Two-Dimensional Radiographs and Cone-beam Computed Tomography Assessment of Concentrated Growth Factor and Platelet-Rich Fibrin Scaffolds in Regenerative Endodontic Treatment of Immature Incisors with Periapical Radiolucency: A Randomized Clinical Trial.

INTRODUCTION: The primary aim of this study was to compare the radiographic changes of immature incisors with periapical radiolucency after treatment with platelet-rich fibrin (PRF) and concentrated growth factor (CGF) platelet concentrate scaffolds as well as assessment of the clinical success rate over 12 months. The secondary aim was to monitor the radiographic changes in terms of reduction of periapical lesion diameter (PALD), root dentine thickness (RDT), root length (RL), and apical foramen width (AFW). The tertiary aim was to assess and pulp responses, after 12 months. METHODS: Fifty six children with seventy necrotic, single-rooted maxillary incisors with periapical radiolucency were treated with either CGF or PRF scaffolds (35 teeth per group). Two patients with 4 teeth (2 teeth in each group) failed to attain the follow-up recalls. Radiographic changes in terms of reduction of PALD, RDT, RL, and AFW were monitored using a 2-dimensional (2D) radiograph and cone-beam computed tomography (CBCT) scan. The clinical performance of teeth receiving both scaffolds was assessed after 6 and 12 months. Categorical and continuous data were analyzed using the chi-square test and the t test, respectively. The time and group effects on the means of different radiographic dimensions were tested using the general linear model. Bland-Altman plots were used to assess the level of agreement between the 2D radiographs and CBCT. The level of significance was defined at 0.05 and a 95% confidence interval. RESULTS: The means of PALD and RL showed significant enhancement in the CGF group compared to the PRF group (P < .05). While the difference between the 2 scaffolds in terms of RDT and AFW was not significant (P > .05). The findings of the 2D radiograph and CBCT were consistent. Clinically, both scaffold success rates were similar (93.9%) over the follow-up intervals. The influence of study independent variables had no significant effect on the success of the regenerative endodontic procedures outcome (P > .05). There was no significant difference in the positive pulp responses to the thermal and electric pulp tests after one year of treatment (P > .05). CONCLUSIONS: According to the short-term follow-up, PRF and CGF were successful in treating immature teeth with periapical radiolucency by regenerative endodontics. Both scaffold systems induced periapical healing and root lengthening with significant superiority of CGF.

Real-World Impact of Prophylactic Growth Factor Use on Timing of Febrile Neutropenia and Infection After High-Risk Chemotherapy.

BACKGROUND: Prophylactic growth-factor therapy with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients with breast cancer initiating myelosuppressive chemotherapy. However, little is known about the protective benefit early in the chemotherapy cycle. METHODS: To assess the relationship between G-CSF prophylaxis and incidence of FN/infection in week 1 versus beyond week 1 of the first chemotherapy cycle, a retrospective study was conducted using Medicare claims from 2005 through 2020 among patients with breast cancer initiating high-risk chemotherapy. Two cohorts were compared based on G-CSF prophylaxis within 3 days following chemotherapy initiation. The primary outcome was FN or infection, defined as hospitalization with neutropenia, fever, or infection diagnosis. Secondary outcomes were a stricter definition of FN and infection-related hospitalization. Unadjusted and regression-adjusted proportions of patients experiencing each outcome during week 1 versus beyond week 1 of the first chemotherapy cycle were compared. RESULTS: Of 78,810 patients meeting all inclusion criteria (>98% female; mean age, 69 years), 79% initiated TC (docetaxel/cyclophosphamide), 14% TCH (docetaxel/carboplatin/trastuzumab), and 7% TAC (docetaxel/doxorubicin/cyclophosphamide). Among patients receiving G-CSF (74%), incidence of first-cycle FN/infection was lower compared with patients not receiving G-CSF (overall, 6% vs 13%; TAC, 12% vs 19%; TC, 6% vs 12%; TCH, 5% vs 15%). However, patients who received G-CSF were generally more likely to experience FN/infection in week 1 (adjusted odds ratio [aOR], 1.24 for all; 1.73 for TAC; 1.35 for TC; and 0.76 for TCH). Results were similar for strictly defined FN (overall aOR, 1.29 for week 1 and 0.12 for beyond week 1) and infection-related hospitalization (overall aOR, 1.33 for week 1 and 0.27 for beyond week 1). CONCLUSIONS: Overall, the rates of chemotherapy-related FN and infection in week 1 of the first chemotherapy cycle are similar for patients receiving and not receiving G-CSF, suggesting continued risk in week 1 despite prophylactic G-CSF.

