Best Bisphosphonate Threshold for 10-Year Vertebral and Non-vertebral Fracture Mitigation.

AIMS: This study was aimed to determine the ideal thresholds for bone mineral densities in our tested Jordanian cohort to initiate bisphosphonate pharmacotherapeutics in order to establish a national protocol for prescribing bisphosphonates that is tailored to the local population, rather than relying on global T and Z scores standards. METHODS: This retrospective study analyzed the entire population of adult patients at Prince Rashid bin Al-Hussein Hospital Rehabilitation and Rheumatology Center between August and October 2023 for the purpose of screening, monitoring, diagnosing, and treating osteoporosis. The study included 328 clients suspected to have osteoporosis, selected based on criteria such as primary osteoporosis or potential secondary osteoporosis. The study used two fracture risk assessment tools (FRAX) dichotomized states: <3% (negative state) and ≥3% (positive state), as well as <20% (negative state) and ≥20% (positive state). Binary logistic regression analysis, receiver-operating characteristic, and sensitivity analysis tests were performed sequentially to analyze the performance of prognosticators and sensitivity indices to evaluate their sensitivity, specificity, and accuracy indexes. RESULTS: The study involved 328 clients at a rehabilitation clinic, with 82.62% (271) females and 17.38% (57) males. The majority were aged between 60 and 69 years, with a slightly higher obesity rate in females. The study found that initiation of bisphosphonates in Jordanian cohorts with optimal bone mineral density thresholds of 0.775 g/cm2 may significantly reduce the risk of hip osteoporosis over 10 years, with sensitivity, specificity, and accuracy indexes of 78.6%, 88.46%, and 50.61%, respectively, with a performance utility of 0.896±0.026 (p-value<0.001), 95% CI (0.846-0.946). CONCLUSION: Due to ethnicity differences, exploring regional or national specific bone mineral density thresholds for bisphosphonates initiation may be a better optional choice than adopting global T-score standards.

Palladium and platinum complexes based on pyridine bases induced anticancer effectiveness via apoptosis protein signaling in cancer cells.

Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes [Pd(SCN)2(4-Acpy)2] (1), [Pd(N3)2(4-Acpy)2] (2) [Pd(paOH)2].2Cl (3) and [Pt(SCN)2(paO)2] (4) were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes 1-4 was confirmed using spectroscopic and X-ray crystallography methods. Complexes 1-4 have similar features in isomerism that include the trans coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes 1-4 was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes 1-4 with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC50 of complex 1 was lowest in MCF-7 cells and complex 2 in T47D cells. Complex 4 has the highest effectiveness on HCT116. The selective index (SI) of complexes 1-4 has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex 2 and platinum complex 4 exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes 1-4 and cisplatin could induce p53. All complexes 1-4 elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.

The Actin Cytoskeleton as a Regulator of Proteoglycan 4.

OBJECTIVE: The superficial zone (SZ) of articular cartilage is responsible for distributing shear forces for optimal cartilage loading and contributes to joint lubrication through the production of proteoglycan 4 (PRG4). PRG4 plays a critical role in joint homeostasis and is chondroprotective. Normal PRG4 production is affected by inflammation and irregular mechanical loading in post-traumatic osteoarthritis (PTOA). THe SZ chondrocyte (SZC) phenotype, including PRG4 expression, is regulated by the actin cytoskeleton in vitro. There remains a limited understanding of the regulation of PRG4 by the actin cytoskeleton in native articular chondrocytes. The filamentous (F)-actin cytoskeleton is a potential node in crosstalk between mechanical stimulation and cytokine activation and the regulation of PRG4 in SZCs, therefore developing insights in the regulation of PRG4 by actin may identify molecular targets for novel PTOA therapies. MATERIALS AND METHODS: A comprehensive literature search on PRG4 and the regulation of the SZC phenotype by actin organization was performed. RESULTS: PRG4 is strongly regulated by the actin cytoskeleton in isolated SZCs in vitro. Biochemical and mechanical stimuli have been characterized to regulate PRG4 and may converge upon actin cytoskeleton signaling. CONCLUSION: Actin-based regulation of PRG4 in native SZCs is not fully understood and requires further elucidation. Understanding the regulation of PRG4 by actin in SZCs requires an in vivo context to further potential of leveraging actin arrangement to arthritic therapeutics.

