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Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors have significantly improved patient outcomes, their effectiveness is mostly limited to tumors with microsatellite instability (MSI-H/dMMR) or an increased tumor mutational burden, which comprise 10% of cases. Advancing personalized medicine in CRC hinges on identifying predictive biomarkers to guide treatment decisions. This comprehensive review examines established tissue markers such as KRAS and HER2, highlighting their roles in resistance to anti-EGFR agents and discussing advances in targeted therapies for these markers. Additionally, this review summarizes encouraging data on promising therapeutic targets and highlights the clinical utility of liquid biopsies. By synthesizing current evidence and identifying knowledge gaps, this review provides clinicians and researchers with a contemporary understanding of the biomarker landscape in CRC. Finally, the review examines future directions and challenges in translating promising biomarkers into clinical practice, with the goal of enhancing personalized medicine approaches for colorectal cancer patients.

Extremophiles, microorganisms blooming in extreme environmental conditions, hold particular significance in the domain of microbial research. This review paper focuses on extremophilic microorganisms, emphasizing their adaptations and the diverse products they generate, with a particular emphasis on exopolysaccharides (EPSs). EPSs, high molecular weight carbohydrate biopolymers, stand out as valuable products with applications across various industries. The review explores EPS production by bacteria in extreme conditions, including thermophilic, halophilic, and psychrophilic environments. Noteworthy examples, such as B. thermantarcticus and H. smyrnensis AAD6T, highlight the vast potential of extremophiles in EPS production. Additionally, the paper explores the major synthesis pathways of EPSs, shedding light on the factors influencing biosynthesis. The commercial significance of EPSs, especially for extremophiles, is underlined by their applications in medicine, food, environmental protection, agriculture, cosmetics, and more. Furthermore, the review sheds light on the role of extremophiles in various ecosystems, such as acidophiles, alkaliphiles, halophiles, hyperthermophiles, oligotrophs, osmophiles, piezophiles, and radioresistant organisms. This comprehensive analysis highlights the broad impact of extremophilic microorganisms and their EPS products in scientific exploration and commercial innovation. [ABSTRACT FROM AUTHOR]

Ubiquitin-conjugating enzyme E2 T (UBE2T) is a crucial E2 enzyme in the ubiquitin-proteasome system (UPS), playing a significant role in the ubiquitination of proteins and influencing a wide range of cellular processes, including proliferation, differentiation, apoptosis, invasion, and metabolism. Its overexpression has been implicated in various malignancies, such as lung adenocarcinoma, gastric cancer, pancreatic cancer, liver cancer, and ovarian cancer, where it correlates strongly with disease progression. UBE2T facilitates tumorigenesis and malignant behaviors by mediating essential functions such as DNA repair, apoptosis, cell cycle regulation, and the activation of oncogenic signaling pathways. High levels of UBE2T expression are associated with poor survival outcomes, highlighting its potential as a molecular biomarker for cancer prognosis. Increasing evidence suggests that UBE2T acts as an oncogene and could serve as a promising therapeutic target in cancer treatment. This review aims to provide a detailed overview of UBE2T's structure, functions, and molecular mechanisms involved in cancer progression as well as recent developments in UBE2T-targeted inhibitors. Such insights may pave the way for novel strategies in cancer diagnosis and treatment, enhancing our understanding of UBE2T's role in cancer biology and supporting the development of innovative therapeutic approaches. [ABSTRACT FROM AUTHOR]

Monoamine oxidase B (MAO-B) is a key enzyme in the mitochondrial outer membrane, pivotal for the oxidative deamination of biogenic amines. Its overexpression has been implicated in the pathogenesis of several cancers, including glioblastoma and colorectal, lung, renal, and bladder cancers, primarily through the increased production of reactive oxygen species (ROS). Inhibition of MAO-B impedes cell proliferation, making it a potential therapeutic target. Various monoamine oxidase B inhibitors have shown promise in inhibiting tumor growth and inducing apoptosis across different cancer types. In this review, we investigate MAO-B network biology, which highlighted glycolysis pathways as notable links between MAO-B and cancer. Further molecular modeling analysis illustrated the basis of MAO-B ligand binding, revealing a hydrophobic binding pocket, with key residues such as Tyr398 and Tyr435 playing crucial roles in substrate oxidation. MAO-B inhibitors that were reportsed in the literature (2012–2024) and their potential application in cancer therapy were discussed, highlighting key molecular scaffolds, such as propargyl analogs of phenyl alkyl amines, hydrazine derivatives, cyclopropylamine derivatives, MAO-B activated pro-drugs, and natural phenylpropanoid derivatives. The reported literature underscores the therapeutic potential of MAO-B inhibitors as versatile anticancer agents, warranting further investigation to optimize their efficacy and specificity across various malignancies. [ABSTRACT FROM AUTHOR]

Highlights: Wildfire smoke contains immuno-toxic components, including fine particles, VOCs, and PAHs. Chronic exposure to wildfire smoke can induce oxidative stress, inflammation, and long-term effects on the immune system. Wildfire smoke poses significant risks to immune health due to the presence of toxic com-ponents. Ongoing exposure to these toxic components may lead to persistent health effects, underlining the need for intervention and protective measures. Wildfires have become a significant environmental and public health concern worldwide, particularly due to their increased frequency and intensity driven by climate change. Wildfire smoke, composed of a complex mixture of particulate matter, gases and chemicals, has been linked to numerous health issues, primarily affecting the respiratory and cardiovascular systems. However, emerging evidence suggests that wildfire smoke exposure also has profound effects on the immune system. This review aims to synthesize current knowledge on how wildfire smoke exposure affects the human immune system, including acute and chronic impacts, underlying mechanisms and potential long-term consequences. The review discusses the role of inflammation, oxidative stress and immune cell modulation in response to wildfire smoke, highlighting the need for further research to fully understand these effects. [ABSTRACT FROM AUTHOR]

Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise and the Mediterranean diet can alleviate POAG. In this work, we for the first time estimated the phylostratigraphic age indices (PAIs) of all 153 POAG-related human genes in the NCBI Gene Database. This allowed us to separate them into two groups: POAG-related genes that appeared before and after the phylum Chordata, that is, ophthalmologically speaking, before and after the camera-type eye evolved. Next, in the POAG-related genes' promoters, we in silico predicted all 3835 candidate SNP markers that significantly change the TATA-binding protein (TBP) affinity for these promoters and, through this molecular mechanism, the expression levels of these genes. Finally, we verified our results against five independent web services—PANTHER, DAVID, STRING, MetaScape, and GeneMANIA—as well as the ClinVar database. It was concluded that POAG is likely to be a symptom of the human self-domestication syndrome, a downside of being civilized. [ABSTRACT FROM AUTHOR]

Cisplatin is an established component of treatment protocols for various solid malignancies but carries a significant potential for serious adverse effects. Ototoxicity from cisplatin treatment is an important dose-limiting toxicity that manifests as bilateral, progressive, irreversible, dose-dependent sensorineural hearing loss, ear pain, tinnitus, and vestibular dysfunction. Despite the recent approval of sodium thiosulphate for the prevention of cisplatin-induced hearing loss (CIHL) in pediatric patients, structured prevention programs are not routinely implemented in most hospitals, and reducing platinum-induced ototoxicity in adults remains an important clinical problem without established treatment options. Cochlear oxidative stress plays a fundamental role in CIHL. Here, we review the molecular mechanisms leading to oxidative stress in CIHL and the clinical and preclinical studies testing antioxidants in CIHL to guide future clinical trials in assessing the efficacy and safety of candidate antioxidant compounds in this clinical setting. [ABSTRACT FROM AUTHOR]