Automated Generation of hiPSC-Derived Hepatic Progeny by Cost-Efficient Compounds.

Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) hold great promise for liver disease modeling, drug discovery, and drug toxicity screens. Yet, several hurdles still need to be overcome, including among others decrease in the cost of goods to generate HLCs and automation of the differentiation process. We here describe that the use of an automated liquid handling system results in highly reproducible HLC differentiation from hPSCs. This enabled us to screen 92 chemicals to replace expensive growth factors at each step of the differentiation protocol to reduce the cost of goods of the differentiation protocol by approximately 79%. In addition, we also evaluated several recombinant extracellular matrices to replace Matrigel. We demonstrated that differentiation of hPSCs on Laminin-521 using an optimized small molecule combination resulted in HLCs that were transcriptionally identical to HLCs generated using the growth factor combinations. In addition, the HLCs created using the optimized small molecule combination secreted similar amounts of albumin and urea, and relatively low concentrations of alfa-fetoprotein, displayed similar CYP3A4 functionality, and a similar drug toxicity susceptibility as HLCs generated with growth factor cocktails. The broad applicability of the new differentiation protocol was demonstrated for 4 different hPSC lines. This allowed the creation of a scalable, xeno-free, and cost-efficient hPSC-derived HLC culture, suitable for high throughput disease modeling and drug screenings, or even for the creation of HLCs for regenerative therapies.

Transcriptional profiles of TGF-ß superfamily members in the lumbar DRGs and the effects of activins A and C on inflammatory pain in rats.

Signaling by the transforming growth factor (TGF)-ß superfamily is necessary for proper neural development and is involved in pain processing under both physiological and pathological conditions. Sensory neurons that reside in the dorsal root ganglia (DRGs) initially begin to perceive noxious signaling from their innervating peripheral target tissues and further convey pain signaling to the central nervous system. However, the transcriptional profile of the TGF-ß superfamily members in DRGs during chronic inflammatory pain remains elusive. We developed a custom microarray to screen for transcriptional changes in members of the TGF-ß superfamily in lumbar DRGs of rats with chronic inflammatory pain and found that the transcription of the TGF-ß superfamily members tends to be downregulated. Among them, signaling of the activin/inhibin and bone morphogenetic protein/growth and differentiation factor (BMP/GDF) families dramatically decreased. In addition, peripherally pre-local administration of activins A and C worsened formalin-induced acute inflammatory pain, whereas activin C, but not activin A, improved formalin-induced persistent inflammatory pain by inhibiting the activation of astrocytes. This is the first report of the TGF-ß superfamily transcriptional profiles in lumbar DRGs under chronic inflammatory pain conditions, in which transcriptional changes in cytokines or pathway components were found to contribute to, or be involved in, inflammatory pain processing. Our data will provide more targets for pain research.

A STUDY OF THE ASSESSMENT OF SERUM ADROPIN LEVEL AS A RISK FACTOR OF ISCHAEMIC HEART DISEASE IN TYPE 2 DIABETES MELLITUS CASES.

Adropin is a peptide hormone that was first identified in 2008 and was first thought to have a significant role in the balance of fatty acids and glucose in peripheral tissues. We look at the relationship between adropin and diabetes individuals' ischemic heart disease. The objective of the study is to evaluate the serum adropin level as a potential indicator of ischemic heart disease in people with type 2 diabetes mellitus. The 90 participants in this case-control study were split into three groups: Group (I) consisted of 30 T2DM patients with ischemic heart disease Group (II) consisted of 30 T2DM patients without ischaemic heart disease Group (III) consisted of 30 healthy persons as the control group. HbA1c, lipid profile (cholesterol, triglycerides, LDL-C, HDL), HOMA IR serum creatinine, AST, ALT, and serum adropin were also evaluated. Fasting plasma glucose, 2h postprandial plasma glucose, Carotid artery intimal thickness using ultrasound, and Carotid artery intimal thickness were also measured. Patients with diabetes who did not have ischemic heart disease had a statistically significant rise in serum Adropin hormone (p value 0.001), with values of (26.867 10.037) ng/L and (87.500 40.509) ng/L, respectively. Additionally, there was a bad correlation between serum adropin and CIMT and fasting insulin. Assessment of serum adropin levels may serve as a risk indicator for the emergence of ischemic heart disease in people with type 2 diabetes mellitus.

