Current and future immunotherapeutic approaches in pancreatic cancer treatment.

Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type of tumor have remained grim for a long time. Currently, it is extremely challenging to prevent or detect it early enough for effective treatment because patients rarely exhibit symptoms and there are no reliable indicators for detection. Most patients have advanced or spreading cancer that is difficult to treat, and treatments like chemotherapy and radiotherapy can only slightly prolong their life by a few months. Immunotherapy has revolutionized the treatment of pancreatic cancer, yet its effectiveness is limited by the tumor's immunosuppressive and hard-to-reach microenvironment. First, this article explains the immunosuppressive microenvironment of pancreatic cancer and highlights a wide range of immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered and chimeric antigen receptor [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced killer cells, immune checkpoint inhibitors, immunomodulators, cancer vaccines, and strategies targeting myeloid cells in the context of contemporary knowledge and future trends. Lastly, it discusses the main challenges ahead of pancreatic cancer immunotherapy.

Comparative Evaluation of Levamisole and Broccoli in Mitigating Testicular Oxidative Stress and Apoptotic Alterations Caused by Cadmium and Lead Exposure in Rats.

Considering the significance of heavy metals in infertility and their reduction through natural and synthetic compounds, a comparative study of broccoli and levamisole in cadmium and lead poisoning was conducted. Male Wistar rats (48 in total) were divided into 8 groups. Control, cadmium, lead, levamisole, and broccoli were administered individually to groups 1-5, while groups 6-8 received combinations. Various measurements were taken, including final weight, testicular weight, and the GSI coefficient. Sperm parameters, spermatogenesis cell count, oxidative stress biomarkers, and apoptosis indices were assessed using ELISA kits and methods in testicular tissue. The results indicated that the GSI coefficient was lowest in group 2 and highest in group 4, showing a significant difference (P < 0.001). Sperm concentration peaked in group 1 and broccoli-treated ones, while motility was highest in group 5. Testicular cell counts and Johnson score were highest in groups 1 and 2, and lowest in cadmium-exposed groups. These differences were statistically significant at P < 0.01. Enzyme activities related to oxidative stress varied. Group 2 exhibited the highest catalase (CAT) and superoxide dismutase (SOD) activities, while glutathione peroxidase (GPx) levels peaked in groups 1, 4, and 5. Malondialdehyde (MDA) concentrations were significantly reduced in the group 5 (P < 0.05). Apoptosis indices revealed that broccoli had the highest Bcl-2 levels and lowest Bax/Bcl-2 ratio, indicating its anti-apoptotic effect. Group 4 showed less efficacy compared to broccoli in protecting fertility indices. In conclusion, cadmium and lead significantly impact male fertility, while broccoli extract demonstrates promising efficacy in mitigating damage when compared to levamisole. This underscores its antioxidant and anti-apoptotic properties.

Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature.

Background: Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, node-negative, or 1 to 3 lymph node-positive early breast cancers (EBCs). The cost of the test, which is not available in low-middle income countries (LMICs), is not within the means of most individuals. The Ki-67 index is a marker of tumor proliferation that is cost-effective and easily performed and has been substituted in many cases to obtain prognostic information. Objective: We aimed to identify the correlation between the ODx recurrence score (RS) and the Ki-67 index in HR-positive EBCs and to determine whether Ki-67, like the ODx, can help facilitate clinical decision-making. Design: Systematic review correlating Ki-67 index and ODx in HR-positive and HER2-negative EBCs as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data sources and methods: We searched different databases between January 2010 and May 2023 and included retrospective/prospective cohorts, clinical trials, case-control, and cross-sectional studies involving HR-positive and HER2-negative EBCs correlating the Ki-67 index and ODx RS categories. Results: Of the 18 studies included, 16 indicated a positive or weakly positive correlation between ODx and the Ki-67 index. The combined P value of the included studies is <0.05 (P = .000), which shows a statistical significance between the 2. Our review also discusses the potential of machine learning and artificial intelligence (AI) in Ki-67 assessment, offering a cost-effective and reproducible alternative. Conclusion: Even although there are limitations, studies indicate a favorable association between ODx and the Ki-67 index in specific situations. This implies that Ki-67 can offer important predictive details, especially regarding the likelihood of relapse in HR-positive EBC. This is particularly significant in LMICs where financial constraints often hinder the availability of costly diagnostic tests.