Antibacterial effectiveness of photo-sonodynamic treatment by methylene blue-incorporated poly(D, L-lactide-co-glycolide) acid nanoparticles to disinfect root canals.

AIM: This in-vitro investigation aimed to assess the antibacterial effectiveness of photo-sonodynamic treatment using methylene blue (MTB)-incorporated poly(D, L-Lactide-Co-Glycolide) acid (PLGA)-nanoparticles for the disinfection of root canals. METHODS: The synthesis of PLGA nanoparticles was achieved using a solvent displacement technique. The morphological and spectral characterization of the formulated PLGA nanoparticles were carried out using scanning electron microscopy (SEM) and Transformed-Fourier infrared spectroscopy (TFIR), respectively. One hundred human premolar teeth were sterilized and then their root canals were infected with Enterococcus faecalis (E. faecalis). Later, the bacterial viability evaluation of the following 5 research groups was conducted: (a) G-1: specimens treated with a diode laser; (b) G-2: specimens treated with antimicrobial photodynamic therapy (aPDT) and 50 µg/mL of MTB-incorporated PLGA nanoparticles; (c) G-3: specimens treated with ultrasound (US); (d) G-4: specimens treated with US and 50 µg/mL of MTB-incorporated PLGA nanoparticles; and (e) G-5: control group consisting of specimens that did not undergo any treatment. RESULTS: Under SEM, the nanoparticles exhibited a uniform spherical shape and were around 100 nm. The formulated nanoparticles' size was validated through zeta potential analysis utilizing dynamic light scattering (DLS). The TFIR images of both PLGA nanoparticles and MTB-incorporated PLGA nanoparticles exhibited absorption bands ranging from around 1000 to 1200/cm and nearly from 1500 to 1750/cm. The G-5 samples (control group) demonstrated the greatest viability against E. faecalis, followed by G-3 (US-conditions specimens), G-1 (diode laser-conditioned specimens), G-2 (aPDT + MTB-incorporated PLGA-nanoparticles-conditioned specimens), and G-5 (US + MTB-incorporated PLGA-nanoparticles-conditioned specimens). Significant statistical differences (p < 0.05) were observed among all research groups, including both the experimental groups and control group. CONCLUSION: The combination of US via MTB-incorporated PLGA nanoparticles exhibited the most effective eradication of E. faecalis, suggestive of a promising therapeutic modality against E. faecalis for disinfecting root canals with complex and challenging anatomy.

The adhesive strength of fiber post-to-canal dentin with Aniline green, Fotoenticine activated by PDT, green tea, and ozone as a final irrigant.

AIM: The effect of novel final disinfection protocols Malachite green (MG), Fotoenticine® (FTC), Green tea extract (GTE), and Ozonated water (OW) on the bond strength of prefabricated glass fiber posts (PGFP) adhered to canal dentin. MATERIAL AND METHOD: The canals of fifty premolars with closed apices were cleansed and obturated. The specimens were randomly assigned to one of five groups based on the final irrigant used, with the control group receiving NaOCl+EDTA and the experimental groups receiving MG, FTC, OW, and GTE. The GFP was cemented with a self-etching, dual-cure paste; the bond strength was estimated with a universal testing machine; and failure analysis was conducted with a stereomicroscope. RESULTS: The highest PBS was observed in the coronal third of Group 4 (using ozonated water as the final irrigant), whereas the lowest bond integrity was observed in the apical section of Group 2 (1.02-0.54 MPa) using Malachite green as the final irrigant. Group 1, Group 4, and Group 5 exhibited no significant difference in the bond integrity of GFP to dentin when compared to Group 2 (p>0.05). In addition, comparable bond score values were obtained for Groups 2 and 3 (p>0.05). CONCLUSION: The results of this study suggest that OW and GTE may be effective final disinfectants for root canals, as they increase the bond strength of resin-luting cement.

