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1. ⭐ GSE314209 微生物诱导结肠癌细胞中MHC-II表达可克服免疫治疗耐药性并限制转移

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、MHC、regex:micro(b|be|bial|organism)、regex:immuno(logy|therapy|suppression)、resistance
• 📝 描述：Contributors : Chung Charlie ; Ozcelik Elif ; Subhash Santhilal ; Beyaz SemirSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe identify commensal microbes that inhibit tumor progression and metastasis, thereby extending survival in four CRC models in two different mouse strains. These microbes exert tumor-suppressive effects by reprogramming the tumor immune microenvironment. This results in improved functionality and increased infiltration of T cells into MSS mCRC, transforming non-immunogenic, ‘cold’ tumors into immunologically active, ‘hot’ ones. We demonstrate that the MHC-II antigen presentation pathway in MSS cancer cells is necessary and sufficient for mediating the anti-tumor effects of the microbiome, and enhanced MHC-II on MSS mCRC tumors improves the efficacy of immunotherapy. Furthermore, elevating MHC-II expression on human MSS mCRC organoids significantly improves interactions between cancer and immune cells, leading to more effective cancer clearance in autologous patient-derived organoid-immune cell co-cultures. These findings suggest that modulation of cancer MHC-II expression, such as via microbes, can boost anti-tumor immunity and potentially improve the efficacy of immunotherapy in patients with MSS and mCRC.
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2. GSE307568 患者来源的类器官-免疫细胞共培养平台用于高级别子宫内膜癌的治疗发现

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、immune
• 📝 描述：Contributors : Charlie Chung ; Brian Yueh ; Santhilal Subhash ; Onur Eskiocak ; Semir BeyazSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensWe established a biobank of 85 patient-derived organoids (PDOs) generated from 44 individuals, encompassing a broad range of endometrial cancer (EC) subtypes, including a majority of high-grade endometrial cancer (HGEC) PDOs from African American patients. From these same patients, we isolated autologous immune cells, enabling the creation of PDO–immune cell co-cultures that reflect each patient’s unique characteristics without evoking allogeneic immune responses. To dissect the roles of antigen presentation pathways and evaluate proof-of-principle immunotherapeutic interventions, we performed bulk RNA sequencing, flow cytometry, and live-cell imaging.
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3. GSE319166 人类肠道对厌氧核黄素的降解 毛螺菌科

• ✍️ 作者：未知作者
• 🏷️ 关键词：gut、regex:gut(-?microbiome)?
• 📝 描述：Contributors : Christian J Quiles-Pérez ; Ami Fofana ; Kamal Deep ; Calissa Carlisle ; Justin A North ; Patrick H BradleySeries Type : Expression profiling by high throughput sequencingOrganism : [Clostridium] scindensVitamins mediate a web of cross-feeding interactions in the human gut. Many Gram-positive gut microbes, in particular, are predicted to be vitamin auxotrophs. Previous studies of these microbes, however, have tended to use rich media, precluding controlled perturbations of low abundance nutrients. We tested the ability of diverse Lachnospiraceae, the most common Gram-positives in the gut, to grow on a chemically defined medium. Even though this medium contained riboflavin, we found that predicted riboflavin auxotrophs grew poorly, including the bile metabolizer Clostridium scindens. Riboflavin supplementation increased C. scindens final density in a concentration-dependent manner up to at least 200μM. Surprisingly, despite being an auxotroph, C. scindens also catabolized riboflavin into lumichrome. The only previously described catabolic pathway for riboflavin requires oxygen and has no homologs in C. scindens. In 200µM riboflavin, a single gene neighborhood with an aldolase, oxidoreductases, and a riboflavin kinase/adenylyltransferase was upregulated, suggesting an alternative anaerobic degradation or overflow pathway. Similar neighborhoods were detected in several other Lachnospiraceae, including Faecalicatena fissicatena, the only other anaerobe reported to degrade riboflavin. Reanalysis of published metabolomic data showed that in vivo, both riboflavin and lumichrome were more abundant in colonized (vs. germ-free) mouse ceca, and that in vitro, Lachnospiraceae isolates depleted riboflavin while certain Gram-negative isolates overproduced it. These results demonstrate that a member of the Lachnospiraceae can anaerobically convert an essential B vitamin into lumichrome, a molecule recently shown to have anti-inflammatory properties. Vitamin catabolism may both structure cross-feeding interactions in the gut and affect host health.
