Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer.

BACKGROUND: Cancer is one of the most serious threats to human health worldwide. Conventional treatments such as surgery and chemotherapy are associated with some drawbacks. In recent years, traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians, and has become an indispensable part of the comprehensive treatment for gastric cancer. AIM: To investigate the mechanism of Xiaojianzhong decoction (XJZ) in the treatment of gastric cancer (GC) by utilizing network pharmacology and experimental validation, so as to provide a theoretical basis for later experimental research. METHODS: We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics. Subsequently, we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8, apoptosis, cell cycle, and clone formation assays. Additionally, we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins. RESULTS: XJZ mainly regulates IL6, PTGS2, CCL2, MMP9, MMP2, HMOX1, and other target genes and pathways in cancer to treat GC. The inhibition of cell viability, the increase of apoptosis, the blockage of the cell cycle at the G0/G1 phase, and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment. In addition, XJZ induced a decrease in the mRNA expression of IL6, PTGS2, MMP9, MMP2, and CCL2, and an increase in the mRNA expression of HOMX1. XJZ significantly inhibited the expression of IL6, PTGS2, MMP9, MMP2, and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein. CONCLUSION: XJZ exerts therapeutic effects against GC through multiple components, multiple targets, and multiple pathways. Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

Immobilizing lead in aqueous solution and loess soil using microbially induced carbonate/phosphate precipitation (MICP/MIPP) under harsh pH environments.

The bioaccumulation of heavy metals due to metallurgical and smelting activities threatens human health. Although microbial-induced carbonate/phosphate precipitation (MICP/MIPP) technology has been applied to heavy metal remediation, the relative merits of MICP and MIPP, especially under extreme pH environments, have not yet been documented. In this study, Sporosarcina pasteurii (SP)-based MICP and Bacillus megaterium (BM)-based MIPP were applied to immobilize lead (Pb) in aqueous solution and loess soil. The results showed that the BM retained a strong phosphorolysis ability when under strongly acidic conditions, while the ureolysis ability of SP approached zero. Furthermore, the bioprecipitates obtained under BM-based MIPP had a denser appearance, presumably due to the enrichment of calcite and apatite crystals. The results also showed that Pb immobilization was achieved through bacterial adsorption, the chelate function of sodium glycerophosphate (SGP), large organic matter complexation, and biomineralization through the MICP/MIPP mechanism. Under SP-based MICP, SP and large organic matter immobilized Pb2+ at rates of 17.6 % and 31.7 %, respectively, while under BM-based MIPP, BM, organic matter, and SGP immobilized Pb2+ at rates of 21.5 %, 23.4 %, and 48.5 % respectively. The MICP and MIPP mechanisms dominated Pb immobilization at rates of 78.6 % and 99.6 %, respectively.

Nickel-Catalyzed Stereoconvergent C(sp2)-F Alkenylation of Monofluoroalkenes.

The stereoconvergent synthesis of a single stereoisomer from E/Z-olefin mixtures remains one of the foremost challenges in organic synthesis. Herein, we describe a nickel-catalyzed stereoconvergent cross-coupling between E- and Z-mixed monofluoroalkenes and alkenyl electrophiles, which allows the construction of C(sp2)-C(sp2) bonds. This defluorinative transformation offers facile access to various 1,3-dienes with E-selectivity and good functional group tolerance. Preliminary mechanistic studies indicate that the reaction most likely proceeds through a migratory insertion/ß-F elimination/isomerization process.

Visible-Light-Driven Iron-Catalyzed 1,2-Difluoroalkylthiolation of Alkenes.

The synthesis of medicinally interesting aryldifluoromethylated compounds has drawn significant research attention in recent years. Herein, we report an unprecedented iron-mediated process for the selective defluorination of trifluoromethylarenes to achieve the 1,2-difluoroalkylthiolation of alkenes. Preliminary mechanistic studies revealed that thiolate anion, trifluoromethylarene, and iron cation could form an electron donor-acceptor (EDA) complex, which induced selective defluorination and then difunctionalization of alkenes to obtain aryldifluoromethylated products. The generated aryldifluoromethylated compounds make it difficult to form an EDA complex again, thus avoiding excessive defluorination. This conversion has concise and ambient reaction conditions and provides an alternative solution for obtaining difluorobenzylic intermediates.