Coffee Staining and Simulated Brushing Induced Color Changes and Surface Roughness of 3D-Printed Orthodontic Retainer Material.

This in vitro study evaluated the influence of combined coffee staining and simulated brushing-induced color changes and surface roughness on 3D-printed orthodontic retainers. Specimens measuring 10 × 10 × 0.75 mm3 were obtained either by conventional vacuum forming or 3D printing at four print angulations (0°, 15°, 30°, and 45°) (n = 10). The prepared specimens were immersed in a coffee beverage and then mechanically brushed using a simulating device. The specimen's color difference (ΔE) and surface roughness (Ra) were quantified using a spectrophotometer and a non-contact profilometer, respectively. The highest and lowest mean ΔE values were recorded for the 3D-printed-45° (4.68 ± 2.07) and conventional (2.18 ± 0.87) groups, respectively. The overall mean comparison of ΔE between the conventional and 3D-printed groups was statistically significant (p < 0.01). After simulated brushing, all groups showed a statistically significant increase in the Ra values (p < 0.01). The highest Ra was in the 3D-printed-45° (1.009 ± 0.13 µm) and conventional (0.743 ± 0.12 µm) groups, respectively. The overall ΔE of 3D-printed orthodontic retainers was not comparable to conventional VFRs. Among the different angulations used to print the retainers, 15° angulations were the most efficient in terms of color changes and surface roughness and were comparable to conventional VFRs.

A Quality Improvement Initiative to Reduce Unnecessary Screening Chest Radiographs in a Pediatric ICU.

BACKGROUND: The Critical Care Societies Collaborative included not ordering diagnostic tests at regular intervals as one of their Choosing Wisely initiatives. A reduction in unnecessary chest radiographs (CXRs) can help reduce exposure to radiation and eliminate health care waste. We aimed to reduce daily screening CXRs in a pediatric ICU (PICU) by 20% from baseline within 4 months of implementation of CXR criteria. METHODS: All intubated patients in the PICU were included in this quality improvement project. Patients with tracheostomies were excluded. We developed criteria delineating which patients were most likely to benefit from a daily screening CXR, and these criteria were discussed for each patient on rounds. Patients on extracorporeal membrane oxygenation, on high-frequency oscillatory ventilation, or on high support on conventional mechanical ventilation were included as needing a daily screening CXR. We tracked the percentage of intubated subjects receiving a screening CXR as an outcome measure. Unplanned extubations and the number of non-screening CXRs per intubated subject were followed as balancing measures. RESULTS: The percentage of intubated subjects receiving a daily screening CXR was reduced from 79% to 31%. There was no increase in frequency of unplanned extubations or number of non-screening CXRs. With an estimated subject charge of roughly $270 and hospital cost of $54 per CXR, this project led to an estimated $300,000 in patient charge savings and $60,000 in hospital cost savings. CONCLUSIONS: Adopting criteria to delineate which patients are most likely to benefit from screening CXRs can lead to a reduction in the percentage of intubated patients receiving screening CXRs without appearing to increase harm.

Cosmeceutical formulations of pro-vitamin E phosphate: In-vitro release testing and dermal penetration into excised human skin.