Comparing Ki-67 and Oncotype-Dx Tests for Predicting Early Breast Cancer Outcomes: A Comprehensive Review The study explored the correlation between the expensive Oncotype-Dx (ODx) test and the more affordable Ki-67 index in predicting outcomes for certain breast cancers. Results from 16 out of 18 studies indicated a significant link between the 2 tests, suggesting Ki-67 could be a cost-effective alternative, especially in low- to middle-income countries.

Bioelectrocatalytic Activity of One-Dimensional Porous Pt Nanoribbons for Efficient Inhibition of Tumor Growth and Metastasis.

Designing and synthesizing one-dimensional porous Pt nanocrystals with unique optical, electrocatalytic, and theranostic properties are gaining lots of attention, especially to overcome the challenges of tumor recurrence and resistance to platinum-based chemotherapy. Herein, we represented an interesting report of a one-step and facile strategy for synthesizing multifunctional one-dimensional (1D) porous Pt nanoribbons (PtNRBs) with highly efficient therapeutic effects on cancer cells based on inherent electrocatalytic activity. The critical point in the formation of luminescent porous PtNRBs was the use of human hemoglobin (Hb) as a shape-regulating, stabilizing, and reducing agent with facet-specific domains on which fluorescent platinum nanoclusters at first are aggregated by aggregation-induced emission phenomena (AIE) and then crystallized into contact and penetration twins, as intermediate products, followed by shaping of the final luminescent porous ribbon nanomaterials, owing to oriented attachment association via the Ostwald ripening mechanism. From a medical point of view, the key strategy for effective cancer therapy occured via using low-dosage ethanol in the presence of electroactive porous PtNRBs based on intracellular ethanol oxidation-mediated reactive oxygen species (ROS) generation. The role of heme groups of Hb, as electrocatalytically active centers, was successfully demonstrated in both kinetically controlled anisotropic growth of NRBs for slowing down the reduction of Pt(II) followed by oligomerization of Pt(II)-Hb complexes via platinophilic interactions as well as electrocatalytic ethanol oxidation for therapy. Interestingly, hyaluronic acid-targeted (HA) Hb-PtNRB in the presence of low-dose ethanol caused extraordinary arrest of tumor growth and metastasis with no recurrence even after the treatment course stopped, which caused elongation of tumor-bearing mice survival. HA/Hb-PtNRB was completely biocompatible and exhibited high tumor-targeting efficacy for fluorescent imaging of breast tumors. Therefore, the synergistic electrocatalytic activity of PtNRBs is presented as an efficient and safe cancer theranostic method for the first time.

The novel anti-fibrillary effects of volatile compounds α-asarone and ß-caryophyllene on tau protein: Towards promising therapeutic agents for Alzheimer's disease.

The abnormal deposition of tau protein is one of the critical causes of tauopathies including Alzheimer's disease (AD). In recent years, there has been great interest in the use of essential oils and volatile compounds in aromatherapy for treating AD, since volatile compounds can directly reach the brain through intranasal administration. The volatile compounds α-asarone (ASA) and ß-caryophyllene (BCP) have revealed various important neuroprotective properties, useful in treating AD. In this study, the volatile compounds ASA and BCP were assessed for their effectiveness in preventing tau fibrillation, disassembly of pre-formed tau fibrils, and disaggregation of tau aggregates. SDS-PAGE and AFM analyses revealed that ASA and BCP inhibited tau fibrillation/aggregation and decreased the mean size of tau oligomers. Tau samples treated with ASA and BCP, showed a reduction in ThT and ANS fluorescence intensities, and a decrease in the ß-sheet content. Additionally, ASA and BCP disassembled the pre-formed tau fibrils to the granular and linear oligomeric intermediates. Treatment of neuroblastoma SH-SY5Y cells with tau samples treated with ASA and BCP, revealed protective effects as shown by reduced toxicity of the cells, due to the inhibition of tau fibrillation/aggregation. Overall, ASA and BCP appeared to be promising therapeutic candidates for AD.

Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis.