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4. GSE289869 印度人群翼状胬肉的全基因组甲基化分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：genome、methylation
• 📝 描述：Contributors : Daipayan Banerjee ; L Mathan ; Tejaswi PrasadSeries Type : Methylation profiling by arrayOrganism : Homo sapiensPterygium is a highly prevalent, progressive conjunctival eye disease and is characterized by wing-shaped conjunctival fibrovascular overgrowth. Persistent sunlight exposure is a causative factor for this ocular surface disease and mostly affects people working outdoors. Surgical excision remains the only treatment option. Ultraviolet (UV) radiation from sunlight is widely recognized as the primary cause of pterygium. While chronic UV exposure induces epigenetic changes in the skin and contributes to skin cancer, the role of epigenetic alterations in pterygium pathogenesis remains largely unexplored. This study aimed to investigate genome-wide methylation changes in pterygium using the Illumina Infinium Epic v2.0 Methylation array. We identified 1,052 hypermethylated CpGs (499 genes) and 686 hypomethylated CpGs (340 genes) in pterygium tissue compared to control conjunctival tissue from cataract patients (Δβ>|0.1|, P<0.05). Hypomethylated genes were mainly associated with the PI3K-Akt and MAPK pathways, while hypermethylated genes were enriched in pathways related to oxidative stress, autophagy, DNA repair, and Wnt signaling inhibition. These findings suggest that dysregulated DNA methylation may contribute to pterygium pathogenesis by upregulating genes involved in cell proliferation, survival, angiogenesis, fibrosis, and extracellular matrix remodeling, while silencing genes associated with oxidative stress response, autophagy, and DNA damage repair.
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5. GSE274448 雌激素受体β靶基因表达揭示侵袭性乳腺癌中的新型抑制功能 [ChIP-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、ChIP-seq
• 📝 描述：Contributors : Spyros Tastsoglou ; Ilias Karagounis ; Marios Miliotis ; Harika Nagandla ; Kristina Zambo ; Maria Liousia ; Naoto Ueno ; Amit Maity ; Artemis G Hatzigeorgiou ; Christoforos ThomasSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensInflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor a (ERα) negativity and limited treatment options. We previously explored the second ER subtype, (ERβ) and reported correlation of its tumor expression with reduced metastasis in patients and in preclinical models of the disease. We initially associated the anti-metastatic function of the receptor with the inhibition of actin-based cell migration and the associated Rho GTPase signaling in IBC cells. We have now followed an integrated genomics approach to fully delineate the signaling underlying the anti-metastatic effects of ERβ. Through mapping binding sites in IBC cells that express endogenous and transfected ERβ in the presence of an agonist and interrogating this information with altered expression of protein coding mRNAs and miRNAs we have defined the interaction of a biologically active receptor with the cancer genome that controls metastatic signals. We reveal key regulatory chromatin binding sites and motifs and identify direct target genes and miRNAs and the associated biological functions. Our new findings implicate the regulation of metabolic pathways and signaling in development and tumor microenvironment in anti-metastatic activity of ERβ. Through a rigorous analysis of target genes in clinical datasets we also associate downstream factors with patient outcomes reporting new molecules with targeting potential and strengthening the relevance of ERβ signaling for the metastatic process in breast cancer. Our findings thus offer an opportunity to validate the tumor repressive role of ERβ through a better understanding of its mechanism of action.
