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Animal Microbiome Jul 2024To promote sustainable aquaculture, the formulation of Atlantic salmon (Salmo salar) feeds has changed in recent decades, focusing on replacing standard marine-based...
Modulation of gut microbiota composition and predicted metabolic capacity after nutritional programming with a plant-rich diet in Atlantic salmon (Salmo salar): insights across developmental stages.
To promote sustainable aquaculture, the formulation of Atlantic salmon (Salmo salar) feeds has changed in recent decades, focusing on replacing standard marine-based ingredients with plant-based alternatives, increasingly demonstrating successful outcomes in terms of fish performance. However, little is known about how these plant-based diets may impact the gut microbiota at first feeding and onwards. Nutritional programming (NP) is one strategy applied for exposing fish to a plant-based (V) diet at an early stage in life to promote full utilisation of plant-based ingredients and prevent potential adverse impacts of exposure to a plant-rich diet later in life. We investigated the impact of NP on gut microbiota by introducing fish to plant ingredients (V fish) during first feeding for a brief period of two weeks (stimulus phase) and compared those to fish fed a marine-based diet (M fish). Results demonstrated that V fish not only maintained growth performance at 16 (intermediate phase) and 22 (challenge phase) weeks post first feeding (wpff) when compared to M fish but also modulated gut microbiota. PERMANOVA general effects revealed gut microbiota dissimilarity by fish group (V vs. M fish) and phases (stimulus vs. intermediate vs. challenge). However, no interaction effect of both groups and phases was demonstrated, suggesting a sustained impact of V diet (nutritional history) on fish across time points/phases. Moreover, the V diet exerted a significant cumulative modulatory effect on the Atlantic salmon gut microbiota at 16 wpff that was not demonstrated at two wpff, although both fish groups were fed the M diet at 16 wpff. The nutritional history/dietary regime is the main NP influencing factor, whereas environmental and host factors significantly impacted microbiota composition in M fish. Microbial metabolic reactions of amino acid metabolism were higher in M fish when compared to V fish at two wpff suggesting microbiota played a role in digesting the essential amino acids of M feed. The excessive mucin O-degradation revealed in V fish at two wpff was mitigated in later life stages after NP, suggesting physiological adaptability and tolerance to V diet. Future studies are required to explore more fully how the microbiota functionally contributes to the NP.
PubMed: 38951941
DOI: 10.1186/s42523-024-00321-8 -
Scientific Reports Jul 2024Using 70 U/ml or 35 U/ml as CA125 routine abnormal threshold may result in omissions in the relapse detection of Ovarian cancer (OvCa). This study aimed to clarify the...
Using 70 U/ml or 35 U/ml as CA125 routine abnormal threshold may result in omissions in the relapse detection of Ovarian cancer (OvCa). This study aimed to clarify the association between a biochemical relapse (only the elevation of CA125) and an image-identified relapse to predict the relapsed lesions better. 162 patients who achieved complete clinical response were enrolled from women diagnosed with stage I-IV serous ovarian, tubal, and peritoneal cancers from January 2013 to June 2019 at our center. The CA125 level of 2 × nadir was defined as the indicator of image-identified relapse (P < 0.001). Compared to CA125 level exceeding 35 U/ml, the 2 × nadir of CA125 improve the sensitivity of image-identified relapse (84.9% vs 67.4%, P < 0.001); the 2 × nadir value can act as an earlier warning relapse signal with a longer median time to image-identified relapse (2.7 vs. 0 months, P < 0.001). Of the relapsed population, there was no difference of CA125 changing trend between the neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) group after initial treatment. Compared with 35 U/ml, CA125 reaching 2 × nadir during the follow-up process might be a more sensitive and early relapse signal in patients with serous OvCa. This criterion may help guide patients to be recommended for imaging examination to detect potential relapse in time.
Topics: Humans; Female; CA-125 Antigen; Middle Aged; Ovarian Neoplasms; Neoplasm Recurrence, Local; Aged; Adult; Cystadenocarcinoma, Serous; Biomarkers, Tumor; Neoadjuvant Therapy; Retrospective Studies; Membrane Proteins
PubMed: 38951620
DOI: 10.1038/s41598-024-65760-4 -
The Journal of Thoracic and... Jun 2024Research into the risk factors associated with late recurrence (>2 years after surgery) of lung adenocarcinoma (LUAD) is limited. We investigated the incidence of and...
OBJECTIVE
Research into the risk factors associated with late recurrence (>2 years after surgery) of lung adenocarcinoma (LUAD) is limited. We investigated the incidence of and clinicopathologic and genomic features associated with late recurrence of resected stage I-IIIA LUAD.