Background: The exposome (e.g., totality of environmental exposures) and its role in Alzheimer's Disease and Alzheimer's Disease and Related Dementias (AD/ADRD) are increasingly critical areas of study. However, little is known about how interventions on the exposome, including personal behavioral modification or policy-level interventions, may impact AD/ADRD disease burden at the population level in real-world settings and the cost-effectiveness of interventions. Methods: We performed a critical review to discuss the challenges in modeling exposome interventions on population-level AD/ADRD burden and the potential of using agent-based modeling (ABM) and other advanced data science methods for causal inference to achieve this. Results: We describe how ABM can be used for empirical causal inference modeling and provide a virtual laboratory for simulating the impacts of personal and policy-level interventions. These hypothetical experiments can provide insight into the optimal timing, targeting, and duration of interventions, identifying optimal combinations of interventions, and can be augmented with economic analyses to evaluate the cost-effectiveness of interventions. We also discuss other data science methods, including structural equation modeling and Mendelian randomization. Lastly, we discuss challenges in modeling the complex exposome, including high dimensional and sparse data, the need to account for dynamic changes over time and over the life course, and the role of exposome burden scores developed using item response theory models and artificial intelligence to address these challenges. Conclusions: This critical review highlights opportunities and challenges in modeling exposome interventions on population-level AD/ADRD disease burden while considering the cost-effectiveness of different interventions, which can be used to aid data-driven policy decisions. [ABSTRACT FROM AUTHOR]

Background: The exposure of environmental bacteria to contaminants in aquatic ecosystems accelerates the dissemination of antibiotic-resistance genes (ARGs) through horizontal gene transfer (HGT). Methods: In this study, we sampled three locations along a contamination gradient of a polluted river, focusing on isolating Enterobacteria from the surface waters to investigate the relationship between urban pollution and antibiotic resistance. The genomes of 15 isolates (5 per site) were sequenced to identify plasmid-borne ARGs and their association with resistance phenotypes. Results: Isolates from the site with the highest contamination (Site 3) showeda larger number of ARGs, plasmids, and resistance phenotypes. Notably, one of the isolates analyzed, E. coli A231-12, exhibited phenotypic resistance to seven antibiotics, presumably conferred by a single plasmid carrying 12 ARGs. Comparative analysis of this plasmid revealed its close evolutionary relationship with another IncH plasmid hosted by Salmonella enterica, underscoring its high ARG burden in the aquatic environment. Other plasmids identified in our isolates carried sul and dfrA genes, conferring resistance to trimethoprim/sulfamethoxazole, a commonly prescribed antibiotic combination in clinical settings. Conclusions: These results highlight the critical need to expand research on the link between pollution and plasmid-mediated antimicrobial resistance in aquatic ecosystems, which can act as reservoirs of ARGs. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma–carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications. [ABSTRACT FROM AUTHOR]

Antimicrobial dosing can be a complex challenge. Although a solid rationale exists for a link between antibiotic exposure and outcome, conflicting data suggest a poor correlation between pharmacokinetic/pharmacodynamic targets and infection control. Different reasons may lead to this discrepancy: poor tissue penetration by β-lactams due to inflammation and inadequate tissue perfusion; different bacterial response to antibiotics and biofilms; heterogeneity of the host's immune response and drug metabolism; bacterial tolerance and acquisition of resistance during therapy. Consequently, either a fixed dose of antibiotics or a fixed target concentration may be doomed to fail. The role of biomarkers in understanding and monitoring host response to infection is also incompletely defined. Nowadays, with the ever-growing stream of data collected in hospitals, utilizing the most efficient analytical tools may lead to better personalization of therapy. The rise of artificial intelligence and machine learning has allowed large amounts of data to be rapidly accessed and analyzed. These unsupervised learning models can apprehend the data structure and identify homogeneous subgroups, facilitating the individualization of medical interventions. This review aims to discuss the challenges of β-lactam dosing, focusing on its pharmacodynamics and the new challenges and opportunities arising from integrating machine learning algorithms to personalize patient treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the prevalence of inappropriate treatment among hospitalised patients affected by SARS-CoV-2 infection before hospital admission during the Omicron era. This single-centre, retrospective observational study included all the patients hospitalised because of SARS-CoV-2 infection during three periods characterised by the Italian prevalence of an Omicron variant of concern: (1) January–May 2022 (BA.1–BA.2), (2) June–October 2022 (BA.5), and (3) November 2022–March 2023 (BQ.1-XBB). Inappropriate treatment was defined as pre-hospitalisation exposure to antibiotics and/or steroids in the absence of a documented bacterial infection or the need for steroid treatment of an underlying medical condition. A total of 931 subjects were hospitalised: 394 in period 1, 334 in period 2, and 203 in period 3. Of the 157 patients undergoing inappropriate treatment (16.9%), 142 (15.3%) received antibiotics and 52 (5.6%) steroids. The proportion of inappropriately treated patients significantly decreased over time, from 23.1% in period 1 to 11.7% in period 2 and 13.3% in period 3 (p < 0.001), and there was a parallel decrease in antibiotic (p < 0.001) and steroid treatment (p < 0.013). Only 13 subjects (1.4%) received early pre-hospitalisation treatment for SARS-CoV-2. A significant proportion of hospitalised COVID-19 patients were exposed to inappropriate treatment before hospital admission. [ABSTRACT FROM AUTHOR]

A few studies have explored the relationship between air pollution exposure and the risk of birth defects; however, the ozone-related (O3) effects on preconception and first-trimester exposures are still unknown. In this time-stratified case-crossover study, conditional logistic regressions were applied to explore the associations between O3 exposure and the risk of birth defects in Chongqing, China, and stratified analyses were constructed to evaluate the modifiable factors. A total of 6601 cases of birth defects were diagnosed, of which 56.16% were male. O3 exposure was associated with an increased risk of birth defects, and the most significant estimates were observed in the first month before pregnancy: a 10 ug/m3 increase of O3 was related to an elevation of 4.2% [95% confidence interval (CI), 3.4–5.1%]. The associations between O3 exposure and congenital malformations and deformations of the musculoskeletal system were statistically significant during almost all exposure periods. Pregnant women with lower education and income, and from rural areas, were more susceptible to O3 exposure, with the strongest odds ratios (ORs) of 1.066 (95%CI, 1.046–1.087), 1.086 (95%CI, 1.034–1.140), and 1.053 (95%CI, 1.034–1.072), respectively. Our findings highlight the health risks of air pollution exposure and raise awareness of pregnant women's vulnerability and the susceptibility window period. [ABSTRACT FROM AUTHOR]

The objective of this research was to create a prognostic model focused on genes related to ubiquitination (UbRGs) for evaluating their clinical significance in head and neck squamous cell carcinoma (HNSCC) patients. The transcriptome expression data of UbRGs were obtained from The Cancer Genome Atlas (TCGA) database, and weighted gene co-expression network analysis (WGCNA) was used to identify specific UbRGs within survival-related hub modules. A multi-gene signature was formulated using LASSO Cox regression analysis. Furthermore, various analyses, including time-related receiver operating characteristics (ROCs), Kaplan–Meier, Cox regression, nomogram prediction, gene set enrichment, co-expression, immune, tumor mutation burden (TMB), and drug sensitivity, were conducted. Ultimately, a prognostic signature consisting of 11 gene pairs for HNSCC was established. The Kaplan–Meier curves indicated significantly improved overall survival (OS) in the low-risk group compared to the high-risk group (p < 0.001), suggesting its potential as an independent and dependable prognostic factor. Additionally, a nomogram with AUC values of 0.744, 0.852, and 0.861 at 1-, 3-, and 5-year intervals was developed. Infiltration of M2 macrophages was higher in the high-risk group, and the TMB was notably elevated compared to the low-risk group. Several chemotherapy drugs targeting UbRGs were recommended for low-risk and high-risk patients, respectively. The prognostic signature derived from UbRGs can effectively predict prognosis and provide new personalized therapeutic targets for HNSCC. [ABSTRACT FROM AUTHOR]