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6. GSE274446 雌激素受体β靶基因表达揭示侵袭性乳腺癌中的新型抑制功能 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、RNA-seq
• 📝 描述：Contributors : Spyros Tastsoglou ; Ilias Karagounis ; Marios Miliotis ; Harika Nagandla ; Kristina Zambo ; Maria Liousia ; Naoto Ueno ; Amit Maity ; Artemis G Hatzigeorgiou ; Christoforos ThomasSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensInflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor a (ERα) negativity and limited treatment options. We previously explored the second ER subtype, (ERβ) and reported correlation of its tumor expression with reduced metastasis in patients and in preclinical models of the disease. We initially associated the anti-metastatic function of the receptor with the inhibition of actin-based cell migration and the associated Rho GTPase signaling in IBC cells. We have now followed an integrated genomics approach to fully delineate the signaling underlying the anti-metastatic effects of ERβ. Through mapping binding sites in IBC cells that express endogenous and transfected ERβ in the presence of an agonist and interrogating this information with altered expression of protein coding mRNAs and miRNAs we have defined the interaction of a biologically active receptor with the cancer genome that controls metastatic signals. We reveal key regulatory chromatin binding sites and motifs and identify direct target genes and miRNAs and the associated biological functions. Our new findings implicate the regulation of metabolic pathways and signaling in development and tumor microenvironment in anti-metastatic activity of ERβ. Through a rigorous analysis of target genes in clinical datasets we also associate downstream factors with patient outcomes reporting new molecules with targeting potential and strengthening the relevance of ERβ signaling for the metastatic process in breast cancer. Our findings thus offer an opportunity to validate the tumor repressive role of ERβ through a better understanding of its mechanism of action.
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7. GSE236530 酶介导的甲基化和炔基化能够实现转录组范围内的假尿苷修饰鉴定

• ✍️ 作者：未知作者
• 🏷️ 关键词：transcriptome、methylation
• 📝 描述：Contributors : Yuru Wang ; Kinga Pajdzik ; Yutao Zhao ; Chang Ye ; Talbot Stone ; Lisheng Zhang ; Wen Zhang ; Mahdi Assari ; Wenxin Zhao ; Caraline Sepich-Poore ; Qing Dai ; Ke Wang ; Minkui Luo ; Tao Pan ; Chuan HeSeries Type : Other ; Expression profiling by high throughput sequencingOrganism : Homo sapiens ; synthetic constructPseudouridine (Ψ) is one of the most abundant chemical modifications and plays important roles in RNA function. Advances in our understanding of Ψ have been hindered by a limit of robust methods to precisely and sensitively map their distributions in cellular RNAs. Here, we present ELAP-seq (Enzymatic Labeling and Pull-down for Sequencing) for Ψ detection, which leverages a naturally occurring N1-methyl pseudouridine methyltransferase from Methanocaldococcus jannaschii (Mj1640). This enzyme promiscuously converts Ψ to N1-methyl-Ψ (m1Ψ) or installs a propargyl group at the same location in vitro under a mild condition, exhibiting high sensitivity and specificity, and is also functional inside cells. ELAP-seq enriches Ψ-containing RNA fragments and enables single-nucleotide-resolution Ψ detection with markedly enhanced signal-to-noise ratio and reduced sequencing and computational demands. Using ELAP-seq, we identify thousands of candidate Ψ sites in human HeLa and HEK 293T transcriptomes, validating many previously identified sites as well as reporting new ones. This versatile enzymatic platform expands the toolkit for sensitive labeling and detection of Ψ, advancing the study of RNA modification biology.
