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Proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol metabolism and cardiovascular diseases, has recently garnered attention for its emerging involvement in cancer biology. The multifunctional nature of PCSK9 extends beyond lipid regulation and encompasses a wide range of cellular processes that can influence cancer progression. Studies have revealed that PCSK9 can modulate signaling pathways, such as PI3K/Akt, MAPK, and Wnt/ß-catenin, thereby influencing cellular proliferation, survival, and angiogenesis. Additionally, the interplay between PCSK9 and cholesterol homeostasis may impact membrane dynamics and cellular migration, further influencing tumor aggressiveness. The central role of the immune system in monitoring and controlling cancer is increasingly recognized. Recent research has demonstrated the ability of PCSK9 to modulate immune responses through interactions with immune cells and components of the tumor microenvironment. This includes effects on dendritic cell maturation, T cell activation, and cytokine production, suggesting a role in shaping antitumor immune responses. Moreover, the potential influence of PCSK9 on immune checkpoints such as PD1/PD-L1 lends an additional layer of complexity to its immunomodulatory functions. The growing interest in cancer immunotherapy has prompted exploration into the potential of targeting PCSK9 for therapeutic benefits. Preclinical studies have demonstrated synergistic effects between PCSK9 inhibitors and established immunotherapies, offering a novel avenue for combination treatments. The strategic manipulation of PCSK9 to enhance tumor immunity and improve therapeutic outcomes presents an exciting area for further investigations. Understanding the mechanisms by which PCSK9 influences cancer biology and immunity holds promise for the development of novel immunotherapeutic approaches. This review aims to provide a comprehensive analysis of the intricate connections between PCSK9, cancer pathogenesis, tumor immunity, and the potential implications for immunotherapeutic interventions.
Assuntos
Imunoterapia , Neoplasias , Pró-Proteína Convertase 9 , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/metabolismo , Neoplasias/patologia , Pró-Proteína Convertase 9/imunologia , Pró-Proteína Convertase 9/metabolismo , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Animais , Inibidores de PCSK9RESUMO
Cancer cells exhibit altered metabolic pathways, prominently featuring enhanced glycolytic activity to sustain their rapid growth and proliferation. Dysregulation of glycolysis is a well-established hallmark of cancer and contributes to tumor progression and resistance to therapy. Increased glycolysis supplies the energy necessary for increased proliferation and creates an acidic milieu, which in turn encourages tumor cells' infiltration, metastasis, and chemoresistance. Circular RNAs (circRNAs) have emerged as pivotal players in diverse biological processes, including cancer development and metabolic reprogramming. The interplay between circRNAs and glycolysis is explored, illuminating how circRNAs regulate key glycolysis-associated genes and enzymes, thereby influencing tumor metabolic profiles. In this overview, we highlight the mechanisms by which circRNAs regulate glycolytic enzymes and modulate glycolysis. In addition, we discuss the clinical implications of dysregulated circRNAs in cancer glycolysis, including their potential use as diagnostic and prognostic biomarkers. All in all, in this overview, we provide the most recent findings on how circRNAs operate at the molecular level to control glycolysis in various types of cancer, including hepatocellular carcinoma (HCC), prostate cancer (PCa), colorectal cancer (CRC), cervical cancer (CC), glioma, non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer (GC). In conclusion, this review provides a comprehensive overview of the significance of circRNAs in cancer glycolysis, shedding light on their intricate roles in tumor development and presenting innovative therapeutic avenues.
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Multiple sclerosis (MS) is a chronic condition affecting the central nervous system (CNS), where the interplay of genetic and environmental factors influences its pathophysiology, triggering immune responses and instigating inflammation. Contemporary research has been notably dedicated to investigating the contributions of gut microbiota and their metabolites in modulating inflammatory reactions within the CNS. Recent recognition of the gut microbiome and dietary patterns as environmental elements impacting MS development emphasizes the potential influence of small, ubiquitous molecules from microbiota, such as short-chain fatty acids (SCFAs). These molecules may serve as vital molecular signals or metabolic substances regulating host cellular metabolism in the intricate interplay between microbiota and the host. A current emphasis lies on optimizing the health-promoting attributes of colonic bacteria to mitigate urinary tract issues through dietary management. This review aims to spotlight recent investigations on the impact of SCFAs on immune cells pivotal in MS, the involvement of gut microbiota and SCFAs in MS development, and the considerable influence of probiotics on gastrointestinal disruptions in MS. Comprehending the gut-CNS connection holds promise for the development of innovative therapeutic approaches, particularly probiotic-based supplements, for managing MS.
