Sporisorium reilianum polysaccharides improve DSS-induced ulcerative colitis by regulating intestinal barrier function and metabolites.

This study investigated the regulatory effects of Sporisorium reilianum polysaccharides (SRPS) on metabolism and the intestinal barrier in mice with colitis induced by dextran sulfate sodium (DSS). SRPS were resistant to the digestion of saliva, gastric juices, and intestinal fluid. SRPS significantly reduced the disease activity index and inhibited DSS-induced colon shortening. The expression of proinflammatory cytokines in the colon was normal (P < 0.05). Acetic acid, propionic acid, butyric acid, isobutyric acid, and isovaleric acid contents increased. Moreover, 64 biomarker metabolites were affected, including 42 abnormal decreases and 22 abnormal increases caused by DSS, which targeted amino acid biosynthesis; tryptophan metabolism; protein digestion and absorption; aminoacyl-tRNA biosynthesis; and glycine, serine, and threonine metabolism. In addition, SRPS reduced goblet cell loss and increased mucin secretion. The short-chain fatty acid receptor GPR41 was activated, and zonula occludens-1 and occludin expression levels were upregulated. Epithelial cell apoptosis was inhibited by increased Bcl-2 and decreased Bax expression NLRP3, ASC, and caspase-1 protein levels decreased. Intestinal barrier damage improved, and colon inflammation was reduced. Thus, our preliminary findings reveal that SRPS regulates metabolism and has the potential to protect the intestinal barrier in ulcerative colitis mice.

A novel disulfidptosis-related lncRNAs signature for predicting survival and immune response in hepatocellular carcinoma.

The accumulation of intracellular disulfides induces a novel and unique form of metabolic-related cell death known as disulfidptosis. A previous study revealed the prognostic value of a risk model of disulfidptosis-related genes in hepatocellular carcinoma (HCC). However, to date, no studies have investigated the relationship between disulfidptosis-related long non-coding RNAs (DRLs) and HCC. In this study, we collected and analyzed RNA sequencing data from 370 HCC samples to explore the DRLs in the tumorigenesis and development of HCC. By employing Lasso Cox regression and multivariate Cox regression analyses, we identified five prognostic DRLs, which were used to construct a prognostic signature. The signature was subsequently validated using receiver operating characteristic (ROC) curves, Kaplan-Meier analysis, Cox regression analyses, nomograms, and calibration curves. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed, revealing that the DRLs signature was associated with HCC and several cancer-related pathways. Furthermore, the DRLs signature showed correlations with the infiltration of M0 and M1 macrophages, immune-related functions, and multiple immune checkpoints, including PDCD1, LAG3, CTLA4, TIGIT, CD47, and others. Analysis using the tumor immune dysfunction and exclusion (TIDE) approach demonstrated that the DRLs signature could predict the response to immunotherapy. Finally, we screened potential chemotherapy drugs that could sensitize HCC. In conclusion, our novel DRLs signature provides valuable insights into predicting patient survival and immunotherapy responses.

A Contribution to Improve Barrier Properties and Reduce Swelling Ratio of κ-Carrageenan Film from the Incorporation of Guar Gum or Locust Bean Gum.

In this study, galactomannan (GM), including guar gum (GG) or locust bean gum (LG), was incorporated into a κ-carrageenan film to improve barrier properties and reduce the swelling ratio (SR). The effects of that with different concentrations on optical, mechanical, barrier, swelling and thermal properties of the κ-carrageenan-based film were researched. SEM and rheological results showed that both κ-carrageenan/GG and κ-carrageenan/LG had good compatibility and stability. FTIR results showed that LG was easier to form hydrogen bonds with κ-carrageenan. The KC-L exhibited excellent mechanical properties, barrier properties, and SR than KC-G. The film with 15% GM had good light transmittance. Moreover, the thermal stability of the film could be improved by adding GMs. This study reports that the κ-carrageenan-GM film has potential in packaging applications.

Poly(ADP-ribose) promotes toxicity of C9ORF72 arginine-rich dipeptide repeat proteins.

Arginine-rich dipeptide repeat proteins (R-DPRs), abnormal translational products of a GGGGCC hexanucleotide repeat expansion in C9ORF72, play a critical role in C9ORF72-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the most common genetic form of the disorders (c9ALS/FTD). R-DPRs form liquid condensates in vitro, induce stress granule formation in cultured cells, aggregate, and sometimes coaggregate with TDP-43 in postmortem tissue from patients with c9ALS/FTD. However, how these processes are regulated is unclear. Here, we show that loss of poly(ADP-ribose) (PAR) suppresses neurodegeneration in c9ALS/FTD fly models and neurons differentiated from patient-derived induced pluripotent stem cells. Mechanistically, PAR induces R-DPR condensation and promotes R-DPR-induced stress granule formation and TDP-43 aggregation. Moreover, PAR associates with insoluble R-DPR and TDP-43 in postmortem tissue from patients. These findings identified PAR as a promoter of R-DPR toxicity and thus a potential target for treating c9ALS/FTD.

