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Gut Microbes 2024The role of the intratumoral microbiome in gastric cancer (GC) has not been comprehensively assessed. Here, we explored the relationship between the microbial community...
The role of the intratumoral microbiome in gastric cancer (GC) has not been comprehensively assessed. Here, we explored the relationship between the microbial community and GC prognosis and therapy efficacy. Several cancer-associated microbial characteristics were identified, including increased α-diversity, differential β-diversity, and decreased abundance. After adjusting for clinical features, prognostic analysis revealed 2 phyla, 14 genera, and 5 species associated with the overall survival of patients with GC. Additionally, 2 phyla, 14 genera, and 6 species were associated with adjuvant chemotherapy (ACT) efficacy in patients with stage II - III GC. Furthermore, we classified GC microbiome structures into three microbial subtypes (MS1, MS2 and MS3) with distinguishing features. The MS1 subtype exhibited high immune activity and enrichment of microbiota related to immunotherapy and butyric acid-producing, as well as potential benefits in immunotherapy. MS2 featured the highest α-diversity and activation of the TFF pathway, MS3 was characterized by epithelial-mesenchymal transition and was associated with poor prognosis and reduced ACT efficacy. Collectively, the results of this study provide valuable insights into the microbial characteristics associated with GC prognosis and therapy efficacy.
Topics: Stomach Neoplasms; Humans; Prognosis; Male; Female; Middle Aged; Bacteria; Gastrointestinal Microbiome; Aged; Helicobacter pylori; Chemotherapy, Adjuvant; Treatment Outcome
PubMed: 38944840
DOI: 10.1080/19490976.2024.2369336 -
Mymensingh Medical Journal : MMJ Jul 2024Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare congenital disorder that affects the female reproductive system and is characterized by an underdeveloped or...
Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare congenital disorder that affects the female reproductive system and is characterized by an underdeveloped or absent uterus and vagina. A 17-year-old unmarried female was admitted into the Department of Endocrinology, Mymensingh Medical College Hospital, Bangladesh in November 2023 for evaluation of primary amenorrhea and poorly controlled diabetes mellitus. She was the 5th issue of non-consanguineous marriage delivered at term by normal vaginal delivery. Her growth pattern and developmental milestones were normal. She had no history of galactorrhea, chronic or cyclic pelvic pain, thyroid dysfunction, excessive exercise, psychiatric illness, or drug abuse. There was no history of such type of illness in her family. She was diagnosed with diabetes mellitus two years back without classic symptoms, and at that time, her blood glucose was 22 mmol/L. She was prescribed metformin and gliclazide. She had no history of hypoglycemia, hyperglycemic crises, or hospital admission. On examination, her body build and nutritional status were normal. Anemia, jaundice, edema, dehydration, lymphadenopathy, acne, hirsutism, acanthosis nigricans, abdominal striae and vitiligo were absent. Her blood pressure was 110/70 without the postural drop, thyroid gland was not enlarged, anthropometric measurements were normal and BMI was 18.4 kg/m2. Her tanner stage was P5 & B4. Genital examination revealed normal female external genitalia, and a blind vaginal pouch was found. Other systemic examinations revealed no abnormality. On laboratory reports, her blood glucose was uncontrolled (HbA1c-10.2%) with glycosuria. Thyroid function test and gonadal hormones were normal. Ultrasonogram of the abdomen revealed uterus, cervix, and upper part of the vagina are absent, and an ectopic left kidney.
Topics: Humans; Female; Adolescent; Amenorrhea; 46, XX Disorders of Sex Development; Congenital Abnormalities; Mullerian Ducts; Diabetes Mellitus
PubMed: 38944743
DOI: No ID Found -
NPJ Science of Food Jun 2024Inflammation acts as a dual role in disease initiation and progression, while Cannabis sativa L. (hemp) seeds, known for their abundance of anti-inflammatory...