Long-term exposure to solar radiation can lead to skin damage such as photoageing, and photocarcinogenesis. This can be prevented by topically applying α-tocopherol phosphate (α-TP). The major challenge is that a significant amount of α-TP needs to reach viable skin layers for effective photoprotection. This study aims to develop candidate formulations of α-TP (gel-like, solution, lotion, and gel), and investigate formulation characteristics' effect on membrane diffusion and human skin permeation. All the formulations developed in the study had an appealing appearance and no signs of separation. All formulations had low viscosity and high spreadability except the gel. The flux of α-TP through the polyethersulfone membrane was the highest for lotion (6.63 ±â€¯0.86 mg/cm2/h), followed by control gel-like (6.14 ±â€¯1.76 mg/cm2/h), solution (4.65 ±â€¯0.86 mg/cm2/h), and gel (1.02 ±â€¯0.22 mg/cm2/h). The flux of α-TP through the human skin membrane was numerically higher for lotion compared to the gel-like (328.6 vs.175.2 µg/cm2/h). The lotion delivered 3-fold and 5-fold higher α-TP in viable skin layers at 3 h and 24 h, respectively, compared to that of the gel-like. The low skin membrane penetration rate and deposition of α-TP in viable skin layers were observed for the solution and gel. Our study demonstrated that dermal penetration of α-TP was influenced by characteristics of formulation such as formulation type, pH, and viscosity. The α-TP in the lotion scavenged higher DPPH free radicals compared to that of gel-like (almost 73% vs. 46%). The IC50 of α-TP in lotion was significantly lower than that of gel-like (397.2 vs. 626.0 µg/mL). The preservative challenge test specifications were fulfilled by Geogard 221 and suggested that the combination of benzyl alcohol and Dehydroacetic Acid effectively preserved 2% α-TP lotion. This result confirms the suitability of the α-TP cosmeceutical lotion formulation employed in the present work for effective photoprotection.

A Quality Improvement Initiative to Reduce Unneeded Screening Chest Radiographs in a Pediatric Cardiovascular ICU.

BACKGROUND: Adult critical care and radiographical societies have recommended changing practice from routine screening radiographs to on-demand chest radiographs (CXRs) for stable mechanically ventilated adult patients. There are no similar recommendations for patients in the pediatric ICU. Reducing the frequency with which unneeded CXRs are obtained can decrease radiation exposure and reduce waste, a substantial contributor to rising health care costs. We aimed to reduce unneeded daily screening CXRs in a pediatric cardiovascular ICU (CICU) by 20% in 6 months. METHODS: Criteria delineating which subjects in the CICU required daily screening CXRs were created and added to the daily rounding sheet for discussion for each subject. The primary goal of this study was to reduce CXRs in mechanically ventilated subjects as our previous practice had been to order daily CXRs. Respiratory therapists increased the frequency of evaluating and documenting endotracheal tube positioning prior to the initiation of this project. The outcome measure was the percentage subjects who received a daily screening CXR. The ratio of daily screening CXRs to the number of total CXRs ordered and unplanned extubations were followed as balancing measures. RESULTS: The number of subjects who received a daily screening CXR decreased from a baseline of 67% to 44% over the course of this project. There was no change in the ratio of daily screening CXRs to the number of total CXRs ordered or an increase in unplanned extubations. With an estimated cost of $268 per CXR, a reduction of 33% in routine screening CXRs saves an estimated $250,000 annually. CONCLUSIONS: A decrease in daily screening CXRs can be sustained through the development of specific criteria to determine which patients need screening radiographs. This can be achieved without an increase in CXRs obtained at other times throughout the day or an increase in unplanned extubations. This eliminates unneeded health care expenditures, improves resource allocation for radiology technicians, and decreases disruptive interventions for patients.

Highly efficient reprogrammable mouse lines with integrated reporters to track the route to pluripotency.

Revealing the molecular events associated with reprogramming different somatic cell types to pluripotency is critical for understanding the characteristics of induced pluripotent stem cell (iPSC) therapeutic derivatives. Inducible reprogramming factor transgenic cells or animals-designated as secondary (2°) reprogramming systems-not only provide excellent experimental tools for such studies but also offer a strategy to study the variances in cellular reprogramming outcomes due to different in vitro and in vivo environments. To make such studies less cumbersome, it is desirable to have a variety of efficient reprogrammable mouse systems to induce successful mass reprogramming in somatic cell types. Here, we report the development of two transgenic mouse lines from which 2° cells reprogram with unprecedented efficiency. These systems were derived by exposing primary reprogramming cells containing doxycycline-inducible Yamanaka factor expression to a transient interruption in transgene expression, resulting in selection for a subset of clones with robust transgene response. These systems also include reporter genes enabling easy readout of endogenous Oct4 activation (GFP), indicative of pluripotency, and reprogramming transgene expression (mCherry). Notably, somatic cells derived from various fetal and adult tissues from these 2° mouse lines gave rise to highly efficient and rapid reprogramming, with transgene-independent iPSC colonies emerging as early as 1 wk after induction. These mouse lines serve as a powerful tool to explore sources of variability in reprogramming and the mechanistic underpinnings of efficient reprogramming systems.

Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation.

Emerging evidence associates translation factors and regulators to tumorigenesis. However, our understanding of translational changes in cancer resistance is still limited. Here, we generated an enzalutamide-resistant prostate cancer (PCa) model, which recapitulated key features of clinical enzalutamide-resistant PCa. Using this model and poly(ribo)some profiling, we investigated global translation changes that occur during acquisition of PCa resistance. We found that enzalutamide-resistant cells exhibit an overall decrease in mRNA translation with a specific deregulation in the abundance of proteins involved in mitochondrial processes and in translational regulation. However, several mRNAs escape this translational downregulation and are nonetheless bound to heavy polysomes in enzalutamide-resistant cells suggesting active translation. Moreover, expressing these corresponding genes in enzalutamide-sensitive cells promotes resistance to enzalutamide treatment. We also found increased association of long non-coding RNAs (lncRNAs) with heavy polysomes in enzalutamide-resistant cells, suggesting that some lncRNAs are actively translated during enzalutamide resistance. Consistent with these findings, expressing the predicted coding sequences of known lncRNAs JPX, CRNDE and LINC00467 in enzalutamide-sensitive cells drove resistance to enzalutamide. Taken together, this suggests that aberrant translation of specific mRNAs and lncRNAs is a strong indicator of PCa enzalutamide resistance, which points towards novel therapeutic avenues that may target enzalutamide-resistant PCa.

The Holistic Review on Occurrence, Biology, Diagnosis, and Treatment of Oral Squamous Cell Carcinoma.

A prevalent head and neck cancer type is oral squamous cell carcinoma (OSCC). It is widespread and associated with a high death rate of around 50% in some regions of the world. We discuss the likelihood of developing OSCC and the impact of age in this review. Prior to examining the vast array of diagnostic indicators, a brief explanation of the biology of the disease is addressed. Finally, the therapeutic strategies for OSCC are listed. The complete literature for this study was compiled by searching Google Scholar and PubMed using the terms "OSCC," "oral squamous cell carcinoma," "diagnosis of OSCC," "oral cancer," and "biomarkers and OSCC." The research finds that OSCC has several critical parameters with a lot of room for additional in-depth study.

Determining epigenetic memory in kidney proximal tubule cell derived induced pluripotent stem cells using a quadruple transgenic reprogrammable mouse.

The majority of nucleated somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs). The process of reprogramming involves epigenetic remodelling to turn on pluripotency-associated genes and turn off lineage-specific genes. Some evidence shows that iPSCs retain epigenetic marks of their cell of origin and this "epigenetic memory" influences their differentiation potential, with a preference towards their cell of origin. Here, we reprogrammed proximal tubule cells (PTC) and tail tip fibroblasts (TTF), from a reprogrammable mouse to iPSCs and differentiated the iPSCs to renal progenitors to understand if epigenetic memory plays a role in renal differentiation. This model allowed us to eliminate experimental variability due to donor genetic differences and transfection of the reprogramming factors such as copy number and integration site. In this study we demonstrated that early passage PTC iPSCs and TTF iPSCs expressed low levels of renal progenitor genes and high levels of pluripotency-associated genes, and the transcriptional levels of these genes were not significantly different between PTC iPSCs and TTF iPSCs. We used ChIP-seq of H3K4me3, H3K27me3, H3K36me3 and global DNA methylation profiles of PTC iPSCs and TTF iPSCs to demonstrate that global epigenetic marks were not different between the cells from the two different sets of tissue samples. There were also no epigenetic differences observed when kidney developmental genes and pluripotency-associated genes were closely examined. We did observe that during differentiation to renal progenitor cells the PTC iPSC-derived renal cells expressed higher levels of three renal progenitor genes compared to progenitors derived from TTF iPSCs but the underlying DNA methylation and histone methylation patterns did not suggest an epigenetic memory basis for this.

