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Nitroimidazoles comprise a class of broad-spectrum anti-microbial drugs with efficacy against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. Among these drugs, metronidazole (MTZ) is commonly used with other antibiotics to prevent infection in open fractures. However, the effect of MTZ on bone remains understudied. In this paper, we evaluated six nitroimidazole drugs for their impact on osteoblast differentiation and identified MTZ as having the highest osteogenic effect. MTZ enhanced bone regeneration at the femur osteotomy site in osteopenic ovariectomized (OVX) rats at the human equivalent dose. Moreover, in OVX rats, MTZ significantly improved bone mass and strength and improved microarchitecture compared to the vehicle-treated rats, which was likely achieved by an osteogenic mechanism attributed to the stimulation of the Wnt pathway in osteoblasts. To mitigate the reported neurological and genotoxic effects of MTZ, we designed an injectable sustained-release in situ gel formulation of the drug that improved fracture healing efficacy by 3.5-fold compared to oral administration. This enhanced potency was achieved through a significant increase in the circulating half-life and bioavailability of MTZ. We conclude that MTZ exhibits osteogenic effects, further accentuated by our sustained-release delivery system, which holds promise for enhancing bone regeneration in open fractures. [ABSTRACT FROM AUTHOR]

Biomedical imaging devices, in general, have been made and used a lot lately to examine the insides of the body during diagnostic and analytic procedures. Biomedical imaging gives accurate information about metabolites, which can be used to find and classify diseases because it is not invasive. For the study of cervical cancer (CC), the pap smear is a crucial type of biological imaging. CC is a crucial reason to enhance the rate of women's mortalities. Proper screening of pap smear images is critical for assisting in the early detection and analysis of CC. Computer‐aided systems for cancerous cell recognition need well established artificial intelligence (AI) methods. In this study, we introduce an automated Cervical Precancerous Lesion Classification using Quantum Invasive Weed Optimization with Deep Learning (CPLC‐QIWODL) on biomedical pap smear images. The presented CPLC‐QIWODL technique examines the pap smear images for cervical cancer classification. To do so, the presented CPLC‐QIWODL technique pre‐processes the biomedical images using a Gabor filtering (GF) approach. Moreover, the CPLC‐QIWODL technique uses a deep convolutional neural network‐based SqueezeNet system for feature extraction. Furthermore, the hyperparameter tuning of the SqueezeNet methodology takes place using the QIWO technique, showing the novelty of the work. Finally, to classify CC, the deep variational autoencoder (DVAE) model is applied. The experimental result analysis of the CPLC‐QIWODL technique is tested using a benchmark medical image database. Extensive comparative results demonstrated the enhanced outcomes of the CPLC‐QIWODL technique over other existing algorithms, with a maximum accuracy of 99.07%. [ABSTRACT FROM AUTHOR]

This editorial discusses the role of posttranslational modifications (PTMs) in cancer biology. It highlights various articles published in the journal "Frontiers in Oncology" that explore PTMs of key proteins and their association with cancer pathogenesis. The articles cover topics such as phosphorylation, ubiquitination, and acetylation, and their impact on protein function and cancer progression. The findings emphasize the importance of PTMs in understanding cancer biology and potentially identifying novel biomarkers and therapeutic targets. [Extracted from the article]

A few ubiquitin ligases have been shown to target Runx2, the key osteogenic transcription factor and thereby regulate bone formation. The regulation of Runx2 expression and function are controlled both at the transcriptional and posttranslational levels. Really interesting new gene (RING) finger ubiquitin ligases of which RNF138 is a member are important players in the ubiquitin‐proteasome system, contributing to the regulation of protein turnover and cellular processes. Here, we demonstrated that RNF138 negatively correlated with Runx2 protein levels in osteopenic ovariectomized rats which implied its role in bone loss. Accordingly, RNF138 overexpression potently inhibited osteoblast differentiation of mesenchyme‐like C3H10T1/2 as well primary rat calvarial osteoblast (RCO) cells in vitro, whereas overexpression of catalytically inactive mutant RNF138Δ18‐58 (lacks RING finger domain) had mild to no effect. Contrarily, RNF138 depletion copiously enhanced endogenous Runx2 levels and augmented osteogenic differentiation of C3H10T1/2 as well as RCOs. Mechanistically, RNF138 physically associates within multiple regions of Runx2 and ubiquitinates it leading to its reduced protein stability in a proteasome‐dependent manner. Moreover, catalytically active RNF138 destabilized Runx2 which resulted in inhibition of its transactivation potential and physiological function of promoting osteoblast differentiation leading to bone loss. These findings underscore the functional involvement of RNF138 in bone formation which is primarily achieved through its modulation of Runx2 by stimulating ubiquitin‐mediated proteasomal degradation. Thus, our findings indicate that RNF138 could be a promising novel target for therapeutic intervention in postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

The present study aims to analyze the role of microRNA‐1 in the regulation of skeletal muscle loss under hypobaric hypoxia (HH). Male Sprague Dawley rats (n = 10) weighing 230–250 g are divided into two groups, control and HH exposure for 7 days at 25 000 ft. After the hypoxia exposure, the animals are sacrificed and hindlimb skeletal muscles are excised for further analysis. Studies found the potential role of miR‐1 (myomiR) as a biomarker under different atrophic conditions. Prolonged exposure to HH leads to enhanced expression of miR‐1 in skeletal muscle as compared to unexposed controls. The Bioinformatics approach is used to identify the validated targets and the biological processes of miR‐1. The target prediction tools identify PAX3 and HSP70 as major targets for miR‐1. Exposure to HH significantly reduces PAX3 and HSP70 expression during 7 days of HH exposure, which further enhances the activity of FOXO3, MSTN, and ATROGIN known for the progression of skeletal muscle atrophy in relation to control rats. This study indicates the increased expressions of miR‐1 and reduced expression of PAX3 and HSP70 lead to impaired myogenesis in skeletal muscle under HH. Further, enhanced expression of muscle degradation genes such as FOXO3, MSTN, and ATROGIN under HH exposure causes skeletal muscle protein loss. [ABSTRACT FROM AUTHOR]