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Colorectal cancer (CRC) is the third most common malignant tumor and the second most fatal cancer worldwide. Several parts of the immune system contribute to fighting cancer including the innate complement system. The complement system is composed of several players, namely component molecules, regulators and receptors. In this review, we discuss the complement system activation in cancer specifically CRC and highlight the possible interactions between the complement system and the various TME components. Additionally, the role of the complement system in tumor immunity of CRC is reviewed. Hence, such work could provide a framework for researchers to further understand the role of the complement system in CRC and explore the potential therapies targeting complement activation in solid tumors such as CRC.

Gene expression is one of the most critical cellular processes. It is controlled by complex mechanisms at the genomic, epigenomic, transcriptomic, and proteomic levels. Any aberration in these mechanisms can lead to dysregulated gene expression. One recently discovered process that controls gene expression includes chemical modifications of RNA molecules by RNA-modifying proteins, a field known as epitranscriptomics. Epitranscriptomics can regulate mRNA splicing, nuclear export, stabilization, translation, or induce degradation of target RNA molecules. Dysregulation in RNA-modifying proteins has been found to contribute to many pathological conditions, such as cancer, diabetes, obesity, cardiovascular diseases, and neurological diseases, among others. This article reviews the role of epitranscriptomics in the pathogenesis and progression of renal cell carcinoma. It summarizes the molecular function of RNA-modifying proteins in the pathogenesis of renal cell carcinoma.

Precision and timeliness in breast cancer detection are paramount for improving patient outcomes. Traditional diagnostic methods have predominantly relied on unimodal approaches, but recent advancements in medical data analytics have enabled the integration of diverse data sources beyond conventional imaging techniques. This review critically examines the transformative potential of integrating histopathology images with genomic data, clinical records, and patient histories to enhance diagnostic accuracy and comprehensiveness in multi-modal diagnostic techniques. It explores early, intermediate, and late fusion methods, as well as advanced deep multimodal fusion techniques, including encoder-decoder architectures, attention-based mechanisms, and graph neural networks. An overview of recent advancements in multimodal tasks such as Visual Question Answering (VQA), report generation, semantic segmentation, and cross-modal retrieval is provided, highlighting the utilization of generative AI and visual language models. Additionally, the review delves into the role of Explainable Artificial Intelligence (XAI) in elucidating the decision-making processes of sophisticated diagnostic algorithms, emphasizing the critical need for transparency and interpretability. By showcasing the importance of explainability, we demonstrate how XAI methods, including Grad-CAM, SHAP, LIME, trainable attention, and image captioning, enhance diagnostic precision, strengthen clinician confidence, and foster patient engagement. The review also discusses the latest XAI developments, such as X-VARs, LeGrad, LangXAI, LVLM-Interpret, and ex-ILP, to demonstrate their potential utility in multimodal breast cancer detection, while identifying key research gaps and proposing future directions for advancing the field.

Background Spatial and temporal control of DNA damage response pathways after DNA damage is crucial for maintenance of genomic stability. Ataxia telangiectasia mutated (ATM) protein plays a central role in DNA damage response pathways. The chain of events following induction of DNA damage that results in full activation of ATM is still evolving. Here we set out to explore the role of CREB-binding protein (CBP), a histone acetyltransferase (HAT), in DNA damage response, particularly in the ATM activation pathway. Results In response to DNA damage, CBP is stabilized and is recruited at sites of DNA double-strand breaks where it acetylates ATM and promotes its kinase activity. Cells deficient in CBP display an impairment in DNA double-strand break repair and high sensitivity to chemo- and radiotherapy. Importantly, re-expressing CBP’s HAT domain in CBP-deficient cells restores the DNA repair capability, demonstrating the essential role of CBP’s HAT domain in repairing DNA double-strand breaks. Conclusions Together, our findings shed the light on CBP as a key participant in the ATM activation pathway and in the subsequent repair of DNA double-strand breaks, which may serve as a potential target to modulate the cellular response to DNA damaging agents in cancer. Graphical Abstract

