‐chelation therapy. Materials and methodsThe children were randomly allocated to either GSE group (n = 30) or control group (n = 30) to receive GSE (100 mg/day) or placebo capsules, respectively, for 4 weeks. The serum levels of iron, ferritin, total iron-binding capacity (TIBC), alanine transaminase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and glutathione (GSH) as well as superoxide dismutase (SOD) activity and hemoglobin (Hb) concentration were measured pre-and post-intervention. ResultsGSE supplement significantly attenuated the serum levels of iron (p = 0.030), ferritin (p = 0.017), ALT (p = 0.000), AST (p = 0.000), TNF-α (p = 0.000), and hs-CRP (p = 0.001). The TIBC level (p = 0.020) significantly enhanced in the GSE group compared with the placebo group. Moreover, GSE supplement remarkably improved the oxidative stress markers, MDA (p = 0.000) and GSH (p = 0.001). The changes in the SOD activity (p = 0.590) and Hb concentration (p = 0.670) were not statistically different between the groups. ConclusionGSE supplement possesses several health beneficial influences on children with β‐TM by alleviating iron burden, oxidative stress, inflammation, and liver dysfunction.

A Survey of the Thermal Analysis of Implanted Antennas for Wireless Biomedical Devices.

Wireless implantable biomedical devices (IBDs) are emerging technologies used to enhance patient treatment and monitoring. The performance of wireless IBDs mainly relies on their antennas. Concerns have emerged regarding the potential of wireless IBDs to unintentionally cause tissue heating, leading to potential harm to surrounding tissue. The previous literature examined temperature estimations and specific absorption rates (SAR) related to IBDs, mainly within the context of thermal therapy applications. Often, these studies consider system parameters such as frequency, input power, and treatment duration without isolating their individual impacts. This paper provides an extensive literature review, focusing on key antenna design parameters affecting heat distribution in IBDs. These parameters encompass antenna design, treatment settings, testing conditions, and thermal modeling. The research highlights that input power has the most significant impact on localized temperature, with operating frequency ranked as the second most influential factor. While emphasizing the importance of understanding tissue heating and optimizing antennas for improved power transfer, these studies also illuminate existing knowledge gaps. Excessive tissue heat can lead to harmful effects such as vaporization, carbonization, and irreversible tissue changes. To ensure patient safety and reduce expenses linked to clinical trials, employing simulation-driven approaches for IBD antenna design and optimization is essential.

Hidradenitis suppurativa: new insights into disease mechanisms and an evolving treatment landscape.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic disabling and debilitating inflammatory disease with a high unmet medical need. The prevalence of HS reported in most studies is 1-2%, although it is likely to be under-reported and estimates vary globally owing to variance in data collection methods, ethnicity, geographical location and under-diagnosis. HS is characterized by persistent, painful cutaneous nodules, abscesses and draining tunnels commonly affecting the axillary, anogenital, inguinal and perianal/gluteal areas. Over time, chronic uncontrolled inflammation results in irreversible tissue destruction and scarring. Although the pathophysiology of HS has not been fully elucidated, the tumour necrosis factor (TNF)-α and interleukin (IL)-17 pathways have an important role, involving multiple cytokines. Currently, treatment options include topical medications; systemic therapies, including repeated and/or rotational courses of systemic antibiotics, retinoids and hormonal therapies; and various surgical procedures. The anti-TNF-α antibody adalimumab is currently the only biologic approved by both the US Food and Drug Administration and the European Medicines Agency for HS; however, its efficacy varies, with a clinical response reported in approximately 50% of patients in phase III trials. HS is a rapidly evolving field of discovery, with a diverse range of agents with distinct mechanisms of action currently being explored in clinical trials. Several other promising therapeutic targets have recently emerged, and agents targeting the IL-17 and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways are the most advanced in ongoing or completed phase III clinical trials. Alongside limited therapeutic options, significant challenges remain in terms of diagnosis and disease management, with a need for better treatment outcomes. Other unmet needs include significant diagnostic delays, thus missing the therapeutic 'window of opportunity'; the lack of standardized outcome measures in clinical trials; and the lack of established, well-defined disease phenotypes and biomarkers.

Mitigation of Fibrosis after Myocardial Infarction in Rats by Using a Porcine Cholecyst Extracellular Matrix.