Histological and hemodynamic characterization of corpus luteum throughout the luteal phase in pregnant and non-pregnant buffalos in relation to nitric oxide levels based on its anatomical determination.

This study aims to compare the complete growth and development of corpus luteum (CL) in domestic buffalos from day 5 until day 40 after ovulation either in pregnant or non-pregnant animals and whether luteal vascularity (LV) with progesterone (P4) and nitric oxide (NO) could determine luteal functionality or not. Pluriparous buffalos (Bubalus bubalis) were categorized as pregnant (n = 6) or non-pregnant (n = 9) after pregnancy check at day 25. Animals were subjected to ultrasound analysis to determine the CL area (cm2) and LV. Blood sampling was performed following the Doppler examination. Ovarian tissue samples from non-pregnant buffalo genitalia (n = 18) and early pregnant buffalo genitalia (n = 3) were collected from great abattoirs. Luteal Doppler indices were lower in the pregnant group, while peak systolic velocity (PSV) was increased (p < 0.05) in the same pregnant females. Both P4 and NOMs were elevated (p < 0.05) in the pregnant group. There was a positive correlation (p < 0.01) between P4 and CL PSV. Based on our macroscopical examination, the CL of non-pregnant buffalos was classified into four stages. Histologically, stage I showed that CL was covered by a highly vascularized connective tissue (CT) capsule. It consisted of small and large lutein cells, whereas stage II was similar to stage I except for the presence of numerous fibroblast cells and vacuolated cells. Stage III was characterized by increasing the number of collagen fibers and the thickness of the blood vessels. Stage IV revealed thickening of the CT capsule and septae, regressed capillaries and arterioles, in addition to shrunken degenerated lutein cells. CL of pregnant buffalos revealed the same structure as CL at stage II. CL area was increased in the pregnant group. The collective data suggested that evaluation of the luteal artery could be extremely helpful to determine the potential benefits of colored and pulsed Doppler in CL vascularization assessment in both luteal and early pregnancy phases.

Ovarian, uterine, and luteal vascular perfusions during follicular and luteal phases in the adult cyclic female rabbits with special orientation to their histological detection of hormone receptor.

Understanding the does reproductive hemodynamic changes during the estrous cycle is crucial for improving reproductive competence and fertility potential in this species. The objective of this study is to investigate the hemodynamic variations in ovarian (OA) and uterine (UA) arteries, histological and morphometric changes in ovarian and uterine tissues throughout the follicular (FP) and luteal (LP) phases in rabbits and determine estrogen (ER), progesterone (PR) receptors, and vascular endothelial growth factor (VEGF) distributions using immunohistochemistry.Fourteen adults pluriparous New Zealand rabbits were divided into rabbits at the FP (Day - 1; n = 7) and those at the LP (Day 9; n = 7). Animals were subjected to Doppler, hormonal (estrogen [E2], progesterone [P4], insulin-like growth factor [ILGF], and VEGF), histological, and immunohistochemical analyses. In LP, OA Doppler indices were significantly increased, whereas peak systolic velocity (PSV) was decreased compared with that in FP. UA Doppler indices were significantly decreased in the LP, whereas PSV was increased (P < 0.05). E2 levels were increased in the FP, whereas P4 levels were increased in the LP. The morphometric analysis of uterine tissues during the LP revealed an increase in the mean uterine endometrium length, endometrial connective tissue area percentage (%), endometrial glands number, myometrial area (%) and thickness. Furthermore, ovarian follicles and corpus luteum (CL) displayed strong positive immunoreactivity for ER, PR, and VEGF-A during both phases. The ovarian sections displayed a substantial (P < 0.05) increase in the area % of VEGF-A in the ovarian follicles during FP while in the CL during LP. Conversely, area percentage of VEGF-A immunoreactivity in the uterine luminal and glandular epithelia during the FP and LP revealed no differences. However, the number of VEGF-A-stained blood capillaries revealed an increase during LP than FP. In conclusion, this study demonstrated for the first time the changes in both ovarian and uterine arteries during two different phases of the rabbit cycle in relation to the histo-morphometric analysis and distribution of ER, PR, and VEGF-A, which regulate uterine functions that play a role in reproduction.