METHODS
We performed a retrospective analysis of patients with completely resected pathologic stage I-IIIA LUAD (2010-2019). Patients with a history of lung cancer, neoadjuvant therapy, or mucinous or noninvasive LUAD, or with follow-up of <2 years were excluded. Cox and logistic regression modeling were used to compare clinicopathologic variables among patients with no, early (≤2 years), and late recurrence. Comparisons of genomic mutations were corrected for multiple testing.
RESULTS
Of the 2349 patients included, 537 developed a recurrence during follow-up. Most recurrences (55% [297/537]) occurred early; 45% (240/537) occurred late. A larger proportion of late recurrences than early recurrences were locoregional (37% vs. 29%; p=0.047). Patients with late recurrence had more aggressive pathologic features (IASLC grade 2 and 3, lymphovascular invasion, visceral pleural invasion) and higher stage than patients without recurrence. Pathologic features were similar between patients with early and late recurrence, except stage IIIA disease was more common in the early cohort. No genomic mutations were associated with late recurrence.
CONCLUSIONS
Late recurrence of LUAD following resection is more common than previously reported. Patients without disease >2 years after surgery who had aggressive pathologic features at the time of resection have an elevated risk of recurrence and may benefit from more-aggressive follow-up.
PubMed: 38950771
DOI: 10.1016/j.jtcvs.2024.06.026 -
Modern Pathology : An Official Journal... Jun 2024Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a recently recognized pancreatic tumor. Here, we aimed to determine the most essential features with... (Review)
Review
Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a recently recognized pancreatic tumor. Here, we aimed to determine the most essential features with the systematic review tool. PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic IOPN. The clinicopathological, immunohistochemical, and molecular data were extracted and summarized. Then, a comparative analysis of the molecular alterations of IOPN with those of pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm from reference cohorts (including The Cancer Genome Atlas) was conducted. The key findings from 414 IOPNs were as follows: 1) Clinicopathological Features: Male-to-female ratio was 1,5:1. Pancreatic head was the most common site (131/237, 55.3%), but a diffuse tumor extension involving more than one pancreatic segment was described in about 1/5 of cases (49/237, 20.6%). The mean size was 45.5 mm. An associated invasive carcinoma was present in 50% of cases (168/336). In those cases, most tumors were pT1/pT2 and pN0 (>80%), and vascular invasion was uncommon (20.6%). Regarding survival, more than 90% of patients were alive after surgical resection. 2) Immunohistochemical and Molecular Features: The most expressed mucins were MUC5AC (110/112, 98.2%) and MUC6 (78/84, 92.8%). Compared with pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, and GNAS were less altered in IOPN (p<0.01). Moreover, fusions involving PRKACA or PRKACB genes were detected in all of 68 cases examined, with PRKACB::ATP1B1 as the most common (27/68 cases, 39.7%). These genomic events emerged as an entity-defining molecular alteration of IOPN (p<0.01). Thus, such fusions represent a promising biomarker for diagnostic purposes. Recent evidence also suggests their role in influencing the acquisition of oncocytic morphology. IOPN is a distinct pancreatic neoplasm with specific clinicopathological and molecular features. Considering the clinical/prognostic implications, its recognition is essential for pathologists and, ultimately, patients' management.
PubMed: 38950698
DOI: 10.1016/j.modpat.2024.100554 -
Journal of Gastroenterology and... Jul 2024
Review
PubMed: 38949457
DOI: 10.1111/jgh.16669 -
BioRxiv : the Preprint Server For... Jun 2024Invasive mucinous adenocarcinoma (IMA) comprises ∼5% of lung adenocarcinoma. There is no effective therapy for IMA when surgical resection is not possible. IMA is...
BACKGROUND
Invasive mucinous adenocarcinoma (IMA) comprises ∼5% of lung adenocarcinoma. There is no effective therapy for IMA when surgical resection is not possible. IMA is sometimes confused with adenocarcinoma with signet ring cell features (SRCC) pathologically since both adenocarcinomas feature tumor cells with abundant intracellular mucin. The molecular mechanisms by which such mucin-producing lung adenocarcinomas develop remain unknown.
METHODS
Using a Visium spatial transcriptomics approach, we analyzed IMA and compared it with SRCC patho-transcriptomically. Combining spatial transcriptomics data with studies using RNA-seq and ChIP-seq, we assessed downstream targets of transcription factors HNF4A and SPDEF that are highly expressed in IMA and/or SRCC.
