Search Results (359)

Background/Objectives: Hepatic cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are major global health concerns due to rising incidence and limited therapeutic success. While traditional risk factors include chronic liver disease and environmental exposures, recent evidence underscores the significance of genetic alterations and gut microbiota in liver cancer development and progression. This review aims to integrate emerging knowledge on the interplay between host genomic changes and gut microbial dynamics in the pathogenesis and treatment of hepatic cancers. Methods: We conducted a comprehensive review of current literature on genetic and epigenetic drivers of HCC and CCA, focusing on commonly mutated genes such as TP53, CTNNB1, TERT, IDH1/2, and FGFR2. In parallel, we evaluated studies addressing the gut–liver axis, including the roles of dysbiosis, microbial metabolites, and immune modulation. Key clinical and preclinical findings were synthesized to explore how host–microbe interactions influence tumorigenesis and therapeutic response. Results: HCC and CCA exhibit distinct but overlapping genomic landscapes marked by recurrent mutations and epigenetic reprogramming. Alterations in the gut microbiota contribute to hepatic inflammation, genomic instability, and immune evasion, potentially enhancing oncogenic signaling pathways. Furthermore, microbiota composition appears to affect responses to immune checkpoint inhibitors. Emerging therapeutic strategies such as probiotics, fecal microbiota transplantation, and precision oncology based on mutational profiling demonstrate potential for personalized interventions. Conclusions: The integration of host genomics with microbial ecology provides a promising paradigm for advancing diagnostics and therapies in liver cancer. Targeting the gut–liver axis may complement genome-informed strategies to improve outcomes for patients with HCC and CCA. Full article

Kawasaki disease (KD), first identified in 1967 by Dr. Tomisaku Kawasaki, is an acute, self-limited vasculitis and remains the leading cause of acquired heart disease in children worldwide, particularly affecting those under the age of five. Clinically, it presents with persistent fever, mucocutaneous inflammation, skin rashes, and lymphadenopathy, with a marked tendency to involve the coronary arteries, potentially leading to serious complications such as coronary artery aneurysms. Despite extensive research spanning more than five decades, the precise etiology of KD remains unclear. However, accumulating evidence supports the significant role of genetic predisposition, highlighting the contribution of inherited factors in modulating immune responses and influencing disease susceptibility and severity. Emerging evidence highlights genetic susceptibility as pivotal, with genome-wide studies identifying polymorphisms in immune-related genes, such as ITPKC, CASP3, BLK, CD40, and ORAI1, which modulate disease risk and coronary complications. Epigenetic mechanisms, including DNA methylation and non-coding RNAs, bridge the gap between genetic and environmental factors, regulating immune responses and endothelial activation. Furthermore, emerging insights into autophagy-related processes provide a deeper understanding of the molecular mechanisms underlying the disease. This review aims to explore the current knowledge on the genetic landscape of KD, examine how these findings contribute to our understanding of its pathophysiology, and investigate the potential for genetically targeted therapeutic strategies in the future. Full article

Researchers are increasingly focusing on understanding the microbiota’s influence on disease susceptibility and overall health. The vast number of microorganisms in our gastrointestinal tract and their extensive surface area underscore their undeniable impact on well-being. Viewing the gut microbiome as a distinct pool of microbial genetic information that interacts with the human genome highlights its pivotal role in genetically predisposed diseases. Investigating this complex crosstalk may lead to the development of novel therapeutic strategies—such as targeting dysbiosis—to complement conventional treatments and improve patient care. Parkinson’s disease (PD) is a multifactorial condition originating from a combination of genetic and environmental risk factors. Compelling evidence points to the enteric nervous system as an initial site of pathological processes that later extend to the brain—a pattern known as the ‘body-first’ model. Furthermore, most patients with PD exhibit both qualitative and quantitative alterations in the composition of the gut microbiota, including dysbiosis and small intestinal overgrowth. Nonetheless, the existing literature predominantly addresses fecal microbiota, while knowledge of upper intestinal sections, like the duodenum, remains scarce. Given the potential for microbiota modulation to impact both motor and gastrointestinal symptoms, further research exploring the therapeutic roles of balanced diets, probiotics, and fecal transplants in PD is warranted. Full article