Fibrosis that occurs after nonfatal myocardial infarction (MI) is an irreversible reparative cardiac tissue remodeling process characterized by progressive deposition of highly cross-linked type I collagen. No currently available therapeutic strategy prevents or reverses MI-associated fibrotic scarring of myocardium. In this study, we used an epicardial graft prepared of porcine cholecystic extracellular matrix to treat experimental nonfatal MI in rats. Graft-assisted healing was characterized by reduced fibrosis, with scanty deposition of type I collagen. Histologically, the tissue response was associated with a favorable regenerative reaction predominated by CD4-positive helper T lymphocytes, enhanced angiogenesis, and infiltration of proliferating cells. These observations indicate that porcine cholecystic extracellular matrix delayed the fibrotic reaction and support its use as a potential biomaterial for mitigating fibrosis after MI. Delaying the progression of cardiac tissue remodeling may widen the therapeutic window for management of scarring after MI.

Abdominal Wall Movements Predict Intra-Abdominal Pressure Changes in Rats: A Novel Non-Invasive Intra-Abdominal Pressure Detection Method.

(1) Background: As increases in intra-abdominal pressure (IAP) result in irreversible tissue damage, monitoring IAP in critically ill patients using the common urinary bladder catheter method is essential. However, this method can result in complications and is not suitable for very low birth weight neonates. The aim of this study was to establish a non-invasive and accurate method to detect IAP changes using an animal model. (2) Methods: IAP changes via intra-abdominal air application (up to 20 mmHg) were measured in 19 Wistar rats via an intra-abdominally placed intracranial pressure probe. Concurrently, abdominal surface tension was measured using a Graseby capsule (GC). (3) Results: A high correlation between abdominal wall distension and IAP (r = 0.9264, CI 0.9249-0.9279) was found for all subjects. (4) Conclusions: IAP changes in rats can be detected non-invasively using a GC. However, further studies are necessary to assess whether IAP changes can be measured using a GC in the neonatal population.

Primary Coenzyme Q10 Deficiency: An Update

Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant and plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Due to the multiplicity of roles in cell function, it is not surprising that a deficiency in CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation; we have attempted to resolve the disparities between previous review articles regarding the usefulness or otherwise of CoQ10 supplementation in these disorders. In addition, we have highlighted several of the potential problems relating to CoQ10 supplementation in primary CoQ10 deficiency, as well as identifying unresolved issues relating to these disorders that require further research.

The angiogenic neuropeptide catestatin exerts beneficial effects on human coronary vascular cells and cardiomyocytes

IntroductionMyocardial infarction (MI) induces irreversible tissue damage, eventually leading to heart failure. Exogenous induction of angiogenesis positively influences ventricular remodeling after MI. Recently, we could show that therapeutic angiogenesis by the neuropeptide catestatin (CST) restores perfusion in the mouse hind limb ischemia model by the induction of angio-, arterio- and vasculogenesis. Thus, we assumed that CST might exert beneficial effects on cardiac cells. Methods/resultsTo test the effect of CST on cardiac angiogenesis in-vitro matrigel assays with human coronary artery endothelial cells (HCAEC) were performed. CST significantly mediated capillary like tube formation comparable to vascular endothelial growth factor (VEGF), which was used as positive control. Interestingly, blockade of bFGF resulted in abrogation of observed effects. Moreover, CST induced proliferation of HCAEC and human coronary artery smooth muscle cells (HCASMC) as determined by BrdU-incorporation. Similar to the matrigel assay blockade of bFGF attenuated the effect. Consistent with these findings western blot assays revealed a bFGF-dependent phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 by CST in these cell lines. Finally, CST protected human cardiomyocytes in-vitro from apoptosis. ConclusionCST might qualify as potential candidate for therapeutic angiogenesis in MI.

Current imaging methods for assessing Graves` orbitopathy activity with particular emphasis on FDG-PET.

The most frequent extrathyroidal Graves' disease manifestation is Graves' orbitopathy (GO). The treatment of GO is determined by its severity and activity. There is currently no reliable, impartial method for assessing it clinically or distinguishing fibrosis from active inflammatory disorders. Today, imaging methods including orbital ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are frequently employed to show pathological abnormalities in the ocular adnexa of GO patients. In addition, a not widely accepted technique - 99mTc-DTPA SPECT - has some potential to evaluate retrobulbar inflammation in GO patients. However, FDG-PET/CT is possibly superior to other imaging modalities in detecting inflammation in GO and it may be useful in assessing disease activity in case of clinical or serological uncertainty. It might also act as an early indicator of GO development and its aggravation before irreversible tissue alterations take place and may be used in the differential diagnosis of inflammatory disorders of the orbit. However, before FDG-PET/CT could be applied in daily clinical practice, the methodology of GO activity assessment with defined cut-off values for radionuclide concentration - standardized units of value (SUV) have to be established and validated. In addition, the limitations of this technique have to be recognized.

