Miracle-dz/UniFAR-FTUs huggingface dataset:
Pregnancy Outcomes in a Cohort of Patients with Inflammatory Bowel Disease: Data from a Multidisciplinary Clinic in a Tertiary Center

Background: Inflammatory bowel disease (IBD) can have an impact on pregnancy outcomes due to the effect of the disease activity and medication use. This study aimed to evaluate the pregnancy outcomes in IBD patients treated at a multidisciplinary clinic. Methods: This study was a retrospective cohort study including consecutive pregnant patients with IBD having a singleton gestation attending a multidisciplinary clinic between 2012 and 2019. The IBD activity and management throughout gestation were assessed. The pregnancy outcomes included: adverse neonatal and maternal outcomes, mode of delivery, and three integrative outcomes: (1) a favorable pregnancy outcome, (2) a poor pregnancy outcome, and (3) an unfavorable maternal outcome. The IBD pregnant cohort was compared with a cohort of non-IBD pregnant women delivering at the same shift. Multivariable logistic regression was used for risk assessment. Results: Pregnant women with IBD (141) and without (1119) were included. Mean maternal age was 32 [±4] years. Patients with IBD had a higher rate of nulliparity (70/141 (50%) vs. 340/1119 (30%), p < 0.001) and lower BMI (21.42 kg/m2 (19.18–23.44) vs. 22.48 (20.31–25.59), p = 0.002). All the other characteristics were comparable. Most patients with IBD 124/141 (88%) were in clinical remission at conception; with maintenance therapy in 117/141 patients (83%). A third of the patients, 43/141 (30.5%), were treated with biologics. Exacerbation occurred during pregnancy in 51/141 (36%). The majority of the maternal and neonatal outcomes and all the composite outcomes were comparable between the patients with IBD and the women without IBD. Cesarean delivery was more frequent in patients with IBD (49/141 (34.8%) vs. 270/1119 (24.1%), p = 0.021). IBD was not associated with composite outcomes. Conclusions: In pregnant patients with IBD followed at a multidisciplinary clinic, the pregnancy outcomes were encouraging and comparable to those of the women without IBD.
Taxifolin Inhibits Breast Cancer Growth by Facilitating CD8+ T Cell Infiltration and Inducing a Novel Set of Genes including Potential Tumor Suppressor Genes in 1q21.3

Simple Summary Breast cancer is the leading cause of cancer deaths in women. The current management of patients with breast cancer needs improvement in two aspects: risk estimation, which forms the basis for treatment, and effective therapies. In our research, we discovered taxifolin to inhibit breast cancer via increasing the expression of 36 genes. These genes, as a group, effectively predict the death probability in patients with breast cancer. Importantly, aggressive breast cancers are frequently associated with increases in the 1q21.3 DNA region, which is home to the HNRN, KPRP, CRCT1, and FLG2 genes. These four genes can inhibit breast cancer, and their expressions are induced by taxifolin, revealing a novel mechanism by which taxifolin suppresses breast cancer. This study thus advances our ability in relation to the risk estimation and treatment of breast cancer. Through using taxifolin as a nutritional supplement, our research reveals an intriguing application of taxifolin in the clinical management of patients with breast cancer. Abstract Taxifolin inhibits breast cancer (BC) via novel mechanisms. In a syngeneic mouse BC model, taxifolin suppressed 4T-1 cell-derived allografts. RNA-seq of 4T-1 tumors identified 36 differentially expressed genes (DEGs) upregulated by taxifolin. Among their human homologues, 19, 7, and 2 genes were downregulated in BCs, high-proliferative BCs, and BCs with high-fatality risks, respectively. Three genes were established as tumor suppressors and eight were novel to BC, including HNRN, KPRP, CRCT1, and FLG2. These four genes exhibit tumor suppressive actions and reside in 1q21.3, a locus amplified in 70% recurrent BCs, revealing a unique vulnerability of primary and recurrent BCs with 1q21.3 amplification with respect to taxifolin. Furthermore, the 36 DEGs formed a multiple gene panel (DEG36) that effectively stratified the fatality risk in luminal, HER2+, and triple-negative (TN) equivalent BCs in two large cohorts: the METABRIC and TCGA datasets. 4T-1 cells model human TNBC cells. The DEG36 most robustly predicted the poor prognosis of TNBCs and associated it with the infiltration of CD8+ T, NK, macrophages, and Th2 cells. Of note, taxifolin increased the CD8+ T cell content in 4T-1 tumors. The DEG36 is a novel and effective prognostic biomarker of BCs, particularly TNBCs, and can be used to assess the BC-associated immunosuppressive microenvironment.
A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4A