RESULTS
Spatial transcriptomics analysis indicated that there are 6 distinct cell clusters in IMA and SRCC. Notably, two clusters (C1 and C3) of mucinous tumor cells exist in both adenocarcinomas albeit at a different ratio. Importantly, a portion of genes (e.g., , , and ) are distinctly expressed while some mucous-related genes (e.g., and ) are expressed in both adenocarcinomas. We determined that HNF4A induces and and that BI 6015, an HNF4A antagonist, suppressed the growth of IMA cells. Using mutant SPDEF that is associated with COVID-19, we also determined that an intact DNA-binding domain of SPDEF is required for SPDEF-mediated induction of mucin genes ( , and ). Additionally, we found that XMU-MP-1, a SPDEF inhibitor, suppressed the growth of IMA cells.
CONCLUSION
These results revealed that IMA and SRCC contain heterogenous tumor cell types, some of which are targetable.
PubMed: 38948839
DOI: 10.1101/2024.06.13.598839 -
Endoscopic Ultrasound 2023Intraductal papillary neoplasm of the bile ducts is a rare tumor. Characteristic features include bile duct dilatation, cystic lesions with communication to the bile... (Review)
Review
Intraductal papillary neoplasm of the bile ducts is a rare tumor. Characteristic features include bile duct dilatation, cystic lesions with communication to the bile ducts, and intraluminal solid nodules arising from the bile duct wall. As in pancreatic intraductal papillary mucinous neoplasia, intestinal, pancreaticobiliary, gastric, and oncocytic types are described. Intraductal papillary neoplasm of the bile ducts has a high potential for malignancy, and patients should be surgically resected when possible. In this review, the complex imaging diagnosis is presented. The main focus is on contrast-enhanced ultrasound, an established method for many other indications whose potential on the biliary system should be better exploited. In the present article, typical contrast-enhanced ultrasound findings in intraductal papillary neoplasm of the bile ducts are demonstrated.
PubMed: 38948129
DOI: 10.1097/eus.0000000000000040 -
IScience Jun 2024A diet lacking dietary fibers promotes the expansion of gut microbiota members that can degrade host glycans, such as those on mucins. The microbial foraging on mucin...
A diet lacking dietary fibers promotes the expansion of gut microbiota members that can degrade host glycans, such as those on mucins. The microbial foraging on mucin has been associated with disruptions of the gut-protective mucus layer and colonic inflammation. Yet, it remains unclear how the co-utilization of mucin and dietary fibers affects the microbiota composition and metabolic activity. Here, we used 14 dietary fibers and porcine colonic and gastric mucins to study the dynamics of mucin and dietary fiber utilization by the human fecal microbiota . Combining metaproteome and metabolites analyses revealed the central role of the genus in the utilization of complex fibers together with mucin while was the main utilizer of sole porcine colonic mucin but not gastric mucin. This study gives a broad overview of the colonic environment in response to dietary and host glycan availability.
PubMed: 38947523
DOI: 10.1016/j.isci.2024.110093 -
The American Journal of Surgical... Jul 2024Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no...
Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS, GNAS, APC, BRAF, CTNNB1, SMAD4, TP53, or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension.
PubMed: 38946042
DOI: 10.1097/PAS.0000000000002279 -
The Journal of Toxicological Sciences 2024To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60%...
To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60% less food, compared to that of controls for four or eight weeks, and clinical observations, measurement of body and organ weights, morphological differentiation analysis, clinical pathology, and macroscopic and microscopic examinations were conducted. The body weight decreased depending on the degree of food restriction (FR). Cleavage of the balano-preputial skinfold was delayed, and cell debris in the epididymal lumen was noted as a related finding after four-week FR. Vaginal opening was also delayed, and some histopathological findings, such as absence of corpus luteum in the ovary, mucinous degeneration in the vagina, and immature uterus, were noted after eight-week FR. Erythrocyte count increased after four-week FR, but slightly decreased in males only after eight-week FR, and decreased leukocyte and/or reticulocyte counts, accompanied by related histopathological findings were noted after four- and eight-week FR. In blood chemistry, the levels of total protein including globulin, glucose, triglyceride, and calcium decreased, and sodium and chloride increased after four- and eight-week FR. Increases in activities of aspartate transaminase and lactate dehydrogenase and total bilirubin levels were noted after four-week FR, which were attenuated after eight-week FR. The effects of FR seemed to be more remarkable after four weeks. In drug safety evaluation, findings caused by malnutrition should be considered in juvenile toxicity studies when decreased food consumption is observed.
Topics: Animals; Male; Female; Body Weight; Organ Size; Rats; Caloric Restriction; Time Factors; Food Deprivation; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 38945843
DOI: 10.2131/jts.49.321