Innovative design of minimal invasive biodegradable poly(glycerol-dodecanoate) nucleus pulposus scaffold with function regeneration

Minimally invasive biodegradable implants with regeneration have been a frontier trend in clinic. Degeneration of nucleus pulposus (NP) is irreversible in most of spine diseases, and traditional spinal fusion or discectomy usually injure adjacent segments. Here, an innovative minimally invasive biodegradable NP scaffold with function regeneration inspired by cucumber tendril is developed using shape memory polymer poly(glycerol-dodecanoate) (PGD), whose mechanical property is controlled to the similar with human NP by adjusting synthetic parameters. The chemokine stromal cell-derived factor-1α (SDF-1α) is immobilized to the scaffold recruiting autologous stem cells from peripheral tissue, which has better ability of maintaining disc height, recruiting autologous stem cells, and inducing regeneration of NP in vivo compared to PGD without chemokine group and hydrogel groups significantly. It provides an innovative way to design minimally invasive implants with biodegradation and functional recovery, especially for irreversible tissue injury, including NP, cartilage and so on.

Toxicological manifestations in gills, liver, kidney and muscles of Channa punctatus exposed to mercuric chloride

Aquatic regimes are exposed to a variety of pollutants that are mainly released by anthropogenic activities. Mercuric chloride (HgCl2) pose serious hazards to freshwater fish resource for its toxicity and long persistence. It is also a threat to humans who consume fish as a food resource. This study aimed to determine the consequences of acute exposure to HgCl2 in the freshwater food fish Channa punctatus (Bloch, 1973). The acute study of 96 hours was composed of three groups (in triplicates), having ten fish in each group which includes group I (control), group II (0.112 mg/l of HgCl2) and group III (0.224 mg/l of HgCl2). Results showed induction in reactive oxygen species (ROS) level in erythrocytes of group III (22159 ± 258.036). The biomarkers of oxidative stress, glutathione reduced (GSH) and lipid peroxidase (LPO) showed significant (p < 0.05) decrement and increment in their activity, respectively, in gills, liver, kidney and muscle tissues of the fish treated with HgCl2. Further, micronuclei (MN) and nuclear abnormalities (NAs) were formed in the erythrocytes of the fish of groups II and III, revealing DNA damage, hence showing genotoxicity. Histopathological studies in sample tissues of HgCl2 treated group demonstrated irreversible tissue injuries and anomalies. Thus, the findings from the study demonstrate that biological stress is induced in fish because of acute exposure to HgCl2, leading to health impairment

Rolling-Circle-Amplification-Assisted DNA Biosensors for Sensitive and Specific Detection of Hypochlorous Acid and Myeloperoxidase

Hypochlorous acid (HClO) is a common reactive oxygen species (ROS), with a high chemical reactivity. Myeloperoxidase (MPO) is an enzyme that catalyzes in vivo redox reactions between H2O2 and Cl− to produce HClO. Abnormal levels of HClO and MPO may lead to oxidative stress, irreversible tissue damage and, thus, serious diseases; they are thus becoming important biomarkers and therapeutic targets. In this work, using HClO-induced site-specific cleavage of phosphorothioate-modified DNA to trigger rolling circle amplification (RCA), RCA-assisted biosensors have been developed for the highly sensitive and specific detection of HClO and MPO. Only two DNA oligonucleotides are used in the sensing systems. The powerful signal-amplification capability of RCA endows the sensing systems with a high sensitivity, and the specific fluorescent response of thioflavin T (ThT) to G-quadruplexes in RCA products makes a label-free signal output possible. The proposed biosensors were demonstrated to work well not only for the sensitive and specific quantitation of HClO and MPO with detection limits of 1.67 nM and 0.33 ng/mL, respectively, but also for the screening and inhibitory capacity evaluation of MPO inhibitors, thus holding great promise in disease diagnosis and drug analysis.

Effect of Biologics on the Need for Procedural Interventions, Systemic Medications, and Healthcare Utilization in Patients with Hidradenitis Suppurativa: Real-World Data from the UNITE Registry.