Low Levels of Natural Killer Cell in Newly Diagnosed Myelodysplastic Syndromes Patients May Confer Poor Prognosis: A Retrospective Cohort Study.

Background: Immune imbalance appears to have a critical role in tumor growth according to emerging research. Peripheral lymphocyte subsets are considered to reflect the systemic immune response and clinical prognosis. The prognostic value of lymphocyte subpopulations in myelodysplastic syndrome (MDS) patients remains unclear. Methods: A total of 94 MDS patients were enrolled for the study. X-tile software was performed to determine the prognostic significance of various lymphocyte subpopulations, CD3, CD4, CD8, CD4/CD8 ratio, natural killer cell (NK) and CD19. Among them, the appropriate threshold of NK percent could be found only. Patients were divided into the high NK percent group and the low NK percent group. The prognostic significance was determined by univariate and multivariate Cox hazard models. Results: MDS patients with lower NK level had significantly shorter overall survival (OS). Based on univariate analysis, male gender (P = 0.030), lower HB (<10 g/dl, P = 0.029), higher BM blast (>5%, P < 0.0001), higher-risk IPSS-R cytogenetic (P = 0.032) and lower NK percent (P < 0.0001) were significantly associated with shorter OS. Multivariate Cox proportional hazards regression analysis indicated that low NK was also independent adverse prognostic factor for OS in MDS. Conclusion: Decreased NK level predicts poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.

MicroRNA-138 promotes the progression of multiple myeloma through targeting paired PAX5.

BACKGROUND: Multiple myeloma cancer stem cells (MMSC) have been considered as the leading cause of multiple myeloma (MM) drug resistance and eventual relapse, microRNAs (miRNAs) collectively participate in the progression of MM. However, the pathogenesis of miR-138 in MMSC is still not fully understood. OBJECTIVE: The intention of this study was to investigate the mechanism and role of miR-138 in multiple myeloma. METHOD: Bone marrow samples and peripheral blood from patients and normal controls were collected. Use Magnet-based Cancer Stem Cell Isolation Kit to separate and extract MMSC. Real-time quantitative PCR (RT-qPCR) was carried out to determine mRNA level. Western blot was applied to detect protein levels. MTT and flow cytometry were conducted to examine the proliferation and apoptosis of MMSC. Finally, dual-luciferase reporter gene assays were performed to confirm that paired box 5 (PAX5) is a direct target for miR-138. RESULTS: Compared with normal group, the expression of miR-138 in patients was significantly up-regulated, and the expression of miR-138 was in a negative correlation with PAX5. Additionally, downregulated miR-138 facilitated the apoptosis and inhibited the proliferation of MMSC in vitro and in vivo. Downregulated miR-138 moderated the expression of PAX5, Bcl-2, Bax, and Caspase-3. PAX5 was a direct target of miR-138. CONCLUSION: Taken together, miR-138 plays a carcinogenic role in MM, and miR-138 adjusted the proliferation and apoptosis of MMSC by targeting PAX5. miR-138 has the probability of becoming a new medicinal target for the treatment of MM.

MorphBungee: A 65-nm 7.2-mm2 27-µJ/image Digital Edge Neuromorphic Chip with On-Chip 802-frame/s Multi-Layer Spiking Neural Network Learning.