Perspectivas atuais da engenharia de tecidos da articulação temporomandibular / Perspectivas Actuales de la Ingeniería de Tejidos para la Articulación Temporomandibular / Current Perspectives of Tissue Engineering for the Temporomandibular Joint

Introdução: As limitações das terapias atuais para doenças degenerativas da articulação temporomandibular (ATM) levaram ao aumento do interesse em estratégias regenerativas. A engenharia de tecidos (ET), combinando células-tronco, arcabouços e fatores de crescimento, pode fornecer uma substituição biológica funcional e permanente das estruturas da ATM, além de prevenir o avanço de doenças degenerativas. Objetivo: Este artigo descreve as perspectivas atuais da ET das estruturas da ATM em modelos animais. Metodologia: As abordagens da ET foram categorizadas de acordo com as estruturas primárias da ATM: 1) o disco articular, 2) o côndilo mandibular e 3) a fossa glenóide e eminência articular. Resultados: As áreas com a maior quantidade de estudos são o côndilo mandibular e disco articular, em estudos que abordam o uso de arcabouços tridimensionais, de origem sintética e/ou natural, podendo ou não estar associados a células tronco (diferenciadas ou não) e a fatores de crescimento. Conclusão: A ET da ATM ainda é uma área relativamente nova, em desenvolvimento e em constante avanço. Os avanços tecnológicos desenvolvidos nessa área têm o potencial de auxiliar no desenvolvimento de terapias mais eficientes e menos invasivos... (AU)

Introducción: Las limitaciones de las terapias actuales para las enfermedades degenerativas de la articulación temporomandibular (ATM) han llevado a un mayor interés en las estrategias regenerativas. La ingeniería de tejidos, que combina células, andamios y factores de crecimiento, puede proporcionar un reemplazo biológico funcional y permanente de las estructuras de la ATM, además de prevenir el avance de enfermedades degenerativas. Objetivo: Este artículo describe las perspectivas actuales de la ingeniería de tecidos de las estructuras de la ATM en modelos animales. Metodología: Los enfoques de ingeniería de tejidos se clasificaron según las estructuras primarias de la ATM: 1) el disco articular, 2) el cóndilo mandibular y 3) la fosa glenoidea y la eminencia articular. Resultados: Las áreas con mayor número de estudios son el cóndilo mandibular y el disco articular, en estudios que abordan el uso de estructuras tridimensionales, de origen sintético y/o natural, que pueden o no estar asociadas a células (diferenciadas o no) y con factores de crecimiento. Conclusión: La ingeniería de tejidos de la ATM es todavía un área relativamente nueva, en desarrollo y en constante avance. Los avances tecnológicos desarrollados en esta área tienen el potencial de ayudar en el desarrollo de terapias más eficientes y menos invasivas... (AU)

Introduction: The limitations of current therapies for degenerative diseases of the temporomandibular joint (TMJ) have led to increased interest in regenerative strategies. Tissue engineering (TE), combining stem cells, scaffolds, and growth factors, can provide a functional and permanent biological replacement of TMJ structures, in addition to preventing the advancement of degenerative diseases. Aim: This article describes current TE perspectives of TMJ structures in animal models. Methods: TE approaches were categorized according to the primary TMJ structures: 1) the articular disc, 2) the mandibular condyle, and 3) the glenoid fossa and articular eminence. Results: The areas with the greatest number of studies are the mandibular condyle and articular disc, in studies that address the use of three-dimensional scaffolds, of synthetic and/ or natural origin, which may or may not be associated with stem cells (differentiated or not) and with growth factors. Conclusion: TE of the TMJ is still a relatively new, developing, and constantly advancing area. The technological advances developed in this area have the potential to assist in the development of more efficient and less invasive therapies... (AU)

[Determination of the prevalence of postcovid syndrome and assessment of the effectiveness of the drug Cortexin in the treatment of neurological disorders in patients with postcovid syndrome. Results of the multicenter clinical and epidemiological observational program CORTEX]. / Opredelenie rasprostranennosti postkovidnogo sindroma i otsenka effektivnosti preparata Korteksin v terapii nevrologicheskikh narushenii u patsientov s postkovidnym sindromom. Rezul'taty mnogotsentrovoi nablyudatel'noi programmy KORTEKS.

