Cichorium intybus L. (chicory) is a globally utilized medicinal plant whose root contains bioactive compounds such as inulin, fructose, chlorogenic acids (CGA), and sesquiterpene lactones (STL). These metabolites are central to its health-promoting properties. This study employed an integrated transcriptomic analysis to elucidate the genetic and molecular mechanisms underlying the effects of these compounds in mice. Microarray datasets (GSE150218 and GSE190056) were analyzed to identify differentially expressed genes (DEGs), hub genes, and associated microRNAs (miRNAs). Gene ontology (GO) enrichment, KEGG pathway analysis, and protein–protein interaction (PPI) networks were applied to characterize functional relevance. Distinct hub genes were identified: Rps28 and Rps2 (inulin), Rplp0, Cct2, and Rps20 (fructose), Mki67, Egfr, and Pparg (STL), and Socs2, Six2, Smtnl2, and Gcsh (CGA). Pathway enrichment revealed significant associations with mRNA surveillance, PPAR signaling, AMPK signaling, ribosome, and coronavirus-related pathways. Furthermore, miRNA analysis highlighted strong predicted regulatory interactions between miRNAs and hub genes, including mmu-miR-204-3p (inulin), mmu-miR-17-5p (fructose), mmu-miR-15a-5p (STL), and mmu-miR-142a-5p (CGA). Collectively, these findings identify molecular pathways and regulatory interactions associated with major chicory root bioactive compounds and provide a basis for future mechanistic studies. Experimental validation is required to confirm these predicted regulatory networks.
Cancer remains one of the leading causes of mortality worldwide, with its progression intimately linked to complex intercellular communication networks within the tumor microenvironment. Exosomes are nanoscale extracellular vesicles (EVs) of endosomal origin acting as active mediators of intercellular communication. Importantly, exosomes have emerged as critical mediators of intracellular communication that can influence microenvironmental homeostasis by transferring their bioactive cargo including proteins, lipids, and nucleic acids between cells. Although exosomes are the best-characterized miRNA carriers, other EV subclasses, including plasma membrane-derived microvesicles, apoptotic bodies, large oncosomes and migrasomes, also convey miRNAs and modify recipient cell behavior, and are therefore considered here alongside exosomes. We further examine mitochondria-derived vesicles (MDVs), a distinct vesicular pathway that connects mitochondrial quality control to the endosomal compartment and that may act upstream of exosomal miRNA loading. Among their cargo, exosome-derived microRNAs (exomiRs) have attracted considerable attention for their ability to negatively regulate gene expression in recipient cells, modulating key oncogenic processes such as angiogenesis, invasion, immune evasion, epithelial-to-mesenchymal transition, drug resistance, and cancer-related stem cell activity. This review aims to synthesize current knowledge on the biogenesis and function of EVs, including exosomes and MDVs, and of exomiRs linked with carcinogenesis and specifically addresses emerging evidence supporting pharmacological and nutraceutical interventions to modulate exomiR profiles as a novel chemopreventive strategy. We further discuss how diet-derived nutraceuticals, including plant polyphenols and isoflavones, can alter the microRNA expression landscape in cancer cells and their secreted exosomes, and we provide a global, cross-study overview of the miRNAs reported to respond to phytochemical exposure. In addition, we discuss the potential consequences of these modulations in several key carcinogenesis-associated processes such as angiogenesis, inflammation, oxidative stress, and stem cell mobilization. While direct targeting of exomiRs remains technically challenging, recent reports support the hypothesis that intracellular miRNA modulation may propagate to the exosomal compartment, thereby influencing intercellular communication. Collectively, this evidence highlights microRNA modulation as an indirect yet promising strategy to influence exosome-mediated intercellular communication in cancer and provides a conceptual framework for understanding exomiRs as a programmable layer of tumor-associated signaling. MicroRNA modulation by nutraceuticals and drugs may extend to the exosomal compartment. Exosome-associated miRNAs (exomiRs) are proposed as a dynamic interface of intercellular signaling. Emerging evidence suggests that intracellular microRNA levels alter the exosomal cargo composition, and that EV subclasses other than exosomes also convey miRNAs. Mitochondria-derived vesicles (MDVs) and mitochondrial stress may act as upstream regulators of exosomal signaling. Modulating miRNAs affects multiple signaling pathways that, in turn, indirectly reshape tumor microenvironment communication.
