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The cognitive impairment known as dementia affects millions of individuals throughout the globe. The use of machine learning (ML) and deep learning (DL) algorithms has shown great promise as a means of early identification and treatment of dementia. Dementias such as Alzheimer's Dementia, frontotemporal dementia, Lewy body dementia, and vascular dementia are all discussed in this article, along with a literature review on using ML algorithms in their diagnosis. Different ML algorithms, such as support vector machines, artificial neural networks, decision trees, and random forests, are compared and contrasted, along with their benefits and drawbacks. As discussed in this article, accurate ML models may be achieved by carefully considering feature selection and data preparation. We also discuss how ML algorithms can predict disease progression and patient responses to therapy. However, overreliance on ML and DL technologies should be avoided without further proof. It's important to note that these technologies are meant to assist in diagnosis but should not be used as the sole criteria for a final diagnosis. The research implies that ML algorithms may help increase the precision with which dementia is diagnosed, especially in its early stages. The efficacy of ML and DL algorithms in clinical contexts must be verified, and ethical issues around the use of personal data must be addressed, but this requires more study.
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Colon cancer (CC) stands as one of the most common malignancies related to the gastrointestinal system, whose increasing incidence and death rates have been reported all over the world. Standard treatments for fighting cancers like CC comprise surgical approaches, chemotherapy, and radiotherapy, which are suggested by clinicians according to patients' conditions and disease stages. However, patients who utilize these modalities may suffer from serious side effects and adverse outcomes, for example, toxicity and tumor recurrence, as well as a low 5-year survival rate. The present shreds of evidence showed that mesenchymal stem cells (MSCs) can have a suitable capacity for treating different health problems, especially neoplasms. These multipotent stem cells can be isolated from several sources, such as the umbilical cord, bone marrow, adipose tissue, and placenta. Among these mesenchymal sources, umbilical cord-MSCs have gathered much attention in scientific societies due to their advantages (e.g., low immunogenicity, lack of ethical problems, and easy collection). These days, the efficacy of umbilical cord-MSCs and umbilical cord-MSCs-based strategies, such as conditioned medium, extracellular vesicles, and exosomes, on CC have been explored, and promising findings have been stated. Therefore, in this review, we aimed to summarize and debate evidence regarding the effects of UC-MSCs and their related products on CC with a focus on molecular and cellular mechanisms involved in its treatment and pathogenesis of this malignant tumor.
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BACKGROUND: Machine learning (ML) has shown exceptional promise in various domains of medical research. However, its application in predicting subsequent fragility fractures is still largely unknown. In this study, we aim to evaluate the predictive power of different ML algorithms in this area and identify key features associated with the risk of subsequent fragility fractures in osteoporotic patients. METHODS: We retrospectively analyzed data from patients presented with fragility fractures at our Fracture Liaison Service, categorizing them into index fragility fracture (n = 905) and subsequent fragility fracture groups (n = 195). We independently trained ML models using 27 features for both male and female cohorts. The algorithms tested include Random Forest, XGBoost, CatBoost, Logistic Regression, LightGBM, AdaBoost, Multi-Layer Perceptron, and Support Vector Machine. Model performance was evaluated through 10-fold cross-validation. RESULTS: The CatBoost model outperformed other models, achieving 87% accuracy and an AUC of 0.951 for females, and 93.4% accuracy with an AUC of 0.990 for males. The most significant predictors for females included age, serum C-reactive protein (CRP), 25(OH)D, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), femoral neck Z-score, menopause age, number of pregnancies, phosphorus, calcium, and body mass index (BMI); for males, the predictors were serum CRP, femoral neck T-score, PTH, hip T-score, BMI, BUN, creatinine, alkaline phosphatase, and spinal Z-score. CONCLUSION: ML models, especially CatBoost, offer a valuable approach for predicting subsequent fragility fractures in osteoporotic patients. These models hold the potential to enhance clinical decision-making by supporting the development of personalized preventative strategies.
