Overexpression of long noncoding RNA DUXAP8 inhibits ER-phagy through activating AKT/mTOR signaling and contributes to preeclampsia.

Preeclampsia (PE) is a life-threatening pregnancy-specific complication with controversial mechanisms and no effective treatment except delivery is available. Currently, increasing researchers suggested that PE shares pathophysiologic features with protein misfolding/aggregation disorders, such as Alzheimer disease (AD). Evidences have proposed defective autophagy as a potential source of protein aggregation in PE. Endoplasmic reticulum-selective autophagy (ER-phagy) plays a critical role in clearing misfolded proteins and maintaining ER homeostasis. However, its roles in the molecular pathology of PE remain unclear. We found that lncRNA DUXAP8 was upregulated in preeclamptic placentae and significantly correlated with clinical indicators. DUXAP8 specifically binds to PCBP2 and inhibits its ubiquitination-mediated degradation, and decreased levels of PCBP2 reversed the activation effect of DUXAP8 overexpression on AKT/mTOR signaling pathway. Function experiments showed that DUXAP8 overexpression inhibited trophoblastic proliferation, migration, and invasion of HTR-8/SVneo and JAR cells. Moreover, pathological accumulation of swollen and lytic ER (endoplasmic reticulum) was observed in DUXAP8-overexpressed HTR8/SVneo cells and PE placental villus trophoblast cells, which suggesting that ER clearance ability is impaired. Further studies found that DUXAP8 overexpression impaired ER-phagy and caused protein aggregation medicated by reduced FAM134B and LC3II expression (key proteins involved in ER-phagy) via activating AKT/mTOR signaling pathway. The increased level of FAM134B significantly reversed the inhibitory effect of DUXAP8 overexpression on the proliferation, migration, and invasion of trophoblasts. In vivo, DUXAP8 overexpression through tail vein injection of adenovirus induced PE-like phenotypes in pregnant rats accompanied with activated AKT/mTOR signaling, decreased expression of FAM134B and LC3-II proteins and increased protein aggregation in placental tissues. Our study reveals the important role of lncRNA DUXAP8 in regulating trophoblast biological behaviors through FAM134B-mediated ER-phagy, providing a new theoretical basis for understanding the pathogenesis of PE.

Correlation of PD-L1 expression with different clinico-pathological and immunohistochemical features of ovarian surface epithelial tumors.

BACKGROUND: Primary carcinoma of the ovary (OCs) are responsible for a significant number of deaths related to cancer, and have the highest rate of death related to cancers of the female reproductive organs. Programmed cell death 1 (PD1) protein, acts as an immune checkpoint, and has an important role in the down-regulation of the immune system by preventing the activation of T-cells, which will weaken the autoimmunity and increases self-tolerance. This study aimed at the evaluation of the immunohistochemical (IHC) expression of PD-L1 in various primary surface ovarian epithelial tumours and to test its correlation with different clinicopathological parameters together with the expression of a panel of P53, ER and PR. METHODS: A set of 102 cases of primary ovarian surface epithelial neoplasms (benign, borderline and malignant) were collected to construct Tissue Microarray (TMA) using 3 tissue cores from each case. IHC for PD-L1, p53, PR and ER was performed. The expression of PD-L1 was evaluated in relation to some clinicopathological parameters and to the expression patterns of other markers. RESULTS: Expression of PD-L1 was detected in about 51% (n = 36) of malignant tumours. The malignant group significantly showed PD-L1 positivity compared to borderline and benign groups. The malignant tumours significantly showed PD-L1 and total p53 positivity in comparison to borderline group. Also, malignant tumours significantly showed higher combined positivity of PD-L1 and either PR or ER compared to borderline and benign lesions. No significant correlation was appreciated between PD-L1 expression and with any of the studied clinicopathological parameters. CONCLUSIONS: This study showed a significant PD-L1 expression in malignant primary surface epithelial tumours. Construction of a panel of IHC markers, including PD-L1, could have a potential value to define patients those would benefit from the addition of immunotherapy to the treatment plan.

Fibroblast growth factor receptor signaling in estrogen receptor-positive breast cancer: mechanisms and role in endocrine resistance.