Vitamin D is a fat-soluble steroid hormone that was initially known only for regulating calcium and phosphorus levels and maintaining bone health. However, it was later discovered that many organs express vitamin D metabolizing enzymes and have a ligand for vitamin D, which regulates the expression of an extensive assortment of genes. As a result, vitamin D is indispensable for the proper function of organs, and its deficiency is believed to be a critical factor in symptoms and disorders such as cardiovascular diseases, autoimmune diseases, and cancers. The significance of vitamin D in reproductive tissues was recognized later, and studies have revealed its crucial role in male and female fertility, as well as proper reproductive function during pregnancy. Vitamin D deficiency has been identified as a risk factor for infertility, gonadal cancers, pregnancy complications, polycystic ovary syndrome, and endometriosis. However, data investigating the association between vitamin D levels and reproductive disorders, including endometriosis, have encountered inconsistencies. Therefore, the present study aims to review existing research on the effect of vitamin D on proper reproductive function, and the role of deficiency in reproductive diseases and specifically focuses on endometriosis.

Cadmium toxicity promotes hormonal imbalance and induces the expression of genes involved in systemic resistances in barley.

Cadmium (Cd) is a widely distributed pollutant that adversely affects plants' metabolism and productivity. Phytohormones play a vital role in the acclimation of plants to metal stress. On the other hand, phytohormones trigger systemic resistances, including systemic acquired resistance (SAR) and induced systemic resistance (ISR), in plants in response to biotic interactions. The present study aimed to investigate the possible induction of SAR and ISR pathways in relation to the hormonal alteration of barley seedlings in response to Cd stress. Barley seedlings were exposed to 1.5 mg g-1 Cd in the soil for three days. The nutrient content, oxidative status, phytohormones profile, and expression of genes involved in SAR and ISR pathways of barley seedlings were examined. Cd accumulation resulted in a reduction in the nutrient content of barley seedlings. The specific activity of superoxide dismutase and the hydrogen peroxide content significantly increased in response to Cd toxicity. Abscisic acid, jasmonic acid, and ethylene content increased under Cd exposure. Cd treatment resulted in the upregulation of NPR1, PR3, and PR13 genes in SAR pathways. The transcripts of PAL1 and LOX2.2 genes in the ISR pathway were also significantly increased in response to Cd treatment. These findings suggest that hormonal-activated systemic resistances are involved in the response of barley to Cd stress.

Enhancing nutritional status, growth, and fruit quality of dried figs using organic fertilizers in rain-fed orchards: A case study in Estahban, Iran.

The majority of Iranian fig production is exported, making it one of the world's most well-known healthy crops. Therefore, the main objective of the current experiment was to investigate the effects of various types of organic fertilizers, such as animal manure (cow and sheep), bird manure (partridge, turkey, quail, and chicken), and vermicompost, on the nutritional status of trees, vegetative and reproductive tree characteristics, fruit yield, and fruit quality traits in dried fig cultivar ("Sabz"). According to the findings, applying organic fertilizers, particularly turkey and quail, significantly improves vegetative and reproductive characteristics. However, other manures such as sheep, chicken, and vermicompost had a similar effect on the growth parameters of fig trees. Additionally, the findings indicated that except for potassium, use of all organic fertilizers had an impact on macro and microelements such as phosphorus, nitrogen, and sodium amount in fig tree leaves. Also, based on fruit color analysis in dried figs, the use of all organic fertilizers improved fruit color. Moreover, the analyses fruit biochemical showed that the use of some organic fertilizers improved that TSS and polyphenol compounds such as coumarin, vanillin, hesperidin gallic acid and trans frolic acid. In general, the results indicated that the addition of organic fertilizers, especially turkey manure, led to increased vegetative productivity and improvement in the fruit quality of the rain-fed fig orchard.

IL-15 as a key regulator in NK cell-mediated immunotherapy for cancer: From bench to bedside.

Interleukin 15 (IL-15) has emerged as a crucial factor in the relationship between natural killer (NK) cells and immunotherapy for cancer. This review article aims to provide a comprehensive understanding of the role of IL-15 in NK cell-mediated immunotherapy. First, the key role of IL-15 signaling in NK cell immunity is discussed, highlighting its regulation of NK cell functions and antitumor properties. Furthermore, the use of IL-15 or its analogs in clinical trials as a therapeutic strategy for various cancers, including the genetic modification of NK cells to produce IL-15, has been explored. The potential of IL-15-based therapies, such as chimeric antigen receptor (CAR) T and NK cell infusion along with IL-15 in combination with checkpoint inhibitors and other treatments, has been examined. This review also addresses the challenges and advantages of incorporating IL-15 in cell-based immunotherapy. Additionally, unresolved questions regarding the detection and biological significance of the soluble IL-15/IL-15Rα complex, as well as the potential role of IL-15/IL-15Rα in human cancer and the immunological consequences of prolonged exposure to soluble IL-15 for NK cells, are discussed.

