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15 pages, 228 KB  
Article
Anxiety and Depression in Patients with Colorectal Cancer Undergoing Ileostomy
by Panagiota Makrygianni, Maria Polikandrioti, Ioannis Koutelekos, Ilias Tsiampouris and Georgios Vasilopoulos
Clin. Pract. 2026, 16(1), 18; https://doi.org/10.3390/clinpract16010018 (registering DOI) - 18 Jan 2026
Abstract
Introduction: Patients with colorectal cancer who undergo ileostomy surgery confront multifaceted challenges that significantly impact their daily lives and cause symptoms of anxiety and depression. The aim of this study was to explore the anxiety and depression experienced by colorectal cancer patients undergoing [...] Read more.
Introduction: Patients with colorectal cancer who undergo ileostomy surgery confront multifaceted challenges that significantly impact their daily lives and cause symptoms of anxiety and depression. The aim of this study was to explore the anxiety and depression experienced by colorectal cancer patients undergoing ileostomy with three assessments. Materials and Methods: This longitudinal study included 96 patients with newly diagnosed colorectal cancer who underwent scheduled ileostomy surgery at two public hospitals in Attica. The Hospital Anxiety and Depression Scale (HADs) was used, which included patients’ characteristics. Measurements were collected at three distinct time points: preoperatively (Time 1), postoperatively between the 12th and 14th day (Time 2), and after stoma closure, approximately one year later (Time 3). Statistical analysis was performed using the SPSS 26.0 statistical package and the statistical significance level was set at p < 0.05. Results: The proportion of participants reporting moderate levels of anxiety (scores 8–10) was 15.6% at Time 1, which increased to 27.1% at Time 2, and had a slight increase to 28.1% at Time 3. The increase was statistically significant between Time 1 and Time 2 and at Time 1 and Time 3 (p < 0.001). Regarding high levels of anxiety (scores >11), the percentage of affected individuals increased from 13.5% at Time 1 to 17.7% at Time 2 and reached 15.6% at Time 3. The comparison between Time 1 and Time 2 revealed a statistically significant increase (p = 0.016), while the subsequent decrease between Time 2 and Time 3 was not statistically significant (p = 0.508). In terms of depression, at Time 1, 84.4% of patients had low depression, which decreased significantly to 56.3% at Time 2 and 39.6% at Time 3 (p < 0.001 for all comparisons). The percentage of patients who were moderately depressed at Time 1 was 9.4%; this percentage increased significantly to 32.3% at Time 2 and remained high, reaching 29.2% at Time 3. Finally, the proportion of patients who had high levels of depression at Time 1 was 6.3%, a figure that rose to 11.5% and 31.3% for Time 2 and Time 3, respectively. Conclusions: Anxiety and depression experienced by colorectal cancer patients undergoing ileostomy surgery escalate postoperatively and remain at high levels after ileostomy closure. Understanding these mental health challenges is crucial for providing comprehensive patient care. Further research is needed on the early recognition and management of these emotional difficulties, which are key elements of holistic oncology care. Full article
42 pages, 3871 KB  
Article
Pharmacologic Modulation of the PAR-2–ERK Axis by Statins Converts Inflammatory Survival Signalling into Apoptosis in Colorectal Cancer Cells
by Layla Amiri, Rajashree Patnaik, Riah Lee Varghese, Bintul Huda and Yajnavalka Banerjee
Int. J. Mol. Sci. 2026, 27(2), 916; https://doi.org/10.3390/ijms27020916 - 16 Jan 2026
Viewed by 43
Abstract
Chronic inflammation constitutes a well-established driver of colorectal carcinogenesis, yet the molecular circuitry linking inflammatory receptor signalling to tumour cell survival remains incompletely delineated. Here we demonstrate that the HMG-CoA reductase inhibitors atorvastatin and rosuvastatin modulate inflammatory survival pathways in colorectal cancer cells [...] Read more.