Elevations in fructose consumption have been reported to contribute significantly to an increased incidence of obesity and metabolic diseases in industrial countries. Mechanistically, a high fructose intake leads to the dysregulation of glucose, triglyceride, and cholesterol metabolism in the liver, and causes elevations in inflammation and drives the progression of nonalcoholic fatty liver disease (NAFLD). A high fructose consumption is considered to be toxic to the body, and there are ongoing measures to develop pharmaceutical therapies targeting fructose metabolism. Although a large amount of work has summarized the effects fructose exposure within the intestine, liver, and kidney, there remains a gap in our knowledge regarding how fructose both indirectly and directly influences immune cell recruitment, activation, and function in metabolic tissues, which are essential to tissue and systemic inflammation. The most recent literature demonstrates that direct fructose exposure regulates oxidative metabolism in macrophages, leading to inflammation. The present review highlights (1) the mechanisms by which fructose metabolism impacts crosstalk between tissues, nonparenchymal cells, microbes, and immune cells; (2) the direct impact of fructose on immune cell metabolism and function; and (3) therapeutic targets of fructose metabolism to treat NAFLD. In addition, the review highlights how fructose disrupts liver tissue homeostasis and identifies new therapeutic targets for treating NAFLD and obesity. [ABSTRACT FROM AUTHOR]

Simple Summary: Cetuximab is a treatment widely used to treat advanced, metastatic colorectal cancer (CRC), and it works by blocking epidermal growth factor receptor signaling. Unfortunately, patients inevitably develop resistance to cetuximab. The most common resistance mechanisms are well established, but there are still patients that become resistant to cetuximab due to unknown mechanisms. The small guanosine triphosphatases (GTPases) RAC1 and RAC1B have been shown to contribute to CRC progression, but their role in cetuximab resistance is unclear. This review highlights the known cetuximab resistance mechanisms and summarizes how RAC1 and RAC1B could contribute to these resistance mechanisms to propose RAC1 and RAC1B as additional therapeutic targets that could increase the efficacy of cetuximab. Colorectal cancer (CRC) is one of the most diagnosed cancers and a leading contributor to cancer-related deaths in the United States. Clinically, standard treatment regimens include surgery, radiation, and chemotherapy; however, there has been increasing development and clinical use of targeted therapies for CRC. Unfortunately, many patients develop resistance to these treatments. Cetuximab, the first targeted therapy approved to treat advanced CRC, is a monoclonal antibody that targets the epidermal growth factor receptor and inhibits downstream pathway activation to restrict tumor cell growth and proliferation. CRC resistance to cetuximab has been well studied, and common resistance mechanisms include constitutive signal transduction through downstream protein mutations and promotion of the epithelial-to-mesenchymal transition. While the most common resistance mechanisms are known, a proportion of patients develop resistance through unknown mechanisms. One protein predicted to contribute to therapy resistance is RAC1, a small GTPase that is involved in cytoskeleton rearrangement, cell migration, motility, and proliferation. RAC1 has also been shown to be overexpressed in CRC. Despite evidence that RAC1 and its alternative splice isoform RAC1B play important roles in CRC and the pathways known to contribute to cetuximab resistance, there is a need to directly study the relationship between RAC1 and RAC1B and cetuximab resistance. This review highlights the recent studies investigating RAC1 and RAC1B in the context of CRC and suggests that these proteins could play a role in resistance to cetuximab. [ABSTRACT FROM AUTHOR]

Growing evidence indicates that human milk oligosaccharides (HMOs) are important bioactive compounds that enhance health and developmental outcomes in breastfed babies. Maternal dietary intake likely contributes to variation in HMO composition, but studies identifying diet–HMO relationships are few and inconsistent. This study aimed to investigate how the maternal intake of macronutrients and micronutrients—specifically proteins, fats, vitamins, and minerals—associated with HMOs at 1 month (n = 210), 6 months (n = 131), and 12 months postpartum (n = 84). Several associations between maternal dietary factors and HMO profiles were identified utilizing partial correlation analysis. For example, maternal free sugar (rho = −0.02, p < 0.01), added sugar (rho = −0.22, p < 0.01), and sugary sweetened beverage (rho = −0.22, p < 0.01) intake were negatively correlated with the most abundant HMO, 2′-fucosyllactose (2′-FL), at 1 month, suggesting that higher sugar consumption was associated with reduced levels of 2′-FL. Further, vitamins D, C, K, and the minerals zinc and potassium were positively correlated with 2′-FL at 1 month (pAll < 0.05). For the longitudinal analysis, a mixed-effects linear regression model revealed significant associations between maternal vitamin intake and HMO profiles over time. For example, for each unit increase in niacin intake, there was a 31.355 nmol/mL increase in 2′-FL concentration (p = 0.03). Overall, the results provide additional evidence supporting a role for maternal nutrition in shaping HMO profiles, which may inform future intervention strategies with the potential of improving infant growth and development through optimal HMO levels in mothers' milk. [ABSTRACT FROM AUTHOR]

In recent years, a series of recommendations have been issued regarding the administration of drugs because of awareness of the serious side effects associated with certain classes of drugs, especially in vulnerable patients. Taking into account the obligation of the continuous improvement of professionals in the medical fields and the fact that we are in the midst of a "malpractice accusations pandemic", through this work, we propose to carry out a "radiography" of the scientific literature regarding adverse effects that may occur as a result of the interaction of drugs with the physiopathological particularities of patients. The literature reports various cases regarding different classes of drugs administration associated with adverse effects in the elderly people, such as fluoroquinolones, which can cause torsade de pointes or tendinopathy, or diuretics, which can cause hypokalemia followed by torsade de pointes and cardiorespiratory arrest. Also, children are more prone to the development of adverse reactions due to their physiological particularities, while for pregnant women, some drugs can interfere with the normal development of the fetus, and for psychiatric patients, the use of neuroleptics can cause agranulocytosis. Considering the physiopathological particularities of each patient, the drug doses must be adjusted or even completely removed from the treatment scheme, thus requiring the mandatory active participation both of clinician pharmacists and specialists in the activity of medical-pharmaceutical analysis laboratories within the structure of hospitals. [ABSTRACT FROM AUTHOR]

Cisplatin is a widely used antineoplastic drug for treating various types of cancers. However, it can cause severe side effects, such as bilateral and irreversible hearing loss, which significantly impacts quality of life. Ferroptosis, an iron-dependent form of programmed cell death, has been implicated in the pathogenesis of cisplatin-induced ototoxicity. Here, we investigated the effects of nuciferine, a natural active ingredient isolated from lotus species, on the ferroptosis of cochlear hair cells. Firstly, our results demonstrated that nuciferine can protect hair cells against RSL3-induced and cisplatin-induced damage. Secondly, nuciferine treatment reduced ferrous iron (Fe2+) overload in cochlear hair cells via inhibiting NCOA4-mediated ferritinophagy. Inhibition of ferritinophagy by knocking down Ncoa4 alleviated cisplatin-induced ototoxicity. Importantly, nuciferine treatment mitigated cochlear hair cell loss and damage to ribbon synapse, and improved mouse hearing function in an acute cisplatin-induced hearing loss model. Our findings highlight the role of NCOA4-mediated ferritinophagy in the pathogenesis of cisplatin-induced ototoxicity and provide evidence for nuciferine as a promising protective agent for treating cisplatin-induced hearing loss. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a leading cause of death worldwide. The costs involved in cancer diagnosis and treatment are extraordinary. Important steps that can be taken that would reduce costs include earlier cancer diagnosis for which significant headway is being made through biomarker identification in bodily fluids and imaging. Other important steps will be to identify treatment approaches that do not 'break the bank' and affect a patient's wellbeing. Herein, we aim to highlight the potential of phytochemicals as a cost-effective approach to aid in the treatment of cancer. We focus on phytochemicals that target ion channels, as molecules that mediate critical communication of a cell with its environment. Ultimately, we posit that phytochemicals targeting ion channels can be employed to aid cancer treatment. Modern chemotherapies offer a broad approach to cancer treatment but eliminate both cancer and non-cancer cells indiscriminately and, thus, are associated with a host of side effects. Advances in precision oncology have brought about new targeted therapeutics, albeit mostly limited to a subset of patients with an actionable mutation. They too come with side effects and, ultimately, 'self-resistance' to the treatment. There is recent interest in the modulation of ion channels, transmembrane proteins that regulate the flow of electrically charged molecules in and out of cells, as an approach to aid treatment of cancer. Phytochemicals have been shown to act on ion channels with high specificity regardless of the tumor's genetic profile. This paper explores the use of phytochemicals in cancer symptom management and treatment. [ABSTRACT FROM AUTHOR]