OBJECTIVE: To study the prevalence of clinical manifestations of postcoid syndrome in patients at an outpatient neurological appointment, to evaluate the effectiveness of therapy regimens using Cortexin at doses of 10 mg and 20 mg IM for 10 days. MATERIALS AND METHODS: 674 neurologists from all regions of the Russian Federation, Azerbaijan, Kyrgyzstan and Kazakhstan took part in the study. A total of 979 COVID-19 patients were recruited. The average age is 54.6±0.45 years. The duration of the transferred SARS-CoV-2 days and from 1 month or more 12. 3 visits were carried out: 1 on the day of treatment (assessment of complaints, analysis of scale indicators, prescription of the drug Cortexin in doses of 10-20 mg/m for 10 days). 2 (telephone survey) visit for 10-14 days, 3 visit - for 30 days at the reception. The condition was assessed using the Asthenia Assessment Scale (MFI-20), the Brief Mental Status Assessment Scale (MMSE questionnaire), the Schulte test, and the Subjective Treatment Quality Assessment Scale. RESULTS: The daily proportion of patients with complaints after a previous coronavirus infection was 30% in the total structure of neurological admission. The most common complaints: fatigue, general weakness, decreased memory and concentration, dizziness, sleep disturbance, irritability, aggression, shortness of breath, pain syndromes, excessive sweating, anosmia, hyposmia, perverted taste of paresthesia, hair loss, blurred vision, unstable blood pressure, tachycardia, allergic reactions, menstrual irregularities, erectile dysfunction, apathy, panic attacks, suicidal thoughts, depression, refusal to eat meat. CONCLUSION: There was no significant correlation of clinical symptoms with the severity of COVID-19, the percentage of lung tissue damage, and different periods of postcovid syndrome. The clinical efficacy of the drug Cortexin in dosages of 10 and 20 mg for the correction of cognitive and asthenic disorders has been proven. Revealed anti-anxiety, antidepressant and anxiolytic activity of Cortexin is more pronounced when using a dosage of 20 mg.

Novel cost-efficient protein-based membrane system for cells cocultivation and modeling the intercellular communication.

In vitro systems serve as compact and manipulate models to investigate interactions between different cell types. A homogeneous population of cells predictably and uniformly responds to external factors. In a heterogeneous cell population, the effect of external growth factors is perceived in the context of intercellular interactions. Indirect cell cocultivation allows one to observe the paracrine effects of cells and separately analyze cell populations. The article describes an application of custom-made cell cocultivation systems based on protein membranes separated from the bottom of the vessel by the 3D printed holder or kept afloat by a magnetic field. Using the proposed cocultivation system, we analyzed the interaction of A549 cells and fibroblasts, in the presence and absence of growth factors. During cocultivation of cells, the expression of genes of the activation for epithelial and mesenchymal transitions decreases. The article proposes the application of a newly available system for the cocultivation of different cell types.

Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diabéticos: Regulação da Expressão de Quemerina e CMKLRI no Coração e Tecidos Adiposos / Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues

Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

Abstract Background L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. Objectives The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Methods Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Results Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). Conclusion The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

Topical Delivery of Rapamycin by Means of Microenvironment-Sensitive Core-Multi-Shell Nanocarriers: Assessment of Anti-Inflammatory Activity in an ex vivo Skin/T Cell Co-Culture Model.