Chronic inflammation constitutes a well-established driver of colorectal carcinogenesis, yet the molecular circuitry linking inflammatory receptor signalling to tumour cell survival remains incompletely delineated. Here we demonstrate that the HMG-CoA reductase inhibitors atorvastatin and rosuvastatin modulate inflammatory survival pathways in colorectal cancer cells in a manner consistent with targeted interference with the protease-activated receptor 2 (PAR-2)–extracellular signal-regulated kinase (ERK)–tumour necrosis factor-α (TNF-α) signalling axis. Using lipopolysaccharide-stimulated HT-29 and Caco-2 cells as complementary models of inflammatory colorectal malignancy, we show that both statins selectively attenuate PAR-2 expression at the protein and transcript levels while leaving structurally related PAR-1 unaffected. This pattern of receptor modulation is accompanied by suppression of total ERK1/2 expression, ERK1/2 phosphorylation, and the transcriptional target DUSP6, together with attenuation of TNF-α secretion. Importantly, these signaling shifts are associated with dual apoptotic programs; the extrinsic pathway, reflected by transcriptional upregulation and proteolytic activation of caspase-8; and the intrinsic mitochondrial pathway, evidenced by reciprocal modulation of Bcl-2 family proteins favoring Bax over Bcl-2. Both pathways converge upon activation of executioner caspase-3 and an increase in Annexin V-defined apoptotic fractions, indicating re-engagement of programmed cell death under inflammatory stress. Notably, rosuvastatin consistently demonstrates superior potency across signaling endpoints, achieving comparable biological effects at lower concentrations than atorvastatin. Collectively, these data indicate that clinically deployed statins target the PAR-2–ERK axis and are associated with re-activation of apoptotic pathways in inflammatory colorectal cancer models, while leaving open the possibility that additional statin-responsive networks contribute to their pro-apoptotic effects. This mechanistic framework provides biological plausibility for epidemiologic observations linking statin use with reduced colorectal cancer risk and improved outcomes, and supports further translational evaluation of PAR-2-directed statin strategies in colorectal malignancy. Full article
(This article belongs to the Special Issue Colorectal Cancer—Emerging Trends and Treatment Strategies)
17 pages, 1112 KB  
Article
Small but Mighty: Low Bio-Accessibility Preserves Polyphenols from Mini Purple Carrots for Direct Action Against Colon Cancer Cells
by Amel Hamdi, Emel Hasan Yusuf, Rocío Rodríguez-Arcos, Ana Jiménez-Araujo, Paulina Nowicka, Rafael Guillén-Bejarano and Sara Jaramillo-Carmona
Antioxidants 2026, 15(1), 113; https://doi.org/10.3390/antiox15010113 - 15 Jan 2026
Viewed by 195
Abstract
Carrots are exceptional sources of bioactive compounds with potential health benefits. This study investigated the relationship between the biodiversity of carrot cultivars (colour and size) and their potential chemopreventive properties. Four distinct carrot cultivars (orange, white, yellow, and purple) of normal and miniature [...] Read more.
Carrots are exceptional sources of bioactive compounds with potential health benefits. This study investigated the relationship between the biodiversity of carrot cultivars (colour and size) and their potential chemopreventive properties. Four distinct carrot cultivars (orange, white, yellow, and purple) of normal and miniature sizes were comprehensively analysed for polyphenolic composition, bio-accessibility through in vitro simulated digestion, and in vitro antiproliferative activity against the HCT-116 colon cancer cell line. Our findings revealed that vegetable size influenced phytochemical composition more than vegetable colour, with mini purple carrots exhibiting exceptionally high polyphenolic concentrations and superior antiproliferative activity compared to orange, yellow, or white varieties. Notably, the bioaccessibility of bioactive compounds remained remarkably low across all samples, suggesting that these phytochemicals reach the colon in intact form, potentially enabling direct interaction with cancer cells. Interestingly, we found no direct correlation between total phenolic content and antiproliferative activity. In vitro cell cycle analysis revealed that mini purple carrot extracts induced S-phase arrest similar to the chemotherapeutic agent 5-FU, whereas other extracts caused G0/G1-phase arrest. The specific polyphenolic composition appears to be fundamentally important for bioactivity, with chlorogenic acid and diferulic acid-derivative isomer 2 potentially acting synergistically. These findings highlight the importance of carrot biodiversity in delivering functional foods with enhanced health-promoting properties, particularly for colorectal cancer prevention. Full article
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15 pages, 1720 KB  
Article
Differential Oxidative Stress Profiles in Circulating and Peritumoral Adipose Tissue Across Stages of Colorectal Cancer
by Somchai Ruangwannasak, Sittichai Khamsai, Poungrat Pakdeechote, Putcharawipa Maneesai, Parichat Prachaney, Wilaiwan Mothong and Chalerm Eurboonyanun
Int. J. Mol. Sci. 2026, 27(2), 707; https://doi.org/10.3390/ijms27020707 - 10 Jan 2026
Viewed by 166
Abstract
This study intends to assess oxidative stress markers and endogenous enzymes in plasma and peritumoral adipose tissues (PATs) obtained from normal subjects and patients with stages I-IV colorectal cancer (CRC). 63 participants were recruited, including 23 patients with colorectal cancer and 40 healthy [...] Read more.