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8. GSE314029 单分子 GIPR:GLP-1R:PPARα,γ,δ 五重激动剂可消除小鼠的肥胖和胰岛素抵抗。

• ✍️ 作者：未知作者
• 🏷️ 关键词：resistance
• 📝 描述：Contributors : Daniela Liskiewicz ; Ahmed Khalil ; Seun Akindehin ; Jon E Campbell ; Russel Castelino ; Callum Coupland ; Jonathan D Douros ; Annette Feuchtinger ; Brian Finan ; Cristina Garcia-Caceres ; Gerald Grandl ; Robert M Gutgesell ; Daniel Hass ; Ezgi Karaoglu ; Pamela Kakimoto ; Christine Kusminski ; Danielle Leander ; Arkadiusz Liskiewicz ; Xue Liu ; Gandhari Maity-Kumar ; Sara Martinez Martinez ; Stephany Mowery ; Ruben Nogueiras ; Marshall Paisley ; Diego Perez-Tilve ; Sneha Prakasch ; Alberto Cebrian-Serrano ; Monica Tost ; Jordan Wean ; Philipp E Scherer ; Randy J Seeley ; Richard D DiMarchi ; Matthias H Tschöp ; Natalie Krahmer ; Patrick Knerr ; Timo D MüllerSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusDrugs to improve obesity-linked metabolic dysfunction are on the rise, with GLP-1:GIP co-agonism being effective in the management of obesity and type 2 diabetes, and with Lanifibranor (Lani), a nuclear acting small molecule triple agonist at the peroxisome proliferator-activated receptors alpha, gamma and delta (PPAR𝛼,𝛾,𝛿) being in phase 3 development for the treatment of metabolic dysfunction-associated steatohepatitis. Seeking to further improve the metabolic efficacy of GLP-1:GIP co-agonism, we here report the design and preclinical evaluation of an unimolecular quintuple agonist, which synergistically combines the body weight and blood glucose lowering effects of GLP-1:GIP co-agonism with the insulin sensitizing effects of Lani through its targeted delivery into only cells that express the receptor for either GIP or GLP-1. In vitro, GLP-1:GIP:Lani is indistinguishable from its GLP-1:GIP backbone in GIPR and GLP-1R signaling and equally stimulates insulin secretion in isolated murine islets. In vivo, however, GLP-1:GIP:Lani is much superior to GLP-1:GIP co-agonism or Semaglutide to decrease body weight, food intake, and hyperglycemia in obese and insulin resistant mice through synergistic incretin and PPAR action in key glucoregulatory tissues. The superior metabolic action of GLP-1:GIP:Lani is demonstrated in mice with genetic (db/db) and diet-induced obesity (DIO), is accelerated in DIO mice with adipose-specific overexpression of GIPR and is absent in DIO double-incretin receptor knock-out mice. Collectively, our data suggest that this novel quintuple polyagonist holds unprecedented therapeutic value to treat obesity and type 2 diabetes.
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9. GSE319170 RNA-seq 分析了经米哚妥林处理或未处理的 CT26 细胞和肿瘤的 RNA 测序结果。

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq
• 📝 描述：Contributors : Zhengzhen Wu ; Xiufeng PangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusImmune checkpoint inhibitor therapy has demonstrated efficacy in a variety of tumors. However, due to the high heterogeneity of colorectal cancer, the clinical efficacy of ICB in the treatment of this disease remains quite limited. Activating mutations of KRAS are detected in 35%–50% of colorectal cancer tissues in clinical. Colorectal cancers with these activating mutations are characterized by an immune desert phenotype and aberrant immune-inflammatory microenvironment. Studies have indicated that oncogene addiction in tumorigenesis (such as KRAS mutation) and non-genetic mechanisms, particularly epigenetic regulation, can synergistically modulate multiple types of plasticity of the tumor microenvironment and tumor cells, but how epigenetic regulators function in the immunosuppressive microenvironment specific to KRAS-mutant colorectal cancer is barely known. In this study, we identify that PHF8 functions as a MHC-I suppressor that limits anti-tumor immunity in KRAS-mutant colorectal cancer. We also find a FDA-approved drug, Midostaurin, which can mimic the phenotype of PHF8 depletion and add to the efficacy of ICB treatment and KRAS inhibition.