An Arctic-specific loss-of-function variant in the gene encoding sucrase-isomaltase (SI) results in the inability to digest sucrose in homozygous carriers, and also a healthier cardiometabolic phenotype. Importantly, the specific impact of the SI variant on food intake and preferences has not been studied in detail. We compared 18 homozygous SI-carriers with 20 non-carriers from Greenland matched on sex, age, BMI, and Inuit genetic ancestry. We assessed food intake using a semi-quantitative food frequency questionnaire and an ad libitum free-choice test meal. We assessed food reward using the Leeds Food Preference Questionnaire as well as participants’ ability to discriminate between sucrose and other sugars and sweetness/liking ratings in a sensory test. In the sensory test, carriers rated liking of sucrose and fructose significantly lower than non-carriers on a 100 mm visual analogue scale (−26 mm, p = 0.001 and −13 mm, p = 0.04, respectively). When comparing sucrose with fructose+glucose for most sweet and most liked sample, choice of sample was not associated with genotype. In the Leeds Food Preference Questionnaire, carriers expressed higher explicit liking and wanting for low-fat savoury foods than non-carriers (p = 0.04 and p = 0.01, respectively) as well as a lower explicit liking for high-fat foods relative to low-fat foods compared to non-carriers (p = 0.01). No significant differences were observed for the remaining food reward outcomes. Nutrient composition of the habitual diet and of the ad libitum test meal was overall similar in the two genotype groups. However, half of the carriers reported avoiding foods high in sugar compared to none of the non-carriers and habitual energy intake from high-fat sweet foods was 66
ObjectiveThis retrospective study evaluated the impact of p53-abnormal (p53abn) status on recurrence patterns and outcomes among patients with non-invasive, high-grade endometrial cancer (EC) treated at the Brazilian National Cancer Institute (INCA) between 2010 and 2025.MethodsEligible patients had high-grade histologies—including endometrioid grade 3 (ECG3), serous (USC), clear cell (CC), carcinosarcoma (CS), mixed, or undifferentiated tumors—without myometrial invasion. Clinical, surgical, and pathological characteristics, as well as recurrence and survival data, were reviewed. Immunohistochemical analysis of p53 expression was performed, and p53 status was correlated with clinical outcomes, particularly recurrence rate.ResultsFifty-nine patients met the inclusion criteria, with a mean age of 65 years. Most underwent total hysterectomy with or without bilateral salpingo-oophorectomy (59.3%); 40.7% also received lymphadenectomy or omentectomy. Histologic distribution was mainly endometrioid (39.0%) and serous (39.0%). Forty-six (78%) and 13 (22%) had p53 abnormal and normal tumors. Seven patients (11.9%) received chemotherapy and 15 (25.4%) received radiotherapy. Three patients had already disease outside uterus. Among 56 patients with FIGO stage IC disease, recurrence occurred in 16.1%, predominantly at extra-pelvic sites (33.3% abdominal, 22.2% distant). Five-year recurrence was 23.2% for p53abn tumors versus 0% for wild-type, and 12.5% of patients died—mostly within the p53abn subgroup.ConclusionThe findings suggest that even in non-invasive high-grade EC, p53 abnormalities confer higher recurrence risk and poorer outcomes, while wild-type tumors show excellent prognosis. These results support individualized treatment approaches and highlight the need for larger, prospective validation studies.