INTRODUCTION: Rapamycin (Rapa) is an immunosuppressive macrolide that inhibits the mechanistic target of rapamycin (mTOR) activity. Thanks to its anti-proliferative effects towards different cell types, including keratinocytes and T cells, Rapa shows promise in the treatment of skin diseases characterized by cell hyperproliferation. However, Rapa skin penetration is limited due to its lipophilic nature (log P = 4.3) and high molecular weight (MW = 914 g/mol). In previous studies, new microenvironment-sensitive core multishell (CMS) nanocarriers capable of sensing the redox state of inflamed skin were developed as more efficient and selective vehicles for macrolide delivery to inflamed skin. METHODS: In this study, we tested such redox-sensitive CMS nanocarriers using an inflammatory skin model based on human skin explants co-cultured with Jurkat T cells. Serine protease (SP) was applied on skin surface to induce skin barrier impairment and oxidative stress, whereas phytohaemagglutinin (PHA), IL-17A, and IL-22 were used to activate Jurkat cells. Activation markers, such as CD45 and CD69, phosphorylated ribosomal protein S6 (pRP-S6), and IL-2 release were monitored in activated T cells, whereas pro-inflammatory cytokines were measured in skin extracts and culture medium. RESULTS: We found that alteration of skin barrier proteins corneodesmosin (CDSN), occludin (Occl), and zonula occludens-1 (ZO-1) as well as oxidation-induced decrease of free thiol groups occurred upon SP-treatment. All Rapa formulations exerted inhibitory effects on T cells after penetration across ex vivo skin. No effects on skin inflammatory markers were detected. The superiority of the oxidative-sensitive CMS nanocarriers over the other formulations was observed with regard to drug delivery as well as downregulation of IL-2 release. CONCLUSION: Overall, our results demonstrate that nanocarriers addressing features of diseased skin are promising approaches to improve the topical delivery of macrolide drugs.

Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues. / Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diabéticos: Regulação da Expressão de Quemerina e CMKLRI no Coração e Tecidos Adiposos.

BACKGROUND: L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. OBJECTIVES: The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. METHODS: Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. RESULTS: Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). CONCLUSION: The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

FUNDAMENTOS: A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. OBJETIVOS: O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. MÉTODOS: Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. RESULTADOS: A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). CONCLUSÃO: Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

Assessment of Growth Factors, Cytokines, and Cellular Markers in Saliva of Patients with Trigeminal Neuralgia.

We proposed to perform a comparative analysis of growth factors, cytokines, and chemokine receptors on the salivary cells in the saliva obtained from trigeminal neuralgia (TN) and normal subjects. Saliva was collected from TN and healthy subjects. Salivary cells were isolated by centrifugation. The expression of the cell surface marker was analyzed by flow cytometry. A cytometric bead array was done to measure the levels of cytokines and growth factors on the flow cytometer. Saliva from TN subjects showed lower growth factor levels of Angiopoietin-2, bFGF, HGF, SCF, TGF-α, and VEGF and higher cytokine levels of IL-1ß, TNF-α, CCL2, IL-17A, IL-6, and CXCL8, as well as higher expression levels of chemokine receptors CCR1 (CD191), CR3 (CD11b), CCR2 (CD192), CXCR5 (CD185), and CCR5 (CD196) in the cells from TN saliva. A certain set of cytokines and growth factors in the saliva, as well as chemokine receptors on salivary cells, could be a useful tool in the diagnostics and prognostics of trigeminal neuralgia. Trigeminal neuralgia is one of the significant pathological conditions in the class of chronic diseases around the world. Many targeted approaches are being tried by various research groups to utilize the information of the inflammatory microenvironment to resolve the pathology of chronic TN.

Role of serum adropin measurement in the assessment of insulin resistance in obesity.

Obesity has recently been mentioned as a metabolic pandemic in developed and developing countries and is an important known risk factor for type 2 diabetes and cardiovascular diseases. The main mechanism responsible for obesity is insulin resistance. Adropin is a peptide-structured regulatory hormone that is suggested to play a role in insulin resistance and metabolic regulation. We aimed to evaluate the associations of serum adropin with insulin resistance and clarify the factors affecting serum adropin concentrations. The study included 50 obese patients and 22 healthy controls. Patients with chronic disease and drug use history were excluded. Serum adropin and other metabolic parameters were obtained after overnight fasting. ELISA was used to measure serum adropin concentrations. The homeostatic model assessment-insulin resistance (HOMA-IR) index was used to calculate insulin resistance. Insulin resistance was defined as HOMA-IR >2.5. Serum adropin values were found to be low in the obese otherwise healthy patient group (p<0.001). Linear regression analysis revealed that age, body mass index (BMI), waist circumference (WC), high-density lipoprotein cholesterol, fasting glucose, and HOMA-IR affect serum adropin level. In multiple regression analysis, age is the most significant factor affecting serum adropin concentration. Serum adropin concentrations were negatively correlated with BMI, WC, diastolic blood pressure, fasting glucose, and insulin. Serum adropin concentrations were low in obese patients and the optimum cut-off point for adropin to indicate HOMA-IR at 2.5 is 216.7 ng/L. The findings suggest that serum adropin may contribute to the regulation of glycolipid metabolism and insulin resistance in obese patients.