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10. GSE319178 pH响应型CS-HA-DAP纳米递送系统通过双重靶向TOP2A/CHK1诱导有丝分裂灾难和混合型细胞死亡，用于三阴性乳腺癌治疗

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer
• 📝 描述：Contributors : Wei Liu ; Rui Han ; Chang Liu ; Xintong HanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTriple-negative breast cancer (TNBC) is characterized by a highly aggressive nature and poor clinical prognosis, largely due to the absence of effective therapeutic targets. Although natural bioactive peptides hold tremendous promise for anti-tumor therapy, their clinical application is restricted by short in vivo half-lives and insufficient targeting specificity. Herein, we aimed to develop a smart nanodelivery system to deliver deer antler polypeptide (DAP) for the precise treatment of TNBC.We constructed a pH-responsive nanoparticle (CS-HA-DAP) comprising chitosan (CS)-coated hyaluronic acid (HA)-DAP conjugates. Tumor accumulation of the drug was enhanced via HA-mediated active targeting of CD44 receptors and the enhanced permeability and retention (EPR) effect of the nanocarrier. Through RNA sequencing (RNA-seq), molecular docking, and multi-dimensional molecular biology experiments, we systematically elucidated the anti-tumor targets and lethal mechanism of DAP. Furthermore, its biodistribution, therapeutic efficacy, and safety were evaluated in a 4T1 tumor-bearing mouse model. CS-HA-DAP exhibited excellent physicochemical stability and tumor-targeting capability. Mechanistic studies revealed, for the first time, that DAP functions as a topoisomerase II alpha (TOP2A) inhibitor to induce extensive DNA double-strand breaks; concurrently, it inhibits checkpoint kinase 1 (CHK1), leading to the functional loss of the S/G2 cell cycle checkpoint. This synergistic effect of DNA damage and repair blockade forces cancer cells harboring severe genomic injury to undergo mitotic slippage, ultimately driving them into irreversible mitotic catastrophe. Subsequent signaling cascades triggered a mixed-type cell death program. In vivo experiments confirmed that CS-HA-DAP significantly suppressed tumor growth without inducing notable systemic toxicity. In summary, we successfully constructed the CS-HA-DAP nanosystem and validated a novel anti-tumor mechanism driven by TOP2A/CHK1 dual-targeting-induced mitotic catastrophe and mixed-type death. This strategy not only overcomes the barriers to peptide druggability but also provides a promising, innovative solution for the treatment of refractory TNBC.
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1. ⭐ 科学家发现一种与健康相关的隐秘肠道细菌

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:bacter(ia|ial|ium)、gut、regex:gut(-?microbiome)?
• 📝 描述：A global study has uncovered a mysterious group of gut bacteria that shows up again and again in healthy people. Known as CAG-170, these microbes were found at lower levels in people with a range of chronic diseases. Genetic clues suggest they help digest food and support the broader gut ecosystem. Researchers say the discovery could reshape how we measure and maintain gut health.
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• GSE319154 HER2d16 通过整合素驱动的信号传导促进乳腺癌转移
• GSE319147 日本虻唾液腺 RNA-seq 分析
• GSE318977 腹腔注射 BSN-37 可激活 Balb/c 小鼠腹膜巨噬细胞并重塑 circRNA-mRNA 转录组
• GSE289716 纵向区域和细胞类型特异性免疫反应维持拟南芥根系抵抗病原体感染
• GSE274444 雌激素受体β靶基因表达揭示侵袭性乳腺癌中的新型抑制功能[sRNA-Seq]
• GSE268991 肿瘤及邻近正常人结直肠样本的转录谱和TCR序列
• GSE263163 鉴定胰腺癌球体中自噬的正向和负向调节因子。
• GSE263031 确定胰腺癌球体中 YAP1 结合基因的模式。
• GSE263002 胰腺癌细胞中基因表达谱与基线自噬通量水平高低相关 [Low-Auto_High-Auto_RNASeq]
• GSE263001 整合素α3 (ITGA3) 敲低对胰腺癌细胞基因表达的影响 [Scr_siITGA3_RNASeq]
• GSE263000 组成型 YAP1 激活对胰腺癌球体基因表达的影响 [EV_YS6A_RNASeq]
• GSE262999 NF2 缺失对胰腺癌球体基因表达的影响 [sgLUC_sgNF2_RNASeq]