Hyperuricemia(HUA) is associated with metabolic and cardiovascular comorbidities. Genetic factors, particularly the ABCG2 rs2231142 polymorphism, and dietary habits such as vegetarianism, significantly influence hyperuricemia risk. However, the interplay between these factors remains unclear in the Taiwanese population. To investigate the association of the ABCG2 rs2231142 polymorphism and vegetarian diet on the risk of hyperuricemia in a Taiwanese cohort. This population-based case-control study utilized data from 11,113 participants in the Taiwan Biobank. Participants carrying the ABCG2 rs2231142 polymorphism (GG and GT/TT genotypes) were analyzed alongside dietary habits (vegetarian vs. non-vegetarian) and various clinical confounders. Logistic regression was used to calculate odds ratios (ORs) and identify gene–diet interactions. Among 11,113 participants, the overall prevalence of HUA was 11.1
BackgroundThe clinical efficacy of anticancer drugs is often limited by dose-dependent toxicity to normal cells, particularly to rapidly dividing stem and progenitor cell populations. Traditional preclinical toxicity screening relies on animal models or primary human cells/immortalized lines, both of which have significant limitations regarding scalability, reproducibility, genetic diversity, and translational relevance.ObjectiveThis study aims to establish and validate a human pluripotent stem cell -based platform for profiling the toxicity of cytostatic drugs on healthy, dividing cell populations, and to compare their sensitivity to that of cancer cell lines.MethodsTwo hiPSC lines (male and female) were reprogrammed from umbilical cord blood cells, fully characterized, and differentiated into neural progenitors and mesenchymal derivatives. Dose–response curves were generated using a dilution series of four anticancer drugs and four other pharmacologically active compounds based on cell viability. Toxic half-maximal values (IC50) were determined for each cell type and compared to those obtained from conventional cancer cell lines.ResultsThe highest sensitivity to DNA-damaging agents was exhibited by pluripotent stem cells, followed by neural progenitors, with mesenchymal derivatives being the least sensitive. Notably, except for mesenchymal cells, both pluripotent stem cells and their differentiated derivatives were more sensitive to cytostatics than cancer cell lines.ConclusionHuman iPSC-derived stem/progenitor cells recapitulate the in vivo sensitivity of healthy dividing cell populations to chemotherapy. This platform offers unlimited, genetically consistent, and reproducible access to human cells, rendering it as a powerful complementary approach or even an alternative to animal models and primary human cells for early-phase drug safety profiling.
Metabolic syndrome (MetS) is a global health issue linked to increased disease risk and economic burden. Traditional biomarkers for MetS reflect disrupted homeostasis but may fail to detect earlier stages of imbalance, i.e., an increase in allostatic load. Health can be defined as the capacity to maintain or recover homeostatic control, and this capacity can be assessed via a standardized nutritional challenge test (e.g., PhenFlex), which provokes adaptive metabolic responses. We aimed to identify a biomarker signature indicative of MetS-associated allostatic load, using data from multiple nutritional challenge test (NCT) studies. A multi-study analysis was performed using data from four human studies with nutritional challenge test (n = 195). We identified 64 analytes with significantly altered postprandial responses in individuals with MetS (n = 78) compared to healthy controls (n = 117). Cluster analysis revealed four clusters with a distinct temporal dynamic response to the NCT. The most prominently affected analytes included total triacylglycerides, C-peptide, leptin, and a range of amino acids (e.g., L-glutamic acid, L-serine, and L-leucine). The response of a subset of these analytes to the nutritional challenge test also changed after a 12-week, 20
Pancreatic amphicrine-like carcinoma (ALC) is an exceptionally rare neoplasm characterized by simultaneous exocrine and endocrine differentiation within the same tumour cells. These tumours represent a diagnostic challenge because they must be distinguished from mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), which consist of morphologically distinct tumour components. We report a case of pancreatic ALC with acinar differentiation harboring a KANK4::RAF1 fusion identified by comprehensive genomic profiling. Histologically, the tumour demonstrated acinar differentiation with expression of trypsin and BCL10 together with neuroendocrine differentiation characterized by synaptophysin and INSM1 expression within the same neoplastic population. Molecular analysis revealed a RAF1 rearrangement, a potentially actionable alteration previously described in a subset of pancreatic acinar carcinomas. The patient showed rapid disease progression despite systemic chemotherapy. Treatment with the MEK inhibitor trametinib was initiated based on the presence of a RAF1 fusion but was discontinued after 1 month because of toxicity, preventing assessment of therapeutic efficacy. This case expands the molecular spectrum of pancreatic ALC with acinar differentiation and highlights the importance of comprehensive molecular profiling in rare pancreatic neoplasms to identify potentially actionable genomic alterations.