This paper presents a digital edge neuromorphic spiking neural network (SNN) processor chip for a variety of edge intelligent cognitive applications. This processor allows high-speed, high-accuracy and fully on-chip spike-timing-based multi-layer SNN learning. It is characteristic of hierarchical multi-core architecture, event-driven processing paradigm, meta-crossbar for efficient spike communication, and hybrid and reconfigurable parallelism. A prototype chip occupying an active silicon area of 7.2 mm2 was fabricated using a 65-nm 1P9M CMOS process. when running a 256-256-256-256-200 4-layer fully-connected SNN on downscaled 16 × 16 MNIST images. it typically achieved a high-speed throughput of 802 and 2270 frames/s for on-chip learning and inference, respectively, with a relatively low power dissipation of around 61 mW at a 100 MHz clock rate under a 1.0V core power supply, Our on-chip learning results in comparably high visual recognition accuracies of 96.06%, 83.38%, 84.53%, 99.22% and 100% on the MNIST, Fashion-MNIST, ETH-80, Yale-10 and ORL-10 datasets, respectively. In addition, we have successfully applied our neuromorphic chip to demonstrate high-resolution satellite cloud image segmentation and non-visual tasks including olfactory classification and textural news categorization. These results indicate that our neuromorphic chip is suitable for various intelligent edge systems under restricted cost, energy and latency budgets while requiring in-situ self-adaptative learning capability.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation.

BACKGROUND: Yigong San (YGS) is a representative prescription for the treatment of digestive disorders, which has been used in clinic for more than 1000 years. However, the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear. AIM: To explore the mechanism of YGS anti-gastric cancer and immune regulation. METHODS: Firstly, collect the active ingredients and targets of YGS, and the differentially expressed genes of gastric cancer. Secondly, constructed a protein-protein interaction network between the targets of drugs and diseases, and screened hub genes. Then the clinical relevance, mutation and repair, tumor microenvironment and drug sensitivity of the hub gene were analyzed. Finally, molecular docking was used to verify the binding ability of YGS active ingredient and hub genes. RESULTS: Firstly, obtained 55 common targets of gastric cancer and YGS. The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6, EGFR, MMP2, MMP9 and TGFB1 as the hub genes. The 5 hub genes were involved in gastric carcinogenesis, staging, typing and prognosis, and their mutations promote gastric cancer progression. Finally, molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets. CONCLUSION: YGS has the effect of anti-gastric cancer and immune regulation.

Elevated pretreatment serum apolipoprotein E level associated with poor prognosis of patients with COVID-19 during the omicron BA.5 and BF.7 wave.

The SARS-CoV-2 virus is responsible for the human disease known as COVID-19. This virus is capable of generating a spectrum of infections ranging from moderate to severe. Serum apolipoprotein E (ApoE) inhibits inflammation by preserving immune regulatory function. Nonetheless, the relationship between serum ApoE and clinical prognosis in omicron remains elusive. A cohort of 231 patients was observed for 65 days, with death as the primary outcome. Based on their ApoE levels, the patients were categorized into patients with elevated ApoE levels and those with lower ApoE levels. To do statistical comparisons, the log-rank test was utilized, and the Kaplan-Meier method was utilized to estimate survival rates. Cox hazard models, both univariate and multivariate, were employed to examine the prognostic relevance. According to our research, omicron had significantly greater ApoE levels. In mild-to-moderate and severe cases, the study identified a statistically significant variation in ApoE levels. Additionally, there was a drop in overall survival that is statistically significant (OS, p < 0.0001) for patients with greater ApoE levels. Multiple Cox proportional hazards regression analysis indicates that an elevated ApoE level was determined to be an adverse and independent prognostic factor of OS in patients with omicron. Taken together, our study found that the level of serum ApoE at the time of initial diagnosis was substantially connected to the severity and prognosis of omicron. Consequently, we propose that ApoE might be a poor prognostic factor in individuals afflicted with the omicron variant.

GLYR1 transcriptionally regulates PER3 expression to promote the proliferation and migration of multiple myeloma.

Period circadian regulator 3 (PER3) functions as a tumor suppressor in various cancers. However, the role of PER3 in multiple myeloma (MM) has not been reported yet. Through this study, we aimed to investigate the potential role of PER3 in MM and the underlying mechanisms. RT-qPCR and western blotting were used to determine the mRNA and protein expression levels of PER3. Glyoxylate reductase 1 homolog (GLYR1) was predicted to be a transcription factor of PER3. The binding sites of GLYR1 on the promoter region of PER3 were analyzed using UCSC and confirmed using luciferase and chromatin immunoprecipitation assays. Viability, apoptosis, and metathesis were determined using CCK-8, colony formation, TUNEL, and transwell assays. We found that PER3 expression decreased in MM. Low PER3 levels may predict poor survival rates; PER3 overexpression suppresses the viability and migration of MM cells and promotes apoptosis. Moreover, GLYR1 transcriptionally activates PER3, and the knockdown of PER3 alleviates the effects of GLYR1 and induces its malignant behavior in MM cells. To conclude, GLYR1 upregulates PER3 and suppresses the aggressive behavior of MM cells, suggesting that GLYR1/PER3 signaling may be a potential therapeutic target for MM.