Systemic Lupus Erythematosus (SLE) is a multifaceted autoimmune disorder characterized by widespread inflammation and immune dysregulation, impacting various organ systems and generating autoantibodies. Oral lesions are a common and distressing manifestation of SLE, significantly affecting patients’ quality of life. Cytokines, key mediators of immune responses, play a crucial role in the pathogenesis of both systemic and oral manifestations of SLE. This review sheds the light on current research on the involvement of various cytokines, including interleukins different interferon types, and growth factors in SLE. The intricate interplay between pro-inflammatory and anti-inflammatory cytokines contributes to the disease’s initiation, progression, and diverse clinical presentations. Elevated levels of pro-inflammatory cytokines exacerbate inflammation, promote apoptosis, and drive autoantibody production. Understanding the specific roles of these cytokines offers potential therapeutic targets for managing SLE and improving patient outcomes.

In addition to its characteristic autoantibody production and multi-organ involvement, SLE frequently presents with oral lesions that significantly impair quality of life.Elemam et al.reviewed evidence implicating interleukins, interferons, and growth factors in shaping inflammation, apoptosis, and autoantibody generation. [...]transcriptional regulation offers another layer of immune regulation.An et al.investigated the transcription factor Kruppel-like factor 4 (KLF4), which is known to regulate immunosuppressive and antithrombotic pathways, and its interaction with CD55, a regulator of T- and B-cell responses. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Breast cancer is the second leading cause of cancer death among women. The present study is an effort to reveal the antiproliferative and antioxidant actions of mango seed kernel extract (KE), peel extract ( PE ), and their combination ( KEPE ) on mammary tumors induced by 7,12 dimethylbenz[a]anthracene ( DMBA ). Seven groups of adult female Sprague–Dawley rats were prepared, including C : (control), DMBA: (rats were administered with DMBA ), ( DMBA-KE), ( DMBA-PE), and ( DMBA-KEPE ): rats were administered with DMBA and then treated with KE, PE, and (both KE and PE ), respectively, ( KE) and ( PE) : rats were administered with KE and PE , separately. The study focused on the assessment of markers of endocrine derangement [serum 17-β estradiol (E2)], apoptosis [caspase-3 and deoxyribonucleic acid fragmentation (DNAF)], and oxidative stress [lipid peroxidation and antioxidants (glutathione, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase)]. Histopathological examination and immunohistochemical expression of caspase-3 and estrogen receptor-α (ER-α) in mammary gland tissues (MGTs) were determined, as well as the characterization of mango extracts. The results showed that DMBA administration induced mammary tumors by increasing cell proliferation and evading apoptosis. In addition, DMBA administration caused oxidative stress by the production of reactive oxygen species, which increased lipid peroxidation and decreased cellular antioxidants, allowing cancer to progress. In contrast, treatment with DMBA-KE, DMBA-PE, or DMBA-KEPE diminished mammary tumors induced by DMBA , where they reduced oxidative stress via increased antioxidant parameters including reduced glutathione, superoxide dismutase, total glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Also, different treatments decreased proliferation through the reduction of E2, and ER-α expression levels. However, these treatments increased the apoptosis of unwanted cells as they increased caspase-3 activity and DNAF. All these changes led to the prevention of breast injuries and the reduction of mammary tumors. This demonstrates that the contents of mango extracts, especially phenolics and flavonoids, have an important role in mammary tumor treatment through their potential antioxidant, antiproliferative, proapoptotic, and anti-estrogenic effects. KE and PE administration for 4 weeks had no adverse effects. Conclusion: Each of KE, PE, and KEPE has a therapeutic effect against DMBA-induced mammary tumors via induction of apoptosis and reduction of each of the OS, proliferation, and estrogenic effects. So, they can play an important role in the pharmacological tole.