Dementia has become a profound public health problem due to the number of patients increasing every year. Previous studies have reported that environmental factors, including greenness, may influence the development and progression of dementia. Studies have found that exposure to green space is associated with a lower incidence of dementia. However, many definitions of green space exist, and the effects of its use may differ with the type of green space. Therefore, two types of green space measures were considered in this study to assess the differences in their impact on the prevalence of dementia among females and males. This study used five years of data (2017–2021) from 235 districts in South Korea. The two green space measures used were open space density and normalized difference vegetation index (NDVI), which were derived from satellite images. The analysis utilized a combination of traditional and spatial panel analyses to account for the spatial and temporal effects of independent variables on dementia prevalence. The spatial autocorrelation results revealed that both measures of greenness were spatially correlated with dementia prevalence. The spatial panel regression results revealed a significant positive association between NDVI and dementia prevalence, and open space had a negative association with dementia prevalence in both genders. The difference in the findings can serve as the basis for further research when choosing a greenspace measure, as it affects the analysis results, depending on the objective of the study. This study adds to the knowledge regarding improving dementia studies and the application of spatial panel analysis in epidemiological studies. [ABSTRACT FROM AUTHOR]

Worldwide, childhood obesity cases continue to rise, and its prevalence is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. Thus, comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is strongly associated with high fructose intake since the excessive consumption of this highly lipogenic sugar leads to white fat accumulation and causes white adipose tissue (WAT) inflammation, oxidative stress, and dysregulated adipokine release. Unfortunately, the global consumption of fructose has increased dramatically in recent years, which is associated with the fact that fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Therefore, here, we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity, and current strategies for reducing high fructose and/or free sugar intake. To achieve such reductions, we conclude that it is important that the population has access to reliable information about food ingredients via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains a significant contributor to cancer-related mortality. Novel high-throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation. Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns. Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation. The hypomethylation of specific repetitive elements generates an epigenetic field effect early in tumorigenesis. Epstein–Barr virus (EBV) infection triggers DNA methylation by dysregulating DNA methyltransferases (DNMT) enzyme activity, while persistent Hp-EBV co-infection leads to aggressive tumor behavior. Distinct histone modifications are also responsible for oncogene upregulation and tumor-suppressor gene silencing in gastric carcinomas. While histone methylation and acetylation processes have been extensively studied, other less prevalent alterations contribute to the development and migration of gastric cancer via a complex network of interactions. Enzymes, such as Nicotinamide N-methyltransferase (NNMT), which is involved in tumor's metabolic reprogramming, interact with methyltransferases and modify gene expression. Non-coding RNA molecules, including long non-coding RNAs, circular RNAs, and miRNAs serve as epigenetic regulators contributing to GC development, metastasis, poor outcomes and therapy resistance. Serum RNA molecules hold the potential to serve as non-invasive biomarkers for diagnostic, prognostic or therapeutic applications. Gastric fluids represent a valuable source to identify potential biomarkers with diagnostic use in terms of liquid biopsy. Ongoing clinical trials are currently evaluating the efficacy of next-generation epigenetic drugs, displaying promising outcomes. Various approaches including multiple miRNA inhibitors or targeted nanoparticles carrying epigenetic drugs are being designed to enhance existing treatment efficacy and overcome treatment resistance. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancers are some of the main public health threats to the world. Even though surgery, chemotherapy, and targeted therapy are available for their treatments, these approaches provide limited success in reducing mortality, making the identification of additional therapeutic targets mandatory. Chromatin remodeling in cancer has long been studied and related therapeutics are widely used, although less is known about factors with prognostic and therapeutic potential in such areas as gastrointestinal cancers. Through applying systematic bioinformatic analysis, we determined that out of 31 chromatin remodeling factors in six gastrointestinal cancers, only PR/SET domain 1 (PRDM1) showed both expression alteration and prognosis prediction. Analyses on pathways, therapies, and mediators showed that cell cycle, bromodomain inhibitor IBET151, and BET protein BRD4 were, respectively involved in PRDM1-high stomach cancer, while cell line experiments validated that PRDM1 knockdown in human stomach cancer cell line SNU-1 decreased its proliferation, BRD4 expression, and responsiveness to IBET151; accordingly, these results indicate the contribution by PRDM1 in stomach cancer formation and its association with BRD4 modulation as well as BET inhibitor treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Lynch syndrome (LS) stands as the predominant inherited cancer condition at present. Currently, surveillance is based on genotype-driven strategies and mostly comprises both invasive and non-invasive medical assessments for early diagnosis. Effective preventive strategies for interrupting the biological sequence of cancer development are yet to be established. Recent findings from randomized controlled trials indicate potential preventive functions of resistant starch and/or aspirin in Lynch syndrome. The use of immunogenic frameshift peptides for vaccination appears to be a promising approach for both treating and preventing Lynch syndrome-associated cancers, based on pre-clinical and early phase 1/2a studies. Background and Aims: Lynch syndrome (LS) is currently one of the most prevalent hereditary cancer conditions, accounting for 3% of all colorectal cancers and for up to 15% of those with DNA mismatch repair (MMR) deficiency, and it was one of the first historically identified. The understanding of the molecular carcinogenesis of LS tumors has progressed significantly in recent years. We aim to review the most recent advances in LS research and explore genotype-based approaches in surveillance, personalized cancer prevention, and treatment strategies. Methods: PubMed was searched to identify relevant studies, conducted up to December 2023, investigating molecular carcinogenesis in LS, surveillance strategies, cancer prevention, and treatment in LS tumors. Results: Multigene panel sequencing is becoming the benchmark in the diagnosis of LS, allowing for the detection of a pathogenic constitutional variant in one of the MMR genes. Emerging data from randomized controlled trials suggest possible preventive roles of resistant starch and/or aspirin in LS. Vaccination with immunogenic frameshift peptides appears to be a promising approach for both the treatment and prevention of LS-associated cancers, as evidenced by pre-clinical and preliminary phase 1/2a studies. Conclusions: Although robust diagnostic algorithms, including prompt testing of tumor tissue for MMR defects and referral for genetic counselling, currently exist for suspected LS in CRC patients, the indications for LS screening in cancer-free individuals still need to be refined and standardized. Investigation into additional genetic and non-genetic factors that may explain residual rates of interval cancers, even in properly screened populations, would allow for more tailored preventive strategies. [ABSTRACT FROM AUTHOR]

