Implications of viral infections and oncogenesis in uterine cervical carcinoma etiology and pathogenesis

BackgroundUterine Cervical Carcinoma (UCC) is the most prevalent gynecological malignancy globally, with a rising incidence in recent years. Accumulating evidence indicates that specific viral infections, including human papillomavirus (HPV), Epstein-Barr virus (EBV), Hepatitis B and C viruses (HBV and HCV), and human herpesvirus (HHV), may contribute to UCC development and progression. Understanding the complex interplay between viral infections and UCC risk is crucial for developing novel preventative and therapeutic interventions.MethodsThis comprehensive review investigates the association between viral infections and UCC risk by examining the roles of various viral pathogens in UCC etiology and pathogenesis, and possible molecular mechanisms. Additionally, we evaluate current diagnostic methods and potential therapeutic strategies targeting viral infections for UCC prevention or treatment.ResultsThe prevention of UCC has been significantly advanced by the emergence of self-sampling for HPV testing as a crucial tool, allowing for early detection and intervention. However, an essential challenge in UCC prevention lies in understanding how HPV and other viral coinfections, including EBV, HBV, HCV, HHV, HIV, or their concurrent presence, may potentially contribute to UCC development. The molecular mechanisms implicated in the association between viral infections and cervical cancer development include: (1) interference of viral oncogenes with cellular regulatory proteins, resulting in uncontrolled cell proliferation and malignant transformation; (2) inactivation of tumor suppressor genes by viral proteins; (3) evasion of host immune responses by viruses; (4) induction of a persistent inflammatory response, contributing to a tumor-promoting microenvironment; (5) epigenetic modifications that lead to aberrant gene expression; (6) stimulation of angiogenesis by viruses; and (7) activation of telomerase by viral proteins, leading to cellular immortalization. Additionally, viral coinfections can also enhance oncogenic potential through synergistic interactions between viral oncoproteins, employ immune evasion strategies, contribute to chronic inflammation, modulate host cellular signaling pathways, and induce epigenetic alterations, ultimately leading to cervical carcinogenesis.ConclusionRecognizing the implications of viral oncogenes in UCC etiology and pathogenesis is vital for addressing the escalating burden of UCC. Developing innovative preventative and therapeutic interventions requires a thorough understanding of the intricate relationship between viral infections and UCC risk

Research on the Performance of Regenerant Modified Cold Recycled Mixture with Asphalt Emulsions

In order to study the mechanical properties and effect of a regenerant on a cold recycled mixture with asphalt emulsions (CRMEs), the moisture susceptibility, high-temperature performance, low-temperature performance, dynamic mechanical properties and durability of CRMEs were analyzed and evaluated by immersion splitting strength tests, freeze-thaw splitting strength tests, rutting tests, semi-circle bending tests, uniaxial compression dynamic modulus tests and indirect tensile tests. Scanning electron microscopy (SEM) was used to analyze the micromorphology of CRMEs modified with regenerant. Finally, a comprehensive evaluation system of five different CRMEs was established based on the efficacy coefficient method to quantitatively analyze the comprehensive performance of the CRMEs. The test results showed that the regenerant can significantly improve the water immersion splitting strength, freeze-thaw splitting strength fracture energy density, and fatigue resistance of CRMEs. However, the addition of regenerant affected the high-temperature performance of the cold recycled mixture. The dynamic modulus of the CRMEs first increased and then decreased with regenerant content increasing. When the regenerant content was 8%, the dynamic modulus of the CRMEs was the highest. Adding styrene-butadiene rubber (SBR) latex can improve the high-temperature performance of CRMEs, but the moisture susceptibility, low temperature performance and fatigue resistance of the cold recycled mixture were not significantly improved, and the dynamic modulus of the mixture was reduced. Based on the efficacy coefficient method, the optimal content of regenerant is 8%. Regenerant are potential modifiers for cold recycled mixture that they can significantly improve the dynamic mechanical properties and durability

The great roundleaf bat (Hipposideros armiger) as a good model for cold-induced browning of intra-abdominal white adipose tissue.