Head and neck squamous cell carcinomas (HNSCCs) are mostly associated with smoking, alcohol intake, and/or human papillomavirus HPV16 and/or HPV18 infection. However, most tumors are diagnosed at an advanced stage. In the search for biomarkers of HNSCC, we studied the prognostic role of SPOCK1, a heparan sulfate proteoglycan. In HNSCC, SPOCK1 expression was tested both at in silico mRNA level using the Kaplan-Meier Plotter and at in situ protein level after SPOCK1 immunohistochemistry after whole slide digitalization. Protein expression results were analyzed using H-Scores, both by eye-control testing and with a machine-learning-based automated image analysis tool, DensitoQuant. SPOCK1 mRNA expression was found to be significantly higher in oral carcinomas than in the normal oral mucosa (log-rank p = 5.76e-06). Elevated SPOCK1 mRNA expression was consistently associated with a strongly reduced overall survival (OS; HR = 1.57 (1.2-2.06); log-rank p = 0.001) in HNSCC. This was particularly true for tumors with high (log-rank p = 0.00085) vs. low (log-rank p = 0.55) neoantigen (NeoAG) levels, at median antigen level stratification. Both the Cox-regression analysis and the log-rank test revealed elevated SPOCK1 protein levels in association with significantly reduced OS in our 97 HNSCC patients (both p = 0.002), which was supported by automated image analysis testing (p = 0.008 and p = 0.044, respectively). Our findings suggest that SPOCK1 can be a candidate adverse prognostic biomarker also in HNSCC. Therefore, SPOCK1 overexpression may specify a group of oral cancers with aggressive tumor biology.
BackgroundThis study aimed to evaluate the efficacy of a single-test, targeted DNA next-generation sequencing (NGS) panel in classifying endometrial carcinoma (EC) into molecular subtypes and to compare its performance with that of the established Sanger sequencing + immunohistochemistry (Sanger + IHC) molecular classification.MethodsTargeted DNA NGS was performed on 131 samples using the clinically validated AmoyDx® Comprehensive Panel, and a commercially available targeted AmoyDx EC Panel covering POLE, TP53, and MSI was used for 63 samples.ResultsThe concordance between the NGS and Sanger + IHC classifications was 93.8% (182/194 cases), with a kappa value of 0.908. The exclusion of seven discordant POLE mutations improved concordance to 97.4% (kappa = 0.962). NGS identified 30 POLE mutations compared to 23 detected by Sanger sequencing, which missed low-frequency variants. Microsatellite instability (MSI) analysis and mismatch repair (MMR) immunohistochemistry (IHC) results were highly concordant (97.9%). However, NGS-based TP53 mutation detection showed moderate agreement with the p53 IHC results (kappa = 0.688). Mutations associated with targeted therapy trials, including PTEN (76.3%), PIK3CA (50.4%), and ARID1A (35.9%), were found in 131 EC samples.ConclusionThese findings indicate that NGS-based molecular classification aligns well with Sanger + IHC molecular classification and offers higher sensitivity than Sanger sequencing, thereby improving the identification of mutations associated with targeted therapy trials. This enhances the prognosis and treatment planning for patients with advanced EC.
Dietary choices influence both risk and development of type 2 diabetes (T2D), but the precise mechanisms remain incompletely described. Dietary intake and lifestyle behaviors can alter epigenetic states with subsequent modulations on gene expression which then can change the risk of T2D. An epigenome-wide association study was conducted to identify any epigenetic links to diabetes risk by investigating epigenetic changes during a 6-year follow-up in 374 participants who were free of T2D at baseline. The identified epigenetic changes were examined for their association with any dietary and lifestyle factors. Additionally, mediation analysis determined whether the associated dietary factors contribute to diabetes risk through epigenetic changes. The epigenome-wide association study identified significant epigenetic changes during the 6-year follow-up at seven loci within genes REPIN1, BMP2, LINC01723, and SEL1L2, all of which were associated with insulin resistance. Further analysis revealed strong associations between three specific differentially methylated sites (DMSs) cg16400647 in REPIN1, cg12344389, and cg00625573, and dietary vitamin B12 intake. Additionally, cg26719314 on the X chromosome showed separate robust correlations with total sugar intake. Mediation analysis showed that higher vitamin B12 intake might reduce insulin resistance through epigenetic modification in REPIN1 and DNAAF9. Conversely, higher total sugar intake correlated significantly with elevated diabetes risk, with cg26719314 acting as a mediator. Furthermore, increased vitamin B12 supplementation was associated with decreased insulin resistance at 6-year follow-up in the entire cohort. These findings suggest that vitamin B12 intake may influence insulin resistance through specific epigenetic changes, thus describing the epigenetic links between diet and development of T2D.