Oncogenic ZMYND11-MBTD1 fusion protein anchors the NuA4/TIP60 histone acetyltransferase complex to the coding region of active genes.

A recurrent chromosomal translocation found in acute myeloid leukemia leads to an in-frame fusion of the transcription repressor ZMYND11 to MBTD1, a subunit of the NuA4/TIP60 histone acetyltransferase complex. To understand the abnormal molecular events that ZMYND11-MBTD1 expression can create, we perform a biochemical and functional characterization comparison to each individual fusion partner. ZMYND11-MBTD1 is stably incorporated into the endogenous NuA4/TIP60 complex, leading to its mislocalization on the body of genes normally bound by ZMYND11. This can be correlated to increased chromatin acetylation and altered gene transcription, most notably on the MYC oncogene, and alternative splicing. Importantly, ZMYND11-MBTD1 expression favors Myc-driven pluripotency during embryonic stem cell differentiation and self-renewal of hematopoietic stem/progenitor cells. Altogether, these results indicate that the ZMYND11-MBTD1 fusion functions primarily by mistargeting the NuA4/TIP60 complex to the body of genes, altering normal transcription of specific genes, likely driving oncogenesis in part through the Myc regulatory network.

MRG Proteins Are Shared by Multiple Protein Complexes With Distinct Functions.

MRG15/MORF4L1 is a highly conserved protein in eukaryotes that contains a chromodomain (CHD) recognizing methylation of lysine 36 on histone H3 (H3K36me3) in chromatin. Intriguingly, it has been reported in the literature to interact with several different factors involved in chromatin modifications, gene regulation, alternative mRNA splicing, and DNA repair by homologous recombination. To get a complete and reliable picture of associations in physiological conditions, we used genome editing and tandem affinity purification to analyze the stable native interactome of human MRG15, its paralog MRGX/MORF4L2 that lacks the CHD, and MRGBP (MRG-binding protein) in isogenic K562 cells. We found stable interchangeable association of MRG15 and MRGX with the NuA4/TIP60 histone acetyltransferase/chromatin remodeler, Sin3B histone deacetylase/demethylase, ASH1L histone methyltransferase, and PALB2-BRCA2 DNA repair protein complexes. These associations were further confirmed and analyzed by CRISPR tagging of endogenous proteins and comparison of expressed isoforms. Importantly, based on structural information, point mutations could be introduced that specifically disrupt MRG15 association with some complexes but not others. Most interestingly, we also identified a new abundant native complex formed by MRG15/X-MRGBP-BRD8-EP400NL (EP400 N-terminal like) that is functionally similar to the yeast TINTIN (Trimer Independent of NuA4 for Transcription Interactions with Nucleosomes) complex. Our results show that EP400NL, being homologous to the N-terminal region of NuA4/TIP60 subunit EP400, creates TINTIN by competing for BRD8 association. Functional genomics indicate that human TINTIN plays a role in transcription of specific genes. This is most likely linked to the H4ac-binding bromodomain of BRD8 along the H3K36me3-binding CHD of MRG15 on the coding region of transcribed genes. Taken together, our data provide a complete detailed picture of human MRG proteins-associated protein complexes, which are essential to understand and correlate their diverse biological functions in chromatin-based nuclear processes.

Efficacy of antimicrobial photodynamic therapy versus antiviral therapy in the treatment of herpetic gingivostomatitis among children: Aa randomized controlled clinical trial.