Inducing beige fat from white adipose tissue (WAT) is considered to be a shortcut to weight loss and increasingly becoming a key area in research into treatments for obesity and related diseases. However, currently, animal models of beige fat are restricted to rodents, where subcutaneous adipose tissue (sWAT, benign WAT) is more liable to develop into the beige fat under specific activators than the intra-abdominal adipose tissue (aWAT, malignant WAT) that is the major source of obesity related diseases in humans.Here we induced beige fat by cold exposure in two species of bats, the great roundleaf bat (Hipposideros armiger) and the rickett's big-footed bat (Myotis ricketti), and compared the molecular and morphological changes with those seen in the mouse. Expression of thermogenic genes (Ucp1 and Pgc1a) was measured by RT-qPCR and adipocyte morphology examined by HE staining at three adipose locations, sWAT, aWAT and iBAT (interscapular brown adipose tissue).Expression of Ucp1 and Pgc1a was significantly upregulated, by 729 and 23 fold, respectively, in aWAT of the great roundleaf bat after exposure to 10°C for 7 days. Adipocyte diameters of WATs became significantly reduced and the white adipocytes became brown-like in morphology. In mice, similar changes were found in the sWAT, but much lower amounts of changes in aWAT were seen. Interestingly, the rickett's big-footed bat did not show such a tendency in beige fat.The great roundleaf bat is potentially a good animal model for human aWAT browning research. Combined with rodent models, this model should be helpful for finding therapies for reducing harmful aWAT in humans

Differential Expression of <i>Meis2</i>, <i>Mab21l2</i> and <i>Tbx3</i> during Limb Development Associated with Diversification of Limb Morphology in Mammals

<div><p>Bats are the only mammals capable of self-powered flight using wings. Differing from mouse or human limbs, four elongated digits within a broad wing membrane support the bat wing, and the foot of the bat has evolved a long calcar that spread the interfemoral membrane. Our recent mRNA sequencing (mRNA-Seq) study found unique expression patterns for genes at the 5′ end of the <i>Hoxd</i> gene cluster and for <i>Tbx3</i> that are associated with digit elongation and wing membrane growth in bats. In this study, we focused on two additional genes, <i>Meis2</i> and <i>Mab21l2</i>, identified from the mRNA-Seq data. Using whole-mount in situ hybridization (WISH) we validated the mRNA-Seq results for differences in the expression patterns of <i>Meis2</i> and <i>Mab21l2</i> between bat and mouse limbs, and further characterize the timing and location of the expression of these two genes. These analyses suggest that <i>Meis2</i> may function in wing membrane growth and <i>Mab21l2</i> may have a role in AP and DV axial patterning. In addition, we found that <i>Tbx3</i> is uniquely expressed in the unique calcar structure found in the bat hindlimb, suggesting a role for this gene in calcar growth and elongation. Moreover, analysis of the coding sequences for <i>Meis2</i>, <i>Mab21l2</i> and <i>Tbx3</i> showed that <i>Meis2</i> and <i>Mab21l2</i> have high sequence identity, consistent with the functions of genes being conserved, but that <i>Tbx3</i> showed accelerated evolution in bats. However, evidence for positive selection in <i>Tbx3</i> was not found, which would suggest that the function of this gene has not been changed. Together, our findings support the hypothesis that the modulation of the spatiotemporal expression patterns of multiple functional conserved genes control limb morphology and drive morphological change in the diversification of mammalian limbs.</p></div

<i>Meis2</i> expression in the fore- (F) and hindlimbs (H) of embryonic bats and mice visualized by WISH.

<p>All images are the dorsal view with anterior pointing up.S14L: Late stage14; S17M: Middle stage 17; S19E: Early stage 19; Scale bars, 200 µm in (A–L) and 500 µm in (M–X).</p