Rhabdomyosarcoma is the third most common extracranial solid tumor in childhood. Treatment of patients is multimodal, based on systemic chemotherapy and local therapy by surgery and/or radiotherapy. Although standard therapies result in an overall survival of more than 75% for patients in the low-risk group, the prognosis for high-risk patients remains poor. For this reason, new therapeutic alternatives are needed. One such option is the use of specific Tropomyosin receptor kinase (TRK) inhibitors, which provides the opportunity of targeted therapeutic treatment for patients carrying Neurotrophic Receptor Tyrosine Kinase (NTRK) translocations. As the frequency of these aberrations is not yet known in rhabdomyosarcomas, the aim of this study was to map the pan-TRK expression profile of rhabdomyosarcomas by an affordable method and to investigate the link between the expression and the clinicopathological features. We studied samples of patients diagnosed with rhabdomyosarcoma at the Pediatric Center, Semmelweis University, Budapest, Hungary. Using immunohistochemistry, we found that pan-TRK expression was detected in 38% of the cases studied. The expression was present in a significantly higher proportion of samples in the unfavorable, alveolar histological subtype. However, no NTRK fusion was detected in the 17 TRK expressing samples.
This study provides a comprehensive nationwide analysis of extensive-stage small cell lung cancer (ES-SCLC) in Hungary, examining incidence rates, demographic trends, treatment patterns, and survival outcomes. We used data from the National Health Insurance Fund (NHIF) covering the period of 2013–2022, and we analyzed 8,104 ES-SCLC patients who received first-line (1L) etoposide-platinum (EP) chemotherapy, all of whom were confirmed to not have received concomitant chemoradiotherapy or curative thoracic surgery and had histology results in line with SCLC. We evaluated epidemiology, regional distribution, radiotherapy use, and subsequent treatment pathways. For the efficacy analysis, we narrowed the cohort to 5,576 patients who initiated EP within 1 year of their first C34-coded lung cancer diagnosis between 2013 and 2019, enabling 3-year follow-up. Key endpoints included overall survival (OS) and progression-free survival (PFS), the latter of which was inferred using time to first subsequent therapy (TFST). Our results revealed a shifting age distribution toward the age group above 70 years, while the male-to-female ratio gradually evened out. Treatment patterns showed the increasing use of carboplatin over cisplatin and frequent short course radiotherapy. Among those who underwent subsequent therapy, EP rechallenge was most widespread. Despite high initial response rates, survival outcomes remained poor: median PFS was 6.5 months (6-month: 52.9%, 1-year: 19%, 3-year: 5.2%), and median OS was 9.3 months (6-month: 69.8%, 1-year: 37.5%, 3-year: 9.2%). These results were in line with international real-world evidence and clinical trial data. Our findings highlight the aggressive nature of ES-SCLC and provide insight to the limited efficacy of chemotherapy-based therapies, underscoring the need to improve existing 1L and subsequent-line treatments and to introduce novel options. As Hungary transitions into the immunotherapy era, future studies with extended follow-up that incorporate staging, radiotherapy intent, comorbidities, and progression data will be essential for optimizing therapeutic strategies.