Management of hidradenitis suppurativa (HS) often requires a combined medical/procedural approach. Biologics are frequently reserved for severe cases after irreversible tissue damage has occurred. We evaluated the association between consistent biologic use and the need for procedural interventions, systemic medications, and healthcare utilization. UNITE, a 4-year, global, prospective, observational, HS disease registry, documented the natural history, diagnostic/treatment patterns, and clinical outcomes of HS. Patients aged 12years or more, with active HS were enrolled between October 2013 and December 2015 and evaluated every 6months for 48months at 73 sites across 12 countries (data cutoff December 2019). Proportions of patients requiring different HS procedures, systemic medications, and healthcare utilization were assessed during the 6-month periods before, during, and after biologic initiation for 12weeks or more (i.e., consistent use). There were 63 instances of initiation of consistent biologic use (adalimumab [81%], infliximab [16%], and ustekinumab [3%]) in 57 patients. Patients' mean age was 40years, 58% were female, and 53%/47% had Hurley stageII/III disease, respectively. Fewer patients required surgical/procedural interventions and systemic medications for the 6-month period during/6-month period after biologic initiation versus the 6-month period before biologic initiation, including intralesional corticosteroid injections (22%/14% vs 24%), incision and drainage (I&D) by physician (10%/10% vs 17%), I&D by patient (10%/10% vs 14%), surgical excision (8%/10% vs 11%), deroofing (5%/2% vs 5%), systemic antibiotics (43%/41% vs 54%), and systemic immunosuppressants (10%/6% vs 13%). Fewer patients required hospital admission for HS (17%/13% vs 21%) or emergency department visits for HS (8%/8% vs 16%) during the 6-month periods in which consistent biologics use started and continued versus the 6-month period before consistent biologic use. Following initiation of consistent biologic use (12weeks or more), fewer patients required acute procedural interventions, systemic medications, and healthcare utilization, supporting the importance of early biologic initiation.

Calibration of a three-state cell death model for cardiomyocytes and its application in radiofrequency ablation

Objective. Thermal cellular injury follows complex dynamics and subcellular processes can heal the inflicted damage if insufficient heat is administered during the procedure. This work aims to the identification of irreversible cardiac tissue damage for predicting the success of thermal treatments. Approach. Several approaches exist in the literature, but they are unable to capture the healing process and the variable energy absorption rate that several cells display. Moreover, none of the existing models is calibrated for cardiomyocytes. We consider a three-state cell death model capable of capturing the reversible damage of a cell, we modify it to include a variable energy absorption rate and we calibrate it for cardiac myocytes. Main results. We show how the thermal damage predicted by the model response is in accordance with available data in the literature on myocytes for different temperature distributions. When coupled with a computational model of radiofrequency catheter ablation, the model predicts lesions in agreement with experimental measurements. We also present additional experiments (repeated ablations and catheter movement) to further illustrate the potential of the model. Significance. We calibrated a three-state cell death model to provide physiological results for cardiac myocytes. The model can be coupled with ablation models and reliably predict lesion sizes comparable to experimental measurements. Such approach is robust for repeated ablations and dynamic catheter-cardiac wall interaction, and allows for tissue remodelling in the predicted damaged area, leading to more accurate in-silico predictions of ablation outcomes.

Antitumor Activity of Berberine by Activating Autophagy and Apoptosis in CAL-62 and BHT-101 Anaplastic Thyroid Carcinoma Cell Lines.

Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid carcinoma. Doxorubicin (DOX) is the only drug approved for anaplastic thyroid cancer treatment, but its clinical use is restricted due to irreversible tissue toxicity. Berberine (BER), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has been proposed to have antitumor activity in many cancers. However, the underlying mechanisms by which BER regulates apoptosis and autophagy in ATC remain unclear. Thus, the present study aimed to assess the therapeutic effect of BER in human ATC cell lines CAL-62 and BHT-101 as well as the underlying mechanisms. In addition, we assessed the antitumor effects of a combination of BER and DOX in ATC cells. The cell viability of CAL-62 and BTH-101 with treatment of BER for different hours was measured by CCK-8 assay, and cell apoptosis was assessed by clone formation assay and flow cytometric analysis. The protein levels of apoptosis protein, autophagy-related proteins and PI3K/AKT/mTORpathway were determined Using Western blot. Autophagy in cells was observed with GFP-LC3 plasmid using confocal fluorescent microscopy. Flow cytometry was used to detect intracellular ROS. The present results showed that BER significantly inhibited cell growth and induced apoptosis in ATC cells. BER treatment also significantly upregulated the expression of LC3B-II and increased the number of GFP-LC3 puncta in ATC cells. Inhibition of autophagy by 3-methyladenine (3-MA) suppressed BER-induced autophagic cell death. Moreover, BER induced the generation of reactive oxygen species (ROS). Mechanistically, we demonstrated that BER regulated the autophagy and apoptosis of human ATC cells through the PI3K/AKT/mTOR pathways. Furthermore, BER and DOX cooperated to promote apoptosis and autophagy in ATC cells. Taken together, the present findings indicated that BER induces apoptosis and autophagic cell death by activating ROS and regulating the PI3K/AKT/mTOR signaling pathway.