LncRNAs: Emerging biomarkers and therapeutic targets in rectal cancer.

According to findings, long non-coding RNAs (lncRNAs) have an important function in the onset and growth of various cancers, including rectal cancer (RC). RC offers unique issues in terms of diagnosis, treatment, and results, needing a full understanding of the cellular mechanisms that cause it to develop. This thorough study digs into the various functions that lncRNAs perform in RC, giving views into their multiple roles as well as possible therapeutic consequences. The function of lncRNAs in RC cell proliferation, apoptosis, migratory and infiltrating capacities, epithelial-mesenchymal shift, and therapy tolerance are discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell functions such as angiogenesis, death, immunity, and growth. Systemic lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. Besides adding to their diagnostic utility, lncRNAs offer therapeutic opportunities as actors, contributing to the expanding landscape of cancer research. Moreover, the investigation looks into the assessment and predictive utility of lncRNAs as RC markers. The article also offers insight into lncRNAs as chemoresistance and drug resistance facilitators in the setting of RC.

Herb Extracellular Vesicle-Chitosan-PEGylated Graphene Oxide Conjugate Delivers Estrogen Receptor α Targeting siRNA to Breast Cancer Cells.

Herb-based extracellular vesicles (EV), inherently replete with bioactive proteins, RNA, lipids, and other medicinal compounds, are noncytotoxic and uniquely capable of cellular delivery to meet the ever-stringent challenges of ongoing clinical applications. EVs are abundant in nature, affordable, and scalable, but they are also incredibly fragile and stuffed with many biomolecules. To address the low drug binding abilities and poor stability of EVs, we demonstrated herb-based EVs (isolated from neem, mint, and curry leaves) conjugated with chitosan (CS) and PEGylated graphene oxide (GP) that led to their transformation into robust and efficient vectors. The designed conjugates successfully delivered estrogen receptor α (ERα1)-targeting siRNA to breast cancer MCF7 cells. Our data revealed that neem-based EV-CS-GP conjugates were most efficient in cellular siRNA delivery, which could be attributed to hyaluronic acid-mediated recognition of neem EVs by MCF7 cells via CD44 receptors. Our approach shows a futuristic direction in designing clinically viable, sustainable, nontoxic EV-based vehicles that can deliver a variety of functional siRNA cargos.

Exploring low-dose gamma radiation effects on monoterpene biosynthesis in Thymus vulgaris: insights into plant defense mechanisms.

Thymus vulgaris, commonly known as thyme, is a plant renowned for producing monoterpenes. This study aimed to understand the effects of low-dose gamma radiation, specifically in the range of 1-5 Gy, on various traits of Thymus vulgaris, providing context on its importance in agricultural and medicinal applications. The research explored morpho-physiological, biochemical, and gene-expression responses in thyme plants under no gamma- and gamma-ray exposure conditions. The study revealed complex relationships between gamma-ray doses and plant characteristics. In particular, shoot and root lengths initially increased with low doses (1-3 Gy) but decreased at higher doses (5 Gy), suggesting a dose-dependent threshold effect. Similarly, shoot and root fresh weights displayed an initial increase followed by a decline with increasing doses. Biochemical parameters showed dose-dependent responses, with low to moderate doses (1-3 Gy) stimulating enzyme activities and high doses (5 Gy) inhibiting them. Gene expression analysis was focused on the following specific genes: thymol synthase, γ-terpinene synthase, and carvacrol synthase. Low to moderate doses increased the expression of these genes, resulting in increased production of bioactive compounds. However, higher doses had diminished effects or suppressed gene expression. Metabolite analysis demonstrated dose-dependent responses, with moderate doses enhancing secondary metabolite production, while higher doses provided limited benefits. These findings underscore the implications of using gamma radiation to enhance secondary metabolite production in plants and its potential applications in agriculture, medicine, and environmental science. The study emphasizes the potential of gamma radiation as an external stressor to influence plant responses and highlights the importance of understanding such effects in various fields.

RIPK3 and RIPK1 gene expression in pterygium: unveiling molecular insights into pathogenesis.