This study intends to assess oxidative stress markers and endogenous enzymes in plasma and peritumoral adipose tissues (PATs) obtained from normal subjects and patients with stages I-IV colorectal cancer (CRC). 63 participants were recruited, including 23 patients with colorectal cancer and 40 healthy subjects. CRC patients had increased circulating malondialdehyde (MDA) and protein carbonyl concentrations, as well as reduced superoxide dismutase (SOD) and catalase activities, compared to normal volunteers. (p < 0.05). The findings aligned with the oxidative parameters assessed in peritumoral adipose tissue. Superoxide production in PAT was dramatically higher in the CRC group compared to the control group (p < 0.05). Moreover, oxidative stress markers were progressively altered in relation to CRC stages. Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) protein expression was reduced in PAT isolated from CRC compared to normal subjects and associated with CRC stages. CRC patients showed a systemic and peritumoral oxidative imbalance, along with elevated superoxide production in the PAT. The oxidative modifications worsened with the progression of CRC stage and were associated with the downregulation of the Nrf2/HO-1 antioxidant cascade in peritumoral adipose tissue. Full article
(This article belongs to the Section Molecular Oncology)
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29 pages, 1171 KB  
Article
Quality of Life of Colorectal Cancer Patients Treated with Chemotherapy
by Monika Ziętarska and Sylwia Małgorzewicz
Nutrients 2026, 18(2), 191; https://doi.org/10.3390/nu18020191 - 7 Jan 2026
Viewed by 161
Abstract
Background/Objectives: Colorectal cancer (CRC) is associated with anorexia–cachexia syndrome, which negatively affects health-related quality of life (HRQoL). This study aimed to evaluate HRQoL and functional status in CRC patients undergoing chemotherapy who were eligible for oral nutritional supplementation (ONS). Methods: In this prospective, [...] Read more.
Background/Objectives: Colorectal cancer (CRC) is associated with anorexia–cachexia syndrome, which negatively affects health-related quality of life (HRQoL). This study aimed to evaluate HRQoL and functional status in CRC patients undergoing chemotherapy who were eligible for oral nutritional supplementation (ONS). Methods: In this prospective, randomized study, 72 patients with stage II–IV CRC were enrolled (40 intervention group [IG], 32 control group [CG]). IG received ONS (2 × 125 mL/day, 600 kcal, 36 g protein) for 12 weeks, while CG received dietary counseling only. HRQoL was assessed every 4 weeks with the Functional Assessment of Anorexia/Cachexia Therapy (FAACT, version 4.0). Functional status was evaluated with the Karnofsky scale. Nutritional status was assessed using the Subjective Global Assessment (SGA), Nutritional Risk Screening (NRS-2002), and body mass index (BMI), and appetite was assessed on a visual analogue scale (VAS). Clinical Trial Registration: ClinicalTrials.gov, NCT02848807. Results: Mean FAACT score did not differ significantly between groups over 12 weeks (101.0 ± 22.8, 95% CI: 94.6–107.4 vs. 105.1 ± 21.4, 95% CI: 99.1–111.1; p = 0.06). However, the observed difference corresponded to an effect size at the lower bound of the moderate range. However, minimally important difference (MID) analysis demonstrated that clinically meaningful improvement was significantly more frequent in IG than in CG for global FAACT (32% vs. 8%; p = 0.03, OR = 5.50, 95% CI: 1.10–27.62, φ = 0.29), physical well-being (32% vs. 8%; p = 0.03, OR = 5.50, 95% CI: 1.10–27.62, φ = 0.29), and emotional well-being (38% vs. 4%; p = 0.002, OR = 14.86, 95% CI: 1.79–123.36, φ = 0.40). Functional well-being and anorexia/cachexia concerns showed favorable, but nonsignificant, trends (FWB improvement: 29% vs. 8%, p = 0.05, OR = 4.79, 95% CI: 0.95–24.27, φ = 0.26; ACS deterioration: 3% vs. 20%, p = 0.07, OR = 0.12, 95% CI: 0.01–1.11, φ = 0.28). HRQoL correlated positively with nutritional status, appetite, and functional performance, while Karnofsky scores remained stable in both groups. Conclusions: ONS did not significantly change the mean QoL scores at the group level but increased the proportion of patients achieving clinically meaningful improvement, particularly in the physical and emotional domains. These findings suggest that ONS may benefit selected patients who respond to nutritional interventions, underscoring the clinical relevance of individualized nutrition strategies in oncology. Full article
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15 pages, 1280 KB  
Article
Oral Microbiota Alterations and Potential Salivary Biomarkers in Colorectal Cancer: A Next-Generation Sequencing Study
by Salih Maçin, Özben Özden, Rugıyya Samadzade, Esra Saylam, Nurullah Çiftçi, Uğur Arslan and Serdar Yormaz
Pathogens 2026, 15(1), 43; https://doi.org/10.3390/pathogens15010043 - 30 Dec 2025
Viewed by 290
Abstract
Colorectal cancer (CRC) has a high mortality rate worldwide. Oral and intestinal microbiota members may have an effect on gastrointestinal tumors’ pathogenesis, particularly in CRC. Designed as a pilot study, this study’s aim was to investigate the relationship between CRC and oral microbiota [...] Read more.