Radical Addition-Enabled C-C σ-Bond Cleavage/Reconstruction to Access Functional Indanones: Total Synthesis of Carexane L.

C-C σ-bond cleavage and reconstruction is a significant tool for structural modification in synthetic chemistry but it remains a formidable challenge to perform on unstrained skeletons. Herein, we describe a radical addition-enabled C-C σ-bond cleavage/reconstruction reaction of unstrained allyl ketones to access various functional indanones bearing a benzylic quaternary center. The synthetic utility of this method has been showcased by the first total synthesis of carexane L, an indanone-based natural product.

Analysis of factors affecting the prognosis of patients with intrauterine adhesions after transcervical resection of adhesions.

OBJECTIVES: To study the factors affecting the prognosis of patients with intrauterine adhesions (IUAs) after transcervical resection of adhesions (TCRA), analyze the reproductive outcome, and guide prognostic improvements. DESIGN: Prospective study. PATIENTS: Our study included 292 patients diagnosed with IUAs who underwent follow-up office hysteroscopy at Shenyang Women's and Children's Hospital between June 2018 and June 2022. INTERVENTIONS: Patients were divided into case (52 patients whose hysteroscopy results indicated the presence of IUAs) and nocase (240 patients whose uterine cavity had returned to normal shape without obvious adhesion) groups on the basis of the results of a 2-month follow-up hysteroscopy following TCRA. Clinical data were collected and compared with various influencing factors, and the combined effect of these factors was assessed using multifactorial logistic regression analysis. A nomogram prediction model was constructed and internally validated on the basis of multifactorial analysis. MAIN OUTCOME MEASURES: Intrauterine re-adhesion was observed at a 2-month follow-up after TCRA. RESULTS: Postoperative re-adhesion occurred in 52 of 292 patients with IUAs. Multifactorial binary logistic regression analysis showed that IUA barrier gel reapplication 5 days after TCRA was a protective factor. In contrast, the preoperative American Fertility Society scores demonstrated that severe IUAs and chronic endometritis were risk factors. The results of the multifactorial analysis were used to build a nomogram model, and the area under the curve value of the nomogram model for predicting postoperative recurrence was 0.914 (95% confidence interval: 0.864-0.956). The bootstrap method was subsequently used to resample 1,000 times for internal validation. The results showed that the internal validation C-index was 0.9135, and the calibration and ideal curves were well-matched. CONCLUSION: The prognosis of patients with IUAs after TCRA is related to the severity of preoperative IUAs, presence of chronic endometritis, and IUA barrier gel reapplication 5 days after TCRA. Therefore, clinicians should monitor patients using targeted data to reduce recurrence risk after TCRA and improve the prognosis of patients with IUAs.

Concurrent JCPyV-DNAemia Is Correlated With Poor Graft Outcome in Kidney Transplant Recipients With Polyomavirus-associated Nephropathy.