BACKGROUND: Pterygium, characterized by the abnormal proliferation of epithelial cells, matrix remodeling, vascularization, and lesion migration, is a prevalent ocular surface disease involving the growth of fibrovascular tissue on the cornea. Despite the unclear underlying causes of pterygium, numerous investigations have indicated the involvement of cell death pathways in the regulation of cell cycle dynamics. Consequently, the objective of this study was to assess the expression levels of necroptosis markers in individuals diagnosed with pterygium, aiming to shed light on the potential role of necroptosis in the pathogenesis of this condition. METHODS: This study aimed to investigate the expression patterns of receptor-interacting serine/threonine kinase 3 (RIPK3) and receptor-interacting serine/threonine kinase 1 (RIPK1) genes in pterygium tissues. 41 patients undergoing pterygium excision surgery were recruited. Resected pterygium samples and normal conjunctival tissues were collected, and RIPK3 and RIPK1 mRNA levels were measured using quantitative real-time PCR. RESULTS: Our findings reveal that the expression of RIPK3 is significantly increased in samples obtained from individuals with pterygium. However, no significant alterations were observed in the expression of RIPK1 in these samples. Results showed significantly higher RIPK3 expression in pterygium tissues compared to controls. Moreover, increased RIPK3 levels correlated negatively with pterygium recurrence rates. CONCLUSIONS: These findings suggest RIPK3 may play a protective role against pterygium recurrence through necroptosis.

The relationship between autophagy and respiratory viruses.

Respiratory viruses have caused severe global health problems and posed essential challenges to the medical community. In recent years, the role of autophagy as a critical process in cells in viral respiratory diseases has been noticed. One of the vital catabolic biological processes in the body is autophagy. Autophagy contributes to energy recovery by targeting and selectively directing foreign microorganisms, organelles, and senescent intracellular proteins to the lysosome for degradation and phagocytosis. Activation or suppression of autophagy is often initiated when foreign pathogenic organisms such as viruses infect cells. Because of its antiviral properties, several viruses may escape or resist this process by encoding viral proteins. Viruses can also use autophagy to enhance their replication or prolong the persistence of latent infections. Here, we provide an overview of autophagy and respiratory viruses such as coronavirus, rhinovirus, parainfluenza, influenza, adenovirus, and respiratory syncytial virus, and examine the interactions between them and the role of autophagy in the virus-host interaction process and the resulting virus replication strategy.

Integrated application of multiple indicators and geographic information system-based approaches for comprehensive assessment of environmental impacts of toxic metals-contaminated agricultural soils and vegetables.

Conventional monitoring and mapping approaches are laborious, expensive, and time-consuming because they need a large number of data and consequently extensive sampling and experimental operations. Therefore, due to the growing concern about the potential of contamination of soils and agricultural products with heavy metals (HMs), a field experiment was conducted on 77 farm lands in an area of 2300 ha in the southeast of Shiraz (Iran) to investigate the source of metal contamination in the soils and vegetables and to model spatial distribution of HMs (iron, Fe; manganese, Mn; copper, Cu; zinc, Zn; cadmium, Cd; nickel, Ni, and lead, Pb) over the region using geographic information system (GIS) and geostatistical (Ordinary Kriging, OK) approaches and compare the results with deterministic approaches (Inverse Distance Weighting, IDW with different weighting power). Furthermore, some ecological and health risks indices including Pollution index (PI), Nemerow integrated pollution index (NIPI), pollution load index (PLI), degree of contamination (Cdeg), modified contamination degree (mCd), PIaverage and PIvector for soil quality, multi-element contamination (MEC), the probability of toxicity (MERMQ), the potential ecological index (RI), total hazard index (THI) and total carcinogenic risk index (TCR) based on ingestion, inhalation, and dermal exposure pathways for adults and children respectively for analyzing the noncarcinogenic and carcinogenic risks were calculated. Experimental semivariogram of the mentioned HMs were calculated and theoretical models (i.e., exponential, spherical, Gaussian, and linear models) were fitted in order to model their spatial structures and to investigate the most representative models. Moreover, principal component analysis (PCA) and cluster analysis (CA) were used to identify sources of HMs in the soils. Results showed that IDW method was more efficient than the OK approach to estimate the properties and HMs contents in the soils and plants. The estimated daily intake of metals (DIM) values of Pb and Ni exceeded their safe limits. In addition, Cd was the main element responsible for ecological risk. The PIave and PIvector indices showed that soil quality in the study area is not suitable. According to mCd values, the soils classified as ultra-high contaminated for Cu and Cd, extremely high for Zn and Pb, very high, high, and very low degree of contamination for Ni, Mn, and Fe, respectively. 36, 60, and 4 % of the sampling sites had high, medium, and low risk levels with 49, 21, and 9 % probability of toxicity, respectively. The maximum health risk index (HRI) value of 20.42 with extremely high risk for children was obtained for Ni and the HI for adults and children were 0.22 and 1.55, respectively. The THI values of Pb and Cd were the highest compared to the other HMs studied, revealing a possible non-cancer risk in children associated with exposure to these metals. The routes of exposure with the greatest influence on the THI and TCR indices were in the order of ingestion > inhalation > dermal. Therefore, ingestion, as the main route of exposure, is the route of greatest contribution to health risks. PCA analysis revealed that Fe, Mn, Cu, and Ni may originate from natural sources, while Fe was appeared to be controlled by fertilizer, and Cu primarily coming from pesticide, while Cd and Pb were mainly associated with the anthropogenic contamination, atmospheric depositions, and terrific in the urban soils. While, Zn mainly originated from fertilization. Findings are vital for developing remediation approaches for controlling the contaminants distribution as well as for monitoring and mapping the quality and health of soil resources.

