The roles of metal ions in gallstones formation.

Gallstones (GSs) disease is a common disease worldwide. The mechanisms of their formation are diverse and complex and are related to cholesterol metabolism, gallbladder motility, biliary tract infection, the immune response, and ion metabolism. In recent years, with the application of inductively coupled plasma‒mass spectrometry and other methods, studies have suggested a correlation between the metabolism of metal ions and GSs formation. A literature search on gallstones and metal ions was instituted on PubMed and EMBASE. The specific topics of interest were etiology, formation mechanism, component Analysis and metabolism. References of papers were subsequently searched to obtain older literature. After reading and summarizing a large amount of literature, we found that calcium, iron, and copper can potentially promote the release of inflammatory factors and increase the level of reactive oxygen species, which is positively correlated with GSs formation. While magnesium and zinc, with their antioxidant effects, are negatively correlated with GSs formation. Metal ions are not only a component of GSs but are also important biological signals. Metal ion metabolism affects the formation of GSs and understanding its mechanism of action is of clinical significance for the prevention, diagnosis and treatment of GSs.

HSP90ß shapes the fate of Th17 cells with the help of glycolysis-controlled methylation modification.

BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is a refractory inflammatory disease associated with immune dysregulation. Elevated levels of heat shock protein (HSP) 90 in the ß but not α subtype were positively associated with disease status in UC patients. This study validated the possibility that pharmacological inhibition or reduction of HSP90ß would alleviate colitis, induced by dextran sulfate sodium, in mice and elucidated its mechanisms. EXPERIMENTAL APPROACH: Histopathological and biochemical analysis assessed disease severity, and bioinformatics and correlation analysis explained the association between the many immune cells and HSP90ß. Flow cytometry was used to analyse the homeostasis and transdifferentiation of Th17 and Treg cells. In vitro inhibition and adoptive transfer assays were used to investigate functions of the phenotypically transformed Th17 cells. Metabolomic analysis, DNA methylation detection and chromatin immunoprecipitation were used to explore these mechanisms. KEY RESULTS: The selective pharmacological inhibitor (HSP90ßi) and shHSP90ß significantly mitigated UC in mice and promoted transformation of Th17 to Treg cell phenotype, via Foxp3 transcription. The phenotypically-transformed Th17 cells by HSP90ßi or shHSP90ß were able to inhibit lymphocyte proliferation and colitis in mice. HSP90ßi and shHSP90ß selectively weakened glycolysis by stopping the direct association of HSP90ß and GLUT1, the key glucose transporter, to accelerate ubiquitination degradation of GLUT1, and enhance the methylation of Foxp3 CNS2 region. Then, the mediator path was identified as the "lactate-STAT5-TET2" cascade. CONCLUSION AND IMPLICATIONS: HSP90ß shapes the fate of Th17 cells via glycolysis-controlled methylation modification to affect UC progression, which provides a new therapeutic target for UC.

Dietary ellagic acid therapy for CNS autoimmunity: Targeting on Alloprevotella rava and propionate metabolism.

BACKGROUND: Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS. RESULTS: We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells. CONCLUSIONS: Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. Video Abstract.

Balance between FeIV-NiIV synergy and Lattice Oxygen Contribution for Accelerating Water Oxidation.

Hydrogen obtained from electrochemical water splitting is the most promising clean energy carrier, which is hindered by the sluggish kinetics of the oxygen evolution reaction (OER). Thus, the development of an efficient OER electrocatalyst using nonprecious 3d transition elements is desirable. Multielement synergistic effect and lattice oxygen oxidation are two well-known mechanisms to enhance the OER activity of catalysts. The latter is generally related to the high valence state of 3d transition elements leading to structural destabilization under the OER condition. We have found that Al doping in nanosheet Ni-Fe hydroxide exhibits 2-fold advantage: (1) a strong enhanced OER activity from 277 mV to 238 mV at 10 mA cm-2 as the Ni valence state increases from Ni3.58+ to Ni3.79+ observed from in situ X-ray absorption spectra. (2) Operational stability is strengthened, while weakness is expected since the increased NiIV content with 3d8L2 (L denotes O 2p hole) would lead to structural instability. This contradiction is attributed to a reduced lattice oxygen contribution to the OER upon Al doping, as verified through in situ Raman spectroscopy, while the enhanced OER activity is interpreted as an enormous gain in exchange energy of FeIV-NiIV, facilitated by their intersite hopping. This study reveals a mechanism of Fe-Ni synergy effect to enhance OER activity and simultaneously to strengthen operational stability by suppressing the contribution of lattice oxygen.

Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

Association Between Dietary Factors and Chronic Sinusitis Among Korean Individuals: Insights From a Large Population-Based Study in Asia.

Objective: Population-based studies on chronic sinusitis have predominantly focused on Europe and the Americas, but research on chronic sinusitis within large Asian populations remains scarce. This study aims to explore the link between dietary factors and chronic sinusitis among ethnic Koreans in Asia. Design: A cross-sectional study. Setting: Data were collected from the Korean National Health and Nutrition Examination Survey (KNHANES) in 2012. Participants: Participants in the study were included based on a doctor's diagnosis of chronic sinusitis, as determined through the ear, nose, and throat examination questionnaires. Results: Adolescents [adjusted P value (aP) < .001, adjusted odds ratio (aOR) = 1.881, 95% confidence interval (CI) = 1.380-2.564] and individuals with college and higher education (aP = .042, aOR = 1.298, 95% CI = 1.009-1.669) were more likely to develop chronic rhinosinusitis. In addition, levels of dietary fat [P = .001, interquartile range (IQR) = 34.085] and energy intake (P = .004, IQR = 981.106) were associated with an increased risk of chronic sinusitis. Moreover, high dietary inflammatory index (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721), and high intake of fried pork chops (aP = .028, aOR = 1.335, 95% CI = 1.033-1.777), bread (aP = .024, aOR = 1.364, 95% CI = 1.042-1.786), and rice (aP = .021, aOR = 1.382, 95% CI = 1.051-1.818) were risk factors for chronic sinusitis, while cucumber consumption (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721) was a protective factor for chronic sinusitis. Conclusion: This study revealed a significant correlation between diet and development of chronic sinusitis. These findings suggest that promoting an anti-inflammatory dietary pattern and providing guidance on healthy eating habits could help reduce the incidence of chronic sinusitis and enhance its management.

Skin mottling score assesses peripheral tissue hypoperfusion in critically ill patients following cardiac surgery.

BACKGROUND: Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. METHODS: Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. RESULTS: Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling. CONCLUSION: In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion.

Physical Stability and Antioxidant Ability of a Sustainable Oil-in-Water Emulsion Containing Perilla Skin Extract and Upcycled Aquasoya Powder.

In response to environmental issues, upcycling has become a growing trend in the food industry. Aquasoya is a promising method to upcycle by-product from soybean processing due to its high protein contents and excellent emulsifying ability. In the present research, Aquasoya powder was used an emulsifier to incorporate the antioxidant compounds from perilla skin extract (PSE), namely rosmarinic acid, into oil-in-water (O/W) emulsion system and its physochemical stability was assessed. As a result, droplet size of the emulsion was smaller in PSE-incorporated emulsion (PO, 350.57 ± 9.60 b nm) than the emulsion without PSE (PX, 1045.37 ± 142.63 a nm). Centrifugal photosedimentometry analysis also revealed that the physical stability was significantly improved in PO, and the stability was maintained over 30 d of storage. Furthermore, as PO had a higher ABTS radical scavenging ability and showed slower initial lipid oxidation, it was concluded that PO has a higher antioxidant ability than PX. Conclusively, Aquasoya can be considered as an emulsifier in O/W emulsion with PSE because it can effectively integrate and stabilize the antioxidant substance derived from perilla skin.

Hypoxia-induced miR-5100 promotes exosome-mediated activation of cancer-associated fibroblasts and metastasis of head and neck squamous cell carcinoma.

The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis. HIF1α expression correlated positively with the levels of miR-5100 as well as α-SMA, the marker of CAFs. Hypoxia/HIF1α regulated transcriptionally miR-5100 to promote the degradation of its target gene QKI, which acts as a tumor suppressor in HNSCC. Hypoxic HNSCC-derived exosomal miR-5100 promoted the activation of CAFs by orchestrating QKI/AKT/STAT3 axis, which further facilitated HNSCC metastasis. Additionally, miR-5100 derived from plasma exosomes indicated HNSCC malignant progression. In conclusion, our findings illuminate a novel HIF1α/miR-5100/QKI pathway in HNSCC metastasis, and suggest that miR-5100 might be a potential biomarker and therapeutic target for HNSCC.