Pathophysiology of multiple sclerosis damage and repair: Linking cerebral hypoperfusion to the development of irreversible tissue loss in multiple sclerosis using magnetic resonance imaging.

Reduced cerebral perfusion has been observed in multiple sclerosis (MS) and may contribute to tissue loss both acutely and chronically. Here, we test the hypothesis that hypoperfusion occurs in MS and relates to the presence of irreversible tissue damage. In 91 patients with relapsing MS and 26 healthy controls (HC), gray matter (GM) cerebral blood flow (CBF) was assessed using pulsed arterial spin labeling. GM volume, T1 hypointense and T2 hyperintense lesion volumes (T1LV and T2LV, respectively), and the proportion of T2-hyperintense lesion volume that appears hypointense on T1-weighted magnetic resonance imaging (T1LV/T2LV) were quantified. GM CBF and GM volume were evaluated globally, as well as regionally, using an atlas-based approach. Global GM CBF was lower in patients (56.9 ± 12.3 mL/100 g/min) than in HC (67.7 ± 10.0 mL/100 g/min; p < 0.001), a difference that was widespread across brain regions. Although total GM volume was comparable between groups, significant reductions were observed in a subset of subcortical structures. GM CBF negatively correlated with T1LV (r = -0.43, p = 0.0002) and T1LV/T2LV (r = -0.37, p = 0.0004), but not with T2LV. GM hypoperfusion occurs in MS and is associated with irreversible white matter damage, thus suggesting that cerebral hypoperfusion may actively contribute and possibly precede neurodegeneration by hampering tissue repair abilities in MS.

Torpor-responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides.

The marsupial Monito del monte (Dromiciops gliroides) utilizes both daily and seasonal bouts of torpor to preserve energy and prolong survival during periods of cold and unpredictable food availability. Torpor involves changes in cellular metabolism, including specific changes to gene expression that is coordinated in part, by the posttranscriptional gene silencing activity of microRNAs (miRNA). Previously, differential miRNA expression has been identified in D. gliroides liver and skeletal muscle; however, miRNAs in the heart of Monito del monte remained unstudied. In this study, the expression of 82 miRNAs was assessed in the hearts of active and torpid D. gliroides, finding that 14 were significantly differentially expressed during torpor. These 14 miRNAs were then used in bioinformatic analyses to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were predicted to be most affected by these differentially expressed miRNAs. Overexpressed miRNAs were predicted to primarily regulate glycosaminoglycan biosynthesis, along with various signaling pathways such as Phosphoinositide-3-kinase/protein kinase B and transforming growth factor-β. Similarly, signaling pathways including phosphatidylinositol and Hippo were predicted to be regulated by the underexpression of miRNAs during torpor. Together, these results suggest potential molecular adaptations that protect against irreversible tissue damage and enable continued cardiac and vascular function despite hypothermia and limited organ perfusion during torpor.

Ultra-short laser structuring of 3D-microfabricated non-resorbable polystyrene polymer to anchor cellular adhesion