Fibroblast Growth Factor Receptors (FGFRs) play a significant role in Estrogen Receptor-positive (ER+) breast cancer by contributing to tumorigenesis and endocrine resistance. This review explores the structure, signaling pathways, and implications of FGFRs, particularly FGFR1, FGFR2, FGFR3, and FGFR4, in ER+ breast cancer. FGFR1 is frequently amplified, especially in aggressive Luminal B-like tumors, and its amplification is associated with poor prognosis and treatment resistance. The co-amplification of FGFR1 with oncogenes like EIF4EBP1 and NSD3 complicates its role as a standalone oncogenic driver. FGFR2 amplification, though less common, is critical in hormone receptor regulation, driving proliferation and treatment resistance. FGFR3 and FGFR4 also contribute to endocrine resistance through various mechanisms, including the activation of alternate signaling pathways like PI3K/AKT/mTOR and RAS/RAF/MEK/ERK. Endocrine resistance remains a major clinical challenge, with around 70% of breast cancers initially hormone receptor positive. Despite the success of CDK 4/6 inhibitors in combination with endocrine therapy (ET), resistance often develops, necessitating new treatment strategies. FGFR inhibitors have shown potential in preclinical studies, but clinical trials have yielded limited success due to off-target toxicities and lack of predictive biomarkers. Current clinical trials, including those evaluating FGFR inhibitors like erdafitinib, lucitanib, and dovitinib, have demonstrated mixed outcomes, underscoring the complexity of FGFR signaling in breast cancer. The interplay between FGFR and other signaling pathways highlights the need for comprehensive molecular profiling and personalized treatment approaches. Future research should focus on identifying robust biomarkers and developing combination therapies to enhance the efficacy of FGFR-targeted treatments. In conclusion, targeting FGFR signaling in ER+ breast cancer presents both challenges and opportunities. A deeper understanding of the molecular mechanisms and resistance pathways is crucial for the successful integration of FGFR inhibitors into clinical practice, aiming to improve outcomes for patients with endocrine-resistant breast cancer.

ATR-FTIR spectroscopy imaging of bone repair in mandibular laser-osteotomy.

The aim of this study was to verify the effectiveness of attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy in the characterization of bone repair in mandibular osteotomy using erbium, chromium-doped yttrium, scandium, gallium and garnet (Er,Cr:YSGG) laser and multilaminate drill on each side. Two mandible bone fragments were removed from 30 rabbits, and the process of bone repair was studied immediately, 3, 7, 15, 21, and 28 days after the surgery. The histological analysis allowed detecting differences in the early stages of tissue repair after bone cutting performed with the Er,Cr:YSGG laser or multilaminate drill. The ATR-FTIR spectroscopy technique was sensitive to changes in the organic content of bone tissue repair process.

KSRP improves pancreatic beta cell function and survival.

Impaired insulin production and/or secretion by pancreatic beta cells can lead to high blood glucose levels and type 2 diabetes (T2D). Therefore, investigating new proteins involved in beta cell response to stress conditions could be useful in finding new targets for therapeutic approaches. KH-type splicing regulatory protein (KSRP) is a protein usually involved in gene expression due to its role in post-transcriptional regulation. Although there are studies describing the important role of KSRP in tissues closely related to glucose homeostasis, its effect on pancreatic beta cells has not been explored so far. Pancreatic islets from diet-induced obese mice (C57BL/6JUnib) were used to determine KSRP expression and we also performed in vitro experiments exposing INS-1E cells (pancreatic beta cell line) to different stressors (palmitate or cyclopiazonic acid-CPA) to induce cellular dysfunction. Here we show that KSRP expression is reduced in all the beta cell dysfunction models tested. In addition, when manipulated to knock down KSRP, beta cells exhibited increased death and impaired insulin secretion, whereas KSRP overexpression prevented cell death and increased insulin secretion. Taken together, our findings suggest that KSRP could be an important target to protect beta cells from impaired functioning and death.

Low doses of malathion impair ovarian, uterine, and follicular integrity by altering oxidative profile and gene expression of rats exposed during the peripubertal period.

Malathion serves as a pivotal pesticide in agriculture and the management of the Aedes aegypti mosquito. Despite its widespread use, there is a notable absence of studies elucidating the mechanisms through which malathion may affect the female reproductive system. Consequently, the objective of this investigation was to assess whether exposing juvenile female rats to low doses of malathion during the juvenile and peripubertal periods could compromise pubertal onset, estradiol levels, and the integrity of the ovaries and uterus while also examining the underlying mechanisms of damage. To achieve this, thirty juvenile female rats were subjected to either a vehicle or malathion (10 mg/kg or 50 mg/kg) between postnatal days 22 and 60, with subsequent verification of pubertal onset. Upon completion of the exposure period, blood samples were collected for estradiol assessment. The ovaries and uterus were then examined to evaluate histological integrity, oxidative stress, and the expression of genes associated with cell proliferation, antiapoptotic responses, and endocrine pathways. Although estradiol levels and pubertal onset remained unaffected, exposure to malathion compromised the integrity and morphometry of the ovaries and uterus. This was evidenced by altered oxidative profiles and changes in the expression of genes regulating the cell cycle, anti-apoptotic processes, and endocrine pathways. Our findings underscore the role of malathion in inducing cell proliferation, promoting cell survival, and causing oxidative damage to the female reproductive system in rats exposed during peripubertal periods.