Nanodiamonds: A Cutting-Edge Approach to Enhancing Biomedical Therapies and Diagnostics in Biosensing.

Nanodiamonds (NDs) have garnered attention in the field of nanomedicine due to their unique properties. This review offers a comprehensive overview of NDs synthesis methods, properties, and their uses in biomedical applications. Various synthesis techniques, such as detonation, high-pressure, high-temperature, and chemical vapor deposition, offer distinct advantages in tailoring NDs' size, shape, and surface properties. Surface modification methods further enhance NDs' biocompatibility and enable the attachment of bioactive molecules, expanding their applicability in biological systems. NDs serve as promising nanocarriers for drug delivery, showcasing biocompatibility and the ability to encapsulate therapeutic agents for targeted delivery. Additionally, NDs demonstrate potential in cancer treatment through hyperthermic therapy and vaccine enhancement for improved immune responses. Functionalization of NDs facilitates their utilization in biosensors for sensitive biomolecule detection, aiding in precise diagnostics and rapid detection of infectious diseases. This review underscores the multifaceted role of NDs in advancing biomedical applications. By synthesizing NDs through various methods and modifying their surfaces, researchers can tailor their properties for specific biomedical needs. The ability of NDs to serve as efficient drug delivery vehicles holds promise for targeted therapy, while their applications in hyperthermic therapy and vaccine enhancement offer innovative approaches to cancer treatment and immunization. Furthermore, the integration of NDs into biosensors enhances diagnostic capabilities, enabling rapid and sensitive detection of biomolecules and infectious diseases. Overall, the diverse functionalities of NDs underscore their potential as valuable tools in nanomedicine, paving the way for advancements in healthcare and biotechnology.

microRNAs, oxidative stress, and genotoxicity as the main inducers in the pathobiology of cancer development.

Cancer is one of the most serious leading causes of death in the world. Many eclectic factors are involved in cancer progression including genetic and epigenetic alongside environmental ones. In this account, the performance and fluctuations of microRNAs are significant in cancer diagnosis and treatment, particularly as diagnostic biomarkers in oncology. So, microRNAs manage and control the gene expression after transcription by mRNA degradation, or also they can inhibit their translation. Conspicuously, these molecular structures take part in controlling the cellular, physiological and pathological functions, which many of them can accomplish as tumor inhibitors or oncogenes. Relatively, Oxidative stress is defined as the inequality between the creation of reactive oxygen species (ROS) and the body's ability to detoxify the reactive mediators or repair the resulting injury. ROS and microRNAs have been recognized as main cancer promoters and possible treatment targets. Importantly, genotoxicity has been established as the primary reason for many diseases as well as several malignancies. The procedures have no obvious link with mutagenicity and influence the organization, accuracy of the information, or fragmentation of DNA. Conclusively, mutations in these patterns can lead to carcinogenesis. In this review article, we report the impressive and practical roles of microRNAs, oxidative stress, and genotoxicity in the pathobiology of cancer development in conjunction with their importance as reliable cancer biomarkers and their association with circulating miRNA, exosomes and exosomal miRNAs, RNA remodeling, DNA methylation, and other molecular elements in oncology.

Functionalization of Defective Zr Metal-Organic Frameworks for Water Decontamination: Mechanistic Insight into the Competitive Roles of -NH2 and -SH Sites in Removal of As(III) Species.