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Aprendizado de Máquina , Fraturas por Osteoporose , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/diagnóstico , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Valor Preditivo dos Testes , Medição de Risco/métodos , Fatores de Risco , Osteoporose/epidemiologia , Osteoporose/diagnóstico , AlgoritmosRESUMO
Diabetes mellitus (DM) is a metabolic illness defined by elevated blood glucose levels, mediating various tissue alterations, including the dysfunction of vital organs. Diabetes mellitus (DM) can lead to many consequences that specifically affect the brain, heart, and kidneys. These issues are known as neuropathy, cardiomyopathy, and nephropathy, respectively. Inflammation is acknowledged as a pivotal biological mechanism that contributes to the development of various diabetes consequences. NF-κB modulates inflammation and the immune system at the cellular level. Its abnormal regulation has been identified in several clinical situations, including cancer, inflammatory bowel illnesses, cardiovascular diseases, and Diabetes Mellitus (DM). The purpose of this review is to evaluate the potential impact of NF-κB on complications associated with DM. Enhanced NF-κB activity promotes inflammation, resulting in cellular harm and compromised organ performance. Phytochemicals, which are therapeutic molecules, can potentially decline the NF-κB level, therefore alleviating inflammation and the progression of problems correlated with DM. More importantly, the regulation of NF-κB can be influenced by various factors, such as TLR4 in DM. Highlighting these factors can facilitate the development of novel therapies in the future.
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Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer, mainly occurring in Asian countries with an increased incidence rate globally. Currently, several kinds of therapies have been deployed for HCC therapy including surgical resection, chemotherapy, radiotherapy and immunotherapy. However, this tumor is still incurable, requiring novel strategies for its treatment. The nanomedicine has provided the new insights regarding the treatment of cancer that liposomes as lipid-based nanoparticles, have been widely applied in cancer therapy due to their biocompaitiblity, high drug loading and ease of synthesis and modification. The current review evaluates the application of liposomes for the HCC therapy. The drugs and genes lack targeting ability into tumor tissues and cells. Therefore, loading drugs or genes on liposomes can increase their accumulation in tumor site for HCC suppression. Moreover, the stimuli-responsive liposomes including pH-, redox- and light-sensitive liposomes are able to deliver drug into tumor microenvironment to improve therapeutic index. Since a number of receptors upregulate on HCC cells, the functionalization of liposomes with lactoferrin and peptides can promote the targeting ability towards HCC cells. Moreover, phototherapy can be induced by liposomes through loading phtoosensitizers to stimulate photothermal- and photodynamic-driven ablation of HCC cells. Overall, the findings are in line with the fact that liposomes are promising nanocarriers for the treatment of HCC.
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RNA therapy involves utilizing RNA-based molecules to control biological pathways, aiming to cure specific diseases. As our understanding of RNA functions and their roles has expanded, the application of RNA therapies has broadened to target various therapeutic points. This approach holds promise for treating a range of diseases, including kidney diseases. Therapeutic RNA can be employed to target specific genes or pathways implicated in the development of kidney conditions, such as inflammation, fibrosis, and oxidative stress. This review highlights the therapeutic potential of RNA-based therapies across different types of kidney diseases, encompassing infection, inflammation, nephrotoxicity, and ischemia/reperfusion injury. Furthermore, studies have pinpointed the specific kidney cells involved in RNA therapy. To address challenges hindering the potential impact of RNA-based drugs on their targets, nanotechnology is integrated, and RNA-loaded vehicles with ligands are explored for more efficient outcomes.