In recent years, significant changes in food consumption habits have emerged due to various factors, including climate change, population growth, urbanization, and the depletion of natural resources. These changes pose a threat to the stability of global food systems and raise serious concerns about food security. Although this process encourages innovative and sustainable food consumption, it also makes individuals more skeptical and concerned about new foods. In this context, understanding consumer intentions regarding behaviors such as purchasing genetically modified (GM) foods is critical for predicting consumer responses and promoting responsible consumption patterns within the scope of sustainability. This study examined the effects of food technology neophobia and perceived information on attitudes and purchase intentions toward genetically modified (GM) foods. Survey data were collected from 324 participants across Turkey and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). The findings revealed that food technology neophobia reduces perceived benefits and increases perceived risks, whereas perceived information enhances perceived benefits and lowers perceived risks. Additionally, attitudes were found to influence the intention to purchase GM foods significantly. Global issues, such as climate change and the depletion of natural resources, highlight the importance of innovations in food technology for sustainable food production. Understanding consumer concerns and perceived knowledge levels regarding genetically modified (GM) foods is critical to ensuring that these products are accepted at the societal level in an informed and conscious way. This study contributes to the promotion of sustainable food technologies and responsible consumer behavior, in line with the objectives of Sustainable Development Goal 12 (Responsible Consumption and Production). Full article

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide. Despite significant advances in pharmacological therapies, responses to treatment vary widely among patients. Growing evidence suggests that genetic factors play a crucial role in influencing individual responses to HF therapies. Genetic variations, including single-nucleotide polymorphisms (SNPs), gene expression profiles, and epigenetic modifications, have been shown to affect drug metabolism, receptor sensitivity, and the molecular pathways involved in HF progression. These genetic determinants may not only predict the efficacy of common therapeutic agents such as angiotensin-converting enzyme inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors, but also help identify patients at risk of adverse drug reactions. As personalized medicine continues to advance, a deeper understanding of the genetic basis of drug response in HF could enable more tailored treatment strategies, improving clinical outcomes and minimizing adverse effects. This review explores the current evidence on the genetic underpinnings of response to HF treatment and discusses its potential implications in clinical practice, highlighting current knowledge gaps. Full article

Celiac disease (CeD) is an autoimmune disorder that is triggered by gluten ingestion in genetically predisposed individuals. Untreated or poorly controlled CeD leads to various disease complications, such as malnutrition, osteoporosis, autoimmune diseases, or refractory celiac disease (RCD). Accumulating recent research has highlighted the association between CeD and the development of malignancies, particularly enteropathy-associated T-cell lymphoma (EATL) and small bowel carcinoma (SBC), which are neoplasms with extremely poor prognoses. Genetic alterations in the JAK1–STAT3 pathway and the high prevalence of microsatellite instability may be the main drivers of CeD-associated lymphomagenesis and small bowel oncogenesis and therefore could be an attractive therapeutic target to block cancer transformation. However, to date, the risk factors and exact mechanisms underlying malignancy development in patients with CeD remain unclear, and prospective cohort studies that include molecular profiling are needed. Moreover, current guidelines on the management of CeD do not provide standardized protocols for cancer surveillance—particularly regarding screening intervals, risk stratification, and monitoring strategies for high-risk patients such as those with RCD. This paper reviews the existing knowledge on malignancies in CeD, highlights diagnostic challenges, and discusses future perspectives on the early detection, monitoring, and treatment of CeD-associated neoplasms. Full article

Atopic dermatitis (AD) is a chronic, complex, and immunologically mediated skin disease. Its exact cause remains complex, multifaceted and yet to be discovered but is likely related to a combination of immunological, genetic and environmental factors. A medical literature search of PubMed (1992–present), Google Schoolar and Embase was performed using appropriate terms without date limitations in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Nevertheless, chronic inflammation is believed to be a major player in the development of AD and a causative element in the development of metabolic syndrome (MetS). Metabolic syndrome is a cluster of common metabolic abnormalities including hypertension, insulin resistance, abdominal obesity, reduced high-density lipoprotein (HDL)–cholesterol levels and elevated triglyceride levels. High waist circumference is positively correlated with the risk of atopic dermatitis, but there is no significant correlation between adult-onset atopic dermatitis and hypertension. Some evidence suggests an association between AD and hypertension but only in patients with severe AD. On the other hand, the relationship between AD and hyperglycemia or AD and cholesterol levels seems inconclusive. The aim of this review is to present current knowledge on the association between atopic dermatitis and metabolic syndrome, including each of the components of metabolic syndrome. Full article