BACKGROUND: Co-infection of JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) is uncommon in kidney transplant recipients, and the prognosis is unclear. This study aimed to investigate the effect of concurrent JCPyV-DNAemia on graft outcomes in BKPyV-infected kidney transplant recipients with polyomavirus-associated nephropathy (PyVAN). METHODS: A total of 140 kidney transplant recipients with BKPyV replication and PyVAN, 122 without concurrent JCPyV-DNAemia and 18 with JCPyV-DNAemia were included in the analysis. Least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to identify prognostic factors for graft survival. A nomogram for predicting graft survival was created and evaluated. RESULTS: The median tubulitis score in the JCPyV-DNAemia-positive group was higher than in JCPyV-DNAemia-negative group ( P  = 0.048). At last follow-up, the graft loss rate in the JCPyV-DNAemia-positive group was higher than in the JCPyV-DNAemia-negative group (50% versus 25.4%; P  = 0.031). Kaplan-Meier analysis showed that the graft survival rate in the JCPyV-DNAemia-positive group was lower than in the JCPyV-DNAemia-negative group ( P  = 0.003). Least absolute shrinkage and selection operator regression and multivariate Cox regression analysis demonstrated that concurrent JCPyV-DNAemia was an independent risk factor for graft survival (hazard ratio = 4.808; 95% confidence interval: 2.096-11.03; P  < 0.001). The nomogram displayed favorable discrimination (C-index = 0.839), concordance, and clinical applicability in predicting graft survival. CONCLUSIONS: Concurrent JCPyV-DNAemia is associated with a worse graft outcome in BKPyV-infected kidney transplant recipients with PyVAN.

Xinshubao tablet rescues cognitive dysfunction in a mouse model of vascular dementia: Involvement of neurogenesis and neuroinflammation.

Vascular dementia (VaD) represents a severe cognitive dysfunction syndrome closed linked to cardiovascular function. In the present study, we assessed the potential of Xinshubao tablet (XSB), a traditional Chinese prescription widely used for cardiovascular diseases, to mitigate neuropathological damage in a mouse model of VaD and elucidated the underlying mechanisms. Our findings revealed that oral administration of XSB rescued the cardiac dysfunction resulting from bilateral common carotid artery stenosis (BCAS), improved the cerebral blood flow (CBF) and cognitive function, reduced white matter injury, inhibited excessive microglial and astrocytic activation, stimulated hippocampal neurogenesis, and reduced neural apoptosis in the brains of BCAS mice. Mechanistically, RNA-seq analysis indicated that XSB treatment was significantly associated with neuroinflammation, vasculature development, and synaptic transmission, which were further confirmed by q-PCR assays. Western blot results revealed that XSB treatment hindered the nuclear translocation of nuclear factor-κB (NF-κB), thereby suppressing the NF-κB signaling pathway. These results collectively demonstrated that XSB could ameliorate cognitive dysfunction caused by BCAS through regulating CBF, reducing white matter lesions, suppressing glial activation, promoting neurogenesis, and mitigating neuroinflammation. Notably, the NF-κB signaling pathway emerged as a pivotal player in this mechanism.

Phenolic compounds induce ferroptosis-like death by promoting hydroxyl radical generation in the Fenton reaction.

Phenolic compounds are industrially versatile chemicals, also the most ubiquitous pollutants. Recently, biosynthesis and biodegradation of phenols has attracted increasing attention, while phenols' toxicity is a major issue. Here, we evolved phloroglucinol-tolerant Escherichia coli strains via adaptive evolution, and three mutations (ΔsodB, ΔclpX and fetAB overexpression) prove of great assistance in the tolerance improvement. We discover that phloroglucinol complexes with iron and promotes the generation of hydroxyl radicals in Fenton reaction, which leads to reducing power depletion, lipid peroxidation, and ferroptosis-like cell death of E. coli. Besides phloroglucinol, various phenols can trigger ferroptosis-like death in diverse organisms, from bacteria to mammalian cells. Furthermore, repressing this ferroptosis-like death improves phloroglucinol production and phenol degradation by corresponding strains respectively, showing great application potential in microbial degradation or production of desired phenolic compounds, and phloroglucinol-induced ferroptosis suppresses tumor growth in mice, indicating phloroglucinol as a promising drug for cancer treatment.

Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification.

BACKGROUND: Pachymic acid (PA) is derived from Poria cocos. PA has a variety of pharmacological and inhibitory effects on various tumors. However, the mechanism of action of PA in gastric cancer (GC) remains unclear. AIM: To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification. METHODS: The GeneCards and OMIM databases were used to derive the GC targets, while the Pharm Mapper database provided the PA targets. Utilizing the STRING database, a protein-protein interaction network was constructed and core targets were screened. The analyses of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis were conducted, and molecular docking and clinical correlation analyses were performed on the core targets. Ultimately, the network pharmacology findings were validated through in vitro cell assays, encompassing assessments of cell viability, apoptosis, cell cycle, cloning, and western blot analysis. RESULTS: According to network pharmacology analysis, the core targets were screened, and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC, according to KEGG enrichment analysis. The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation, induce apoptosis, and pause the cell cycle. CONCLUSION: Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets. This has also been supported by in vitro cell studies, which serve as benchmarks for further research.