Background: Air pollution can cause numerous health problems and increase the need for medicines to treat and prevent asthma in affected areas. There is limited evidence about the association between airborne particles with a diameter of 2.5 micrometres or smaller (PM2.5) and asthma medicine usage. This study examined the potential association between the levels of PM2.5 and the supply of prescription asthma medicines in the Australian Capital Territory (ACT), Australia, during the severe bushfire season between November 2019–January 2020. Methods: Daily data was obtained from an ACT air quality monitoring station from November 2019 to January 2020 (study period) and November 2018 to January 2019 (control period, no bushfire). The number and types of government-funded asthma medicine prescriptions were obtained from the Services Australia (government) website by searching under 'Pharmaceutical Benefits Scheme Item Reports' and using relevant item codes during the study and control periods. Results: The medians for PM2.5 levels for the study period were significantly higher than those for the control period (p < 0.001). There were increases in the number of dispensed prescriptions of short-acting beta-2 agonists (SABA), inhaled corticosteroids, and long-acting beta-2 agonists combined with inhaled corticosteroids. The greatest difference was seen with the inhaled corticosteroids: a 138% increase. Conclusions: The increase in the number of dispensed asthma prescriptions during the bushfire season should be used to inform the stock holdings of these medicines in preparation for future events to ensure access to lifesaving asthma medicines. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is the female genital malignancy with the highest lethality. Patients present a poor prognosis mainly due to the late clinical presentation allied with the common acquisition of chemoresistance and a high rate of tumour recurrence. Effective screening, accurate diagnosis, and personalised multidisciplinary treatments are crucial for improving patients' survival and quality of life. This comprehensive narrative review aims to describe the current knowledge on the aetiology, prevention, diagnosis, and treatment of OC, highlighting the latest significant advancements and future directions. Traditionally, OC treatment involves the combination of cytoreductive surgery and platinum-based chemotherapy. Although more therapeutical approaches have been developed, the lack of established predictive biomarkers to guide disease management has led to only marginal improvements in progression-free survival (PFS) while patients face an increasing level of toxicity. Fortunately, because of a better overall understanding of ovarian tumourigenesis and advancements in the disease's (epi)genetic and molecular profiling, a paradigm shift has emerged with the identification of new disease biomarkers and the proposal of targeted therapeutic approaches to postpone disease recurrence and decrease side effects, while increasing patients' survival. Despite this progress, several challenges in disease management, including disease heterogeneity and drug resistance, still need to be overcome. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the leading cause of cancer deaths, and treatment, especially in the metastatic stage, is challenging. Immune checkpoint inhibitors (ICIs) have revolutionized CRC treatment, but response varies, emphasizing the need for effective biomarkers. This study explores SPEN mutations as potential biomarkers. Methods: Using data from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA)—Colorectal Cancer, this research applied bioinformatics tools and statistical analysis to SPEN (Split Ends) mutant and wild-type CRC patients treated with ICIs. Focus areas included mutation rates, immune cell infiltration, and DNA damage response pathways. Results: The SPEN mutation rate was found to be 13.8% (15/109 patients) in the MSKCC cohort and 6.65% (35/526 patients) in the TCGA cohort. Our findings indicate that CRC patients with SPEN mutations had a longer median overall survival (OS) than the wild-type group. These patients also had higher tumor mutational burden (TMB), microsatellite instability (MSI) scores, and programmed death-ligand 1 (PD-L1) expression. SPEN mutants also exhibited increased DNA damage response (DDR) pathway mutations and a greater presence of activated immune cells, like M1 macrophages and CD8+ T cells, while wild-type patients had more resting/suppressive immune cells. Furthermore, distinct mutation patterns, notably with TP53, indicated a unique molecular subtype in SPEN-mutated CRC. Conclusions: We conclude that SPEN mutations might improve ICI efficacy in CRC due to increased immunogenicity and an inflammatory tumor microenvironment. SPEN mutations could be predictive biomarkers for ICI responsiveness, underscoring their value in personalized therapy and highlighting the importance of genomic data in clinical decisions. This research lays the groundwork for future precision oncology studies. [ABSTRACT FROM AUTHOR]

Wildfires are a global natural phenomenon. In North America, wildfires have not only become more frequent, but also more severe and longer in duration, a trend ascribed to climate change combined with large fuel stores left from modern fire suppression. The intensification of wildfire activity has significant implications for planetary health and public health, as exposure to fine particulate matter (PM2.5) in wildfire smoke is linked to adverse health effects. This review focuses on respiratory morbidity from wildfire smoke exposure. Inhalation of wildfire PM2.5 causes lung injury via oxidative stress, local and systemic inflammation, airway epithelium compromise, and increased vulnerability to infection. Wildfire PM2.5 exposure results in exacerbations of pre-existing asthma and chronic obstructive pulmonary disease, with an escalation in healthcare utilization, including emergency department visits and hospitalizations. Wildfire smoke exposure may be associated with asthma onset, long-term impairment of lung function, and increased all-cause mortality. Children, older adults, occupationally-exposed groups, and possibly women are the most at risk from wildfire smoke. Future research is needed to clarify best practices for risk mitigation and wildfire management. [ABSTRACT FROM AUTHOR]

This research comprehensively examines 88 infant formulas available in the US market, with an emphasis on their diverging nutritional attributes based on lactose content. We stratified formulas into three categories: lactose-free, lactose-reduced, and entirely lactose-based. The formulas' nutritional content for 58 nutrients was obtained from the Nutrition Data System for Research (NDSR). Nutritional analysis revealed significant differences in nutrient composition across formula categories. For example, the results showed significant associations between the lactose content and glycemic index (GI) of the formula as well as 25 other nutrients. Specifically, we showed that for every gram of lactose per 100 g of formula that is removed, there was a 10.1% increase in GI (β = −10.12, p ≤ 0.000), a 19%,5%, and a 2% increase in added sugar (β = −0.19, p < 0.01), protein (β = −0.05, p < 0.001), and polyunsaturated fatty acids (β = −0.01, p < 0.01). The substitution of lactose in infant formulas significantly alters their nutritional profile, inducing changes in GI, added sugar, protein, and polyunsaturated fatty acids. These modifications have potential consequences for infant growth and metabolic responses and could influence long-term health trajectories. The clinical relevance of the composition differences between formulas should be further explored. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the second most common tumor of the female reproductive organs in the world. Taking into account the immunological mechanisms of defense against cancer, an important role is attributed to cytokines. In this case-control study, we aimed to identify the possible associations between selected single nucleotide polymorphisms (SNPs), localized in the CCL2, CCL5, CXCL8, and CXCR2 genes, and the onset and progression of endometrial cancer. We found that CCL5 and CXCR2 polymorphisms were associated with increased cancer risk, while the relationships remained significant after adjustments for age, diabetes, hypertension, or endometrial thickening. The selected haplotypes for CCL5 and CCL2 SNPs also correlated with an increased risk of cancer. We concluded that the four polymorphisms studied were significantly associated with an increased risk of endometrial cancer. The obtained results may be useful for identifying the signaling pathways involved in observed genetic changes, which is important for the tumorigenesis of endometrial cancer. Significant relationships with endometrial cancer were demonstrated, both for CCL2, CCL5, and CXCL8 chemokines and for the chemokine receptor CXCR2. The reported case-control study of genetic associations was designed to establish the role of selected single nucleotide polymorphisms (SNPs) of the CCL2, CCL5, CXCL8, and CXCR2 genes in the onset and progression of endometrial cancer. This study was conducted on 282 women, including 132 (46.8%) patients with endometrial cancer and 150 (53.2%) non-cancerous controls. The genotypes for CCL2 rs4586, CCL5 rs2107538 and rs2280789, CXCL8 rs2227532 and −738 T>A, and CXCR2 rs1126580 were determined, using PCR-RFLP assays. The AA homozygotes in CCL5 rs2107538 were associated with more than a quadruple risk of endometrial cancer (p ≤ 0.050). The GA heterozygotes in the CXCR2 SNP were associated with approximately threefold higher cancer risk (p ≤ 0.001). That association also remained significant after certain adjustments, carried out for age, diabetes mellitus, arterial hypertension, or endometrial thickness above 5 mm (p ≤ 0.050). The A-A haplotypes for the CCL5 polymorphisms and T-A-A haplotypes for the CCL2 and CCL5 SNPs were associated with about a twofold risk of endometrial cancer (p ≤ 0.050). In conclusion, CCL2 rs4586, CCL5 rs2107538 and rs2280789, and CXCR2 rs1126580 demonstrated significant associations with an increased risk of endometrial cancer. [ABSTRACT FROM AUTHOR]