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Nefropatias , RNA , Humanos , Rim , Estresse Oxidativo , Inflamação , Nefropatias/genética , Nefropatias/terapiaRESUMO
Seventy percent of breast cancer patients have an active estrogen receptor. Tamoxifen interferes with estrogen's ability to bind to cancer cells. The most challenging aspect of tamoxifen, however, is that breast cancer cells become resistant to its effects. Some studies have shown that alterations in miRNA expression contribute significantly to drug resistance in breast cancer. Therefore, the present systematic review aims to investigate miRNAs that significantly influence the response to tamoxifen treatment. The present study follows the PRISMA instructions. The Web of Science, PubMed, and Scopus databases were searched to retrieve English articles. The searches were conducted up to September 11, 2022. The search strategy included the terms "Tamoxifen", "Breast Neoplasm", and "MicroRNA". The inclusion criteria of this study are English, original, and experimental studies investigating miRNAs that are effective in the treatment efficacy of tamoxifen. A total of 565 articles were retrieved. After screening, 75 studies met our inclusion criteria. This systematic review study examined 105 miRNAs, of which 44 have a positive effect, and 47 miRNAs inhibit tamoxifen function. Fourteen miRNAs have a controversial effect, ie, some studies show positive and negative effects. The study of miRNAs affecting tamoxifen function in breast cancer patients may facilitate the identification of individuals at higher risk of disease recurrence. Conversely, it can potentially utilize appropriate interventions to defeat drug resistance effectively.
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Antineoplásicos Hormonais , Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , MicroRNAs , Tamoxifeno , Humanos , Tamoxifeno/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , MicroRNAs/genética , Feminino , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Lymphoma is a cancer affecting the lymphatic system that fights infections and diseases. In addition to surgery, radiotherapy, and chemotherapy, novel approaches have recently been investigated, such as phytostilbenes in treating lymphoma. Phytostilbenes are natural compounds present in various plants and have been shown to have different therapeutic effects, including anticancer properties. Resveratrol is a main phytostilbene with various derivates followed by pterostilbene and piceatannol. Studies have revealed that phytostilbenes can suppress the growth and proliferation of lymphoma cells by inducing apoptosis and inhibiting specific enzyme activity in cancer cell survival. The compounds also have antiinflammatory effects contributing to reducing lymphoma-associated inflammation. Additionally, phytostilbenes have been shown to increase the immune system's ability to fight cancer cells by activating immune cells (T-cells and natural killer cells). This review investigates the potential therapeutic effects of phytostilbenes, including resveratrol, pterostilbene, piceatannol, and pinosylvin, against lymphoma.
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Linfoma , Fitoalexinas , Estilbenos , Humanos , Resveratrol/uso terapêutico , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Linfoma/tratamento farmacológicoRESUMO
RNA therapy is one of the new treatments using small RNA molecules to target and regulate gene expression. It involves the application of synthetic or modified RNA molecules to inhibit the expression of disease-causing genes specifically. In other words, it silences genes and suppresses the transcription process. The main theory behind RNA therapy is that RNA molecules can prevent the translation into proteins by binding to specific messenger RNA (mRNA) molecules. By targeting disease-related mRNA molecules, RNA therapy can effectively silence or reduce the development of harmful proteins. There are different types of RNA molecules used in therapy, including small interfering RNAs (siRNAs), microRNAs (miRNAs), aptamer, ribozyme, and antisense oligonucleotides (ASOs). These molecules are designed to complement specific mRNA sequences, allowing them to bind and degrade the targeted mRNA or prevent its translation into protein. Nanotechnology is also highlighted to increase the efficacy of RNA-based drugs. In this chapter, while examining various methods of RNA therapy, we discuss the advantages and challenges of each.
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MicroRNAs , Humanos , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Oligonucleotídeos/uso terapêutico , Oligonucleotídeos Antissenso/química , Oligonucleotídeos Antissenso/farmacologia , Oligonucleotídeos Antissenso/uso terapêutico , RNA Mensageiro/genéticaRESUMO
The D. cinnabari plant was loaded into the chitosan (Chn)/polycaprolactone (PCL) nanofibers in two forms: resin (D. cinnabari) and its ethyl acetate fraction. The Chn/PCL, Chn/PCL/D. cinnabari (CPD, 1, 3, and 5 %), and Chn/PCL/ethyl acetate extract D. cinnabari (CPED, 1, 3, and 5 %) showed no toxicity against human dermal fibroblast cells. The lactate dehydrogenase assay results indicated that the toxicity of pour, coated D. cinnabari, and CPED nanofibers were lower than 10 and 15 % after 1 and 3 days, respectively. The antibacterial results showed the inhibition zone for ethyl acetate extract D. cinnabari (ED-3 %), the Chn/PCL-2, and CPED3% nanofibers was 8.1, 7.4, 4.2, 5.1 mm, 12.8, 12.4, 21.7, 17.2 mm, and 24.7, 22.9, 37.1, 30.2 mm against S. aureus, B. subtilis, E. coli, and P. aeruginosa, respectively. The antibacterial activity results showed synergistic effect between the Chn/PCL and ethyl acetate extract D. cinnabari occurred. The diameter of wounds (1.50 × 1.50 cm diameter) made on the dorsal surface of rabbits reduced to 1.50 × 0.70, 0.50 × 0.30, 1.00 × 1.00, 0.60 × 0.50, 0.20 × 0.05, and 0.00 × 0.00 cm in the presence of ordinary gauze dressing, silver sulfadiazine, ED-3 %, Chn/PCL-2, CPD3%, and CPED3%nanofibers, respectively, after 14 days.