Inflammation acts as a dual role in disease initiation and progression, while Cannabis sativa L. (hemp) seeds, known for their abundance of anti-inflammatory phytochemicals, present a promising food source. Additionally, fermentation may optimize the food matrix, thereby augmenting its developmental prospects. This study explores the anti-inflammatory potential of hemp seeds fermented with 10 different probiotic strains. Among these, Lactiplantibacillus plantarum fermented hemp seeds (FHS) demonstrated a significant anti-inflammatory ability, accompanied by a reduction in the expression of critical inflammatory markers such as TLR4, NF-κBp65, and iNOS. Moreover, there is a noteworthy dose-dependent inhibition of inflammatory cytokines TNF-α, IL-6, IL-1β, and NO within a concentration range of 50 to 500 µg/mL. Subsequently, metabolomics analysis using UHPLC-QTOF-MS highlighted significant metabolic alterations in FHS compared to raw hemp seeds (RHS). Through multivariate, univariate, and correlation analyses, indolelactic acid (IA) and homovanillic acid (HVA) emerged as the main anti-inflammatory metabolites in FHS. Validation via HPLC confirmed the concentration of IA and HVA in RHS and FHS and both organic acids demonstrated lower IC values for TNF-α, IL-1β, IL-6, IL-18, and NO inhibition, showcasing their potent anti-inflammatory abilities. Furthermore, in vitro gastro-intestinal digestion coupled with the Caco-2 cell monolayer model validates the uptake and bioaccessibility of FHS, further affirming IA and HVA as major anti-inflammatory compounds. Overall, this research sets the stage for the development of novel hemp seed-based products targeting inflammation-associated disorders.
PubMed: 38944646
DOI: 10.1038/s41538-024-00285-8 -
International Journal of Biological... Jun 2024Cotesia ruficrus presents a promising local natural enemy for controlling the invasive fall armyworm Spodoptera frugiperda in China. However, the mechanisms underlying...
Cotesia ruficrus presents a promising local natural enemy for controlling the invasive fall armyworm Spodoptera frugiperda in China. However, the mechanisms underlying how C. ruficrus locates its target pest remain unclear. In this study, we analyzed the expression patterns of 18 CrufOBPs across different developmental stages of C. ruficrus, and found that CrufOBP1 exhibited consistent and high expression levels in female adults. CrufOBP1 transcript was predominantly localized in sensilla placodea and sensilla trichodea on the antennae. Additionally, we confirmed the binding properties of CrufOBP1 protein to various cuticular compounds of S. frugiperda larvae. Subsequent electroantennogram and behavioral assays revealed that 1-(2-hydroxy-5-methylphenyl)-ethanone attracted female C. ruficrus, consequently increased the parasitism rate. However, upon silencing CrufOBP1, females exhibited reduced attraction towards 1-(2-hydroxy-5-methylphenyl)-ethanone, indicating the crucial role of CrufOBP1 in the chemoreception of C. ruficrus. These findings shed light on the kairomone-based mechanism employed by C. ruficrus to locate S. frugiperda larvae and hold a promise for the development of environmentally friendly pest management strategies.
PubMed: 38944096
DOI: 10.1016/j.ijbiomac.2024.133491 -
Molekuliarnaia Biologiia 2024Regulation of retrotransposon activity in somatic tissues is a complex mechanism that has still not been studied in detail. It is strongly believed that siRNA...
Regulation of retrotransposon activity in somatic tissues is a complex mechanism that has still not been studied in detail. It is strongly believed that siRNA interference is main mechanism of retrotransposon activity regulation outside the gonads, but recently was demonstrated that piRNA interference participates in retrotransposon repression during somatic tissue development. In this work, using RT-PCR, we demonstrated that during ontogenesis piRNA interference determinates retrotransposon expression level on imago stage and retrotransposons demonstrate tissue-specific expression. The major factor of retrotransposon tissue-specific expression is presence of transcription factor binding sites in their regulatory regions.