DNA methylation is an epigenetic mechanism that regulates gene expression without altering gene sequences in health and disease. DNA methyltransferases (DNMTs) are enzymes responsible for DNA methylation, and their dysregulation is both a pathogenic mechanism of disease and a therapeutic target. DNMTs change gene expression by methylating CpG islands within exonic and intergenic DNA regions, which typically reduces gene transcription. Initially, mutations in the DNMT genes and pathologic DNMT protein expression were found to cause hematologic diseases, like myeloproliferative disease and acute myeloid leukemia, but recently they have been shown to promote cardiovascular diseases, including coronary artery disease and pulmonary hypertension. We reviewed the regulation and functions of DNMTs, with an emphasis on somatic mutations in DNMT3A, a common cause of clonal hematopoiesis of indeterminant potential (CHIP) that may also be involved in the development of pulmonary arterial hypertension (PAH). Accumulation of somatic mutations in DNMT3A and other CHIP genes in hematopoietic cells and cardiovascular tissues creates an inflammatory environment that promotes cardiopulmonary diseases, even in the absence of hematologic disease. This review summarized the current understanding of the roles of DNMTs in maintenance and de novo methylation that contribute to the pathogenesis of cardiovascular diseases, including PAH. [ABSTRACT FROM AUTHOR]

The vaginal microbiota undergoes subtle changes during pregnancy, which may affect different pregnancy responses. This study used the Illumina MiSeq high-throughput sequencing method to analyze the 16S rRNA gene amplicons of pregnant women and the vaginal microbiota structure of pregnant women at different pregnancy periods. There were a total of 15 pregnant women, with 45 samples were taken from these women, within half a year before becoming pregnant, in the last trimester, and 42 days postpartum. Before and after pregnancy, the female vaginal microbiota was mainly composed of Firmicutes, followed by Actinobacteriota and Proteobacteria. The abundance of Lactobacillus was relatively high. The α-diversity and microbial abundance were relatively low, and there was no significant difference in microbial composition between the two. After childbirth, the diversity and abundance of women's vaginal bacterial communities were higher, with a decrease in the number of Firmicutes and a higher abundance of Actinobacteria, Proteobacteria, and Bacteroidota. There was a significant difference in the microbial community structure before and after pregnancy. This study showed that the microbiota structure of the vagina of pregnant women was similar to before pregnancy, but after childbirth, there were significant changes in the microbiota of the vagina, with a decrease in the number of probiotics and an increase in the number of harmful bacteria, increasing the risk of illness. [ABSTRACT FROM AUTHOR]

Individuals with psychosocial stress often experience an exaggerated response to air pollutants. Ozone (O3) exposure has been associated with the activation of the neuroendocrine stress-response system. We hypothesized that preexistent mild chronic stress plus social isolation (CS), or social isolation (SI) alone, would exacerbate the acute effects of O3 exposure on the circulating adrenal-derived stress hormones, and the expression of the genes regulating glucocorticoid stress signaling via an altered stress adaptation in a brain-region-specific manner. Male Wistar–Kyoto rats (5 weeks old) were socially isolated, plus were subjected to either CS (noise, confinement, fear, uncomfortable living, hectic activity, and single housing), SI (single housing only, restricted handling and no enrichment) or no stress (NS; double housing, frequent handling and enrichment provided) for 8 weeks. The rats were then exposed to either air or O3 (0.8 ppm for 4 h), and the samples were collected immediately after. The indicators of sympathetic and hypothalamic–pituitary axis (HPA) activation (i.e., epinephrine, corticosterone, and lymphopenia) increased with O3 exposure, but there were no effects from CS or SI, except for the depletion of serum BDNF. CS and SI revealed small changes in brain-region-specific glucocorticoid-signaling-associated markers of gene expression in the air-exposed rats (hypothalamic Nr3c1, Nr3c2 Hsp90aa1, Hspa4 and Cnr1 inhibition in SI; hippocampal HSP90aa1 increase in SI; and inhibition of the bed nucleus of the stria terminalis (BNST) Cnr1 in CS). Gene expression across all brain regions was altered by O3, reflective of glucocorticoid signaling effects, such as Fkbp5 in NS, CS and SI. The SI effects on Fkbp5 were greatest for SI in BNST. O3 increased Cnr2 expression in the hypothalamus and olfactory bulbs of the NS and SI groups. O3, in all stress conditions, generally inhibited the expression of Nr3c1 in all brain regions, Nr3c2 in the hippocampus and hypothalamus and Bdnf in the hippocampus. SI, in general, showed slightly greater O3-induced changes when compared to NS and CS. Serum metabolomics revealed increased sphingomyelins in the air-exposed SI and O3-exposed NS, with underlying SI dampening some of the O3-induced changes. These results suggest a potential link between preexistent SI and acute O3-induced increases in the circulating adrenal-derived stress hormones and brain-region-specific gene expression changes in glucocorticoid signaling, which may partly underlie the stress dynamic in those with long-term SI. [ABSTRACT FROM AUTHOR]

Simple Summary: The majority of metastatic colorectal cancer cases are mismatch-repair-proficient and microsatellite-stable, and unfortunately this condition is associated with an inherent resistance to Immune Checkpoint Inhibitors. However, several trials are investigating the right way to overcome resistance in these tumors, so as to expand the application scope of immunotherapy. Future perspectives include mainly a combination of immune checkpoint inhibitors with chemotherapy and bevacizumab or cetuximab; sequential treatment with Temozolomide in O6-methylguanine-DNA methyltransferase (MGMT)-methylated tumors; validation of Immunohistochemical biomarkers of response, such as tumor mutational burden or Immunoscore. Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths in Europe. About 5% of metastatic CRC (mCRC) are characterized by high microsatellite instability (MSI) due to a deficient DNA mismatch repair (dMMR), and this condition has been related to a high sensitivity to immunotherapy, in particular to the Immune Checkpoint Inhibitors (ICIs). In fact, in MSI-H or dMMR mCRC, treatment with ICIs induced remarkable response rates and prolonged survival. However, the majority of mCRC cases are mismatch-repair-proficient (pMMR) and microsatellite-stable (MSS), and unfortunately these conditions involve resistance to ICIs. This review aims to provide an overview of the strategies implemented to overcome ICI resistance and/or define subgroups of patients with MSS or dMMR mCRC who may benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species and lipid peroxidation. It plays a critical role not only in promoting drug resistance in tumors, but also in shaping therapeutic approaches for various malignancies. This review aims to elucidate the relationship between ferroptosis and head and neck cancer treatment by discussing its conceptual framework, mechanism of action, functional aspects, and implications for tumor therapy. In addition, this review consolidates strategies aimed at improving the efficacy of head and neck cancer treatment through modulation of ferroptosis, herein serving as a valuable reference for advancing the treatment landscape for this patient population. [ABSTRACT FROM AUTHOR]

The composition, viability and metabolic functionality of intestinal microbiota play an important role in human health and disease. Studies on intestinal microbiota are often based on fecal samples, because these can be sampled in a non-invasive way, although procedures for sampling, processing and storage vary. This review presents factors to consider when developing an automated protocol for sampling, processing and storing fecal samples: donor inclusion criteria, urine–feces separation in smart toilets, homogenization, aliquoting, usage or type of buffer to dissolve and store fecal material, temperature and time for processing and storage and quality control. The lack of standardization and low-throughput of state-of-the-art fecal collection procedures promote a more automated protocol. Based on this review, an automated protocol is proposed. Fecal samples should be collected and immediately processed under anaerobic conditions at either room temperature (RT) for a maximum of 4 h or at 4 °C for no more than 24 h. Upon homogenization, preferably in the absence of added solvent to allow addition of a buffer of choice at a later stage, aliquots obtained should be stored at either −20 °C for up to a few months or −80 °C for a longer period—up to 2 years. Protocols for quality control should characterize microbial composition and viability as well as metabolic functionality. [ABSTRACT FROM AUTHOR]