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Acetatos , Quitosana , Nanofibras , Extratos Vegetais , Animais , Humanos , Coelhos , Quitosana/farmacologia , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cicatrização , Poliésteres/farmacologiaRESUMO
As a clinically approved treatment strategy, chemotherapy-mediated tumor suppression has been compromised, and in spite of introducing various kinds of anticancer drugs, cancer eradication with chemotherapy is still impossible. Chemotherapy drugs have been beneficial in improving the prognosis of cancer patients, but after resistance emerged, their potential disappeared. Oxaliplatin (OXA) efficacy in tumor suppression has been compromised by resistance. Due to the dysregulation of pathways and mechanisms in OXA resistance, it is suggested to develop novel strategies for overcoming drug resistance. The targeted delivery of OXA by nanostructures is described here. The targeted delivery of OXA in cancer can be mediated by polymeric, metal, lipid and carbon nanostructures. The advantageous of these nanocarriers is that they enhance the accumulation of OXA in tumor and promote its cytotoxicity. Moreover, (nano)platforms mediate the co-delivery of OXA with drugs and genes in synergistic cancer therapy, overcoming OXA resistance and improving insights in cancer patient treatment in the future. Moreover, smart nanostructures, including pH-, redox-, light-, and thermo-sensitive nanostructures, have been designed for OXA delivery and cancer therapy. The application of nanoparticle-mediated phototherapy can increase OXA's potential in cancer suppression. All of these subjects and their clinical implications are discussed in the current review.
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Gynecologic cancer is a significant cause of death in women worldwide, with cervical cancer, ovarian cancer, and endometrial cancer being among the most well-known types. The initiation and progression of gynecologic cancers involve a variety of biological functions, including angiogenesis and metastasis-given that death mostly occurs from metastatic tumors that have invaded the surrounding tissues. Therefore, understanding the molecular pathways underlying gynecologic cancer metastasis is critical for enhancing patient survival and outcomes. Recent research has revealed the contribution of numerous non-coding RNAs (ncRNAs) to metastasis and invasion of gynecologic cancer by affecting specific cellular pathways. This review focuses on three types of gynecologic cancer (ovarian, endometrial, and cervical) and three kinds of ncRNAs (long non-coding RNAs, microRNAs, and circular RNAs). We summarize the detailed role of non-coding RNAs in the different pathways and molecular interactions involved in the invasion and metastasis of these cancers.
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Regulatory T cells (Tregs), possess a pivotal function in the maintenance of immune homeostasis. The dysregulated activity of Tregs has been associated with the onset of autoimmune diseases and cancer. Hence, Tregs are promising targets for interventions aimed at steering the immune response toward the desired path, either by augmenting the immune system to eliminate infected and cancerous cells or by dampening it to curtail the damage to self-tissues in autoimmune disorders. The activation of Tregs has been observed to have a potent immunosuppressive effect against T cells that respond to self-antigens, thus safeguarding our body against autoimmunity. Therefore, promoting Treg cell stability presents a promising strategy for preventing or managing chronic inflammation that results from various autoimmune diseases. On the other hand, Tregs have been found to be overactivated in several forms of cancer, and their role as immune response regulators with immunosuppressive properties poses a significant impediment to the successful implementation of cancer immunotherapy. However, the targeting of Tregs in a systemic manner may lead to the onset of severe inflammation and autoimmune toxicity. It is imperative to develop more selective methods for targeting the function of Tregs in tumors. In this review, our objective is to elucidate the function of Tregs in tumors and autoimmunity while also delving into numerous therapeutic strategies for reprogramming their function. Our focus is on reprogramming Tregs in a highly activated phenotype driven by the activation of key surface receptors and metabolic reprogramming. Furthermore, we examine Treg-based therapies in autoimmunity, with a specific emphasis on Chimeric Antigen Receptor (CAR)-Treg therapy and T-cell receptor (TCR)-Treg therapy. Finally, we discuss key challenges and the future steps in reprogramming Tregs that could lead to the development of novel and effective cancer immunotherapies.