Screening of Sugarcane Proteins Associated with Defense against Leifsonia xyli subsp. xyli, Agent of Ratoon Stunting Disease.

Sugarcane is the most important sugar crop and one of the leading energy-producing crops in the world. Ratoon stunting disease (RSD), caused by the bacterium Leifsonia xyli subsp. xyli, poses a huge threat to ratoon crops, causing a significant yield loss in sugarcane. Breeding resistant varieties is considered the most effective and fundamental approach to control RSD in sugarcane. The exploration of resistance genes forms the foundation for breeding resistant varieties through molecular technology. The pglA gene is a pathogenicity gene in L. xyli subsp. xyli, encoding an endopolygalacturonase. In this study, the pglA gene from L. xyli subsp. xyli and related microorganisms was analyzed. Then, a non-toxic, non-autoactivating pglA bait was successfully expressed in yeast cells. Simultaneously the yeast two-hybrid library was generated using RNA from the L. xyli subsp. xyli-infected sugarcane. Screening the library with the pglA bait uncovered proteins that interacted with pglA, primarily associated with ABA pathways and the plant immune system, suggesting that sugarcane employs these pathways to respond to L. xyli subsp. xyli, triggering pathogenicity or resistance. The expression of genes encoding these proteins was also investigated in L. xyli subsp. xyli-infected sugarcane, suggesting multiple layers of regulatory mechanisms in the interaction between sugarcane and L. xyli subsp. xyli. This work promotes the understanding of plant-pathogen interaction and provides target proteins/genes for molecular breeding to improve sugarcane resistance to L. xyli subsp. xyli.

Protective effect of novel angiotensin receptor neprilysin inhibitor S086 on target organ injury in spontaneously hypertensive rats.

BACKGROUND: Hypertension is a clinical syndrome characterized by elevated systemic arterial blood pressure associated with injury to the heart, kidney, brain, and other organs. Angiotensin receptor neprilysin inhibitors (ARNi), including angiotensin receptor blockers (ARBs) and neprilysin inhibitors (NEPi), have been shown to be safe and effective at reducing blood pressure and alleviating development of target organ injury. This study was used to develop S086 as a novel ARNi and conducted preclinical studies in animal models to evaluate the protective effects of S086 on target organs. METHODS: This study used a 14-month-old spontaneously hypertensive rat (SHR) model to evaluate the protective effects of S086 on the cardiovascular system and organs such as heart and kidney by blood pressure monitoring, urine and blood examination, pathological examination, and immunological index detection. RESULTS: After administering S086 orally to the SHR, their blood pressure and levels of renal injury indicators such as serum creatinine and urinary microalbumin were reduced, and myocardial cell necrosis and cardiac fibrosis of the heart were significantly improved. In addition, there were also significantly improvements in the histological lesions of blood vessels and the kidneys. CONCLUSIONS: The findings showed that S086 effectively reduced the blood pressure of SHR and had effects on alleviating development of heart, blood vessels and kidney.