Simple Summary Our study investigates a specific genetic loss and duplication in elephants by comparing genomic data from 12 different mammalian species. We created a synteny map and phylogenetic tree of the selected species, which suggested that elephant CYP1–4 genes have undergone independent duplication, particularly in the CYP2A, CYP2C, and CYP3A genes, a unique cluster found only in elephants. In contrast, CYP2E and CYP4A might have decayed to a state of genetic dysfunction (pseudogene). These results suggest the need for further investigations into elephant genomics to evaluate the species’ metabolic mechanisms. Abstract Cytochrome P450 is an important enzyme that metabolizes a variety of chemicals, including exogenous substances, such as drugs and environmental chemicals, and endogenous substances, such as steroids, fatty acids, and cholesterol. Some CYPs show interspecific differences in terms of genetic variation. As little is known about the mechanisms of elephant metabolism, we carried out a comparative genomic and phylogenetic analysis of CYP in elephants. Our results suggest that elephant CYP genes have undergone independent duplication, particularly in the CYP2A, CYP2C, and CYP3A genes, a unique cluster specific to elephant species. However, while CYP2E and CYP4A were conserved in other Afrotheria taxa, their decay in elephants resulted in genetic dysfunction (pseudogene). These findings outline several remarkable characteristics of elephant CYP1–4 genes and provide new insights into elephant xenobiotic metabolism. Further functional investigations are necessary to characterize elephant CYP, including expression patterns and interactions with drugs and sensitivities to other chemicals.
Effect of Carrier Agents on Quality Parameters of Spray-Dried Encapsulated Diosgenin Powder and the Optimization of Process Parameters

Fenugreek seeds are a rich source of bioactive compounds, such as diosgenin, which is one of the most crucial steroidal sapogenins emerging in the field with its spectacular health benefits. Plant-based diosgenin is bitter in taste and has remarkably low consumption levels, making it unable to fulfil the role of improving health benefits. Diosgenin is spray dried to mask bitterness and astringent flavors with two different wall materials, such as maltodextrin (MD) and whey protein concentrate (WPC), separately. The spray-drying condition of the selected optimization process was inlet air temperature (IAT 150–170 °C), feed flow rate (FFR 300–500 mL/h), and carrier agent concentration (CAC 10–20%). The optimization of the process variable was conducted for producing optimized encapsulated diosgenin powder (EDP) with both MD and WPC. The selected parameters, such as yield, encapsulation efficiency, moisture content, antioxidant activity, hygroscopicity, and solubility, are investigated in this current work. Based on the experimental results, the significant R2 values depict the model fitting to the responses. EDP revealed an optimization condition at 170 °C IAT, 500 mL/h FFR, and 20% CAC for MD and WPC. The highest responses were observed with WPC-EDP, such as yield at 82.25%, encapsulation efficiency at 88.60%, antioxidant activity at 53.95%, and hygroscopicity at 12.64%. MD-EDP revealed higher solubility at 96.64% and moisture content at 2.58%. EDP was studied using micrographs and diffractograms for the optimized samples, which revealed a smooth and dented surface with an amorphous nature for MD-EDP and WPC-EDP, respectively. EDP exhibited acceptable powder properties with regard to fulfilling the set purpose. EDP can be a better potential ingredient in different food matrices to act as a delivery vehicle for various health aliments.
Thymoquinone Inhibition of Chemokines in TNF-α-Induced Inflammatory and Metastatic Effects in Triple-Negative Breast Cancer Cells