Background: Ovarian carcinoma (OC) is one of the foremost factors in female carcinoma-related fatalities worldwide. Matrix metalloproteinases (MMPs) are key mediators of tissue remodeling and are linked to tumor aggressiveness, yet there is still a lack of information on the link between genetic changes in MMPs-1,3 and the onset and progression of OC in Egyptian women. This study examines the effects of immunoreactive biomolecule variations of MMPs-1,3, as well as the MMP-1 (1607 1G/2G) and MMP-3 (-1171 5A/6A) genetic variants, on OC risk and progression in Egyptian women. Methods: Tissue specimens embedded in paraffin from 100 OC patients and 60 controls were stained using immunohistochemistry to examine expression of MMPs-1,3. MMP levels were quantified using ELISA, and single-nucleotide polymorphisms (SNPs) of MMPs-1,3 were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Results: Increased levels of MMPs-1,3 in OC patients relative to controls, with more of an increase in the late stages (III and IV) than in the early OC stages (I and II). Additionally, the MMP-1 2G/2G and MMP-3 6A/6A genotypes were more prevalent in OC patients than in controls. Ovarian MMPs-1,3 were comparatively elevated in the identified genotypes compared to the 1G/1G and 5A/5A genotypes, respectively. The transcriptional activity of MMPs-1,3 showed strong potential for distinguishing patients with epithelial ovarian carcinoma (EOC) from controls, boasting an area under the curve (AUC) of 0.956 and 0.816, respectively. Sensitivity and specificity were 94.0% and 90.0% for MMP-1 and 80.0% and 73.3% for MMP-3, respectively. Conclusions: The MMP-1 2G/2G and MMP-3 6A/6A genotypes are correlated with elevated MMP-1 and MMP-3 levels and immunohistochemical expression in carcinomatous ovarian tissues, particularly in advanced stages of OC. This indicates that genetic variations of MMPs-1,3 could be valuable diagnostic and prognostic markers for OC in Egyptian women. Our findings may carry clinical relevance for optimizing OC therapeutic effectiveness, contribute to the growing body of knowledge on the role of MMPs, and shed new light on the genetic background of OC. Future studies with larger sample sizes and comprehensive MMP genetic profiling are needed for results validation. Full article

Background/Objectives: Aneurysmal bone cysts (ABCs) are rare bone tumors that can occur in the skull, leading to extensive bone destruction and compression of surrounding tissues. Due to the rarity of these lesions, there are limited data available in the literature, which primarily consists of case reports. We aimed to collect and analyze the available data to summarize the current state of knowledge on this rare pathology, while also conducting a statistical analysis to identify potential risk factors and management strategies. Methods: A review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, covering studies published from January 1950 to December 2023. A total of 60 articles and 74 case reports were included. Results: The mean age at diagnosis was 14.8 ± 12.5 years, with slightly higher male gender predominance. Regarding the different skull bones, a statistically significant higher growth trend of ABCs was found at the parietal bone in the male population (p = 0.025). At the occipital bone, a significant correlation was observed with the age of incidence for symptomatic lesions (p = 0.007) and development from fibrous dysplasia (p = 0.019). Secondary lesions showed a higher frequency of complications within the first months post-surgery (p = 0.041). Conclusions: No significant correlation was found between ABCs and fibrous dysplasia (FD) or head trauma. Male patients with FD showed a higher tendency to develop an aneurysmal cyst at the occipital bone at an older age and a higher tendency for growth in ABCs at the parietal bone. However, to date, no molecular or genetic correlation with male hormones has been reported in the literature. Surgery remains the only effective treatment, but complications should be carefully considered, particularly in patients with pre-existing pathological conditions. Full article