Colorectal cancer (CRC) has a high mortality rate worldwide. Oral and intestinal microbiota members may have an effect on gastrointestinal tumors’ pathogenesis, particularly in CRC. Designed as a pilot study, this study’s aim was to investigate the relationship between CRC and oral microbiota and to identify potential biomarkers for CRC diagnosis. Saliva samples were collected from recently diagnosed CRC patients (n = 14) and healthy controls (n = 14) between March 2023 and December 2023. Microbiota (16S rRNA) analyses were conducted on these saliva samples using a next-generation sequencing method. Phylogenetic analyses, including alpha diversity, principal component analysis (PCA), principal coordinate analysis (PCoA), beta diversity, biomarker, and phenotype analyses, were conducted using the Qiime2 (Quantitative Insights Into Microbial Ecology) platform. Alpha diversity indices (Shannon: p = 0.78, Cho1: p = 0.28, Simpson: p = 0.81) showed no significant difference between CRC and control groups. Beta diversity analysis using Bray–Curtis PCoA indicated significant differences in the microbial community between the two groups (p = 0.003). Examination of OTU distributions revealed that the Mycoplasmatota phylum was undetectable in the oral microbiota of healthy controls but was significantly elevated in CRC patients (CRC: 0.13 ± 0.30, Control: 0.00 ± 0.00, p < 0.05). Additionally, Metamycoplasma salivarium, Bacteroides intestinalis, and Pseudoprevotella muciniphila were undetectable in healthy controls but significantly more prevalent in CRC patients (p < 0.05 for all three species). LEfSe analysis identified eight species with an LDA score > 2, Granulicatella adiacens, Streptococcus thermophilus, Streptococcus gwangjuense, Capnocytophaga sp. FDAARGOS_737, Capnocytophaga gingivalis, Granulicatella elegans, Bacteroides intestinalis, and Pseudoprevotella muciniphila, as potential biomarkers. The results of this study contribute critical evidence of the role of oral microbiota in the pathogenesis of colorectal cancer. Alterations in the microbiota suggest potential biomarkers in understanding the biological mechanisms underlying CRC and developing diagnostic and therapeutic strategies. Full article
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6 pages, 990 KB  
Case Report
Primary Colorectal Signet-Ring Cell Carcinoma with Synchronous Colonic Metastases in an Asymptomatic Patient: Case Presentation and Comprehensive Literature Review
by Oana-Bogdana Barboi, Radu-Alexandru Vulpoi, Diana-Elena Floria, Vadim Rosca, Constantin Simiras, Andriescu Elena-Corina, Amitoaie Iulia and Vasile-Liviu Drug
Life 2026, 16(1), 60; https://doi.org/10.3390/life16010060 - 30 Dec 2025
Viewed by 286
Abstract
Background: Less than 1% of all colorectal cancers (CRCs) are primary colorectal signet-ring cell carcinomas (SRCCs), which represent an uncommon and aggressive histological subtype. Given their subtle onset and rapid progression, these are often diagnosed in an advanced stage, and can be distinguished [...] Read more.
Background: Less than 1% of all colorectal cancers (CRCs) are primary colorectal signet-ring cell carcinomas (SRCCs), which represent an uncommon and aggressive histological subtype. Given their subtle onset and rapid progression, these are often diagnosed in an advanced stage, and can be distinguished by the presence of mucin-producing signet-ring cells. Synchronous colonic metastases at initial diagnosis are rather uncommon. Case presentation: We report the case of a 65-year-old male patient who underwent a routine colonoscopy following a positive fecal immunochemical test (FIT). The patient had no remarkable medical history and was asymptomatic. A 3 cm semi-pedunculated polyp and several smaller depressed lesions, 2 cm maximum in diameter, were observed in the descending colon during the colonoscopy. Multiple biopsies were obtained. The lesions were found to be SRCC according to histopathological examination. There was no sign of extra-colonic metastases on the computed tomography (CT). The patient was referred for extensive hemicolectomy, regional lymphadenectomy, and adjuvant chemotherapy. Conclusions: This article provides a thorough literature review on this uncommon presentation and discussion regarding the current understanding of the pathogenesis, clinical manifestations, and management strategies of SRCC. This case highlights the importance of routine screening in detecting aggressive malignancies like SRCC in asymptomatic individuals. Early identification through colonoscopy can lead to timely intervention, potentially improving prognosis. Full article
(This article belongs to the Section Medical Research)
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19 pages, 1407 KB  
Review
Regulation of Intestinal Butyrate Transporters by Oxidative and Inflammatory Status
by Fátima Martel
Antioxidants 2026, 15(1), 48; https://doi.org/10.3390/antiox15010048 - 30 Dec 2025
Viewed by 381
Abstract
Beneficial effects of the microbiota-derived metabolite butyrate at the colonic level are well established, particularly through its relevance in colorectal cancer (CRC) and inflammatory bowel disease (IBD), two major intestinal pathologies. Therefore, the mechanisms involved in butyrate transport across colonic epithelial cell membranes [...] Read more.