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Microbioma Gastrointestinal , Esclerose Múltipla , Humanos , Sistema Nervoso Central , Colo , Ácidos Graxos Voláteis , InflamaçãoRESUMO
Activation of autophagy, a process of cellular stress response, leads to the breakdown of proteins, organelles, and other parts of the cell in lysosomes, and can be linked to several ailments, such as cancer, neurological diseases, and rare hereditary syndromes. Thus, its regulation is very carefully monitored. Transcriptional and post-translational mechanisms domestically or in whole organisms utilized to control the autophagic activity, have been heavily researched. In modern times, microRNAs (miRNAs) are being considered to have a part in post-translational orchestration of the autophagic activity, with miR-21 as one of the best studied miRNAs, it is often more than expressed in cancer cells. This regulatory RNA is thought to play a major role in a plethora of processes and illnesses including growth, cancer, cardiovascular disease, and inflammation. Different studies have suggested that a few autophagy-oriented genes, such as PTEN, Rab11a, Atg12, SIPA1L2, and ATG5, are all targeted by miR-21, indicating its essential role in the regulation.
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Autofagia , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Autofagia/genética , Autofagia/fisiologia , Animais , Transdução de Sinais/genética , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismoRESUMO
The thermal degradation kinetics of flaxseed oil (FSO) and moringa oil (MO) blends with soyabean oil (SOY; 80%), rice bran oil (RBO; 80%), cotton seed oil (CSO; 80%) and sunflower oil (SFO; 80%) with Rancimat equipment. There was no significant (p ≤ 0.05) difference observed in the specific gravity (SG), density (D), and refractive index (RI) values of the MO and FSO blends, while the rancidity parameters showed the opposite variations. The FTIR spectra showed absorption bands at 966 cm-1, 1097 cm-1, 1160 cm-1, 1217 cm-1, 1377 cm-1, 1464 cm-1, 1743 cm-1, 2945 cm-1, 2852 cm-1 and 3008 cm-1. Oil blends' kinetic degradation (Ea, ΔH, ΔS, A) is represented by the semilogarithmic relationship between the oxidative stability index (OSI) and temperature. The activation energy (Ea) ranged from 77.1 ± 0.21 to 106.9 ± 0.03 kJ/mol and 73.2 ± 0.01 to 104.4 ± 0.02 kJ/mol for flaxseed oil (FSO) and moringa oil (MO) blends, respectively. The enthalpy (ΔH) and entropy (ΔS) ranged from 67.3 to 121.6 kJ/mol, and - 60.2 to - 8.4 J/mol, and 63.55 to 95.59 kJ/mol and - 20.66 to - 4.11 J/mol for FSO blends and MO blends, respectively.
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The purpose of this review is to summarize the current literature on reductive C-N coupling of nitro compounds and boronic acids, with special emphasis on the mechanistic features of the reactions. The metal-catalyzed reactions are discussed first. This is followed by electro-synthesis and organophosphorus-catalyzed reactions. Finally, the available examples of catalyst-free reactions will be covered at the end of this review.
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Daidzein (DDZ) is a well-known nutraceutical supplement belonging to the class of isoflavones. It is isolated from various sources such as alfalfa, soybean, and red clover. It demonstrates a broad array of pharmacological/beneficial properties such as cardiovascular exercise, cholesterol reduction, and anticancer, antifibrotic, and antidiabetic effects, which make it effective in treating a wide range of diseases. Its structure and operation are the same as those of human estrogens, which are important in preventing osteoporosis, cancer, and postmenopausal diseases. It is thus a promising candidate for development as a phytopharmaceutical. Addressing safety, efficacy, and physicochemical properties are the primary prerequisites. DDZ is already ingested every day in varying amounts, so there should not be a significant safety risk; however, each indication requires a different dose to be determined. Some clinical trials are already being conducted globally to confirm its safety, efficacy, and therapeutic potential. Furthermore, as a result of its therapeutic influence on health, in order to establish intellectual property, patents are utilized. In light of the vast potential of eugenol, this review presents a detailed data collection on DDZ to substantiate the claim to develop it in the therapeutic category.
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BACKGROUND: Over the last two decades, humanity has observed the extraordinary anomaly caused by novel, weird coronavirus strains, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). As the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has made its entry into the world, it has dramatically affected life in every domain by continuously producing new variants. The vaccine development is an ongoing process, although some vaccines got marketed. The big challenge is now whether the vaccine candidates can provide long-lasting protection or prevention against mutant variants. METHODS: The information was gathered from various journals, electronic searches via Internet-based information such as PubMed, Google Scholar, Science Direct, online electronic journals, WHO landscape, world meters, WHO website, and News. RESULTS: This review will present and discuss some coronavirus disease 19 (COVID-19) related aspects including: the pathophysiology, epidemiology, mutant variants vaccine candidates, vaccine efficacy, and management strategies. Due to the high death rate, continuous spread, an inadequate workforce, lack of required therapeutics, and incomplete understanding of the viral strain, it becomes crucial to build the knowledge of its biological characteristics and make available the rapid diagnostic and vital therapeutic machinery for the combat and management of an infection. CONCLUSION: The data summarizes current research on the COVID 19 infection and therapeutic interventions, which will direct future decision-making on the effort-worthy phases of the COVID 19 and the development of critical therapeutics. The only possible solution is the vaccine development targeting against all variant strains to halt its progress; the identified theoretical and practical knowledge can eliminate the gaps to improve a better understanding of the novel coronavirus structure and its design of a vaccine. In addition, to that the long-lasting protection is another challenging objective that need to be looked into.