Background/Objectives: Thyroid cancer is the most common endocrine malignancy in Saudi Arabia, with rising incidence and notable gender disparities. However, public awareness and understanding, particularly in the Northern region, remain limited. This study aims to assess knowledge, awareness, and preventive practices regarding thyroid cancer among northern Saudi Arabian residents and identify sociodemographic factors associated with levels of knowledge, awareness, and engagement in preventive practices. Methods: A cross-sectional survey of 702 participants from northern Saudi Arabia was conducted using a validated online questionnaire. Participants were recruited via social media platforms and online community groups. The survey assessed sociodemographic data, knowledge of risk factors, symptoms, and screening practices, perceptions of curability and prevention, and engagement with awareness campaigns. Descriptive statistics and chi-square tests were used to analyze associations. Results: The majority of respondents were young, female, and highly educated. Only 1.3% reported a personal history of thyroid cancer. Knowledge gaps regarding risk factors, screening practices, and curability were evident: 54.6% had never undergone thyroid hormone analysis, and 91% had not received thyroid imaging. Nearly half (48.6%) were uncertain about the curability of thyroid cancer, and only 27.8% recognized its genetic basis. While 62.1% believed thyroid cancer could be prevented, just 18.4% participated in awareness campaigns. Significant associations were found between knowledge of screening practices and age, education, nationality, and having family or friends in the medical field (p < 0.05). Conclusions: Significant gaps in awareness of thyroid cancer risk factors and early detection practices exist among northern Saudi residents. Culturally tailored educational interventions and integration of thyroid health into primary care are urgently needed to address these deficiencies and improve outcomes. Full article

SHBG is a glycoprotein that not only controls serum sex hormone levels but is also strongly correlated with metabolic syndrome, cardiovascular risk, thyroid function, gynecological conditions, and even the process of carcinogenesis. Synthesis of SHBG is controlled by many factors related to obesity, lipogenesis, inflammatory status, and genetic predisposition. By influencing the bioavailability of sex hormones, SHBG regulates their effects not only on the reproductive system, but also cardiomyocytes, vascular epithelium, and more. In this review, we aim to gather and summarize current knowledge on the physiology of SHBG and its association with cardiovascular disease, metabolic syndrome, DM 2, thyroid function, PCOS, hypogonadism, infertility, and its correlations with oral contraception. What is more, genetic alterations are mentioned to highlight SHBG as a potential new diagnostic marker. Furthermore, we assess the clinical usefulness of this parameter in the diagnosis and treatment of patients suffering from the above-specified conditions. Full article

Understanding the risk and protective factors associated with Parkinson’s disease (PD) is crucial for improving outcomes for patients, individuals at risk, healthcare providers, and healthcare systems. Studying these factors not only enhances our knowledge of the disease but also aids in developing effective prevention, management, and treatment strategies. This paper reviews the key risk and protective factors associated with PD, with a particular focus on the biological mechanisms underlying these factors. Risk factors include genetic mutations, racial predispositions, and environmental exposures, all of which contribute to an increased likelihood of developing PD or accelerating its progression. Conversely, protective factors, such as regular physical exercise, adherence to a Mediterranean diet, and higher urate levels, have the potential to reduce inflammation and support mitochondrial function, thereby mitigating the risk of disease. However, identifying and validating these factors presents significant challenges. These challenges include the absence of reliable biomarkers, intricate interactions between genetic and environmental components, and clinical heterogeneity observed in patients with PD. These barriers complicate the establishment of clear causal relationships and hinder the development of targeted preventive strategies. To overcome these challenges, we propose several solutions and recommendations. Understanding the mechanisms underlying risk factors may inform future research aimed at developing standardized and more accurate biomarkers for PD, facilitating earlier diagnosis and improved monitoring of disease progression. Additionally, we offer actionable recommendations for PD prevention and management tailored to healthy individuals, patients diagnosed with PD, and healthcare systems. These strategies aim to improve clinical outcomes, enhance the quality of life, and optimize healthcare delivery for PD. Full article