Assessment of salusin alpha and salusin beta levels in patients with newly diagnosed dipper and non-dipper hypertension.

OBJECTIVE: The pathophysiology of non-dipper hypertension has not been clarified. The relationship between salusins with atherosclerosis and hypertension has gained attention in recent years. The aim of this paper is to investigate whether salusins are associated with circadian blood pressure, left ventricular mass index, and diastolic functions in newly diagnosed hypertensives. METHODS: The study included 88 newly diagnosed hypertensive individuals. Twenty-four-hour ambulatory blood pressure monitoring and echocardiographic examinations were performed. The patients were assigned to dipper hypertension (n = 41) and non-dipper hypertension (n = 47) groups based on the ambulatory blood pressure monitoring results according to the presence of ≥ a 10% decrease in nighttime blood pressure values or not. Serum salusin α and ß levels were determined by electrochemiluminescence immunological test method. RESULTS: Compared to dipper hypertension, non-dipper hypertension group demonstrated lower salusin α levels (1818.71 ± 221.67 vs 1963 ± 200.75 pg/mL, p = .002), mitral E/A, septal E'/A' and higher salusin ß levels (576.24 ± 68.15 vs 516.13 ± 90.7 pg/ml, p = .001) and left ventricular mass index. Multivariate logistic regression analysis revealed salusin-α (OR 0.474, 95% CI 0.262 to 0.986, p = .001), salusin-ß (OR 2.550, 95% CI 2.123 to 2.991, p = .018), and left ventricular mass index (OR 2.620, 95% CI 2.124 to 2.860, p = .011) as independent predictors of non-dipper hypertension. As candidate markers to predict non-dipper hypertension, decreased salusin α, and increased salusin ß levels may mediate crosstalk between sympathetic and parasympathetic systems and indicate poor cardiovascular prognosis in hypertension.

Level of Evidence and Industry Sponsorship Associated with Favorable Outcomes in Publications on Platelet-Rich-Plasma Therapy in Musculoskeletal Disorders / Nível de evidência e patrocínio industrial associado a desfechos favoráveis nas publicações sobre terapia com plasma rico em plaquetas nas doenças osteomusculares

Abstract Platelet-rich plasma is derived from centrifuging whole blood. There is increasing interest in the sports medicine and athlete community about providing endogenous growth factors directly to the injury site, using autologous blood products such as platelet-rich plasma. The aim of the present study is to evaluate the association between research financing, conflict of interests, level of evidence and author affiliation with the interpretation of results in articles published on platelet-rich plasma therapy in musculoskeletal ailments. A review of the current literature was performed. The outcome was classified as favorable or unfavorable. The declaration of conflict of interests and the type of funding was extracted from each article. The financing was classified as industry-sponsored; not industry-sponsored; or unidentifiable. The level of evidence was categorized from I to IV. Higher positive outcomes were observed in 134 studies with industry sponsorship compared with not industry-sponsored studies (odds ratio [OR]: 0.26; 95% confidence interval [95%CI]: 0.08-0.85; p < 0.05). Compared with level of evidence I, levels II and IV increase the probability of positive outcomes by 12.42 times (p < 0.01) and 10.97 times (p < 0.01) respectively. Proportionally, industry-sponsored studies are more likely to present positive results, as well as articles with a lower quality of evidence.