AIM: The aim of the present study was to evaluate the effect of antimicrobial photodynamic therapy (aPDT) as an adjunctive treatment to topical antiviral therapy for the treatment of children having herpetic gingivostomatitis. MATERIALS AND METHODS: 45 individuals (age group 12-18 years) with herpetic gingivostomatitis (HG) were divided into three groups on the basis of provision of treatment. (a) Group A: topical anti-viral therapy (TAT) (n = 14, mean age = 17.0 years) (b) Group B: antimicrobial photodynamic therapy (aPDT) (n = 15, mean age =17.7 years) and (c) Group C: topical anti-viral therapy + adjunctive aPDT (n = 16, mean age = 18.0 years) respectively. Pain scores [visual analogue scale (VAS) and McGill Pain Questionnaire (MPQ)] were assessed and HSV-1 was quantified. ENZYME LINKED IMMUNOSORBENT ASSAY (ELISA) was used to compute the pro-inflammatory cytokine including interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α). The analysis of the mean values and inter group comparisons were evaluated with the Mann-Whitney test. The Friedman test was used to establish the comparison of the changes observed in HSV quantification, pain scores, and pro-inflammatory cytokines. ANOVA tests were employed for the quantification of differences observed at follow-ups. The assessments for the clinical trial were done at baseline, immediate after post-op, two, and four weeks, and three and six months respectively. RESULTS: According to the analysis of the data obtained after the clinical assessment, the three groups reported a decrease in the pain scores, HSV-1 quantification and levels of the pro-inflammatory cytokines. However, Group C (TAT + aPDT) reported improvement in the observed parameters which was statistically significant in comparison to Group A (TAT) and Group B (aPDT) respectively. CONCLUSION: Antimicrobial photodynamic therapy (aPDT) in conjunction with topical antiviral therapy (TAT) helped in reducing the pain scores and pro-inflammatory cytokine levels in herpetic gingivostomatitis among children.

Signal requirement for cortical potential of transplantable human neuroepithelial stem cells.

The cerebral cortex develops from dorsal forebrain neuroepithelial progenitor cells. Following the initial expansion of the progenitor cell pool, these cells generate neurons of all the cortical layers and then astrocytes and oligodendrocytes. Yet, the regulatory pathways that control the expansion and maintenance of the progenitor cell pool are currently unknown. Here we define six basic pathway components that regulate proliferation of cortically specified human neuroepithelial stem cells (cNESCs) in vitro without the loss of cerebral cortex developmental potential. We show that activation of FGF and inhibition of BMP and ACTIVIN A signalling are required for long-term cNESC proliferation. We also demonstrate that cNESCs preserve dorsal telencephalon-specific potential when GSK3, AKT and nuclear CATENIN-ß1 activity are low. Remarkably, regulation of these six pathway components supports the clonal expansion of cNESCs. Moreover, cNESCs differentiate into lower- and upper-layer cortical neurons in vitro and in vivo. The identification of mechanisms that drive the neuroepithelial stem cell self-renewal and differentiation and preserve this potential in vitro is key to developing regenerative and cell-based therapeutic approaches to treat neurological conditions.

Topographical changes and bactericidal efficacy of antimicrobial photodynamic therapy on titanium implant surface.

BACKGROUND: reExtensive rsearch has been done on various disinfection modalities used to achieve an aseptic implant surface. However, the bacterial efficacy and the topographical alterations resulting from the use of these techniques have never been compared. OBJECTIVE: This study aimed to evaluate and compare the disinfection efficacy and surface changes on a bacteria contaminated titanium block following application of various disinfectants. METHOD: Ultrasonically cleaned titanium blocks were contaminated with Porphyromonas gingivalis and Tannerella forsythia. The infected titanium implants were randomly divided into four experimental groups and decontaminated using antimicrobial photodynamic therapy (aPDT), laser therapy, chlorhexidine and hydrogen peroxide. Bacterial viability and surface changes following decontamination were analyzed. RESULT: Bacterial viability decreased in all the groups, with aPDT having the highest reduction. Surface roughness remained unchanged whereas the contact angle lessened in the aPDT group. CONCLUSION: aPDT could possibly be a suitable alternative to other disinfection regimen to treat periimplantitis.