The escalating crisis of environmental degradation, with waste fires acting as a potent accelerant, has reached a critical juncture that demands immediate attention. This crisis disproportionately affects developing and low-income nations, where unregulated disposal and incineration in open areas have become rampant. These open waste fires serve as hotbeds for many environmental hazards ranging from air and water pollution to soil degradation. In addition, they contribute to the growing threat of marine litter and are a significant source of greenhouse gas emissions, exacerbating global climate change. Beyond their environmental toll, waste fires present an immediate and long-term threat to human health, causing respiratory problems and skin conditions and potentially leading to more serious health outcomes, such as cancer. Their impacts are multidimensional, affecting not only the environment but also pose severe health risks to communities, especially those near waste-burning sites. In this technologically advanced era, the application of artificial intelligence (AI), Machine Learning (ML), and deep learning technologies has the potential to revolutionize waste fire management. These technologies can significantly improve the accuracy of identifying, monitoring, and ultimately mitigating waste fires, making them indispensable tools in the fight against this complex issue. This article offers a comprehensive and in-depth examination of the historical evolution of waste fires, with the aim of shedding light on the critical factors that contribute to their occurrence. We explore the scientific mechanisms by which waste fires lead to environmental pollution and public health crises, providing a holistic understanding of their far-reaching impacts. We present an overview of significant research initiatives, policy interventions, and technological solutions that have been proposed or implemented by authoritative bodies around the world. By synthesizing existing research and offering new insights, this paper aims to facilitate a deeper understanding of the intricacies of waste fires and spur innovative solutions for their sustainable management and eventual eradication. Therefore, this article focuses on environmental and human health problems while outlining the comprehensive approach and potential contributions to solving this critical issue. [ABSTRACT FROM AUTHOR]

Simple Summary: The management of colorectal cancer has improved significantly due to advances in molecular techniques. Thanks to these techniques, it has been possible to identify markers in these tumors, which allows for the use of specific treatments. However, research on this subject is evolving so rapidly that previous information is quickly rendered obsolete. In addition, these techniques offer a large amount of information, which makes them difficult to interpret. The aim of this article is to describe how these markers are determined from a practical point of view. Advances in genomic technologies have significantly improved the management of colorectal cancer (CRC). Several biomarkers have been identified in CRC that enable personalization in the use of biologic agents that have shown to enhance the clinical outcomes of patients. However, technologies used for their determination generate massive amounts of information that can be difficult for the clinician to interpret and use adequately. Through several discussion meetings, a group of oncology experts from Spain and several Latin American countries reviewed the latest literature to provide practical recommendations on the determination of biomarkers in CRC based on their clinical experience. The article also describes the importance of looking for additional prognostic biomarkers and the use of histopathology to establish an adequate molecular classification. Present and future of immunotherapy biomarkers in CRC patients are also discussed, together with several techniques for marker determination, including liquid biopsy, next-generation sequencing (NGS), polymerase chain reaction (PCR), and fecal immunohistochemical tests. Finally, the role of Molecular Tumor Boards in the diagnosis and treatment of CRC is described. All of this information will allow us to highlight the importance of biomarker determination in CRC. [ABSTRACT FROM AUTHOR]

Disulfidptosis, a novel form of regulated cell death (RCD) associated with metabolism, represents a promising intervention target in cancer therapy. While abnormal lncRNA expression is associated with colon cancer development, the prognostic potential and biological characteristics of disulfidptosis-related lncRNAs (DRLs) remain unclear. Consequently, the research aimed to discover a novel indication of DRLs with significant prognostic implications, and to investigate their possible molecular role in the advancement of colon cancer. Here, we acquired RNA-seq data, pertinent clinical data, and genomic mutations of colon adenocarcinoma (COAD) from the TCGA database, and then DRLs were determined through Pearson correlation analysis. A total of 434 COAD patients were divided in to three subgroups through clustering analysis based on DRLs. By utilizing univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) algorithm, and multivariate Cox regression analysis, we ultimately created a prognostic model consisting of four DRLs (AC007728.3, AP003555.1, ATP2B1.AS1, and NSMCE1.DT), and an external database was used to validate the prognostic features of the risk model. According to the Kaplan–Meier curve analysis, patients in the low-risk group exhibited a considerably superior survival time in comparison to those in the high-risk group. Enrichment analysis revealed a significant association between metabolic processes and the genes that were differentially expressed in the high- and low-risk groups. Additionally, significant differences in the tumor immune microenvironment landscape were observed, specifically pertaining to immune cells, function, and checkpoints. High-risk patients exhibited a low likelihood of immune evasion, as indicated by the Tumor Immune Dysfunction and Exclusion (TIDE) analysis. Patients who exhibit both a high risk and high Tumor Mutational Burden (TMB) experience the least amount of time for survival, whereas those belonging to the low-risk and low-TMB category demonstrate the most favorable prognosis. In addition, the risk groups determined by the 4-DRLs signature displayed distinct drug sensitivities. Finally, we confirmed the levels of expression for four DRLs through rt-qPCR in both tissue samples from colon cancer patients and cell lines. Taken together, the first 4-DRLs-based signature we proposed may serve for a hopeful instrument for forecasting the prognosis, immune landscape, and therapeutic responses in colon cancer patients, thereby facilitating optimal clinical decision-making. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients' clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10−3; p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10−3). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms can regulate how DNA is expressed independently of sequence and are known to be associated with various diseases. Among those epigenetic mechanisms, DNA methylation (DNAm) is influenced by genotype and the environment, making it an important molecular interface for studying disease etiology and progression. In this study, we examined the whole blood DNA methylation profiles of a large group of people with (pw) multiple sclerosis (MS) compared to those of controls. We reveal that methylation differences in pwMS occur independently of known genetic risk loci and show that they more strongly differentiate disease (AUC = 0.85, 95% CI 0.82–0.89, p = 1.22 × 10−29) than known genetic risk loci (AUC = 0.72, 95% CI: 0.66–0.76, p = 9.07 × 10−17). We also show that methylation differences in MS occur predominantly in B cells and monocytes and indicate the involvement of cell-specific biological pathways. Overall, this study comprehensively characterizes the immune cell-specific epigenetic architecture of MS. [ABSTRACT FROM AUTHOR]

Among preterm infants, the risk of developing asthma is a matter of debate. This review discusses the state of the art of poorly understood prematurity-associated asthma. Impaired pulmonary function is common in children born prematurely. Preterm infants are prone to developing viral respiratory tract infections, bronchiolitis in the first year of life, and recurrent viral wheezing in preschool age. All of these conditions may precede asthma development. We also discuss the role of both atopic sensitization and intestinal microbiome and, consequently, immune maturation. Diet and pollution have been considered to better understand how prematurity could be associated with asthma. Understanding the effect of factors involved in asthma onset may pave the way to improve the prediction of this asthma phenotype. [ABSTRACT FROM AUTHOR]

Simple Summary: Protein arginine methyltransferases (PRMTs) are a group of enzymes that play pivotal roles in post-translational modifications (PTMs) and are involved in the regulation of various cellular processes. Although PRMTs are recognized for their impact on the development and prognosis of various cancers, their specific involvement in hepatocellular carcinoma (HCC) remains relatively limited. In this study, we systematically evaluated the association between PRMTs and HCC prognosis, revealing their potential as prognostic biomarkers. We also highlighted the importance of PRMT1 and elucidated its role in HCC progression, especially in the context of T cell exhaustion (Tex). Our study underscores the prospective utility of PRMTs, particularly PRMT1, as promising prognostic indicators for HCC, as well as therapeutic targets for this malignancy. HCC is a major contributor to cancer-related mortality worldwide. Curative treatments are available for a minority of patients diagnosed at early stages; however, only a few multikinase inhibitors are available and are marginally effective in advanced cases, highlighting the need for novel therapeutic targets. One potential target is the protein arginine methyltransferase, which catalyzes various forms of arginine methylation and is often overexpressed in various cancers. However, the diverse expression patterns and clinical values of PRMTs in HCC remain unclear. In the present study, we evaluated the transcriptional expression of PRMTs in HCC cohorts using publicly available datasets. Our results revealed a significant association between PRMTs and prognosis in HCC patients with diverse clinical characteristics and backgrounds. This highlights the promising potential of PRMTs as prognostic biomarkers in patients with HCC. In particular, single-cell RNA (scRNA) sequencing analysis coupled with another human cohort study highlighted the pivotal role of PRMT1 in HCC progression, particularly in the context of Tex. Translating these findings into specific therapeutic decisions may address the unmet therapeutic needs of patients with HCC. [ABSTRACT FROM AUTHOR]