Topics: Animals; Drosophila melanogaster; Retroelements; RNA, Small Interfering; Gene Expression Regulation, Developmental; Transcription Factors; Drosophila Proteins; Organ Specificity; Binding Sites; RNA Interference
PubMed: 38943583
DOI: No ID Found -
Pest Management Science Jun 2024Root-knot nematodes (RKNs), Meloidogyne spp., are one of the most destructive polyphagous plant-parasitic nematodes. They pose a serious threat to global food security...
BACKGROUND
Root-knot nematodes (RKNs), Meloidogyne spp., are one of the most destructive polyphagous plant-parasitic nematodes. They pose a serious threat to global food security and are difficult to control. Entomopathogenic nematodes (EPNs) show promise in controlling RKNs. However, it remains unclear whether the volatile organic compounds (VOCs) emitted from EPN-infected cadavers can control RKNs.
RESULTS
We investigated the fumigation activity of VOCs released from cadavers infected by five different species of EPNs on RKNs in Petri dishes, and found that VOCs released from Steinernema feltiae (SN strain) and S. carpocapsae (All strain) infected cadavers had a significant lethal effect on second-stage juveniles (J2s) of Meloidogyne incognita. The VOCs released from the cadavers infected with S. feltiae were analyzed using SPME-GC/MS. Dimethyl disulfide (DMDS), tetradecane, pentadecane, and butylated hydroxytoluene (BHT), were selected for a validation experiment with pure compounds. The DMDS compound had significant nematicidal activity and repelled J2s. DMDS also inhibited egg hatching and the invasion of tomato roots by J2s. In a pot experiment, the addition of S. feltiae-infected cadavers and cadavers wrapped with a 400-mesh nylon net also significantly reduced the population of RKNs in tomato roots after 7 days. The number of root knots and eggs was reduced by 58% and 74.34%, respectively, compared to the control.
CONCLUSION
These results suggested that the VOCs emitted by the EPN-infected cadavers affected various developmental stages of M. incognita and thus have the potential to be used in controlling RKNs through multiple methods. © 2024 Society of Chemical Industry.
PubMed: 38943354
DOI: 10.1002/ps.8268 -
Advanced Science (Weinheim,... Jun 2024Starch and seed storage protein (SSP) composition profoundly impact wheat grain yield and quality. To unveil regulatory mechanisms governing their biosynthesis,...
Starch and seed storage protein (SSP) composition profoundly impact wheat grain yield and quality. To unveil regulatory mechanisms governing their biosynthesis, transcriptome, and epigenome profiling is conducted across key endosperm developmental stages, revealing that chromatin accessibility, H3K27ac, and H3K27me3 collectively regulate SSP and starch genes with varying impact. Population transcriptome and phenotype analyses highlight accessible promoter regions' crucial role as a genetic variation resource, influencing grain yield and quality in a core collection of wheat accessions. Integration of time-serial RNA-seq and ATAC-seq enables the construction of a hierarchical transcriptional regulatory network governing starch and SSP biosynthesis, identifying 42 high-confidence novel candidates. These candidates exhibit overlap with genetic regions associated with grain size and quality traits, and their functional significance is validated through expression-phenotype association analysis among wheat accessions and loss-of-function mutants. Functional analysis of wheat abscisic acid insensitive 3-A1 (TaABI3-A1) with genome editing knock-out lines demonstrates its role in promoting SSP accumulation while repressing starch biosynthesis through transcriptional regulation. Excellent TaABI3-A1 with enhanced grain weight is selected during the breeding process in China, linked to altered expression levels. This study unveils key regulators, advancing understanding of SSP and starch biosynthesis regulation and contributing to breeding enhancement.
PubMed: 38943260
DOI: 10.1002/advs.202401383 -
Breast Cancer Research : BCR Jun 2024The cell cycle of mammary stem cells must be tightly regulated to ensure normal homeostasis of the mammary gland to prevent abnormal proliferation and susceptibility to...