The lack of identifiable molecular targets or biomarkers hinders the development of treatment options in triple-negative breast cancer (TNBC). However, natural products offer a promising alternative by targeting inflammatory chemokines in the tumor microenvironment (TME). Chemokines are crucial in promoting breast cancer growth and metastasis and correlate to the altered inflammatory process. In the present study, we evaluated the anti-inflammatory and antimetastatic effects of the natural product thymoquinone (TQ) on TNF-α-stimulated TNBC cells (MDA-MB-231 and MDA-MB-468) to study the cytotoxic, antiproliferative, anticolony, antimigratory, and antichemokine effects using enzyme-linked immunosorbent assays, quantitative real-time reverse transcription–polymerase chain reactions, and Western blots were used in sequence to validate the microarray results further. Four downregulated inflammatory cytokines were identified, CCL2 and CCL20 in MDA-MB-468 cells and CCL3 and CCL4 in MDA-MB-231 cells. Furthermore, when TNF-α-stimulated MDA-MB-231 cells were compared with MDA-MB-468 cells, the two cells were sensitive to TQ’s antichemokine and antimetastatic effect in preventing cell migration. It was concluded from this investigation that genetically different cell lines may respond to TQ differently, as TQ targets CCL3 and CCL4 in MDA-MB-231 cells and CCL2 and CCL20 in MDA-MB-468 cells. Therefore, the results indicate that TQ may be recommended as a component of the therapeutic strategy for TNBC treatment. These outcomes stem from the compound’s capacity to suppress the chemokine. Even though these findings support the usage of TQ as part of a therapy strategy for TNBC associated with the identified chemokine dysregulations, additional in vivo studies are needed to confirm these in vitro results.
A Local and Abscopal Effect Observed with Liposomal Encapsulation of Intratumorally Injected Oncolytic Adenoviral Therapy

Simple Summary Oncolytic adenoviruses are genetically engineered to selectively replicate within cancer cells by exploiting their unique characteristics while sparing normal cells. However, adenoviruses generally require the coxsackie and adenovirus receptor (CAR) to enter the cells. This study investigated the activity of an oncolytic adenovirus in tumors with low CAR expression. The results showed that 58% and 33% of the tumors treated with liposome-encapsulated virus and viruses without liposome encapsulation achieved complete remission, respectively. Microscopic tissue analysis shows that an increased inflammatory infiltrate inside the tumor microenvironment is key to achieving effective therapeutic results in tumors independent of CAR expression. In the bilateral tumor model, both unencapsulated and encapsulated viruses reduced local tumor growth. However, only encapsulated virus reduced growth in distant tumors. Encapsulated adenovirus demonstrated an increased inflammatory infiltrate, including CD-8 and NK cells in both the treated and untreated tumors, whereas unencapsulated virus demonstrated limited inflammatory infiltrate in both tumors. Abstract This study evaluated the in vivo therapeutic efficacy of oncolytic serotype 5 adenovirus TAV255 in CAR-deficient tumors. In vitro experiments were performed with cell lines that expressed different levels of CAR (HEK293, A549, CT26, 4T1, and MCF-7). Low CAR cells, such as CT26, were poorly transduced by Ad in vitro unless the adenovirus was encapsulated in liposomes. However, the CT26 tumor in an immune-competent mouse model responded to the unencapsulated TAV255; 33% of the tumors were induced into complete remission, and mice with complete remission rejected the rechallenge with cancer cell injection. Encapsulation of TAV255 improves its therapeutic efficacy by transducing more CT26 cells, as expected from in vitro results. In a bilateral tumor model, nonencapsulated TAV255 reduced the growth rate of the locally treated tumors but had no effect on the growth rate of the distant tumor site. Conversely, encapsulated TAV255-infected CT26 induced a delayed growth rate of both the primary injected tumor and the distant tumor, consistent with a robust immune response. In vivo, intratumorally injected unencapsulated adenoviruses infect CAR-negative cells with only limited efficiency. However, unencapsulated adenoviruses robustly inhibit the growth of CAR-deficient tumors, an effect that constitutes an ‘in situ vaccination’ by stimulating cytotoxic T cells.
The Impact of Gold Nanoparticles on Somatic Embryogenesis Using the Example of Arabidopsis thaliana