Kidney cancer has several types, with renal cell carcinoma (RCC) being the most prevalent and severe type, accounting for more than 85% of adult patients. The manual analysis of whole slide images (WSI) of renal tissues is the primary tool for RCC diagnosis and prognosis. However, the manual identification of RCC is time-consuming and prone to inter-subject variability. In this paper, we aim to distinguish between benign tissue and malignant RCC tumors and identify the tumor subtypes to support medical therapy management. We propose a novel multiscale weakly-supervised deep learning approach for RCC subtyping. Our system starts by applying the RGB-histogram specification stain normalization on the whole slide images to eliminate the effect of the color variations on the system performance. Then, we follow the multiple instance learning approach by dividing the input data into multiple overlapping patches to maintain the tissue connectivity. Finally, we train three multiscale convolutional neural networks (CNNs) and apply decision fusion to their predicted results to obtain the final classification decision. Our dataset comprises four classes of renal tissues: non-RCC renal parenchyma, non-RCC fat tissues, clear cell RCC (ccRCC), and clear cell papillary RCC (ccpRCC). The developed system demonstrates a high classification accuracy and sensitivity on the RCC biopsy samples at the slide level. Following a leave-one-subject-out cross-validation approach, the developed RCC subtype classification system achieves an overall classification accuracy of 93.0% ± 4.9%, a sensitivity of 91.3% ± 10.7%, and a high classification specificity of 95.6% ± 5.2%, in distinguishing ccRCC from ccpRCC or non-RCC tissues. Furthermore, our method outperformed the state-of-the-art Resnet-50 model.

Background: Doxorubicin (DOX) is a very powerful chemotherapy drug. However, its severe toxicity and potential for resistance development limit its application. Withania somnifera L. Dunal (WIT) has therapeutic capacities, including anti-inflammatory, antioxidant, and anticancer activities. This study investigates the preventative benefits of a standardized WIT extract against DOX-induced renal damage in vivo. We also investigate the synergistic effects of combining WIT and DOX to improve therapeutic efficacy in breast cancer cells (MCF7-ADR). Methods: This study employed an animal model where rats were administered 300 mg/kg/day of WIT orally for a duration of 14 days. Rats received DOX injections at a dose of 5 mg/kg, for a total of 15 mg, on the 6th, 8th, and 10th days. Results: Present results revealed that WIT reduced DOX-induced increase levels of blood urea and creatinine and the activity of kidney injury molecule-1. WIT also reduced renal tissue damage, oxidative stress, and levels of pro-inflammatory markers. WIT alleviated the effects of DOX on nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and sirtuin 1 in the renal tissues. WIT modulated nuclear factor-κB activity and decreased apoptotic indicators. Furthermore, WIT improves DOX’s capacity to kill drug-resistant MCF7-ADR cells by arresting the cell cycle and promoting apoptosis. Chemical analysis of WIT root extract revealed 34 distinct compounds, including alkaloids, withanolides, flavanones, and fatty acids. Conclusions: These constituents synergistically contribute to WIT’s antioxidant, anti-inflammatory, and anti-apoptotic properties. In addition, they confirm its ability to reduce systemic toxicity while improving treatment efficacy.

Ozone has been successfully used in medicine for over 100 years due to its microbiological qualities. Its powerful oxidation impact, which results in the production of free radicals, and its ability to cause the direct death of nearly all microorganisms is the basis for its bactericide, virucide, and fungicide properties. Ozone also has a medicinal impact that speeds up blood flow and aids wound healing. Ozone may be applied as a gas or dissolved in water for medical purposes. Despite the benefits of using ozone therapeutically, concerns about its use in dentistry still exist. We aimed to provide a summary of the current uses of ozone in medicine and dentistry. An electronic search was performed for all English scientific papers published between 2012 and 2023 using PubMed, Cochrane, and Google Scholar search engines. Ozone, clinical applications, medicine, and dentistry were the search terms used. Seventy full-text articles describing the use of ozone therapy in medicine and dentistry were included in the present review. Ozone has shown several beneficial effects in the medical field. However, despite the encouraging in vitro evidence, the clinical use of ozone in dentistry has not yet been demonstrated as highly effective.