Tissue engineering is emerging as a preferred choice for regeneration of irreversible bone tissue defects. It’s main “weapons” are the artificially created biocompatible three-dimensional cellular matrices that mimic the extracellular matrix’s structure and provide a mechanically stable inert substrate for the natural growth of cells. These porous scaffolds provide sufficient inner surface for cell adhesion, migration, proliferation and protrusion “inside” the temporal implant, facilitating in that way the natural bone ingrowth and vascularization. This leads, eventually, to overgrowing the outer and inner surface of the biomimetic implant with recipient self-formed bone tissue, thus avoiding a possible immune response.In the current study 3D Polystyrene (PS) non-resorbable synthetic cellular bone scaffolds, produced by 3D microfabrication technology, were additionally structured by applying femtosecond (fs) laser radiation with variable parameters thus achieving optimal laser processing conditions, for creation of 3D matrix with enhanced fiber surface properties. The main aim is the establishment of surface structured microporous biomimetic scaffolds, providing improved cell adhesion, infiltration and formation of extracellular matrix. The 3D laser functionalized PS samples were investigated by Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray analysis (EDX), confocal (optical profilometer) and roughness analyses for evaluation of their morphological and chemical properties before and after fs structuring was performed. Water contact angle (WCA) evaluation was also conducted. Future experimental work will include in vitro cellular studies for determining the optimal structuring laser parameters, providing osteoconductive and osteoinductive qualities of the 3D fs-microstructured PS scaffolds.

Characterization of ZG16b protein exocrine function and biomarker potential for salivary gland damage in chronic graft vs. host disease

Abstract The oral cavity is a frequent target of chronic Graft versus Host Disease (cGVHD) following allogenic hematopoietic stem cell transplant (allo-HSCT). Detection of early cGVHD-induced damage to exocrine tissues, such as salivary glands, is challenging to detect prior to irreversible tissue fibrosis. Recent work in our laboratory used shotgun proteomics to identify putative salivary biomarkers at salivary gland cGVHD onset. Saliva samples from patients affected with oral cGVHD post allo-HSCT had a drop in protein content of zymogen granule 16b (ZG16b), recapitulated in immunohistochemical staining of human minor salivary gland (MSG) biopsy sections. ZG16b loss correlated with CD45+ cells infiltration. This protein is poorly characterized, and immunofluorescence tissue staining suggested ZG16b protein localization to acinar cells. ZG16b cellular expression localized to serous and serous mucous acinar cell populations in single cell RNAseq (scRNA seq) data from healthy human labial MSG. Little is known about the function of this ZG16b in other exocrine tissues such as pancreas. scRNA seq analysis of repository data suggests ZG16b colonization in the pancreatic ductal cells. Similar to MSG, the pancreatic Zg16b gene was expressed in mucus secretion pathways and additional interactions with cell migration and homeostasis markers. Ongoing work is being done to further probe for binding partners for ZG16b (endogenous proteins, components of the oral microbiome and immune cell receptors) to distinguish the protein from its homologs. In parallel, the utility of salivary ZG16b as a cGVHD and general salivary gland damage biomarker is being tested. This work will bring clarity Zg16b’s role in exocrine tissues and alloimmune disease. NIH, NIDCR Intramural program

Preliminary research of the classification of the brain acute stroke lesions by the Diffusion Kurtosis Imaging (DKI) and Diffusion Weighted Imaging (DWI) parameters.

Diffusion-weighted magnetic resonance imaging (DWI) is a mature scanning technique. With high sensitivity in detecting cerebral infractions, it has become an essential part of the clinical evaluation of acute stroke. However, with the update in medical ideals and treatment, clinicians are now focusing on distinguishing between reversible and irreversible brain tissue damage rather than detecting ischaemic lesions alone. We supposed that Diffusion Kurtosis Imaging (DKI) could classify heterogeneous DWI lesions, deepening the understanding of tissue injury. We systematically studied the different parameters of DKI in acute stroke patients in the literature. We collected 41 patients (26 male, 15 female), including different infarctions with acute cerebral infarction in different brain regions. Of all patients, 20 were single-infarction, while others were multi-infarctions. In this paper, we categorized acute cerebral infarction lesions into two types according to the parametric characteristics of both DKI and DWI. Type I means the DKI and DWI were matched, and Type II means the DKI and DWI were mismatched. Based on each parametric map, the region of interest (ROI) is outlined in each most severe lesion area (as large as possible in the center of the lesion). In the control group, ROIs of the same size are located in the corresponding regions of the contralateral hemisphere. In both Type I and Type II, all parameters conform to a normal distribution. An independent sample T-test was used to compare the differences between each group. In Type I, we found the FA, MD, Da, Dr, MK and Ka values were statistically different (P< 0.05), while in Type II, only the MK and Ka values were statistically different (P< 0.05). DKI, compared to DWI, can provide more imaging information about intracranial ischemic infarction, which can deepen the understanding of the mechanism of ischemic tissue damage. Our classification of the brain acute stroke lesions by DKI parameters and DWI may help us rediscover the real core of infraction.