Sphingomyelin synthase 2 regulates the malignant biological behaviors of ovarian cancer TOV-21G cells through Wnt/β-catenin pathway / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨鞘磷脂合成酶2（SMS2）是否通过Wnt/β-catenin信号通路调控卵巢癌（OC）TOV-21G细胞增殖、迁移、侵袭、凋亡及其机制。方法：收集武汉市第三医院2022年7月至2023年5月间确诊的21例OC患者的癌及癌旁组织标本，免疫组化法检测OC组织SMS2表达水平。体外培养TOV-21G细胞，将细胞分为对照组、shRNA慢病毒阴性对照组（sh-NC组）、SMS2 shRNA慢病毒组（sh-SMS2组）、Wnt/β-catenin通路激活剂组LiCl（LiCl组）和sh-SMS2+LiCl组。Edu染色法、Transwell法、流式细胞术分别检测各组细胞的增殖、迁移和侵袭能力及凋亡水平，WB法检测细胞中SMS2、Ki67、cyclin D1、BAX、c-caspase3、Bcl-2及Wnt/β-catenin通路蛋白（β-catenin、c-Myc、MMP-9）的表达。构建TOV-21G细胞裸鼠移植瘤模型，观察敲低SMS2对移植瘤生长和SMS2、β-catenin表达的影响。结果：与癌旁组织比较，OC组织中SMS2呈高表达（P<0.01）。转染sh-SMS2后，TOV-21G细胞中SMS2表达水平显著降低（P<0.05），细胞的增殖、迁移和侵袭能力及Bcl-2、β-catenin、c-Myc、MMP-9蛋白表达均显著降低（均P<0.05），细胞凋亡率、BAX、c-caspase3蛋白表达均显著升高（均P<0.05）；LiCl处理能逆转敲低SMS2对TOV-21G细胞增殖、迁移和侵袭及Wnt/β-catenin通路的抑制作用（均P<0.05）。体内成瘤实验显示，敲低SMS2抑制裸鼠移植瘤的生长及SMS2、β-catenin蛋白的表达（均P<0.05）。结论：敲低SMS2表达通过Wnt/β-catenin信号通路抑制OC TOV-21G细胞的增殖、迁移、侵袭并促进细胞凋亡，同时LiCl处理则能逆转敲低SMS2对TOV-21G细胞增殖、迁移和侵袭的抑制作用。

Effects of Potassium Bicarbonate on Gel, Antioxidant and Water Distribution of Reduced-Phosphate Silver Carp Surimi Batter under Cold Storage.

The changes in storage loss, water distribution status, gel characteristics, thiobarbituric acid reactive substances (TBARSs), total volatile basic nitrogen, and total plate count of cooked reduced-phosphate silver carp surimi batter during cold storage at 4 °C were investigated. The storage loss, content of free water, pH, hardness, TBARSs, total volatile basic nitrogen value, and total plate count of all cooked silver carp surimi batters significantly increased (p < 0.05) with an increase in cold storage time. Meanwhile, the content of immobilized water, whiteness, springiness, and cohesiveness significantly decreased (p < 0.05). At the same cold storage time, the sample of cooked reduced-phosphate silver carp surimi batter had lower water mobility, darker color, and better texture characteristics than the cooked silver carp surimi batter without potassium bicarbonate; however, the values of TBARSs, total volatile basic nitrogen, and total plate count were not significantly different (p > 0.05). This meant that there was no difference between potassium bicarbonate and sodium tripolyphosphate in antioxidant and antibacterial activity during the cold storage of silver carp surimi batter. To summarize, the use of potassium bicarbonate instead of sodium tripolyphosphate could produce cooked reduced-phosphate silver carp surimi batter with better water-holding capacity and gel characteristics during cold storage.

Effect of glucocorticoid for patients with type A aortic dissection undergoing surgical repair with deep hypothermic circulatory arrest: A single-center, retrospective study.

BACKGROUND: Postoperative patients with Type A aortic dissection (TAAD) often experience severe inflammatory responses caused by multiple factors perioperatively. However, the effect of postoperative glucocorticoid (GC) use, which is a potent anti-inflammatory agent, on complications or all-cause mortality is unclear. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest between January 2020 and December 2021 were included in the study. Characteristics of patients treated with and without GCs were compared. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Propensity score matching was used to balance baseline differences between groups. Kaplan-Meier curves were used to compare survival probability. RESULTS: A total of 393 postoperative patients with TAAD were included in the study. Forty of them (10.2%) received GC treatment at a median daily methylprednisolone-equivalent dose of 0.6 mg/kg (0.4-0.7) for a median period of 2 (1-3) days. Patients on GCs had more intraoperative blood transfusions, higher postoperative APACHE II (12 vs 9, p = .004) and SOFA (9 vs 6, p < .001) scores, worse perioperative hepatic, renal and cardiac function. The in-hospital mortality in the matched cohort did not differ between groups [GC n = 11/40 (27.5%) versus Non-GC n = 19/80 (23.8%); p = .661]. CONCLUSIONS: The propensity to use GCs correlated with the critical status of the patient. However, low dose and short-term postoperative GC treatment did not reduce in-hospital mortality rates among patients with TAAD. A more appropriate regimen should be further investigated.

Deubiquitinase YOD1 suppresses tumor progression by stabilizing E3 ligase TRIM33 in head and neck squamous cell carcinoma.