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Ten percent of people who are of reproductive age experience infertility. Sometimes the most effective therapies, including technology for assisted reproduction, may lead to unsuccessful implantation. Because of the anticipated epigenetic alterations of in vitro as well as in vitro fertilization growth of embryos, these fertility techniques have also been linked to unfavorable pregnancy outcomes linked to infertility. In this regard, a variety of non-coding RNAs such as long noncoding RNAs (lncRNAs) act as epigenetic regulators in the various physiological and pathophysiological events such as infertility. LncRNAs have been made up of cytoplasmic and nuclear nucleotides; RNA polymerase II transcribes these, which are lengthier than 200 nt. LncRNAs perform critical roles in a number of biological procedures like nuclear transport, X chromosome inactivation, apoptosis, stem cell pluripotency, as well as genomic imprinting. A significant amount of lncRNAs were linked into a variety of biological procedures as high throughput sequencing technology advances, including the development of the testes, preserving spermatogonial stem cells' capacity for differentiation along with self-renewal, and controlling spermatocyte meiosis. All of them point to possible utility of lncRNAs to be biomarkers and treatment aims for female infertility. Herein, we summarize various lncRNAs that are involved in female infertility.
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Hydrogels represent intricate three-dimensional polymeric structures, renowned for their compatibility with living systems and their ability to naturally degrade. These networks stand as promising and viable foundations for a range of biomedical uses. The practical feasibility of employing hydrogels in clinical trials has been well-demonstrated. Among the prevalent biomedical uses of hydrogels, a significant application arises in the context of wound healing. This intricate progression involves distinct phases of inflammation, proliferation, and remodeling, often triggered by trauma, skin injuries, and various diseases. Metabolic conditions like diabetes have the potential to give rise to persistent wounds, leading to delayed healing processes. This current review consolidates a collection of experiments focused on the utilization of hydrogels to expedite the recovery of wounds. Hydrogels have the capacity to improve the inflammatory conditions at the wound site, and they achieve this by diminishing levels of reactive oxygen species (ROS), thereby exhibiting antioxidant effects. Hydrogels have the potential to enhance the growth of fibroblasts and keratinocytes at the wound site. They also possess the capability to inhibit both Gram-positive and Gram-negative bacteria, effectively managing wounds infected by drug-resistant bacteria. Hydrogels can trigger angiogenesis and neovascularization processes, while also promoting the M2 polarization of macrophages, which in turn mitigates inflammation at the wound site. Intelligent and versatile hydrogels, encompassing features such as pH sensitivity, reactivity to reactive oxygen species (ROS), and responsiveness to light and temperature, have proven advantageous in expediting wound healing. Furthermore, hydrogels synthesized using environmentally friendly methods, characterized by high levels of biocompatibility and biodegradability, hold the potential for enhancing the wound healing process. Hydrogels can facilitate the controlled discharge of bioactive substances. More recently, there has been progress in the creation of conductive hydrogels, which, when subjected to electrical stimulation, contribute to the enhancement of wound healing. Diabetes mellitus, a metabolic disorder, leads to a slowdown in the wound healing process, often resulting in the formation of persistent wounds. Hydrogels have the capability to expedite the healing of diabetic wounds, facilitating the transition from the inflammatory phase to the proliferative stage. The current review sheds light on the biological functionalities of hydrogels, encompassing their role in modulating diverse mechanisms and cell types, including inflammation, oxidative stress, macrophages, and bacteriology. Additionally, this review emphasizes the significance of smart hydrogels with responsiveness to external stimuli, as well as conductive hydrogels for promoting wound healing. Lastly, the discussion delves into the advancement of environmentally friendly hydrogels with high biocompatibility, aimed at accelerating the wound healing process.