Using expression quantitative trait loci data and graph-embedded neural networks to uncover genotype-phenotype interactions.

Motivation: A central goal of current biology is to establish a complete functional link between the genotype and phenotype, known as the so-called genotype-phenotype map. With the continuous development of high-throughput technology and the decline in sequencing costs, multi-omics analysis has become more widely employed. While this gives us new opportunities to uncover the correlation mechanisms between single-nucleotide polymorphism (SNP), genes, and phenotypes, multi-omics still faces certain challenges, specifically: 1) When the sample size is large enough, the number of omics types is often not large enough to meet the requirements of multi-omics analysis; 2) each omics' internal correlations are often unclear, such as the correlation between genes in genomics; 3) when analyzing a large number of traits (p), the sample size (n) is often smaller than p, n << p, hindering the application of machine learning methods in the classification of disease outcomes. Results: To solve these issues with multi-omics and build a robust classification model, we propose a graph-embedded deep neural network (G-EDNN) based on expression quantitative trait loci (eQTL) data, which achieves sparse connectivity between network layers to prevent overfitting. The correlation within each omics is also considered such that the model more closely resembles biological reality. To verify the capabilities of this method, we conducted experimental analysis using the GSE28127 and GSE95496 data sets from the Gene Expression Omnibus (GEO) database, tested various neural network architectures, and used prior data for feature selection and graph embedding. Results show that the proposed method could achieve a high classification accuracy and easy-to-interpret feature selection. This method represents an extended application of genotype-phenotype association analysis in deep learning networks.

Microcystic urothelial carcinoma: a case report.

Microcystic urothelial carcinoma (MUC) is a rare variant of urothelial carcinoma that is highly aggressive with poor prognosis. Due to the scarcity of cases, its histologic morphology and immunohistochemical characteristics are still not clear. This paper reports a 71-year old female patient with gross hematuria and abdominal pain. Imaging examination showed that the bladder wall was thickened, and rough. A soft tissue mass was seen in the bladder and the left lower ureter, and the boundary between the bladder and the uterus and bilateral adnexa was not clear. Multiple enlarged lymph nodes were seen around the abdominal aorta and left iliac artery. Cystoscopy showed diffuse thickening and edema of the left wall of the bladder, local rough bleeding, and histopathologic results showed that the lesions were consistent with high-grade invasive urothelial carcinoma. Radical cystectomy and bilateral ovariectomy were performed. By microscopic observation the tumor showed infiltrative growth with cystic structures of different sizes. Mitotic figures were frequent and a large amount of mucus was in the stroma. The same type of cancer was found in the left ovary. Immunohistochemistry showed CK5/6 +, p63 +, Pax-8, MUC5AC, CK7, and Ki67 was 50%. Postoperative pathology confirmed that MUC involved the left ureter with ovarian metastasis. Two months after the operation, the patient died of vascular invasion. Because tumor cells were bland in morphology and had no specific immunohistochemical markers, they were easily missed and misdiagnosed by pathologists. Here, we describe this case and analyze it with relevant literature to deepen understanding of MUC.

Mixed malignant peripheral nerve sheath tumor in the inguinal region: a case report.

Malignant peripheral nerve sheath tumor (MPNST) is a rare malignant soft tissue tumor that accounts for approximately 5% of all soft tissue sarcomas. This tumor originates from the peripheral nerves and occurs mainly in the limbs, head and neck, and spine. As a more aggressive tumor, it has higher recurrence and metastasis rates, and patient prognosis is poor. MPNST has a variety of histologic subtypes such as classic MPNST and epithelioid malignant peripheral nerve sheath tumors (EMPNSTs). Due to the diversity of histologic types, these tumors have a high histologic similarity to other benign and malignant soft tissue tumors. Due to the lack of specific diagnostic criteria, pathologic diagnosis is extremely difficult, since these tumors should be differentiated from other sarcomas according to the site of tumor occurrence and morphologic characteristics, which can be determined using immunohistochemical staining. The specific pathogenesis of MPNST is not well understood. Studies have shown that approximately 50% of MPNSTs are closely related to neurofibromatosis I (NF1), while other causes of these tumors include radiotherapy. Herein, we report the first case of a mixed tumor composed of classic MPNST and EMPNST elements in the inguinal region.