BACKGROUND
The cell cycle of mammary stem cells must be tightly regulated to ensure normal homeostasis of the mammary gland to prevent abnormal proliferation and susceptibility to tumorigenesis. The atypical cell cycle regulator, Spy1 can override cell cycle checkpoints, including those activated by the tumour suppressor p53 which mediates mammary stem cell homeostasis. Spy1 has also been shown to promote expansion of select stem cell populations in other developmental systems. Spy1 protein is elevated during proliferative stages of mammary gland development, is found at higher levels in human breast cancers, and promotes susceptibility to mammary tumourigenesis when combined with loss of p53. We hypothesized that Spy1 cooperates with loss of p53 to increase susceptibility to tumour initiation due to changes in susceptible mammary stem cell populations during development and drives the formation of more aggressive stem like tumours.
METHODS
Using a transgenic mouse model driving expression of Spy1 within the mammary gland, mammary development and stemness were assessed. These mice were intercrossed with p53 null mice to study the tumourigenic properties of Spy1 driven p53 null tumours, as well as global changes in signaling via RNA sequencing analysis.
RESULTS
We show that elevated levels of Spy1 leads to expansion of mammary stem cells, even in the presence of p53, and an increase in mammary tumour formation. Spy1-driven tumours have an increased cancer stem cell population, decreased checkpoint signaling, and demonstrate an increase in therapy resistance. Loss of Spy1 decreases tumor onset and reduces the cancer stem cell population.
CONCLUSIONS
This data demonstrates the potential of Spy1 to expand mammary stem cell populations and contribute to the initiation and progression of aggressive, breast cancers with increased cancer stem cell populations.
Topics: Animals; Female; Mice; Tumor Suppressor Protein p53; Mammary Glands, Animal; Mice, Transgenic; Humans; Cell Cycle Proteins; Neoplastic Stem Cells; Cell Transformation, Neoplastic; Carcinogenesis; Cell Proliferation; Breast Neoplasms; Stem Cells; Cell Cycle; Gene Expression Regulation, Neoplastic
PubMed: 38943151
DOI: 10.1186/s13058-024-01862-1 -
Nature Medicine Jun 2024Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies...
Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.
PubMed: 38942992
DOI: 10.1038/s41591-024-03075-7 -
Biological Trace Element Research Jun 2024The edible mushroom Amanita rubescens Pers., regularly collected and consumed in Slovakia, was assessed for health risk due to the mercury content in its fruiting body...
The edible mushroom Amanita rubescens Pers., regularly collected and consumed in Slovakia, was assessed for health risk due to the mercury content in its fruiting body parts. For this purpose, 364 both from the soil/substrate and mushroom samples from 40 localities in Slovakia were evaluated. At the same time, 21 samples of 7 developmental stages of the fruiting body of A. rubescens were taken in the Žakýlske pleso locality. The total mercury content in the soil and mushroom samples was determined using an AMA-254 analyzer. The contamination factor (C) and index of geoaccumulation (I) were used to detect the level of soil pollution by mercury. The ability of A. rubescens to accumulate mercury from the soil environment was evaluated using the bioconcentration factor (BCF), and the distribution of mercury in the mushroom body was evaluated using the translocation quotient (Q). To determine the health risks resulting from mushroom consumption, the percentages of provisional tolerable weekly intake (%PTWI) and target hazard quotient (THQ) were used. The obtained results have confirmed serious content of mercury soil pollution, especially in former mining areas, where the situation is alarming from a health risk point of view. Consumption of A. rubescens was found to be risky, not only in former mining areas, but higher values of mercury were also detected in other parts of Slovakia. Evaluation of the developmental stages of the fruiting body of A. rubescens showed that the highest bioconcentration factor was determined at developmental stage no. VI for caps with a value of 2.47 mg kg and developmental stage VII for stipes with a value of 1.65 mg kg DW.
PubMed: 38942969
DOI: 10.1007/s12011-024-04280-8