Multigene signatures like Oncotype DX and Prosigna Prediction Analysis of Microarray 50 (PAM50) help estimate distant recurrence risk in patients with luminal breast cancer receiving endocrine therapy. Determining the benefit of adjuvant chemotherapy, tests are costly and not always supported through reimbursement. We aimed to assess the utility of the APIS Breast cancer subtyping kit (BCSK) and its proliferation score (PS), as a potential prognostic assay. We analysed 141 adult patients with early luminal HER2- breast cancer diagnosed between 2020 and 2022 at Cantonal Hospital Basel-Land and Basel University Hospital. All patients had a valid OncotypeDX® Recurrence Score (RS) and received at least one line of adjuvant therapy. Molecular subtype and PS were obtained using the APIS BCSK. We performed the Prosigna PAM50 risk of recurrence (ROR) test on a subset of 59 patients. Our findings showed high concordance at the single marker level (estrogen receptor -ESR1, progesterone receptor - PGR, human epidermal growth factor receptor 2 - ERBB2 and marker of proliferation Ki-67 - MKI67), and between the BCSK and PAM50 subtype (overall percent agreement, OPA-71.2%). Notably, BCSK showed stronger agreement with immunohistochemistry (IHC)-based subtypes (OPA: 71.2%) than PAM50 with IHC (OPA: 54.2%). The BCSK PS correlated moderately with Prosigna PAM50 ROR (ρ = 0.4787) and more weakly with Oncotype DX RS (ρ = 0.4006). The correlation between ROR and RS was weak (ρ = 0.2255). In this preliminary comparison, the APIS BCSK and PS demonstrate promising potential as an initial molecular subtyping and risk stratification tool for breast cancer patients.
Glucose is at the center of liver metabolism, and together with NADPH, it is an essential factor in hepatic regulation and adaptation to different metabolic states. The liver plays a fundamental role in the development of obesity. Excess food intake, particularly excess glucose, primarily burdens liver metabolism. The hepatocyte-specific glycogenoreticular system, a functional unit based on the tight interaction between glycogen particles and the ER, is central to the storage and distribution of glucose throughout the body. Additionally, the liver converts excess glucose into ketogenic molecules. The liver is the most important site for glucogenic to ketogenic conversion in the body. However, the escape route offered by unrestricted fatty acid synthesis and deposition takes its toll in the long run. An NADPH pool is also a pivotal connection among intermediary metabolism, redox homeostasis, and drug metabolism in hepatocytes. Preservation and recovery of excess glucose is a commitment, which presents a potential pitfall. Overfeeding can lead to pathological consequences by disrupting regulatory mechanisms. The fulfillment of metabolic goals by the liver plays a significant role in the development of various pathological conditions, such as fatty liver, obesity, insulin resistance, and metabolic syndrome.
Extranodal natural killer/T-cell lymphomas (ENKTCL) are rare, aggressive neoplasms primarily occurring in adults of Asian or Native American descent. Most are associated with Epstein-Barr virus (EBV) and originate in the nasopharyngeal region. We present the case of a fulminant, disseminated, non-nasal, EBV negative, seemingly de novo ENKTCL in an infant who presented with a five-day history of progressive abdominal distention, respiratory distress, irritability, non-bilious emesis, right eye proptosis, and pallor. Initial labs revealed leukocytosis, anemia and thrombocytopenia. Computerized axial tomography revealed densities in the right optic nerve, superior orbits, thymus, posterior mediastinum, pericardium, myocardium, axillary lymph nodes, adrenal glands, kidneys and pancreas. The patient rapidly deteriorated, and despite extensive resuscitation, ultimately died. Autopsy revealed tumors in many organs, displaying vascular damage and tissue necrosis with lymphoid infiltration. The likely diagnosis of EBV-negative ENKTCL was confirmed after further histologic analysis. Pediatric ENKTCL is a particularly uncommon tumor, especially given our patient's very young age and EBV-negative status. Determining the best treatment regimen for these children is challenging due to limited data. Treatment typically consists of combination chemotherapy and radiation, but targeted therapies are being explored with promising results.