Introduction: Alkaptonuria is an autosomal-recessive disorder affecting the metabolism of tyrosine and phenylalanine which results in accumulation of homogentisic acid in connective tissues. The joints are most commonly affected, while the most common cardiac damage is aortic valve stenosis. The treatment focuses on reducing the symptoms. Aortic stenosis in alkaptonuria is treated with surgical aortic valve replacement; however, transcatheter aortic valve implantation procedures are increasing in number with excellent outcomes. Case presentation: We report a case of a 67-year-old female with chronic back pain and large-joint arthralgia, who was recently diagnosed with alkaptonuria. She reported a long-known heart murmur and intermittent dark-brown staining of her underwear since childhood. Bilateral dark-brown pigmentation of the sclera and both ear cartilages were visualised. ECG confirmed atrial fibrillation and left ventricular hypertrophy. Cardiac ultrasonography showed severe aortic stenosis, reduced global longitudinal strain and preserved ejection fraction. According to the latest recommendations, the choice between surgical and transcatheter intervention must be based upon careful evaluation of clinical, anatomical and procedural factors by the Heart Team, weighing the risks and benefits of each approach for an individual patient. The advantages and disadvantages of both procedures were explained to the patient. It was emphasised that the genetic disease present has no etiopathogenetic definitive treatment and the pigment may continue to deposit on the biological valve (in transcatheter aortic valve implantation) and less likely on the mechanical valve prosthesis (in Surgical Aortic Valve Replacement), highlighting the fact that in the literature worldwide, there are only single reports of ochronosis and severe aortic stenosis. At this stage of knowledge, it is difficult to give the patient clear guarantees when choosing a methodology for performing a valve correction. Along with the standard therapy the patient underwent transcatheter aortic valve implantation with Boston Scientific prosthesis with a very good post-procedural outcome. Conclusions: There is scarce information on transcatheter aortic valve implantation success rate in patients with alkaptonuria. In the population, transcatheter aortic valve implantation outcome is generally good; however, the individual success in alkaptonuria patients depends on the severity of their heart valve damage and overall health. Full article

Cardiovascular diseases increase among pregnant women and complicate 1–4% of pregnancies worldwide. The incidence of maternal deaths due to cardiovascular causes has increased dramatically, rising from 3% three decades ago to 15% in recent years. The aim of this study is to provide a comprehensive overview of the current status of knowledge in sudden maternal death (SMD) described in the literature and to present two cases of autopsy findings in sudden cardiac death in pregnant women. Among the most common causes of sudden maternal deaths are peripartum cardiomyopathies, aortic dissection, acute myocardial infarction, arrhythmias, ischemic heart disease, and coronary artery dissection, and among the less common causes, we list coronary artery dissection, congenital heart diseases, valvulopathies, hypertension, fibroelastosis, and borderline myocarditis. The Centers for Disease Control and Prevention (CDC) reported that over 80% of pregnancy-related deaths were preventable. To reduce the number of maternal deaths caused by cardiovascular diseases, the implementation of specialized multidisciplinary teams has been proposed. Molecular biology techniques are proving their effectiveness in forensic medicine. PCR or DNA sequencing can be utilized in “molecular autopsy”, which holds particular value in cases of sudden death where the forensic autopsy is negative but there is a suspicion that death was caused by arrhythmia. Susceptibility genes can be analyzed, such as KCNQ1, KCNH2, KCNE1, and KCNE2, which are involved in long QT syndrome, the RYR2 gene implicated in catecholaminergic polymorphic ventricular tachycardia type 1, or the SCN5A gene associated with Brugada syndrome. Early identification of risk factors involved in sudden maternal death prenatally and during pregnancy is essential. At the same time, genetic determinations and molecular biology techniques are absolutely necessary to prevent the occurrence of sudden deaths among close relatives. Full article

Background/Objectives: Several genetic factors are related to the risk of Alzheimer’s disease (AD) and the response to cholinesterase inhibitors (ChEIs) (donepezil, galantamine, and rivastigmine) or memantine. However, findings have been controversial, and, to the best of our knowledge, admixed populations have not been previously evaluated. We aimed to determine the impact of genetic and non-genetic factors on the risk of AD and the short-term response to ChEIs and memantine in patients with AD from Mexico. Methods: This study included 117 patients from two specialty hospitals in Mexico City, Mexico. We evaluated cognitive performance via clinical evaluations and neuropsychological tests. Nineteen variants in ABCB1, ACHE, APOE, BCHE, CHAT, CYP2D6, CYP3A5, CHRNA7, NR1I2, and POR were assessed through TaqMan assays or PCR. Results: Minor alleles of the ABCB1 rs1045642, ACHE rs17884589, and CHAT rs2177370 and rs3793790 variants were associated with the risk of AD; meanwhile, CHRNA7 rs6494223 and CYP3A5 rs776746 were identified as low-risk variants in AD. BCHE rs1803274 was associated with worse cognitive functioning. None of the genetic and non-genetic factors studied were associated with the response to pharmacological treatment. Conclusions: We identified potential genetic variants related to the risk of AD; meanwhile, no factor was observed to impact the response to pharmacological therapy in patients with AD from Mexico. Full article