Fox eyes lift-A new protocol for eyebrow elevation with laser Fotona.

BACKGROUND: The eyelids play an important role in our appearance and are usually the first to show signs of age. The Fotona SP Spectro Systems consist of a range of noninvasive laser treatments that work together synergistically to tighten the collagen in four dimensions and provide long-lasting firmness to the face. The Fotona SP Spectro combines two wavelengths: Er:YAG (2940 nm) and Nd:YAG (1064 nm) with four distinct treatments: SmoothLiftingTM, FRAC3®, PIANO®, and SupErficialTM, allowing safe, painless, noninvasive, and no downtime rejuvenation. AIMS: To present a new protocol of treatment with Fotona SP Spectro for eyebrow elevation, which we call fox eyes lift (FEL), and compare it to the standard SmoothEye® (SE) protocol. METHODS: This is a prospective, interventional, split-face study. The sample consisted of 21 subjects (19 women) with a mean age of 50.1 ± 7.9 years who underwent two different protocols, that is, SE on one side and FEL on the other. The protocol used on each side was selected by drawing lots. Three sessions were held at 1-month intervals. Standardized photographic documentation was obtained before and 30 days after the end of treatment. Eyebrow position before and after complete treatment was quantified using ImageJ software. RESULTS: Statistical analysis by ANOVA showed a significant improvement in eyebrow position after treatment with both protocols, with a significantly greater effect of FEL (p = 0.0003 d = 0.95). CONCLUSION: Fox eyes lift is an efficient and safe technique providing significant improvement in the position of the eyebrow.

Prognostic model of ER-positive, HER2-negative breast cancer predicted by clinically relevant indicators.

PURPOSE: To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. METHODS: In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. RESULTS: Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043-1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142-2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102-3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084-12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672-28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan-Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. CONCLUSION: To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation.

DNAJB12 and DNJB14 are non-redundant Hsp40 redox chaperones involved in endoplasmic reticulum protein reflux.

BACKGROUND: The endoplasmic reticulum (ER) transmembrane chaperones DNAJB12(B12) and DNAJB14(B14) are cofactors that cooperate with cytosolic Heat Shock-70 protein (HSC70) facilitating folding/degradation of nascent membrane proteins and supporting the ER-membrane penetration of viral particles. Here, we assessed structural/functional features of B12/B14 with respect to their regulation by ER stress and their involvement in ER stress-mediated protein reflux. METHODS: We investigated the effect of Unfolded Protein Response(UPR)-eliciting drugs on the expression/regulation of B12-B14 and their roles in ER-to-cytosol translocation of Protein Disulfide Isomerase-A1(PDI). RESULTS: We show that B12 and B14 are similar but do not seem redundant. They share predicted structural features and show high homology of their cytosolic J-domains, while their ER-lumen DUF1977 domains are quite dissimilar. Interactome analysis suggested that B12/B14 associate with different biological processes. UPR activation did not significantly impact on B12 gene expression, while B14 transcripts were up-regulated. Meanwhile, B12 and B14 (33.4 kDa isoform) protein levels were degraded by the proteasome upon acute reductive challenge. Also, B12 degradation was impaired upon sulfenic-acid trapping by dimedone. We originally report that knockdown of B12/B14 and their cytosolic partner SGTA in ER-stressed cells significantly impaired the amount of the ER redox-chaperone PDI in a cytosolic-enriched fraction. Additionally, B12 but not B14 overexpression increased PDI relocalization in non-stressed cells. CONCLUSIONS AND GENERAL SIGNIFICANCE: Our findings reveal that B12/B14 regulation involves thiol redox processes that may impact on their stability and possibly on physiological effects. Furthermore, we provide novel evidence that these proteins are involved in UPR-induced ER protein reflux.

Antimicrobial activity of Er, Cr: YSGG and Ultrasonic on E. faecalisbiofilm in the mesial root canal systems of lower molars / Atividade antimicrobiana de Er, Cr: YSGG e Ultrassônico no biofilme de E. faecalis nos sistemas de canais radiculares mesiais de molares inferiores

