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Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives.
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BACKGROUND: Several studies have highlighted the possible positive effects of soluble receptor for advanced glycation end products (sRAGE) against obesity. However, due to their inconsistent results, this systematic review and meta-analysis aimed to quantitatively evaluate and critically review the results of studies evaluating the relationship between sRAGE with obesity among adult population. METHODS: In the systematic search, the eligibility criteria were as follows: studies conducted with a cross-sectional design, included apparently healthy adults, adults with obesity, or obesity-related disorders, aged over 18 years, and evaluated the association between general or central obesity indices with sRAGE. RESULTS: Our systematic search in electronic databases, including PubMed, Scopus, and Embase up to 26 October, 2023 yielded a total of 21,612 articles. After removing duplicates, screening the titles and abstracts, and reading the full texts, 13 manuscripts were included in the final meta-analysis. According to our results, those at the highest category of circulating sRAGE concentration with median values of 934.92 pg/ml of sRAGE, had 1.9 kg/m2 lower body mass index (BMI) (WMD: -1.927; CI: -2.868, -0.986; P < 0.001) compared with those at the lowest category of sRAGE concentration with median values of 481.88 pg/ml. Also, being at the highest sRAGE category with the median values of 1302.3 pg/ml sRAGE, was accompanied with near 6 cm lower waist circumference (WC) (WMD: -5.602; CI: -8.820, -2.383; P < 0.001 with 86.4% heterogeneity of I2) compared with those at the lowest category of sRAGE concentration with median values of 500.525 pg/ml. Individuals with obesity had significantly lower circulating sRAGE concentrations (WMD: -135.105; CI: -256.491, -13.72; P = 0.029; with 79.5% heterogeneity of I2). According to the subgrouping and meta-regression results, country and baseline BMI were possible heterogeneity sources. According to Begg's and Egger's tests and funnel plots results, there was no publication bias. CONCLUSION: According to our results, higher circulating sRAGE concentrations was associated with lower BMI and WC among apparently healthy adults. Further randomized clinical trials are warranted for possible identification of causal associations.
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Productos Finales de Glicación Avanzada , Obesidad , Adulto , Humanos , Persona de Mediana Edad , Receptor para Productos Finales de Glicación Avanzada , Estudios Transversales , Índice de Masa Corporal , Pérdida de PesoRESUMEN
Parkinson's disease (PD) is one of the most prevalent diseases of central nervous system that is caused by degeneration of the substantia nigra's dopamine-producing neurons through apoptosis. Apoptosis is regulated by initiators' and executioners' caspases both in intrinsic and extrinsic pathways, further resulting in neuronal damage. In that context, targeting apoptosis appears as a promising therapeutic approach for treating neurodegenerative diseases. Non-coding RNAs-more especially, microRNAs, or miRNAs-are a promising target for the therapy of neurodegenerative diseases because they are essential for a number of cellular processes, including signaling, apoptosis, cell proliferation, and gene regulation. It is estimated that a substantial portion of coding genes (more than 60%) are regulated by miRNAs. These small regulatory molecules can have wide-reaching consequences on cellular processes like apoptosis, both in terms of intrinsic and extrinsic pathways. Furthermore, it was recommended that a disruption in miRNA expression levels could also result in perturbation of typical apoptosis pathways, which may be a factor in certain diseases like PD. The latest research on miRNAs and their impact on neural cell injury in PD models by regulating the apoptosis pathway is summarized in this review article. Furthermore, the importance of lncRNA/circRNA-miRNA-mRNA network for regulating apoptosis pathways in PD models and treatment is explored. These results can be utilized for developing new strategies in PD treatment.
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Cancer is still one of the deadliest diseases, and diagnosing and treating it effectively remains difficult. As a result, advancements in earlier detection and better therapies are urgently needed. Conventional chemotherapy induces chemoresistance, has non-specific toxicity, and has a meager efficacy. Natural materials like nanosized clay mineral formations of various shapes (platy, tubular, spherical, and fibrous) with tunable physicochemical, morphological, and structural features serve as potential templates for these. As multifunctional biocompatible nanocarriers with numerous applications in cancer research, diagnosis, and therapy, their submicron size, individual morphology, high specific surface area, enhanced adsorption ability, cation exchange capacity, and multilayered organization of 0.7-1 nm thick single sheets have attracted significant interest. Kaolinite, halloysite, montmorillonite, laponite, bentonite, sepiolite, palygorskite, and allophane are the most typical nanoclay minerals explored for cancer. These multilayered minerals can function as nanocarriers to effectively carry a variety of anticancer medications to the tumor site and improve their stability, dispersibility, sustained release, and transport. Proteins and DNA/RNA can be transported using nanoclays with positive and negative surfaces. The platform for phototherapeutic agents can be nanoclays. Clays with bio-functionality have been developed using various surface engineering techniques, which could help treat cancer. The promise of nanoclays as distinctive crystalline materials with applications in cancer research, diagnostics, and therapy are examined in this review.