Investigating the Promoter of FAT10 Gene in HCC Patients.

FAT10, which is also known as diubiquitin, has been implicated to play important roles in immune regulation and tumorigenesis. Its expression is up-regulated in the tumors of Hepatocellular Carcinoma (HCC) and other cancer patients. High levels of FAT10 in cells have been shown to result in increased mitotic non-disjunction and chromosome instability, leading to tumorigenesis. To evaluate whether the aberrant up-regulation of the FAT10 gene in the tumors of HCC patients is due to mutations or the aberrant methylation of CG dinucleotides at the FAT10 promoter, sequencing and methylation-specific sequencing of the promoter of FAT10 was performed. No mutations were found that could explain the differential expression of FAT10 between the tumor and non-tumorous tissues of HCC patients. However, six single nucleotide polymorphisms (SNPs), including one that has not been previously reported, were identified at the promoter of the FAT10 gene. Different haplotypes of these SNPs were found to significantly mediate different FAT10 promoter activities. Consistent with the experimental observation, differential FAT10 expression in the tumors of HCC patients carrying haplotype 1 was generally higher than those carrying haplotype II. Notably, the methylation status of this promoter was found to correlate with FAT10 expression levels. Hence, the aberrant overexpression of the FAT10 gene in the tumors of HCC patients is likely due to aberrant methylation, rather than mutations at the FAT10 promoter.

TRPC1/3/6 inhibition attenuates the TGF-ß1-induced epithelial-mesenchymal transition in gastric cancer via the Ras/Raf1/ERK signaling pathway.

Gastric cancer (GC) is one of the most common malignancies worldwide. TGF-ß1 induces the epithelial-mesenchymal transition (EMT) in GC, mainly through Smad-dependent pathways. Nevertheless, few studies have focused on the activation of non-canonical transduction pathways. TRPC, Ca2+ entry channels, are ubiquitously expressed in various cell types and are involved in many cellular functions. However, their roles in GC are not well elucidated. This study aimed to determine whether TRPC participates in the TGF-ß1-induced EMT of GC and to investigate the potential mechanisms. Immunofluorescence staining was performed to examine the distribution and expression of TRPCs and EMT-related proteins in SGC-7901 cells incubated with or without TGF-ß1. The expression of TRPC1/3/6 and EMT-related molecules, including E-cadherin, vimentin, and α-SMA, was detected by qRT-PCR and Western blotting. Additionally, the underlying mechanism was determined by treating cells with pharmacological inhibitors and examining the levels of proteins involved in the main signaling cascades using Western blotting. TRPC1/3/6 were expressed at high levels in SGC-7901 cells. Following TGF-ß1 stimulation, the expression of vimentin, α-SMA, and TRPC1/3/6 increased and E-cadherin expression decreased, accompanied by activation of the Ras/Raf1/ERK1/2 signaling pathway. Notably, activation of the Ras/Raf1/ERK1/2 signaling cascade was suppressed by SKF96365 and 2-APB. Both TRPC and ERK inhibitors mitigated EMT progression. Based on these results, TRPC1/3/6 inhibition attenuated the TGF-ß1-induced EMT in GC by suppressing Ras/Raf1/ERK signal transduction.

Hepatitis B Virus X Protein and Hepatocarcinogenesis.

Chronic hepatitis B virus (HBV) infection is one of the most associated factors in hepatocarcinogenesis. HBV is able to integrate into the host genome and encode the multi-functional hepatitis B virus x protein (HBx). Although the mechanism between HBx and carcinogenesis is still elusive, recent studies have shown that HBx was able to influence various signaling pathways, as well as epigenetic and genetic processes. This review will examine and summarize recent literature about HBx's role in these various processes.

Computed Tomography Imaging Measurement for Safer Cavernous Sinus Biopsy.

The aim of this study was to measure the relative location between foramen ovale and internal carotid artery. The results can guide surgeons to avoid damaging internal carotid artery in cavernous sinus biopsy. One hundred twenty people (73 men and 47 women) were involved in this study anonymously. Five parameters of both sides were measured on 2 planes. This study provides data for safer cavernous sinus biopsy.

The safe zone of posterior semicircular canal resection in suboccipital retrosigmoid sinus approach for acoustic neuroma surgery.