The internal topography of the root canal is complex, especially for the permanent molar's mesial root. In response to such issues, improved irrigation techniques have been created, which use laser pulses to agitate fluids and improve microbial deposit removal. Objective: To assess the effectiveness of the Er,Cr:YSGG laser with a wavelength of 2,780 nm via photon-induced photoacoustic streaming (PIPS) protocol which agitated of 2% chlorohexidine (CHX) in removing mature Enterococcus faecalis (E. faecalis) biofilm in root canal systems of lower molars. Material and Methods: The mesial roots of lower first and second molars were separated and inoculated with E. faecalis bacterial suspension for 30 days. The roots were irrigated with CHX, some of them were agitated with a passive ultrasonic device (PUI), while the other roots were agitated by an Er,Cr:YSGG laser in PIPS at 60 µs/pulse, 5 Hz, (0.25, 0.5, 0.75, and 1) W. An atomic force microscope (AFM) was used as a new method to get the results in the isthmus area; the obtained results from each group were compared with each other. Results: Based on the AFM and SEM analyses, laser and ultrasonic activation groups showed higher antimicrobial efficacy than the conventional syringe irrigation group (P<0.05). Conclusion: Based on the investigation's findings, the activation of 2% CHX solution by Er,Cr:YSGG laser in PIPS and PUI offers better mature bacterial biofilm removal in the mesial root of lower human molars than the same irrigant with the SI technique (AU)

A topografia interna do canal radicular é complexa, especialmente para a raiz mesial do molar permanente. Em resposta a esses problemas, foram criadas técnicas aprimoradas de irrigação, que utilizam pulsos de laser para agitar fluidos e melhorar a remoção de depósitos microbianos. Objetivo: Avaliar a eficácia do laser Er,Cr:YSGG com comprimento de onda de 2.780 nm via protocolo de streaming fotoacústico induzido por fótons (PIPS) que agitou clorohexidina a 2% (CHX) na remoção de Enterococcus faecalis maduro (E. faecalis) biofilme em sistemas de canais radiculares de molares inferiores. Material e Métodos: As raízes mesiais de 28 primeiros e segundos molares inferiores foram separadas e inoculadas com suspensão bacteriana de E. faecalis por 30 dias. As raízes foram irrigadas com CHX, sendo algumas delas agitadas com aparelho ultrassônico passivo (PUI), enquanto as demais raízes foram agitadas com laser Er,Cr:YSGG em PIPS a 60 µs/pulso, 5 Hz (0,25, 0,5, 0,75 e 1) W. Um microscópio de força atômica (AFM) foi utilizado como um novo método para obter os resultados na área do istmo; os resultados obtidos de cada grupo foram comparados entre si. Resultados: Com base nas análises de AFM e SEM, os grupos de ativação por laser e ultrassom apresentaram maior eficácia antimicrobiana do que o grupo de irrigação com seringa convencional (P<0.05). Conclusão: Com base nos achados da investigação, a ativação da solução de CHX a 2% pelo laser Er,Cr:YSGG em PIPS a (60 µs/pulso, 5 Hz, 0,75 W) oferece melhor remoção de biofilme (AU)

Histological evaluation of the surgical margins of oral soft tissue incisions using a dual-wavelength diode laser and an Er, Cr:YSGG laser; an ex vivo study

Abstract Oral soft tissue lesions require a precise diagnosis by oral biopsy with the ability to recognize these lesions within histopathological levels, so the instrument used for the incisions should be safe and cause little to no harm to the surrounding tissue. Objective This study compared a dual-wavelength diode laser and an Er, Cr:YSGG laser in oral soft tissue incisions to determine the most effective and safest laser system at the histopathological level. Methodology The (810 and 980 nm) dual-wavelength diode laser was used at 1.5 W and 2.5 W (CW) power settings, and the (2780 nm) Er, Cr:YSGG laser was used at 2.5 W and 3.5 W (PW) power settings. Both laser systems were used to incise the tissues of freshly dissected sheep tongue pieces to obtain the following histopathological criteria: epithelial tissue changes, connective tissue changes, and lateral thermal damage extent by optical microscopy. Results The epithelial and connective tissue damage scores were significantly higher in the dual-wavelength diode laser groups than in the Er, Cr:YSGG laser groups (P<0.001), and there was a significant difference between some groups. The extent of lateral thermal damage was also significantly higher in the diode laser groups than in the Er, Cr: YSGG laser groups (P<0.001), and there was a significant difference between groups. Group 2 (2.5 W) of the diode laser was the highest for all three criteria, while group 3 (2.5 W) of the Er, Cr:YSGG laser was the lowest. Conclusion The Er, Cr:YSGG laser with an output power of 2.5 W is, histologically, the most effective and safest laser for oral soft tissue incision. The dual-wavelength diode laser causes more damage than the Er, Cr:YSGG laser, but it can be used with a low output power and 1 mm safety distance in excisional biopsy.