Beneficial effects of the microbiota-derived metabolite butyrate at the colonic level are well established, particularly through its relevance in colorectal cancer (CRC) and inflammatory bowel disease (IBD), two major intestinal pathologies. Therefore, the mechanisms involved in butyrate transport across colonic epithelial cell membranes (uptake transporters: monocarboxylate transporter 1 (MCT1) and sodium-coupled monocarboxylate transporter 1 (SMCT1); efflux transporters: breast cancer resistance protein (BCRP) and MCT1/monocarboxylate transporter 4 (MCT4)), which are determinant for its intracellular levels, are of primary importance for its beneficial effects at the colonic level. The available data suggest that all these butyrate transporters can be modulated by redox and inflammatory status, but the evidence is scarce and rather inconsistent. Nevertheless, a role of nuclear factor erythroid 2-related factor 2 (Nrf2) and of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mediating the effect of oxidative stress and inflammation, respectively, on MCT1 and SMCT1 is suggested. So, more investigation on this subject is needed, given the fact that increased oxidative stress levels and inflammatory status are present in a series of intestinal conditions and pathologies, including CRC and IBD, which could help to establish these transporters as potential cellular targets in these diseases. Full article
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22 pages, 6353 KB  
Review
Sprouty in Tumors of the Nervous System
by Petra Obexer and Barbara Hausott
Int. J. Mol. Sci. 2026, 27(1), 377; https://doi.org/10.3390/ijms27010377 - 29 Dec 2025
Viewed by 231
Abstract
The Sprouty (SPRY) proteins are evolutionarily conserved modulators of growth factor-induced signaling pathways. The four different SPRY isoforms (SPRY1-4) are implicated in different types of cancer, acting as oncogenes or tumor suppressors depending on the SPRY isoform and the malignancy. Despite being tumor [...] Read more.
The Sprouty (SPRY) proteins are evolutionarily conserved modulators of growth factor-induced signaling pathways. The four different SPRY isoforms (SPRY1-4) are implicated in different types of cancer, acting as oncogenes or tumor suppressors depending on the SPRY isoform and the malignancy. Despite being tumor suppressors in many types of cancer, SPRY1 is an oncogene in rhabdomyosarcoma, SPRY2 in colorectal cancer, and SPRY4 in gastric cancer. In this review, we summarize the current literature about the functions of SPRY1-4 in glioblastoma (GB) and neuroblastoma (NB). To further delineate the effects of SPRY1-4 in the tumorigenesis of the nervous system, we analyzed the association of SPRY1-4 with the overall and event/progression-free survival of patients with pediatric and adult glioma, GB, and NB using public datasets. Together, there is evidence that SPRY1 and -2 are oncogenes in GB, whereas the role of SPRY3 and -4 in GB is not well defined. In NB, SPRY2 acts as a tumor suppressor, whereas the effects of SPRY1, -3, and -4 in NB have not been investigated so far, although the survival analysis revealed increased survival of NB patients with low SPRY3 levels in different datasets. Thus, this review demonstrates the requirement for further studies about the functions of the SPRY proteins in tumors of the nervous system to define their clinical relevance as potential therapeutic targets in the future. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Sprouty Proteins in Cancer)
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21 pages, 2096 KB  
Article
Modulation of Peripheral Immune Cells Following Vitamin D3 Supplementation in Vitamin D-Insufficient Cancer Patients
by Alexandra Kalmar, Zsofia Brigitta Nagy, Liza Dalma Sumegi, Barbara Kinga Bartak, Csaba Kiss, Sandor Spisak, Bela Molnar and Istvan Takacs
Nutrients 2026, 18(1), 116; https://doi.org/10.3390/nu18010116 - 29 Dec 2025
Viewed by 511
Abstract
Background and aims: Low vitamin D3 levels are common in cancer patients, and these patients might benefit from vitamin D3 level normalization in parallel with the conventional oncology treatment. This study aimed to examine the molecular effects of moderate–high-dose vitamin [...] Read more.