BackgroundB vitamins play key roles in one-carbon metabolism, DNA synthesis and methylation, and redox regulation. Their potential association with cancer risk remains debated due to heterogeneous findings and methodological limitations across studies.ObjectiveThis structured narrative review aimed to summarize and clinically contextualize the available evidence on the relationship between the intake of vitamins B2 (riboflavin), B6 (pyridoxine), B12 (cobalamin) and folate (vitamin B9) and the risk of selected cancers.MethodsA structured literature search was performed in PubMed up to 2 September 2025. Evidence was synthesized narratively, prioritizing meta-analyses (including dose–response meta-analyses) of observational studies, and including randomized controlled trials on B-vitamin supplementation when clinically relevant. Methodological quality and risk of bias were appraised narratively focusing on key domains such as exposure assessment, confounding, selection bias, and outcome assessment.ResultsMost evidence derives from observational studies assessing dietary intake and circulating biomarkers. Riboflavin and vitamin B6 intake were generally associated with a reduced risk of colorectal cancer in several meta-analyses, including dose–response analyses. Vitamin B12 showed inconsistent associations across cancer sites, with concerns regarding confounding by diet and baseline nutritional status. Folate intake and folic acid supplementation showed mixed findings, with some evidence suggesting protective effects in specific populations, while randomized trials raised concerns about potential adverse effects in selected contexts and dosages. Overall, heterogeneity across studies was substantial, partly explained by differences in exposure definitions, baseline folate fortification policies, and co-interventions.ConclusionAvailable evidence suggests potentially protective associations for riboflavin and vitamin B6—particularly for colorectal cancer—whereas findings for vitamin B12 and folate remain inconsistent and context-dependent. Given relevant methodological limitations and potential biases, further well-designed prospective studies and targeted trials are needed to clarify dose, timing and population-specific effects of B vitamins on cancer risk.
Angioimmunoblastic T-cell lymphoma (AITL) frequently involves the skin, typically presenting as rash or pruritus. However, AITL presenting primarily with multiple subcutaneous nodules is exceedingly rare and poses significant diagnostic challenges, often leading to misdiagnosis. We reported a 53-year-old man who presented with widespread subcutaneous nodules. He had a 1-month history of multiple painless subcutaneous nodules on the trunk and upper limbs. Physical examination revealed multiple firm nodules measuring 0.5–2 cm, accompanied by dark red plaques. Laboratory investigations showed mild anemia, elevated inflammatory markers, decreased IgA levels, and increased IgE levels. Imaging findings demonstrated generalized lymphadenopathy. Histopathological examination revealed effacement of the lymph node architecture with atypical lymphoid cells; immunohistochemistry was positive for CD3, CD4, PD-1, and EBER. A diagnosis of AITL of stage III was established. The patient achieved complete remission (CR) after 6 cycles of chidamide plus CHOP chemotherapy, with no evidence of recurrence at 6 months. This case broadens the recognized cutaneous spectrum of AITL and underscores the importance of considering lymphoma in the differential diagnosis of unexplained subcutaneous nodules.
Obesity is associated with metabolic dysfunction-associated steatotic liver disease (MASLD), for which drugs and nutraceuticals are being developed. We investigated whether camelina seeds from the Brassicaceae family and their components can attenuate metabolic disorders in animal models of genetic obesity, including fatty liver. In two separate 5-week experiments, female obese (fa/fa) Zucker rats and female db/db mice were used. By appropriately incorporating camelina seeds or their oil into the diet, we investigated, in the rat model, the effects of the oil and non-oil fractions on intestinal and liver function, as well as on lipid metabolism. Subsequently, in a mouse model, oral administration of glucocamelinin, the main camelina glucosinolate, was performed to determine whether this group of compounds might be responsible for the observed beneficial effects. Dietary camelina seeds counteracted liver hypertrophy and steatosis in obese rats, as confirmed by macroscopic and histological images, along with a several-fold lower content of total fat, triglycerides, and cholesterol (p < 0.01 for each). The rat experiment indicated that the non-oil fraction of camelina seeds was responsible for these beneficial effects. Oral glucocamelinin attenuated liver hypertrophy and steatosis in obese mice, as confirmed by macroscopic and histological images, along with considerably lower total fat (p < 0.05) and cholesterol (p < 0.01) contents. In both obese rats and mice, these and other beneficial effects were associated with alterations in the hepatic expression of genes crucial to lipid and glucose metabolism, including a higher expression of those encoding thyroid hormone receptor β (THR-β; p < 0.01 and p < 0.05) and fibroblast growth factor 21 (FGF21; p < 0.01 and p < 0.05). These findings indicate that camelina seeds may be considered both a dietary component and a source of bioactive glucosinolates relevant to MASLD. The mechanism behind the lipid-lowering effect of glucocamelinin may involve hepatic activation of FGF21 signaling through THR-β.