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Diabetes Mellitus , Hidrogéis , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio , Antibacterianos/farmacologia , Medicina de Precisão , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Cicatrização , InflamaçãoRESUMO
The latest advancements in oncology involves the creation of multifunctional nanostructures. The integration of nanoparticles into the realm of cancer therapy has brought about a transformative shift, revolutionizing the approach to addressing existing challenges and limitations in tumor elimination. This is particularly crucial in combating the emergence of resistance, which has significantly undermined the effectiveness of treatments like chemotherapy and radiotherapy. GO stands as a carbon-derived nanoparticle that is increasingly finding utility across diverse domains, notably in the realm of biomedicine. The utilization of GO nanostructures holds promise in the arena of oncology, enabling precise transportation of drugs and genetic material to targeted sites. GO nanomaterials offer the opportunity to enhance the pharmacokinetic behavior and bioavailability of drugs, with documented instances of these nanocarriers elevating drug accumulation at the tumor location. The GO nanostructures encapsulate genes, shielding them from degradation and facilitating their uptake within cancer cells, thereby promoting efficient gene silencing. The capability of GO to facilitate phototherapy has led to notable advancements in reducing tumor progression. By PDT and PTT combination, GO nanomaterials hold the capacity to diminish tumorigenesis. GO nanomaterials have the potential to trigger both cellular and innate immunity, making them promising contenders for vaccine development. Additionally, types of GO nanoparticles that respond to specific stimuli have been applied in cancer eradication, as well as for the purpose of cancer detection and biomarker diagnosis. Endocytosis serves as the mechanism through which GO nanomaterials are internalized. Given these advantages, the utilization of GO nanomaterials for tumor elimination comes highly recommended.
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The use of phytochemicals for purpose of cancer therapy has been accelerated due to resistance of tumor cells to conventional chemotherapy drugs and therefore, monotherapy does not cause significant improvement in the prognosis and survival of patients. Therefore, administration of natural products alone or in combination with chemotherapy drugs due to various mechanisms of action has been suggested. However, cancer therapy using phytochemicals requires more attention because of poor bioavailability of compounds and lack of specific accumulation at tumor site. Hence, nanocarriers for specific delivery of phytochemicals in tumor therapy has been suggested. The pharmacokinetic profile of natural products and their therapeutic indices can be improved. The nanocarriers can improve potential of natural products in crossing over BBB and also, promote internalization in cancer cells through endocytosis. Moreover, (nano)platforms can deliver both natural and synthetic anti-cancer drugs in combination cancer therapy. The surface functionalization of nanostructures with ligands improves ability in internalization in tumor cells and improving cytotoxicity of natural compounds. Interestingly, stimuli-responsive nanostructures that respond to endogenous and exogenous stimuli have been employed for delivery of natural compounds in cancer therapy. The decrease in pH in tumor microenvironment causes degradation of bonds in nanostructures to release cargo and when changes in GSH levels occur, it also mediates drug release from nanocarriers. Moreover, enzymes in the tumor microenvironment such as MMP-2 can mediate drug release from nanocarriers and more progresses in targeted drug delivery obtained by application of nanoparticles that are responsive to exogenous stimulus including light.