Direct removal of trivalent arsenic, As(III), arsenite, or H3AsO3, is a great challenge in accessing clean sources of water. Different methodologies and materials were applied in this regard, but among them, direct removal of As(III) species using a metal-organic framework (MOF)-based adsorbent shows a great deal of potential. Although some studies were conducted on As(III) removal using MOFs, studies of functional groups are still quite rare. For this purpose, three novel functionalized defective Zr-MOFs, using UiO-66 [Zr6(OH)4O4(BDC)6, where BDC2- = benzene-1,4-dicarboxylate], were fabricated to investigate the competitive or cooperative roles of the free -NH2 and/or -SH site in the removal of As(III). UiO-66 was functionalized with monocarboxylate linkers, including glycine (Gly, NH2-CH2-COOH), cysteine [Cys, SH(CH2)-NH2(CH)-COOH], and mercaptopropionic acid [Mer, SH-(CH2)2-COOH]. Gly@UiO-66, Cys@UiO-66, and Mer@UiO-66 were applied for the direct removal of As(III) species. Although Cys@UiO-66 is functionalized with both amine and thiol functional groups, Gly@UiO-66 has a higher adsorption capacity (301.4 mg g-1) with respect to As(III), which is among the best reported values. This is due to the fact that (1) the affinity of amine sites in Gly@UiO-66 for As(III) is higher than that of thiol sites in Mer@UiO-66 and (2) Cys@UiO-66 has a very small surface area compared to that of Gly@UiO-66. Mechanistic studies using X-ray photoelectron spectroscopy and vibrational spectroscopy reveal that not only the functionalization and chemical nature of the function but also other parameters such as the protonation-deprotonation mechanisms and chemical state of the function are other critical factors for designing a functional MOF-based adsorbent with high affinity for and maximum capacity with respect to the target analyte.

Development of a hollow fiber-liquid phase microextraction method using tissue culture oil for the extraction of free metoprolol from plasma samples.

In this research, a method known as a hollow fiber-liquid-phase microextraction was employed to extract and concentrate free metoprolol from plasma samples. The extracted analyte was subsequently determined using high-performance liquid chromatography coupled with a diode-array detector. Several parameters, including hollow fiber length, sonication time, extraction temperature, and salt addition, were investigated and optimized to enhance extraction efficiency. After extracting the analyte under optimum conditions from plasma samples, the enrichment factor and extraction recovery were 50 and 86 %, respectively. Moreover, the method exhibited detection and quantification limits of 0.41 and 1.30 ng mL-1, respectively. The analysis of real samples demonstrated satisfactory relative recoveries in the range of 91-99 %.

Immune landscape in APC and TP53 related tumor microenvironment in colon adenocarcinoma: A bioinformatic analysis.

Introduction: APC and TP53 are the two most regularly mutated genes in colon adenocarcinoma (COAD), especially in progressive malignancies and antitumoral immune response. The current bioinformatics analysis investigates the APC and TP53 gene expression profile in colon adenocarcinoma as a prognostic characteristic for survival, particularly concentrating on the correlated immune microenvironment. Methods: Clinical and genetic data of colon cancer and normal tissue samples were obtained from The Cancer Genome Atlas (TCGA)-COAD and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan-Meier survival curves were applied to estimate the overall survival (OS). P < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and APC and TP53 status was assessed through Spearman's correlation analysis. Results: APC and TP53 were found mutated in 66.74% and 85.71% of the 454 and 7 TCGA-COAD patients in colon and rectosigmoid junction primary sites, respectively with a higher log2-transcriptome per million reads compared to the GTEx group (318 samples in sigmoid and 368 samples in transverse). Survival curves revealed a worse significant OS for the high-APC and TP53 profile colon. Spearman's analysis of immune cells demonstrated a strong positive correlation between the APC status and infiltration of T cell CD4+, T cell CD8+, NK cell, and macrophages and also a positive correlation between status and infiltration of T cell CD4+, T cell CD8+. Conclusions: APC and TP53 gene mutations prevail in colon cancer and are extremely associated with poor prognosis and shortest survival. The infiltrating T cell CD4+, T cell CD8+, NK cell, and macrophages populate the colon microenvironment and regulate the mechanisms of tumor advancement, immune evasion, and sensitivity to standard chemotherapy. More comprehensive research is needed to demonstrate these results and turn them into new therapeutic outlooks.