Resumo O plasma rico em plaquetas é derivado da centrifugação do sangue total. Há um interesse crescente, na medicina esportiva e na comunidade atlética, no fornecimento de fatores de crescimento endógeno diretamente ao sítio da lesão, usando componentes sanguíneos autólogos, como o plasma rico em plaquetas. O objetivo deste estudo é avaliar a associação entre financiamento de pesquisa, conflito de interesses, nível de evidência e afiliação dos autores com a interpretação dos resultados em publicações sobre terapia com plasma rico em plaquetas nas doenças osteomusculares. Foi realizada uma revisão da literatura atual. O desfecho foi classificado como favorável ou desfavorável. A declaração de conflito de interesses e o tipo de financiamento foram extraídos de cada artigo. O financiamento foi qualificado em patrocínio industrial; não patrocinado pela indústria; ou não identificável. O nível de evidência foi categorizado de I a IV. Foram obtidos os resultados positivos mais altos com 134 estudos financiados pelo setor industrial, em comparação com estudos não financiados pela indústria (razão de probabilidades [RP]: 0,26; intervalo de confiança de 95% [95%IC]: 0,08-0,85; p < 0,05). Em comparação com o nível de evidência I, os níveis II e IV aumentam a probabilidade de resultado positivo em 12,42 vezes (p < 0,01) e 10,97 vezes (p < 0,01), respectivamente. Demonstrou-se que, proporcionalmente, estudos patrocinados pela indústria têm maior probabilidade de apresentar resultados positivos, bem como artigos com menor qualidade de evidência.

The seasonal development dynamics of the yak hair cycle transcriptome.

BACKGROUND: Mammalian hair play an important role in mammals' ability to adapt to changing climatic environments. The seasonal circulation of yak hair helps them adapt to high altitude but the regulation mechanisms of the proliferation and differentiation of hair follicles (HFs) cells during development are still unknown. Here, using time series data for transcriptome and hormone contents, we systematically analyzed the mechanism regulating the periodic expression of hair development in the yak and reviewed how different combinations of genetic pathways regulate HFs development and cycling. RESULTS: This study used high-throughput RNA sequencing to provide a detailed description of global gene expression in 15 samples from five developmental time points during the yak hair cycle. According to clustering analysis, we found that these 15 samples could be significantly grouped into three phases, which represent different developmental periods in the hair cycle. A total of 2316 genes were identified in these three consecutive developmental periods and their expression patterns could be divided into 9 clusters. In the anagen, genes involved in activating hair follicle growth are highly expressed, such as the WNT pathway, FGF pathway, and some genes related to hair follicle differentiation. In the catagen, genes that inhibit differentiation and promote hair follicle cell apoptosis are highly expressed, such as BMP4, and Wise. In the telogen, genes that inhibit hair follicle activity are highly expressed, such as DKK1 and BMP1. Through co-expression analysis, we revealed a number of modular hub genes highly associated with hormones, such as SLF2, BOP1 and DPP8. They may play unique roles in hormonal regulation of events associated with the hair cycle. CONCLUSIONS: Our results revealed the expression pattern and molecular mechanisms of the seasonal hair cycle in the yak. The findings will be valuable in further understanding the alpine adaptation mechanism in the yak, which is important in order to make full use of yak hair resources and promote the economic development of pastoral plateau areas.

Assessment of Serum Concentrations of Adropin, Afamin, and Neudesin in Children with Type 1 Diabetes.

INTRODUCTION: The increasing knowledge of adropin, afamin, and neudesin and the regulation of glucose metabolism and insulin resistance allows for the assessment of the differences in their concentrations between the groups with varied duration of diabetes mellitus (DM). AIM OF THE STUDY: Assessment of serum levels of adropin, afamin, and neudesin in children with type 1 diabetes, with respect to the disease duration. MATERIALS AND METHODS: The study consisted of 138 patients aged 5-18 years (M 40.58%). Children with type 1 diabetes (n = 68) were compared to the control group (n = 70). The diabetic group was divided into 4 subgroups: (I) newly diagnosed patients, after an episode of ketoacidosis (n = 14), (II) duration no longer than 5 years (n = 18), (III) 5 to 10 years (n = 27), and (IV) longer than 10 years (n = 9). Serum concentrations of adropin, afamin, and neudesin were assessed and compared between the groups of patients. The criterion for statistical significance was p < 0.05. RESULTS: The concentrations of adropin and afamin across all subgroups were lower than that in the control group, while neudesin levels were higher in diabetic patients compared to the control group. The differences were statistically significant. CONCLUSIONS: Adropin, afamin, and neudesin may play a major role in the regulation of glucose metabolism and have a significant potential as novel biomarkers to predict future metabolic disorders. However, further multicentre studies on a larger cohort of patients are necessary to specify the role of these substances in the course and treatment of type 1 diabetes.