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Nanopartículas , Nanoestruturas , Neoplasias , Humanos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
Pseudoexfoliation syndrome (PEX) is a critical clinical and biological extracellular matrix systemic disorder. Despite the unknown nature of PEX etiopathogenesis, it is proven to be associated with various genes and factors. The present research focused on analyzing the expression of miR and inflammatory cytokines in PEX. Serum and aqueous humor (AH) were collected prior to cataract surgery or trabeculectomy from 99 participants (64 with PEX glaucoma, and 35 controls). Real-time PCR was used for assessing the expression pattern of some miRNAs namely let-7b, miR-29a, miR-126, miR-34a, and miR-181a-5p. ELISA was carried out to explore the transcription of some inflammatory cytokines such as TGF-ß, TNF-α, and IL-6. The indication of our results was a significant enhancement in the expression of let-7, miR-34a, and miR-181a-5p in PEX in contrast to the control group. Notwithstanding a significant suppression in miR-29a, and miR-126 expression levels in PEX in contrast to the control group. Analysis of ROC curve revealed that miR-29a and miR-34a are able to act as useful markers in order to discriminate the PEX group from the PEX negative subjects which were determined as the control group. According to the results obtained, the mean levels of TGF-ß, TNF-α, and IL-6 upregulated among PEX subjects in contrast to control samples. In conclusion, our findings indicated that the selected cytokines alongside the selected miRNAs could be introduced as a biomarker panel in the diagnosis of PEX.
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Síndrome de Exfoliação , MicroRNAs , Humanos , MicroRNAs/genética , Fator de Necrose Tumoral alfa , Síndrome de Exfoliação/genética , Interleucina-6 , Fator de Crescimento Transformador beta/genética , CitocinasRESUMO
Brain tumors, which are highly malignant, pose a significant threat to health and often result in substantial rates of mortality and morbidity worldwide. The brain cancer therapy has been challenging due to obstacles such as the BBB, which hinders effective delivery of therapeutic agents. Additionally, the emergence of drug resistance further complicates the management of brain tumors. TMZ is utilized in brain cancer removal, but resistance is a drawback. ncRNAs are implicated in various diseases, and their involvement in the cancer is particularly noteworthy. The focus of the current manuscript is to explore the involvement of ncRNAs in controlling drug resistance, specifically in the context of resistance to the chemotherapy drug TMZ. The review emphasizes the function of ncRNAs, particularly miRNAs, in modulating the growth and invasion of brain tumors, which significantly influences their response to TMZ treatment. Through their interactions with various molecular pathways, miRNAs are modulators of TMZ response. Similarly, lncRNAs also associate with molecular pathways and miRNAs, affecting the efficacy of TMZ chemotherapy. Given their functional properties, lncRNAs can either induce or suppress TMZ resistance in brain tumors. Furthermore, circRNAs, which are cancer controllers, regulate miRNAs by acting as sponges, thereby impacting the response to TMZ chemotherapy. The review explores the correlation between ncRNAs and TMZ chemotherapy, shedding light on the underlying molecular pathways involved in this process.
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Neoplasias Encefálicas , Glioblastoma , MicroRNAs , RNA Longo não Codificante , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , RNA Longo não Codificante/genética , Epigênese Genética , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , MicroRNAs/genética , MicroRNAs/uso terapêutico , Linhagem Celular Tumoral , Glioblastoma/patologiaRESUMO
In addition to environmental conditions, lifestyle factors, and chemical exposure, aberrant gene expression and mutations involve in the beginning and development of urological tumors. Even in Western nations, urological malignancies are among the top causes of patient death, and their prevalence appears to be gender dependent. The prognosis for individuals with urological malignancies remains dismal and unfavorable due to the ineffectiveness of conventional treatment methods. PI3K/Akt is a popular biochemical mechanism that is activated in tumor cells as a result of PTEN loss. PI3K/Akt escalates growth and metastasis. Moreover, due to the increase in tumor cell viability caused by PI3K/Akt activation, cancer cells may acquire resistance to treatment. This review article examines the function of PI3K/Akt in major urological tumors including bladder, prostate, and renal tumors. In prostate, bladder, and kidney tumors, the level of PI3K and Akt are notably elevated. In addition, the activation of PI3K/Akt enhances the levels of Bcl-2 and XIAP, hence increasing the tumor cell survival rate. PI3K/Akt ] upregulates EMT pathways and matrix metalloproteinase expression to increase urological cancer metastasis. Furthermore, stimulation of PI3K/Akt results in drug- and radio-resistant cancers, but its suppression by anti-tumor drugs impedes the tumorigenesis.