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Bentonita , Neoplasias , Humanos , Bentonita/química , Caolín , Arcilla , Minerales , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológicoRESUMEN
In recent decades, analytical techniques have increasingly focused on the precise quantification. Achieving this goal has been accomplished with conventional analytical approaches that typically require extensive pretreatment methods, significant reagent usage, and expensive instruments. The need for rapid, simple, and highly selective identification platforms has become increasingly pronounced. Molecularly imprinted polymer (MIP) has emerged as a promising avenue for developing advanced sensors that can potentially surpass the limitations of conventional detection methods. In recent years, the application of MIP-silica materials-based sensors has garnered significant attention owing to their distinctive characteristics. These types of probes hold a distinct advantage in their remarkable stability and durability, all of which provide a suitable sensing platform in severe environments. Moreover, the substrate composed of silica materials offers a vast surface area for binding, thereby facilitating the efficient detection of even minuscule concentrations of targets. As a result, sensors based on MIP-silica materials have the potential to be widely applied in various industries, including medical diagnosis, and food safety. In the present review, we have conducted an in-depth analysis of the latest research developments in the field of MIPs-silica materials based sensors, with a focus on succinctly summarizing and elucidating the most crucial findings. This is the first comprehensive review of integration MIPs with silica materials in electrochemical (EC) and optical probes for biomedical analysis and food safety.
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Inocuidad de los Alimentos , Polímeros Impresos Molecularmente , Dióxido de Silicio , Dióxido de Silicio/química , Polímeros Impresos Molecularmente/química , Técnicas Biosensibles/métodos , Humanos , Impresión Molecular , Técnicas Electroquímicas/métodosRESUMEN
Cyclooxygenase (COX) enzymes are pivotal in inflammation and cancer development. COX-2, in particular, has been implicated in tumor growth, angiogenesis, and immune evasion. Recently, COX-2 inhibitors have arisen as potential therapeutic agents in cancer treatment. In addition, combining COX inhibitors with other treatment modalities has demonstrated the potential to improve therapeutic efficacy. This review aims to investigate the effects of COX inhibition, both alone and in combination with other methods, on signaling pathways and carcinogenesis in various cancers. In this study, a literature search of all major academic databases was conducted (PubMed, Scholar google), including the leading research on the mechanisms of COX-2, COX-2 inhibitors, monotherapy with COX-2 inhibitors, and combining COX-2-inhibitors with chemotherapeutic agents in tumors. The study encompasses preclinical and clinical evidence, highlighting the positive findings and the potential implications for clinical practice. According to preclinical studies, multiple signaling pathways implicated in tumor cell proliferation, survival, invasion, and metastasis can be suppressed by inhibiting COX. In addition, combining COX inhibitors with chemotherapy drugs, targeted therapies, immunotherapies, and miRNA-based approaches has enhanced anti-tumor activity. These results suggest that combination therapy has the potential to overcome resistance mechanisms and improve treatment outcomes. However, caution must be exercised when selecting and administering combination regimens. Not all combinations of COX-2 inhibitors with other drugs result in synergistic effects; some may even have unfavorable interactions. Therefore, personalized approaches that consider the specific characteristics of the cancer and the medications involved are crucial for optimizing therapeutic strategies. In conclusion, as monotherapy or combined with other methods, COX inhibition bears promise in modulating signaling pathways and inhibiting carcinogenesis in various cancers. Additional studies and well-designed clinical trials are required to completely elucidate the efficacy of COX inhibition and combination therapy in enhancing cancer treatment outcomes. This narrative review study provides a detailed summary of COX-2 monotherapy and combination targeted therapy in cancer treatment.
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Inhibidores de la Ciclooxigenasa 2 , Neoplasias , Humanos , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Ciclooxigenasa 2 , Terapia Combinada , Neoplasias/tratamiento farmacológico , CarcinogénesisRESUMEN
Despite great advances in diagnostic and treatment options for cancer, like chemotherapy surgery, and radiation therapy it continues to remain a major global health concern. Further research is necessary to find new biomarkers and possible treatment methods for cancer. MicroRNAs (miRNAs), tiny non-coding RNAs found naturally in the body, can influence the activity of several target genes. These genes are often disturbed in diseases like cancer, which perturbs functions like differentiation, cell division, cell cycle, apoptosis and proliferation. MiR-146a is a commonly and widely used miRNA that is often overexpressed in malignant tumors. The expression of miR-146a has been correlated with many pathological and physiological changes in cancer cells, such as the regulation of various cell death paths. It's been established that the control of cell death pathways has a huge influence on cancer progression. To improve our understanding of the interrelationship between miRNAs and cancer cell apoptosis, it's necessary to explore the impact of miRNAs through the alteration in their expression levels. Research has demonstrated that the appearance and spread of cancer can be mitigated by moderating the expression of certain miRNA - a commencement of treatment that presents a hopeful approach in managing cancer. Consequently, it is essential to explore the implications of miR-146a with respect to inducing different forms of tumor cell death, and evaluate its potential to serve as a target for improved chemotherapy outcomes. Through this review, we provide an outline of miR-146a's biogenesis and function, as well as its significant involvement in apoptosis. As well, we investigate the effects of exosomal miR-146a on the promotion of apoptosis in cancer cells and look into how it could possibly help combat chemotherapeutic resistance.