Dentinal Tubule Occluding Efficacy Of Er: YAG Laser And Universal Adhesive Loaded With Nano-Carbonated Apatite

Abstract ER:YAG laser and experimental resin-based dental adhesive loaded with functionalized carbonated apatite filler were used in this study to evaluate the dentin interaction in terms of penetration and occlusion of the dentinal tubules aiding in the control of dentin hypersensitivity (DH). Spheroidal Carbonated apatite nanoparticles (N-CAP), with an average size of 20±5 nm diameter, were synthesized, characterized, and incorporated in a universal adhesive "All Bond Universal, Bisco, USA", in (2% weight) concentration. Er:YAG laser "Lightwalker, FOTONA, EU" was adjusted to an energy output of 40mJ/ pulse and pulse repetition of 10 Hz for 10 seconds. Dentin specimens were prepared from the buccal surface of 75 extracted sound human molars. The specimens were randomly divided into five groups (n=15) according to the surface treatment: Group (L): Laser only; Group (LB): Laser in combination with adhesive; Group (LBN): Laser in combination with adhesive loaded with N-CAP; Group (B): adhesive only; and Group (BN): adhesive loaded with N-CAP. Depth of penetration and occlusion of the dentinal tubules were assessed using Environmental Scanning Electron Microscope Examination (ESEM). One-way ANOVA was used to compare groups, followed by a pairwise test for multiple comparisons (α=0.05). Groups (LB), and (LBN) showed the highest mean of dentinal tubules' penetration, with a non-significant difference between them. In contrast, the specimens treated with laser only (L) showed the most minor penetration. The employment of ER-YAG laser irradiation with the adhesive loaded with N-CAP was evaluated to be effective in penetrating and occluding the opened dentinal tubules.

Resumo O laser ER-YAG e o adesivo dentário experimental à base de resina carregado com carga de apatita carbonatada funcionalizada foram usados neste estudo para avaliar a interação com a dentina em termos de penetração e oclusão dos túbulos dentinários, auxiliando no controle da hipersensibilidade dentinária (HD). Nanopartículas de apatita carbonatada esferoidal (N-CAP), com tamanho médio de 20±5 nm de diâmetro, foram sintetizadas, caracterizadas e incorporadas em um adesivo universal "All Bond Universal, Bisco, EUA", na concentração de 2% em peso. O laser Er:YAG "Lightwalker, FOTONA, EU" foi ajustado para uma saída de energia de 40mJ/pulso e repetição de pulso de 10 Hz por 10 segundos. Os espécimes de dentina foram preparados a partir da superfície vestibular de 75 molares humanos sadios extraídos. Os espécimes foram divididos aleatoriamente em cinco grupos (n=15) de acordo com o tratamento da superfície: Grupo (L): Somente laser; Grupo (LB): Laser em combinação com adesivo; Grupo (LBN): Laser em combinação com adesivo carregado com N-CAP; Grupo (B): somente adesivo; e Grupo (BN): adesivo carregado com N-CAP. A profundidade de penetração e a oclusão dos túbulos dentinários foram avaliadas por meio do Exame de Microscópio Eletrônico de Varredura Ambiental (ESEM). ANOVA de um fator foi usada para comparar os grupos, seguida pelo teste de pares para comparações múltiplas (α=0,05). Os grupos (LB) e (LBN) apresentaram a maior média de penetração dos túbulos dentinários, com uma diferença não significativa entre eles. Em contraste, os espécimes tratados apenas com laser (L) apresentaram menor penetração. O emprego da irradiação do laser ER-YAG com o adesivo carregado com N-CAP foi avaliado como eficaz na penetração e oclusão dos túbulos dentinários abertos.

Rebonding strengths of lithium disilicate and feldspathic veneers debonded by Er, Cr: YSGG laser / Resistência de recolagem de facetas de dissilicato de lítio e feldspáticas descoladas por laser Er, Cr: YSGG

Objective: The aim of this study is to identify the shear bond strength of rebonded CAD/CAM laminates made of lithium disilicate or feldspathic ceramics after debonding using Er,Cr:YSGG lasers. Material and Methods:Eighty bovine teeth (N=80) were used as a bonding substrate, which were divided into four main groups (20 each) according to the ceramic material and cement-curing mode used as follows: Group AL: lithium disilicate (IPS E.max) with light-cured resin cement, Group AD: lithium disilicate (IPS E.max) with dual-cured resin cement, Group BL: feldspathic porcelain (VITA MARK II) with light-cured resin cement, and Group BD: feldspathic porcelain (VITA MARK II) with dual-cured resin cement. Half the number of each subgroup (n=10/subdivisions) were tested for their shear bond strength without debonding, while the other half of the specimens were tested after Er,Cr:YSGG laser debonding and rebonding. A three-way ANOVA test was used to study the effect of ceramic and curing on shear bond strength. Bonferroni's post-hoc test was used for pairwise comparisons when the ANOVA test was significant. Results: After rebonding and using the light-cure mode, there was no statistically significant difference between the mean shear bond strength of the two ceramics (P-value = 0.065). However, after rebonding and using the dual-cured mode, E.max showed significantly lower shear bond strength than VITA (P-value < 0.001). Conclusion: Ceramic type, the cement's curing mode, and rebonding after laser irradiation all had a significant effect on the mean shear bond strength (AU)