The aim of the study was to find the safe zone of posterior semicircular canal resection that can avoid structure damage in suboccipital retrosigmoid sinus approach for acoustic neuroma. One hundred twenty subjects (72 male and 48 female subjects) were involved in this study anonymously. Five parameters are measured in computed tomography: L1 is the line that goes through the common bony crus and parallel to the plane that contains posterior semicircular canal at axial plane. L2 is the middle sagittal line at axial plane. A is the point of posterior wall of the internal auditory canal at the level of the common bony crus. B is the intersection point of L1 and posterior wall of auditory canal. L3 is the line that goes through the plane that contains posterior semicircular canal at coronary plane. L4 is the middle sagittal line at coronary plane. C is the common bony crus. D is the ampulla. E is the most posterior point of posterior wall of auditory canal at the plane that goes through the posterior semicircular canal. The angle between L1 and L2 was 41.76 (SD, 5.64) degrees on the right and 43.40 (SD, 5.25) degrees on the left (P = 0.003). The distance between A and B was 0.59 (SD, 0.13) cm. The angle between L3 and L4 was 16.57 (SD, 6.51) degrees on the right and 17.57 (SD, 6.98) degrees on the left (P = 0.017). The distance between C and D was 0.60 (SD, 0.05) cm. The distance between E and line CD was 0.48 (SD, 0.09).

Locating of the pituitary stalk for craniopharyngioma surgery of transfrontobasal interhemispheric approach.

The aim of this study was to provide a relatively safe operation range for the protection of the pituitary stalk in transfrontobasal interhemispheric approach for craniopharyngioma surgery by measuring the related parameters of the pituitary stalk. Based on the whole-head magnetic resonance imaging scans of 119 healthy subjects (57 men and 62 women) anonymously, three-dimensional reconstructions were rebuilt. The results of the study are as follows: M is the common midpoint of anterior and inferior border of anterior commissure. O and P are the midpoint of the anterior border of the pituitary stalk's superior and inferior extremity, respectively. The distance between M and O (D1) was 12.42 (SD, 2.35) mm. The distance between M and P (D2) was 22.47 (SD, 2.57) mm. The length of the pituitary stalk (D3) was 10.68 (SD, 2.34) mm. The widest diameter of the pituitary stalk (D4) was 2.78 (SD, 0.50) mm. The inclination of the pituitary stalk at the coronal plane (A1) was 2.73 (SD, 2.60) degrees. Of the 119 pituitary stalks involved in this study, 14.29% were centered, 47.06% inclined to the left with the value (A1L) of 3.41 (SD, 2.58) degrees and 38.66% inclined to the right with the value (A1R) of 2.93 (SD, 2.49) degrees. The angle between MO and MP(A2) was 11.81 (SD, 4.76) degrees. No statistical difference was found between male and female subjects for all the measurements (P > 0.05). With the parameters measured in this study, we can locate the pituitary stalk by anterior commissure; thus, it is relatively safe to do the craniopharyngioma surgery through frontobasal interhemispheric approach when the pituitary stalk cannot be seen clearly because of the shelter of tumor, which will reduce both the unnecessary damage to the pituitary stalk and the probability of postoperative complications.

Optic canal location by computed tomography.

The aim of this study was to provide anatomic data for optic canal decompression. One hundred twenty people (55 males and 65 females) were involved in this study anonymously. Twelve parameters are measured in computed tomography: P1 is the nasal bone tip; P2 is the middle point of tuberculum sellae; P3 is the root of columella nasi; P4 is the cranium end of the optic canal; P5 is the orbit end of the optic canal; P1' is P1's projection on L2; L1 is the line that links P1 and P2; L2 goes through P3 and parallel to L1; L3 is the bisector of right and left and goes through P1. The distance between LI and L2 was 30.47 ± 3.71 mm. The distance between P3 and P1' was 11.66 ± 2.82 mm. The medial canal wall length was 10.64 ± 1.10 mm on the right and 10.51 ± 1.07 mm on the left (P = 0.001). The distance between P1 and P4 was 66.74 ± 5.97 mm. The distance between P1 and P5 was 73.04 ± 6.33 mm on the right and 72.82 ± 6.33 mm on the left (P = 0.004). The distance between P5 and L3 was 6.62 ± 1.33 mm. The distance between P4 and L3 was 12.26 ± 1.63 mm. The distance between P3 and P4 was 75.82 ± 4.63 mm. The distance between P3 and P5 was 82.87 ± 4.60 mm on the right and 82.25 ± 4.86 mm on the left (P = 0.003). The angle between P1P4 and L3 was 12.26 ± 1.63 degrees. The angle between P1P5 and L3 was 5.28 ± 1.13 degrees. The angle between P3P5 and P3P4 was 5.80 ± 0.97 degrees. These results provide a precise location of the optic canal.