Although the influence of nanoparticles (NPs) on developmental processes is better understood, little is known about their impact on somatic embryogenesis (SE). This process involves changes in the direction of cell differentiation. Thus, studying the effect of NPs on SE is essential to reveal their impact on cell fate. This study aimed to examine the influence of gold nanoparticles (Au NPs) with different surface charges on the SE of 35S:BBM Arabidopsis thaliana, with particular emphasis on the spatiotemporal localization of pectic arabinogalactan proteins (AGPs) and extensin epitopes in cells changing the direction of their differentiation. The results show that under the influence of nanoparticles, the explant cells of 35S:BBM Arabidopsis thaliana seedling origin did not enter the path of SE. Bulges and the formation of organ-like structures were observed in these explants, in contrast to the control, where somatic embryos developed. Additionally, spatiotemporal changes in the chemical composition of the cell walls during the culture were observed. Under the influence of Au NPs, the following effects were observed: (1) explant cells did not enter the SE pathway, (2) the impacts of Au NPs with different surface charges on the explants were variable, and (3) the compositions of the analyzed pectic AGPs and extensin epitopes were diverse in the cells with different developmental programs: SE (control) and non-SE (treated with Au NPs).
The Effects of a High-Fat Diet on Inflammatory Bowel Disease

The interactions among diet, intestinal immunity, and microbiota are complex and play contradictory roles in inflammatory bowel disease (IBD). An increasing number of studies has shed light on this field. The intestinal immune balance is disrupted by a high-fat diet (HFD) in several ways, such as impairing the intestinal barrier, influencing immune cells, and altering the gut microbiota. In contrast, a rational diet is thought to maintain intestinal immunity by regulating gut microbiota. In this review, we emphasize the crucial contributions made by an HFD to the gut immune system and microbiota.
Age of Onset Moderates the Association between Total Antioxidant Capacity and Cognitive Deficits in Patients with Drug-Naïve Schizophrenia

Schizophrenia patients with an earlier age of onset have been found to have more serious negative symptoms and cognitive deficits. Oxidative stress is thought to be implicated in cognitive impairment in schizophrenia. Total antioxidant capacity (TAOC) is an essential indicator of oxidative stress. However, the association between age of onset, TAOC, and cognitive performance in schizophrenia remains unexplored. In this study, 201 patients (age: 26.5 ± 9.6 years; male: 53.2%) with drug-naïve schizophrenia were recruited. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma TAOC levels were analyzed using established procedures. Results showed that early-onset (EO) patients had higher TAOC levels, more severe negative symptoms and performed worse on visuospatial/constructional, language and RBANS total scores than non-EO patients. After Bonferroni correction, only non-EO patients showed a significant inverse relationship between TAOC levels and RBANS language, attention, and total scores. Our findings suggest that an early/late age of onset may be correlated with psychopathological symptoms, cognitive impairment and oxidative responses in schizophrenia. Furthermore, the age of onset may moderate the relationship between TAOC and cognitive function in patients with schizophrenia. These findings suggest that improving oxidative stress status in non-EO schizophrenia patients may enhance their cognitive function.
Leukocyte differentiation in bronchoalveolar lavage fluids using higher harmonic generation microscopy and deep learning

Background In diseases such as interstitial lung diseases (ILDs), patient diagnosis relies on diagnostic analysis of bronchoalveolar lavage fluid (BALF) and biopsies. Immunological BALF analysis includes differentiation of leukocytes by standard cytological techniques that are labor-intensive and time-consuming. Studies have shown promising leukocyte identification performance on blood fractions, using third harmonic generation (THG) and multiphoton excited autofluorescence (MPEF) microscopy. Objective To extend leukocyte differentiation to BALF samples using THG/MPEF microscopy, and to show the potential of a trained deep learning algorithm for automated leukocyte identification and quantification. Methods Leukocytes from blood obtained from three healthy individuals and one asthma patient, and BALF samples from six ILD patients were isolated and imaged using label-free microscopy. The cytological characteristics of leukocytes, including neutrophils, eosinophils, lymphocytes, and macrophages, in terms of cellular and nuclear morphology, and THG and MPEF signal intensity, were determined. A deep learning model was trained on 2D images and used to estimate the leukocyte ratios at the image-level using the differential cell counts obtained using standard cytological techniques as reference. Results Different leukocyte populations were identified in BALF samples using label-free microscopy, showing distinctive cytological characteristics. Based on the THG/MPEF images, the deep learning network has learned to identify individual cells and was able to provide a reasonable estimate of the leukocyte percentage, reaching >90% accuracy on BALF samples in the hold-out testing set. Conclusions Label-free THG/MPEF microscopy in combination with deep learning is a promising technique for instant differentiation and quantification of leukocytes. Immediate feedback on leukocyte ratios has potential to speed-up the diagnostic process and to reduce costs, workload and inter-observer variations.
Crafting a Personalized Prognostic Model for Malignant Prostate Cancer Patients Using Risk Gene Signatures Discovered through TCGA-PRAD Mining, Machine Learning, and Single-Cell RNA-Sequencing