Objetivo: Identificar a resistência de cisalhamento de laminados CAD/CAM recolados, feitos de cerâmica de disilicato de lítio ou feldspática, após descolamento utilizando lasers Er,Cr:YSGG. Material e Métodos: Oitenta dentes bovinos (N=80) foram utilizados como substrato de colagem, divididos em quatro grupos principais (20 cada) de acordo com o material cerâmico e o modo de cura do cimento utilizado da seguinte forma: Grupo AL: disilicato de lítio (IPS E.max) com cimento resinoso fotopolimerizável, Grupo AD: disilicato de lítio (IPS E.max) com cimento resinoso de dupla cura, Grupo BL: porcelana feldspática (VITA MARK II) com cimento resinoso fotopolimerizável, e Grupo BD: porcelana feldspática (VITA MARK II) com cimento resinoso de dupla cura. Metade do número de cada subgrupo (n=10/subdivisões) foi testada quanto à resistência de cisalhamento sem descolamento, enquanto a outra metade dos espécimes foi testada após descolamento e recolagem a laser Er,Cr:YSGG. Um teste ANOVA de três vias foi usado para estudar o efeito da cerâmica e da cura na resistência de cisalhamento. O teste post-hoc de Bonferroni foi usado para comparações pareadas quando o teste ANOVA foi significativo. Resultados: Após a recolagem e usando o modo de fotopolimerização, não houve diferença estatisticamente significativa entre a resistência de cisalhamento média das duas cerâmicas (valor de P = 0,065). No entanto, após a recolagem e usando o modo de dupla cura, o E.max apresentou resistência de cisalhamento significativamente menor que o VITA (valor de P < 0,001). Conclusão: O tipo de cerâmica, o modo de cura do cimento e a recolagem após irradiação a laser tiveram efeito significativo na resistência de cisalhamento média (AU)

Use of Phototherapy and Er-YAG Laser in the Management of Mandible Osteoradionecrosis: A Case Report.

Introduction: Osteoradionecrosis (ORN) is a secondary complication from radiotherapy, which is difficult to manage and significantly reduces the life quality of the affected patients. Case Report: A 59-year-old female patient, diagnosed with infiltration by squamous cell carcinoma in the left cervical region, underwent adjuvant cervical-facial radiotherapy with a total dose of 66.6 Gy of radiation. Eight years after the diagnosis, the patient underwent multiple extractions and, subsequently, the installation of osseointegrated implants, evolving to extensive intraoral bone exposure associated with oral cutaneous fistula. The patient was initially exposed to photobiomodulation therapy (PBMT), with a low-power laser at wavelengths of 660 nm and 808 nm, and thereafter to antimicrobial photodynamic therapy (aPDT). After an improvement in the clinical condition and resolution of the oral cutaneous fistula, a surgical procedure with the Er: YAG laser was performed to remove the remaining necrotic bone. Once the ORN condition was completely treated, the patient's oral rehabilitation was implemented by the installation of an upper mucous-supported total prosthesis and a lower implant-supported prosthesis. Conclusion: The patient is in a clinical follow-up and has no signs of bone necrosis recurrence, suggesting that low and high-power laser treatment can be an effective therapeutic alternative to resolve this condition.

Tauroursodeoxycholic Acid Supplementation in In Vitro Culture of Indicine Bovine Embryos: Molecular and Cellular Effects on the In Vitro Cryotolerance.

During embryo development, the endoplasmic reticulum (ER) acts as an important site for protein biosynthesis; however, in vitro culture (IVC) can negatively affect ER homeostasis. Therefore, the aim of our study was to evaluate the effects of the supplementation of tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, in the IVC of bovine embryos. Two experiments were carried out: Exp. 1: an evaluation of blastocyst rate, hatching kinetics, and gene expression of hatched embryos after being treated with different concentrations of TUDCA (50, 200, or 1000 µM) in the IVC; Exp. 2: an evaluation of the re-expansion, hatching, and gene expression of hatched embryos previously treated with 200 µM of TUDCA at IVC and submitted to vitrification. There was no increase in the blastocyst and hatched blastocyst rates treated with TUDCA in the IVC. However, embryos submitted to vitrification after treatment with 200 µM of TUDCA underwent an increased hatching rate post-warming together with a down-regulation in the expression of ER stress-related genes and the accumulation of lipids. In conclusion, this work showed that the addition of TUDCA during in vitro culture can improve the cryotolerance of the bovine blastocyst through the putative modulation of ER and oxidative stress.