Ubiquitination is a reversible process that not only controls protein synthesis and degradation, but also is essential for protein transport, localization and biological activity. Deubiquitinating enzyme (DUB) dysfunction leads to various diseases, including cancer. In this study, we aimed to explore the functions and mechanisms of crucial DUBs in head and neck squamous cell carcinoma (HNSCC). Based on bioinformatic analysis and immunohistochemistry detection, YOD1 was identified to be significantly downregulated in HNSCC specimens compared with adjacent normal tissues. Further analysis revealed that reduced YOD1 expression was associated with the malignant progression of HNSCC and indicated poor prognosis. The results of the in vitro and in vivo experiments verified that YOD1 depletion significantly promoted growth, invasion, and epithelial-mesenchymal transition in HNSCC. Mechanistically, YOD1 inhibited the activation of the ERK/ß-catenin pathway by suppressing the ubiquitination and degradation of TRIM33, leading to the constriction of HNSCC progression. Overall, our findings reveal the molecular mechanism underlying the role of YOD1 in tumor progression and provide a novel potential therapeutic target for HNSCC treatment.

Characteristics of mesenchymal stem cells and their exosomes derived from giant panda (Ailuropoda melanoleuca) endometrium.

Conservation of genetic resources is an important way to protect endangered species. At present, mesenchymal stem cells (MSCs) have been isolated from the bone marrow and umbilical cords of giant pandas. However, the types and quantities of preserved cell resources were rare and limited, and none of MSCs was derived from female reproductive organs. Here, we first isolated MSCs from the endometrium of giant panda. These cells showed fibroblast morphology and expressed Sox2, Klf4, Thy1, CD73, CD105, CD44, CD49f, and CD105. Endometrium mesenchymal stem cells (eMSCs) of giant panda could induce differentiation into three germ layers in vitro. RNA-seq analysis showed that 833 genes were upregulated and 716 genes were downregulated in eMSCs compared with skin fibroblast cells. The results of GO and the KEGG analysis of differentially expressed genes (DEGs) were mainly focused on transporter activity, signal transducer activity, pathways regulating pluripotency of stem cells, MAPK signaling pathway, and PI3K-Akt signaling pathway. The genes PLCG2, FRK, JAK3, LYN, PIK3CB, JAK2, CBLB, and MET were identified as hub genes by PPI network analysis. In addition, the exosomes of eMSCs were also isolated and identified. The average diameter of exosomes was 74.26 ± 13.75 nm and highly expressed TSG101 and CD9 but did not express CALNEXIN. A total of 277 miRNAs were detected in the exosomes; the highest expression of miRNA was the has-miR-21-5p. A total of 14461 target genes of the whole miRNAs were predicted and proceeded with functional analysis. In conclusion, we successfully isolated and characterized the giant panda eMSCs and their exosomes, and analyzed their functions through bioinformatics techniques. It not only enriched the conservation types of giant panda cell resources and promoted the protection of genetic diversity, but also laid a foundation for the application of eMSCs and exosomes in the disease treatment of giant pandas.

Inhibition of neuroactive ligand-receptor interaction pathway can enhance immunotherapy response in colon cancer: an in silico study.

BACKGROUND: The potential mechanism underlying the association between Homologous recombination deficiency (HRD) and immunotherapy in colon cancer has not been investigated. METHODS: The exon sequencing data and transcriptome data of 456 colon adenocarcinoma (COAD) patients were obtained from the TCGA database. Pathway activity score was calculated by GSVA methods and engaged in further survival analysis. The prognostic value of the candidate pathways was validated in an external GEO cohort and an immunotherapy cohort. RESULTS: Patients with high HRD were associated with poor prognosis, lower tumor mutation burden and microsatellite instability, higher fraction genome alteration, and less sensitivity to immunotherapy in COAD. And then, the neuroactive ligand-receptor interaction pathway was over-activated in high-HRD tumors and associated with immunosuppression in colon cancer with high HRD. Besides, the pathway was associated with prognosis and immunotherapy response in COAD. Moreover, genes in this pathway such as LTB4R2 can be used as a novel target for therapy development in colon cancer. CONCLUSION: Our study not only revealed the potential mechanism of HRD and the function of the neuroactive ligand-receptor interaction pathway in colon cancer but also provided new clues for the improvement of immunotherapy response in colon cancer.