Background and aims: Low vitamin D3 levels are common in cancer patients, and these patients might benefit from vitamin D3 level normalization in parallel with the conventional oncology treatment. This study aimed to examine the molecular effects of moderate–high-dose vitamin D3 supplementation in vitamin D-deficient cancer patients. Methods: Eight patients under oncological treatment (5 lung cancer, 2 colorectal cancer, and 1 urothelial carcinoma) received 30,000 IU of vitamin D3 per week for two months. Blood samples were collected before and after supplementation, and peripheral blood mononuclear cells (PBMCs) were isolated. With the aim of assessing further potential epigenetic alterations, global DNA methylation level was estimated on the basis of LINE-1 bisulfite-sequencing experiments on cfDNA and PBMC cells. In order to explore the chromatin accessibility alterations after the treatment in PBMCs, an assay for transposase-accessible chromatin with sequencing (ATAC-Seq) was performed using the (10x Genomics, Pleasanton, CA, USA) on a NextSeq 550 instrument using High Output Sequencing kit (Illumina, San Diego, CA, USA). DNA integrity was assessed by the alkaline Comet-assay and telomere qPCR was also performed. Results: After serum 25-hydroxy-vitamin D levels were normalized, DNA integrity in mononuclear cells improved significantly (p = 0.01), while no significant changes were found in granulocytes. Vitamin D3 supplementation also led to significant changes in telomere length in mononuclear cells (p = 0.007). No significant differences were observed in cfDNA levels or DNA methylation in PBMCs and cfDNA after supplementation. ATAC-Seq revealed changes in PBMC composition, including an increased number of NK, pDC cells, and monocytes, especially in patients treated with Pembrolizumab in parallel with vitamin D supplementation. Conclusions: These exploratory findings suggest that the observed immune cell and chromatin changes after vitamin D3 level normalization are compatible with immunomodulatory effects and warrant confirmation in larger, controlled cohorts. Full article
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17 pages, 698 KB  
Systematic Review
Stool- and Blood-Associated Colorectal Cancer Biomarkers: A Systematic Review
by Pumelela Hallom, Pragalathan Naidoo, Sibusiso Senzani, Sayed S. Kader and Zilungile L. Mkhize-Kwitshana
Cancers 2026, 18(1), 96; https://doi.org/10.3390/cancers18010096 - 27 Dec 2025
Viewed by 420
Abstract
Background/Objectives: Colorectal cancer (CRC) is a major contributor to cancer-related deaths worldwide. While existing screening tools are effective, their high cost and limited availability restrict widespread adoption, particularly in low- and middle-income settings. The identification of affordable, non-invasive biomarkers is therefore critical [...] Read more.
Background/Objectives: Colorectal cancer (CRC) is a major contributor to cancer-related deaths worldwide. While existing screening tools are effective, their high cost and limited availability restrict widespread adoption, particularly in low- and middle-income settings. The identification of affordable, non-invasive biomarkers is therefore critical to improve early CRC detection and survival outcomes. Methods: A systematic literature search was performed through PubMed, ScienceDirect, Medline, ISI Web of Knowledge, and Google Scholar to identify studies reporting stool- and blood-based biomarkers for CRC detection. Data were extracted using a standardized template, including study details, specimen type, detection method, and diagnostic performance parameters such as sensitivity and specificity. Results: DNA methylation biomarkers demonstrated high diagnostic potential. Syndecan 2 (SDC2) and Short Stature Homeobox 2 (SHOX2) achieved a combined stool sensitivity of 91.35%. Other methylation markers, including NDRG4, SEPT9, and BCAT1, showed a composite sensitivity of 82.7%. Plasma-based methylation markers such as GATA5, FOXE1, and SYNE1 reported sensitivities ranging from 18–47% and specificities of 93–99%. Hypermethylation of SFRP2 and WIF-1 achieved 81.3% sensitivity in CRC and precursor lesions. Matrix metalloproteinases (MMP-2 and MMP-9) were elevated in CRC patients, with stool MMP-9 yielding 72.2% sensitivity and 95% specificity. A stool gene panel (UBE2N, IMPDH1, DYNC1LI1, HRASLS2) reached 96.6% sensitivity and 89.7% specificity, while a methylation-based panel (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, VIM) achieved 90.7% sensitivity. MicroRNAs (miR-21, miR-92a, miR-223, miR-182) showed excellent diagnostic performance, with sensitivities exceeding 96% and specificities above 75%. Conclusions: DNA methylation and microRNA biomarkers hold strong promises for non-invasive CRC screening. Multi-marker panels demonstrate superior diagnostic accuracy and may provide a cost-effective, scalable approach for early CRC detection in resource-limited settings. Full article
(This article belongs to the Section Cancer Biomarkers)
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30 pages, 1801 KB  
Review
Microbiota-Mediated Bile Acid Metabolism as a Mechanistic Framework for Precision Nutrition in Gastrointestinal and Metabolic Diseases
by Suna Kang, Do-Youn Jeong, Jeowon Seo, James W. Daily and Sunmin Park
Cells 2026, 15(1), 23; https://doi.org/10.3390/cells15010023 - 22 Dec 2025
Viewed by 792
Abstract
Gut microbiota play a central role in shaping bile acid (BA) metabolism through community-specific capacities for deconjugation, dehydroxylation, and other transformation reactions. Distinct microbiome compositional patterns—often referred to as enterotype-like clusters—correspond to reproducible functional profiles that generate unique BA metabolic signatures with relevance [...] Read more.