Er:YAG laser in selective caries removal and dentin treatment with chitosan: a randomized clinical trial in primary molars.

This study evaluated the effect of chitosan on dentin treatment after selective removal of caries lesions with Er:YAG laser in reducing Streptococcus mutans, as well as its effect on the performed restorations. The sample consisted of children (aged 7 to 9 years) with active carious lesions and dentin cavitation located on the occlusal surface of deciduous molars. Eighty teeth were randomly distributed into 4 groups according to the caries removal method: Er:YAG laser (250 mJ/4 Hz) or bur and dentin surface treatment: 2.5% chitosan solution or distilled water. The bacterial load of caries-affected dentin was quantified by counting CFU/mg (n = 10). The teeth were restored and evaluated at 7 days, 6 months, and 12 months using modified USPHS criteria (n = 20). Microbiological data was analyzed by Mann-Whitney and clinical analyses were done using Kruskal-Wallis and Dunn test (α = 0.05). The results showed that the Er:YAG laser significantly reduced the amount of Streptococcus mutans (p = 0.0068). After dentin treatment with chitosan, there was a significant reduction in the amount of Streptococcus mutans for both removal methods (p = 0.0424). For the retention and secondary caries criteria, no significant differences were observed along the evaluated time (p > 0.05). The laser-treated group was rated "bravo" for discoloration (p = 0.0089) and marginal adaptation (p = 0.0003) after 6 and 12 months compared to baseline. The Er:YAG laser reduced the amount of Streptococcus mutans and the chitosan showed an additional antibacterial effect. After 1 year, the Er:YAG laser-prepared teeth, regardless of the dentin treatment, showed greater discoloration and marginal adaptation of the restorations.

Experience of a TelEmergency program in Colombia South America: descriptive observational study between 2019 and 2021.

INTRODUCTION: Colombia has 50,912,429 inhabitants, but only 50-70% of the population can effectively access health care services. The emergency room (ER) is a main contributor to the in-hospital care system since up to half of the admissions come through it. Telemedicine has become a tool to facilitate effective access to health care services, improve the timeliness of care, reduce diagnostic variability, and reduce costs associated with health. The aim of this study is to describe the experience of a Distance Emergency Care Program through Telemedicine (TelEmergency) to improve specialist access for patients at the Emergency Room (ER) in low- and medium-level care hospitals in Colombia. METHODS: An observational descriptive study of a cohort including 1,544 patients during the program's first two years was conducted. Descriptive statistics were used to analyze the available data. The data are presented with summarized statistics of sociodemographic, clinical, and patient-care variables. RESULTS: The study included a total of 1,544 patients, and the majority were adults between 60 and 79 years of age (n = 491, 32%). More than half were men (n = 832, 54%), and 68% (n = 1,057) belonged to the contributory health care regime. The service was requested from 346 municipalities, 70% (n = 1,076) from intermediate and rural settings. The most common diagnoses were related to COVID-19 (n = 356, 22%), respiratory diseases (n = 217, 14%), and cardiovascular diseases (n = 162, 10%). We observed 44% (n = 681) of local admissions either under observation (n = 53, 3%) or hospitalization (n = 380, 24%), limiting the need for hospital transfers. Program operation data revealed that 50% (n = 799) of requests were answered within two hours by the medical staff. The initial diagnosis was modified in 7% (n = 119) of the patients after being evaluated by specialists at the TelEmergency program. CONCLUSIONS: This study shows the operational data collected during the first two years after the implementation of the TelEmergency program in Colombia, the first of its kind in the country. Its implementation offered specialized timely management of patients at the ER in low- and medium-level care hospitals, where there is no availability of specialized doctors.

Impact of interorganelle coordination between the conventional early secretory pathway and autophagy in cellular homeostasis and stress response.

The conventional early secretory pathway and autophagy are two essential interconnected cellular processes that are crucial for maintaining cellular homeostasis. The conventional secretory pathway is an anabolic cellular process synthesizing and delivering proteins to distinct locations, including different organelles, the plasma membrane, and the extracellular media. On the other hand, autophagy is a catabolic cellular process that engulfs damaged organelles and aberrant cytosolic constituents into the double autophagosome membrane. After fusion with the lysosome and autolysosome formation, this process triggers digestion and recycling. A growing list of evidence indicates that these anabolic and catabolic processes are mutually regulated. While knowledge about the molecular actors involved in the coordination and functional cooperation between these two processes has increased over time, the mechanisms are still poorly understood. This review article summarized and discussed the most relevant evidence about the key molecular players implicated in the interorganelle crosstalk between the early secretory pathway and autophagy under normal and stressful conditions.