Inflammation-Related Patterns in the Clinical Staging and Severity Assessment of Chronic Kidney Disease.

Chronic kidney disease (CKD) is an irreversible loss of kidney function, and it represents a major global public health burden due to both its prevalence and its continuously increasing incidence. Mineral bone disorders (MBDs) constitute a hallmark of CKD, and alongside cardiovascular complications, they underlie a poor prognosis for these patients. Thus, our study focused on novel CKD biomarker patterns and their impact on the clinical staging of the disease. As a first testing approach, the relative expression levels of 105 proteins were assessed by the Proteome Profiler Cytokine Array Kit for pooled CKD stage 2-4 serum samples to establish an overall view regarding the proteins involved in CKD pathogenesis. Among the molecules that displayed significant dysregulation in the CKD stages, we further explored the involvement of Dickkopf-related protein 1 (Dkk-1), a recognised inhibitor of the Wnt signalling pathway, and its crosstalk with 1,25OH2D3 (calcitriol) as new players in renal bone and vascular disease. The serum levels of these two molecules were quantified by an ELISA (76 samples), and the results reveal decreasing circulating levels of Dkk-1 and calcitriol in advanced CKD stages, with their circulating expression showing a downward trend as the CKD develops. In the next step, we analysed the inflammation and MBD biomarkers' expression in CKD (by xMAP array). Our results show that the molecules involved in orchestrating the inflammatory response, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα), as well as the mineral biomarkers osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), and fibroblast growth factor 23 (FGF-23), correlate with Dkk-1 and calcitriol, raising the possibility of them being potential useful CKD biomarkers. These results reveal the impact of different biomarker patterns in CKD staging and severity, thus opening up novel approaches to be explored in CKD clinical management.

Thromboinflammation as bioactivity assessment of H2O2-alkali modified titanium surfaces.

The release of growth factors from platelets, mediated by the coagulation and the complement system, plays an important role in the bone formation around implants. This study aimed at exploring the thromboinflammatory response of H2O2-alkali soaked commercially pure titanium grade 2 discs exposed to whole human blood, as a way to assess the bioactivity of the discs. Commercially pure titanium grade 2 discs were modified by soaking in H2O2, NaOH and Ca(OH)2. The platelet aggregation, coagulation activation and complement activation was assessed by exposing the discs to fresh whole blood from human donors. The platelet aggregation was examined by a cell counter and the coagulation and complement activation were assessed by ELISA-measurements of the concentration of thrombin-antithrombin complex, C3a and terminal complement complex. The modified surface showed a statistically significant increased platelet aggregation, coagulation activation and complement activation compared to unexposed blood. The surface also showed a statistically significant increase of coagulation activation compared to PVC. The results of this study showed that the H2O2-alkali soaked surfaces induced a thromboinflammatory response that indicates that the surfaces are bioactive.

Organoid culture media formulated with growth factors of defined cellular activity.

The media formulations necessary for deriving and sustaining organoids from epithelial tissues such as prostate, colon, gastric, liver, pancreas, and others have been established. Critical components of organoid media are a set of growth factors that include R-spondins and BMP signalling antagonists such as Noggin or Gremlin 1. Currently, the practical limitations for formulating organoid media of reproducible potency and larger-scale media production that have hampered further technological applications of organoid technology include: the cost of growth factors such as R-spondins and Gremlin 1/Noggin and their production as defined specific activities free of contaminants that may affect organoid growth. Here we report the production of highly pure recombinant Gremlin 1 and R-spondin 1 from bacterial expression for use in organoid media. We detail the workflow for Gremlin 1 and R-spondin 1 expression, purification, quantification of cellular activity, quality control and use in media formulated for culturing organoids derived from a number of tissues. The development of precisely formulated, cost-effective media of defined specific activity will engender the development of novel applications for organoid technology.