Gut microbiota play a central role in shaping bile acid (BA) metabolism through community-specific capacities for deconjugation, dehydroxylation, and other transformation reactions. Distinct microbiome compositional patterns—often referred to as enterotype-like clusters—correspond to reproducible functional profiles that generate unique BA metabolic signatures with relevance for metabolic and gastrointestinal health. This narrative review synthesizes current evidence describing the interplay between microbial composition, BA metabolism, and metabolic dysfunction. A structured literature search was conducted in PubMed, Web of Science, EMBASE, and Scopus using predefined keywords related to bile acids, microbiome composition, metabolic disorders, and enterotypes. Studies were screened for human clinical relevance and mechanistic insights into BA–microbiome interactions. Across the evidence base, Bacteroides-, Prevotella-, and Ruminococcus-associated community types consistently demonstrate different BA transformation capacities that influence secondary BA production and downstream host signaling through FXR and TGR5. These differences are linked to variation in metabolic dysfunction-associated steatotic liver disease, obesity, type 2 diabetes, inflammatory bowel disease, and colorectal cancer. Host genetic variations in BA synthesis, transport, and signaling further modify these microbiome–BA interactions, contributing to the heterogeneity of dietary intervention responses. Overall, the literature supports a model in which microbiome-derived BA profiles act as metabolic phenotypes that shape host lipid and glucose homeostasis, inflammation, and gut–liver axis integrity. Emerging clinical applications include microbiome-stratified dietary strategies, targeted probiotics with defined BA-modifying functions, and therapeutic approaches that align BA-modulating interventions with an individual’s microbial metabolic capacity. Establishing integrated biomarker platforms combining microbiome clustering with BA profiling will be essential for advancing precision nutrition and personalized management of metabolic and gastrointestinal diseases. Full article
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28 pages, 5602 KB  
Article
Microinflammation-Driven Gene Expression Dynamics in the Pathogenesis of Metabolic Disorders and Cancer
by Marian Elisa Gabrielle T. Cadungog and Lemmuel L. Tayo
Biology 2026, 15(1), 19; https://doi.org/10.3390/biology15010019 - 21 Dec 2025
Viewed by 424
Abstract
Microinflammation serves as a central mechanism linking metabolic diseases and cancer. This study integrates gene expression profiles from irritable bowel syndrome (IBS), obesity, type 2 diabetes (T2D), colorectal cancer (CRC), renal cell carcinoma (RCC), and pancreatic cancer (PC) to identify shared molecular drivers [...] Read more.
Microinflammation serves as a central mechanism linking metabolic diseases and cancer. This study integrates gene expression profiles from irritable bowel syndrome (IBS), obesity, type 2 diabetes (T2D), colorectal cancer (CRC), renal cell carcinoma (RCC), and pancreatic cancer (PC) to identify shared molecular drivers of inflammation-mediated pathology. Weighted gene co-expression network analysis (WGCNA) revealed three highly preserved modules (blue, brown, turquoise) enriched in RNA processing, spliceosome assembly, ribosome biogenesis, and proteostasis regulation. Key hub genes, along with regulatory miRNAs have interconnected networks that modulate transcription, mRNA maturation, protein synthesis, and inflammatory signaling. Although classical inflammatory pathways were not directly enriched, their activity appears to be indirectly shaped by disruptions in RNA-processing and proteostasis machinery. Additionally, gut microbiota-derived products and altered metabolic states may further reinforce these transcriptional and post-transcriptional imbalances. Collectively, these findings reveal conserved molecular signatures that bridge microinflammation, metabolic disease, and oncogenesis, and highlight potential diagnostic and therapeutic targets centered on RNA regulation, proteostasis, and miRNA-mediated control Full article
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12 pages, 1365 KB  
Article
Impact of Transanal Drainage Tube Placement on Anastomosis Leakage Incidence After Rectal Cancer Surgery
by Maria-Manuela Răvaș, Marian Marincaș, Eugen Brătucu, Vrgiliu Prunoiu, Laurentiu Simion, Laura-Maria Manea and Mircea-Nicolae Brătucu
Life 2026, 16(1), 5; https://doi.org/10.3390/life16010005 - 19 Dec 2025
Viewed by 388
Abstract
Background: Anastomotic leakage (AL) following rectal cancer surgery is a significant cause of mortality and morbidity. Although transanal drainage tubes are expected to reduce the rate of AL, their preventive effect remains controversial. Aim: To evaluate whether transanal drainage tube (TAD) [...] Read more.