Appendiceal cancers (AC) are a rare and heterogeneous group of malignancies. Historically, appendiceal neoplasms have been grouped with colorectal cancers (CRC), and treatment strategies have been modeled after CRC management guidelines due to their structural similarities and anatomical proximity. However, the two have marked differences in biological behavior and treatment response, and evidence suggests significant discrepancies in their respective genetic profiles. In addition, while the WHO classification for appendiceal cancers is currently based on traditional histopathological criteria, studies have demonstrated that histomorphology does not correlate with survival or treatment response in AC. Due to their rarity, appendiceal cancers have not been studied as extensively as other gastrointestinal cancers. However, their incidence has been increasing steadily over the past decade, making it crucial to identify new and more effective strategies for detection and treatment. Recent efforts to map and understand the molecular landscape of appendiceal cancers have unearthed a wealth of information that has made it evident that appendiceal cancers possess a unique molecular profile, distinct from other gastrointestinal cancers. This review focuses on the epigenetic landscape of epithelial appendiceal cancers and aims to provide a comprehensive overview of the current state of knowledge of epigenetic changes across different appendiceal cancer subtypes, highlighting the challenges as well as the promise of employing epigenetics in the quest for the detection of biomarkers, therapeutic targets, surveillance markers, and predictors of treatment response and survival in epithelial appendiceal neoplasms. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite its small size, the vermiform appendix is an organ with several physiological roles and various pathologies, the most common of which is acute appendicitis. The other pathologies of the vermiform appendix, especially its neoplasia are rare and often go unnoticed and are accidentally identified during appendectomies performed for other reasons. In the early stages, most appendiceal neoplasms are not detected; however, in the advanced stages, they may mimic the symptoms of acute appendicitis. In addition, due to massive mucus production, mucinous neoplasms, especially adenocarcinomas, may fistulize into adjacent structures, some identified after perforated organ pathology. The general treatment for appendiceal pathologies, including neoplasms, is complete surgical excision of the appendix, with or without the right hemicolectomy. Life expectancy is somewhat longer for low-grade mucinous tumors and peaks for well-differentiated, small, metastasis-free neuroendocrine tumors of the appendix occurring in children. The vermiform appendix is a muscular cylindrical structure originating near the junction of the cecum and ileum, averaging 9 cm (5–35 cm) in size. As the most mobile viscera, it can adopt several positions, the most common being the retrocecal position. Perceived as an atavistic organ lacking physiological relevance, the vermiform appendix appears to be involved in immune function, serving in the maturation of B lymphocytes and the production of immunoglobulin A, in endocrine function, excreting amines and hormones in the 2–3 mL of mucus secreted daily, and in digestive function, by storing beneficial bacteria from where they can recolonize the colon. With a lumen of about 6 mm, the vermiform appendix has a reduced storage capacity, so any blockage of the appendix with fecoliths (fecaliths), seeds derailed from the colon, or enlarged lymph nodes prevents drainage and intraluminal accumulation of secreted mucus. Unable to relax, the appendix wall severely limits its intraluminal volume, so mucus accumulation leads to inflammation of the appendix, known generically as appendicitis. In addition, the vermiform appendix may be the site of the development of neoplastic processes, which may or may not involve mucus production, some of which can significantly affect the standard of living and ultimately lead to death. In general, mucinous tumors may have a better prognosis than non-mucinous tumors. This review takes a comprehensive path, starting by describing the anatomy and embryology of the vermiform appendix and further detailing its inflammatory pathologies, pathologies related to congenital anomalies, and appendix tumors, thus creating an up-to-date framework for better understanding, diagnosis, and treatment of these health problems. [ABSTRACT FROM AUTHOR]

Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether the sex of the newborn affects the lymphocyte subpopulations in the cord blood. Nine B and twenty-one T cell subpopulations were characterized using flow cytometry in human cord blood from sixteen male and twenty-one female newborns, respectively. Except for transitional B cells and naïve B cells, frequencies of B cell counts across all subsets was higher in the cord blood of male newborns than in female newborns. The frequency of naïve thymus-negative Th cells was significantly higher in male cord blood, whereas the remaining T cell subpopulations showed a higher count in the cord blood of female newborns. Our study is the first revealing sex differences in the B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system, urging the need to expand research in this area. [ABSTRACT FROM AUTHOR]

Gastric cancer is a heterogeneous disease with diverse histological and genomic subtypes, making it difficult to demonstrate treatment efficacy in clinical trials. However, recent efforts have been made to identify molecular biomarkers with prognostic and predictive implications to better understand the broad heterogeneity of gastric cancer and develop effective targeted therapies for it. HER2 overexpression, HER2/neu amplification, MSI-H, and PD-L1+ are predictive biomarkers in gastric cancer, and a growing number of clinical trials based on novel biomarkers have demonstrated the efficacy of targeted therapies alone or in combination with conventional chemotherapy. Enrichment design clinical trials of targeted therapies against FGFR2b and claudin 18.2 have demonstrated efficacy in unresectable advanced gastric cancer. Nonetheless, it is essential to continuously validate promising molecular biomarkers and introduce them into clinical practice to optimize treatment selection and improve patient outcomes. In this review, we focused on established (PD-L1, HER2, MSI) and emerging biomarkers (FGFR2, CLDN18.2) in gastric cancer, their clinical significance, detection methods, limitations, and molecular agents that target these biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: An analysis of the presence of mutations of 105 genes in appendiceal cancers through the lens of the reviewed literature supports the view that in most of them, the inactivation of tumor suppressor genes, such as TP53 and SMAD4, is required in parallel with the reactivation of genes with oncogenic potentials, such as KRAS, GNAS, and BRAF, which support the main tumor processes, cell proliferation, angiogenesis, and evasion of apoptosis. Of all appendiceal cancers, the most mutated genes are reported in mucinous neoplasms of the appendix, not including those in the RAS–RAF–MEK–ERK signaling pathway, followed by low-grade appendiceal mucinous neoplasms, appendiceal goblet cell adenocarcinomas, and mucinous adenocarcinomas of the appendix, in which this signaling pathway is most frequently affected, showing its importance in their tumorigenesis. Microsatellite instability rarely occurs in appendix cancers, being reported only in adenocarcinomas. In appendiceal cancers, the most frequently mutated genes are (i) KRAS, which, when reactivated, restores signal transduction via the RAS–RAF–MEK–ERK signaling pathway and stimulates cell proliferation in the early stages of tumor transformation, and then angiogenesis; (ii) TP53, whose inactivation leads to the inhibition of programmed cell death; (iii) GNAS, which, when reactivated, links the cAMP pathway to the RAS–RAF–MEK–ERK signaling pathway, stimulating cell proliferation and angiogenesis; (iv) SMAD4, exhibiting typical tumor-suppressive activity, blocking the transmission of oncogenic TGFB signals via the SMAD2/SMAD3 heterodimer; and (v) BRAF, which is part of the RAS–RAF–MEK–ERK signaling pathway. Diverse mutations are reported in other genes, which are part of secondary or less critical signaling pathways for tumor progression, but which amplify the phenotypic diversity of appendiceal cancers. In this review, we will present the main genetic mutations involved in appendix tumors and their roles in cell proliferation and survival, and in tumor invasiveness, angiogenesis, and acquired resistance to anti-growth signals. [ABSTRACT FROM AUTHOR]