Background: Prostate cancer is a significant clinical issue, particularly for high Gleason score (GS) malignancy patients. Our study aimed to engineer and validate a risk model based on the profiles of high-GS PCa patients for early identification and the prediction of prognosis. Methods: We conducted differential gene expression analysis on patient samples from The Cancer Genome Atlas (TCGA) and enriched our understanding of gene functions. Using the least absolute selection and shrinkage operator (LASSO) regression, we established a risk model and validated it using an independent dataset from the International Cancer Genome Consortium (ICGC). Clinical variables were incorporated into a nomogram to predict overall survival (OS), and machine learning was used to explore the risk factor characteristics’ impact on PCa prognosis. Our prognostic model was confirmed using various databases, including single-cell RNA-sequencing datasets (scRNA-seq), the Cancer Cell Line Encyclopedia (CCLE), PCa cell lines, and tumor tissues. Results: We identified 83 differentially expressed genes (DEGs). Furthermore, WASIR1, KRTAP5-1, TLX1, KIF4A, and IQGAP3 were determined to be significant risk factors for OS and progression-free survival (PFS). Based on these five risk factors, we developed a risk model and nomogram for predicting OS and PFS, with a C-index of 0.823 (95% CI, 0.766–0.881) and a 10-year area under the curve (AUC) value of 0.788 (95% CI, 0.633–0.943). Additionally, the 3-year AUC was 0.759 when validating using ICGC. KRTAP5-1 and WASIR1 were found to be the most influential prognosis factors when using the optimized machine learning model. Finally, the established model was interrelated with immune cell infiltration, and the signals were found to be differentially expressed in PCa cells when using scRNA-seq datasets and tissues. Conclusions: We engineered an original and novel prognostic model based on five gene signatures through TCGA and machine learning, providing new insights into the risk of scarification and survival prediction for PCa patients in clinical practice.
Epigenetic and Immunological Features of Bladder Cancer

Bladder cancer (BLCA) is one of the most common types of malignant tumors of the urogenital system in adults. Globally, the incidence of BLCA is more than 500,000 new cases worldwide annually, and every year, the number of registered cases of BLCA increases noticeably. Currently, the diagnosis of BLCA is based on cystoscopy and cytological examination of urine and additional laboratory and instrumental studies. However, cystoscopy is an invasive study, and voided urine cytology has a low level of sensitivity, so there is a clear need to develop more reliable markers and test systems for detecting the disease with high sensitivity and specificity. Human body fluids (urine, serum, and plasma) are known to contain significant amounts of tumorigenic nucleic acids, circulating immune cells and proinflammatory mediators that can serve as noninvasive biomarkers, particularly useful for early cancer detection, follow-up of patients, and personalization of their treatment. The review describes the most significant advances in epigenetics of BLCA.
Fungal Drug Discovery for Chronic Disease: History, New Discoveries and New Approaches

Fungal-derived drugs include some of the most important medicines ever discovered, and have proved pivotal in treating chronic diseases. Not only have they saved millions of lives, but they have in some cases changed perceptions of what is medically possible. However, now the low-hanging fruit have been discovered it has become much harder to make the kind of discoveries that have characterised past eras of fungal drug discovery. This may be about to change with new commercial players entering the market aiming to apply novel genomic tools to streamline the discovery process. This review examines the discovery history of approved fungal-derived drugs, and those currently in clinical trials for chronic diseases. For key molecules, we discuss their possible ecological functions in nature and how this relates to their use in human medicine. We show how the conservation of drug receptors between fungi and humans means that metabolites intended to inhibit competitor fungi often interact with human drug receptors, sometimes with unintended benefits. We also plot the distribution of drugs, antimicrobial compounds and psychoactive mushrooms onto a fungal tree and compare their distribution to those of all fungal metabolites. Finally, we examine the phenomenon of self-resistance and how this can be used to help predict metabolite mechanism of action and aid the drug discovery process.