Design, synthesis and biological evaluation of fluorinated selective estrogen receptor degraders (FSERDs) --- A promising strategy for advanced ER positive breast cancer.

Although endocrine therapies involving pharmaceuticals, such as tamoxifen and aromatase inhibitors, had initially demonstrated good responses in patients with estrogen receptor-positive (ER+) breast cancer, they often led to drug resistance. ER plays a vital role in the progression of metastatic diseases. Fulvestrant, a first generation selective estrogen receptor degrader (SERD), can effectively downregulate the ER protein and inhibit its downstream signaling pathways. However, as the drug needs to be intramuscularly injected, its widespread use is limited owing to poor patient compliance. Herein, we described a novel class of orally bioavailable fluorine-substituted SERDs that exhibit improved pharmacokinetic profiles. We substituted the hydroxyl group of clinical SERD candidate 6 with a fluorine atom to diminish phase II metabolism. The subsequent structure-activity relationship (SAR) investigation identified 22h and 27b, which can effectively degrade ER in a dose-dependent manner and exhibit considerable antiproliferative potency and efficacy in vitro and in vivo. The excellent pharmacokinetic profiles of 27b render it promising candidate of clinically useful oral SERD.

Influence of different surface treatments on bond strength of a Self-Adhesive resin cement to CAD-CAM materials / Influencia de los diferentes tratamientos superficiales en la unión del cemento resinoso autoadhesivo a los materiales CAD-CAM

To evaluate the shear bond strength (SBS) of self-adhesive resin cement when used with two different computer-aided design (CAD)-computer-aided manufacturing (CAM) materials after various surface treatments. Nanoceramic resin Lava Ultimate (LU) and feldspathic ceramic Vita Mark II (VM) CAD-CAM block samples were prepared with 1.5-mm thickness, and a total of 90 samples were obtained (N=90), with five samples of each block. The samples were divided into the following five groups according to the surface treatments (n=9): group 1, untreated (control); group 2,5% hydrofluoric acid etching; group 3, Er: YAG laser irradiation; group 4, tribochemical silica coating (Cojet); and group 5, air-abrasion with Al2O3. After silane application, resin cement was applied on a transparent matrix (diameter, 3mm; height, 2mm) on the blocks. SBS was determined using a universal testing device at a crosshead speed of 1mm/min. Two-way analysis of variance (ANOVA) and Tukey's post hoc tests were used to analyze the SBS values. LU showed the highest SBS value in group 4. The average SBS values in groups 3 and were found to be lower than that in the control group (p<0.05). When VM was examined, while all surface treatments increased the SBS values significantly, the highest SBS value was observed in group 4 (p<0.05). This study revealed that all surface treatments used negatively affected the bond strength values of self-adhesive resin cement to LU, except for Cojet application. The SBS values of resin cement with VM increased in all surface treatment application groups.

Evaluar la resistencia de unión al corte (SBS) del cemento de resina autoadhesivo cuando se utiliza con dos materiales diferentes de diseño asistido por computadora (CAD) y fabricación asistida por computadora (CAM) después de varios tratamientos superficiales. Se prepararon muestras de bloques CAD-CAM de resina Lava Ultimate (LU) y cerámica feldespática Vita Mark II (VM) con un espesor de 1,5mm, y se obtuvieron un total de 90 muestras (N=90), con cinco muestras de cada bloque. Las muestras se dividieron en los siguientes cinco grupos según los tratamientos superficiales (n=9): grupo 1, sin tratar (control); grupo 2, grabado con ácido fluorhídrico al 5%; grupo 3, irradiación con láser Er: YAG; grupo 4, recubrimiento triboquímico de sílice (Cojet); y grupo 5, aire-abrasión con Al2O3. Después de la aplicación de silano, se aplicó cemento de resina sobre una matriz transparente (diámetro, 3mm; altura, 2mm) sobre los bloques. La SBS se determinó usando un dispositivo de prueba universal a una velocidad de cruceta de 1mm/min. Se utilizaron análisis de varianza bidireccional (ANOVA) y pruebas post hoc de Tukey para analizar los valores de SBS. LU mostró el valor más alto de SBS en el grupo 4. Los valores promedio de SBS en los grupos 3 y fueron más bajos que en el grupo de control (p<0,05). Cuando se examinó VM, mientras que todos los tratamientos superficiales aumentaron significativamente los valores de SBS, el valor más alto de SBS se observó en el grupo 4 (p<0,05). Este estudio reveló que todos los tratamientos de superficie utilizados afectaron negativamente los valores de resistencia de la unión del cemento de resina autoadhesivo a LU, a excepción de la aplicación Cojet. Los valores de SBS del cemento de resina con VM aumentaron en todos los grupos de aplicación de tratamiento de superficie.