Background: Anastomotic leakage (AL) following rectal cancer surgery is a significant cause of mortality and morbidity. Although transanal drainage tubes are expected to reduce the rate of AL, their preventive effect remains controversial. Aim: To evaluate whether transanal drainage tube (TAD) provides protection against AL in patients without other protective methods after low anterior resection (LAR). Methods: A retrospective cohort study was performed in patients undergoing LAR for rectal cancer between 2018 and 2023. Based on postoperative management, patients were divided into four distinct groups as follows: in TAD group, after colorectal anastomosis, a 32F silicone tube was inserted through the anus by more than 5 cm above the anastomosis. The tube was secured around the anus with a skin suture and a drainage bag was attached. The tube was removed after 3–5 days after surgery. In the non-TAD group, no transanal drainage tube and no diverting stomas, respectively, were used after the anastomosis. In the ileostomy and colostomy group a stoma was often performed as a primary measure in preventing anastomotic leakage. Clinical characteristics and postoperative complications were compared among the groups. Complications were categorized as general (eventration, seroma) or septic (fistula, abscess) and further classified as early (<7 days after surgery) or tardive (between 7 and 30 days after surgery). Statistical significance was defined as a p-value < 0.05. Results: A total of 171 patients were included: 47 (27.5%) in the TAD group, 54 (32.2%) in the non-TAD group, 25 (14.6%) in colostomy group, and 45 (26.3%) in ileostomy group. Overall, eight patients (4.7%) developed anastomotic leakage (AL). In the non-TAD group, 3 patients experienced AL (all early); in the ileostomy group, 2 patients (1 early, 1 tardive); and in the colostomy group, 2 patients (both tardive). The TAD group had one patient with AL as a tardive complication. The incidence of early general complications was significant lower in TAD group compared with the non-TAD group (OR 0.23, 95% CI [0.06–0.85]; p = 0.004), while there was no significant difference in early septic complications between TAD and ileostomy group (p = 0.71). The incidence of tardive general complications was significantly more frequent in the ileostomy group (OR 0.10, 95% CI [0.02–0.44]; p = 0.0008) compared with TAD group. Overall, total complications were significantly lower in TAD group compared to non-TAD (OR 0.15, 95% CI [0.05–0.44]; p < 0.001), ileostomy (OR 0.20, 95% CI [0.07–0.56]; p = 0.003), and colostomy ((OR 0.46 CI [0.21–0.99]; p = 0.049) groups. Furthermore, the TAD group showed a reduction rate of AL compared to the ileostomy, colostomy, and non-TAD groups (2.12% vs. 4.4%, 8%, and 5.5%) but the incidence of AL was almost similar (p = 0.65). Conclusions: The elective use of TAD is a simple and effective protective method for the prevention of overall postoperative complications, also helping to reduce the rate of AL in patients. Nevertheless, there is limited information in the literature regarding the optimal size and material of TAD, despite these factors playing an important role in the viability and effectiveness of the method. Full article
(This article belongs to the Section Medical Research)
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Article
Equisetum hyemale L. Extracts: Phytochemistry, Biological Performance, ADMET Profiling, and Toxicity Predictions
by Yulianna Minutti-Calva, Karen Schürenkämper-Carrillo, Edwin E. Reza-Zaldívar, Oscar E. Del Razo-Rodríguez, Ian Vitola, Jorge Manuel Silva-Jara, José Daniel Lozada-Ramírez, Daniel A. Jacobo-Velázquez, Diego E. Navarro-López, Marco Chávez-Tinoco, Edgar R. López-Mena, Jorge L. Mejía-Méndez and Eugenio Sánchez-Arreola
Pharmaceuticals 2025, 18(12), 1901; https://doi.org/10.3390/ph18121901 - 17 Dec 2025
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Abstract
Background: Equisetum hyemale L., commonly known as scouring rush or horsetail, is a perennial plant with significant applications in traditional medicine. Methods: The aerial parts of E. hyemale L. were macerated with hexane, chloroform, and ethyl acetate. The phytochemical profile of the [...] Read more.
Background: Equisetum hyemale L., commonly known as scouring rush or horsetail, is a perennial plant with significant applications in traditional medicine. Methods: The aerial parts of E. hyemale L. were macerated with hexane, chloroform, and ethyl acetate. The phytochemical profile of the extracts was investigated using chromatography approaches. The biological performance of the extracts was determined using antibacterial, antioxidant, anticancer, and toxicity in vitro and in vivo models. Molecular docking and ADMET analyses were employed to determine interactions with structural components of multidrug resistant bacteria and assess potential toxicological risks. Results: The extracts exert high scavenging activity against ABTS radicals (IC50 2.57–2.68 μg/mL), but poor antibacterial activity. It was evidenced that treatment with extracts exerts in moderate cytotoxicity on hepatocellular and colorectal cancer cell lines. Toxicity assays unveiled that the extracts decrease the survival rate of C. elegans nematodes after 2 h of exposure to treatment. In silico studies evidenced a high affinity of campesterol and calcitriol towards the DNA gyrase, and the oral bioavailability of farnesol and limonene. Conclusions: Our findings demonstrated the presence of biologically active secondary metabolites in hexane, chloroform, and ethyl acetate extracts from E. hyemale L. This work also demonstrated the biological performance of these extracts in in vitro and in vivo models, and validated the potential pharmacokinetic and pharmacodynamic profile of their phytoconstituents. Full article
(This article belongs to the Section Natural Products)
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