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10, MC38 and Hep1-6 Tumor Models.

OBJECTIVE: To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model. METHODS: Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment. RESULTS: PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4+ T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8+ T cells (P<0.01 or P<0.05). CONCLUSION: This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Down-regulation of Musashi-2 exerts antileukemic effects on acute lymphoblastic leukemia cells and increases sensitivity to dexamethasone.

Musashi-2 (MSI2), implicated in the oncogenesis and propagation of a broad array of malignancies, inclusive of certain leukemia, remains a nascent field of study within the context of acute lymphoblastic leukemia (ALL). Using lentiviral transfection, ALL cells with stable MSI2 knockdown were engineered. A suite of analytic techniques - a CCK-8 assay, flow cytometry, qRT-PCR, and western blotting - were employed to evaluate cellular proliferation, cell cycle arrest, and apoptosis and to confirm differential gene expression. The suppression of MSI2 expression yielded significant results: inhibition of cell proliferation, G0/G1 cell cycle arrest, and induced apoptosis in ALL cell lines. Furthermore, it was noted that MSI2 inhibition heightened the responsiveness of ALL cells to dexamethasone. Significantly, the depletion of MSI2 prompted the translocation of GR from the cytoplasm to the nucleus upon dexamethasone treatment, consequently leading to enhanced sensitivity. Additionally, the FOXO1/4 signaling pathway contributed to the biological effects of ALL cells evoked by MSI2 silencing. Our study offers novel insight into the inhibitory effects of MSI2 suppression on ALL cells, positing MSI2 as a promising therapeutic target in the treatment of ALL.

Characterizing Genetic Alterations Related to Radioiodine Avidity in Metastatic Thyroid Cancer.

CONTEXT: Patients with differentiated thyroid cancer (DTC) with distant metastasis (DM) are usually not recognized as radioactive iodine (RAI)-refractory DTC in a timely manner. The elucidation of genetic features related to RAI uptake patterns may shed light on the early recognition of RAI-refractory DTC. OBJECTIVE: This work aimed to elucidate the underlying molecular features behind different RAI uptake patterns. METHODS: A total of 214 patients with DM-DTC were retrospectively included in the analysis. RAI uptake patterns were defined as initially RAI refractory (I-RAIR) and initially RAI avid (I-RAIA) according to the first post-treatment scan, then I-RAIA was further divided into continually RAIA (C-RAIA), partly RAIR (P-RAIR), and gradually RAIR (G-RAIR) according to subsequent scans. The molecular subtype groups-BRAFV600E mutated, RAS mutated, fusions, and others-were classified according to main driver genes status. RESULTS: BRAF, TERT promoter, and TP53 mutations are more frequently detected in the I-RAIR pattern while RET fusions and RAS mutations are more frequent in the I-RAIA pattern. A late-hit mutation including TERT, TP53, or PIK3CA is more common in I-RAIR than that in I-RAIA (50.0% vs 26.9%, P = .001), particularly for those with RAS mutations in the I-RAIR group, always accompanied by TERT promoter. Isolated RET fusions accounts for 10% of I-RAIR. When compared among driver gene groups, BRAFV600E-mutated tumors have a higher rate of the I-RAIR pattern (64.4%) than RAS-mutated (4.5%, P < .001) and fusion-positive (20.7%, P < .001) tumors. In I-RAIA subgroups, BRAFV600E-mutated tumors have lower prevalence of the C-RAIA pattern than those with RAS mutation or fusions. CONCLUSION: Patients with the I-RAIR pattern predominantly featured mutations of the BRAF and/or TERT promoter, of which RAS mutations were usually accompanied by late-hit mutations, while fusions mostly occurred alone.

Research progress of ginger in the treatment of gastrointestinal tumors.

Cancer seriously endangers human health. Gastrointestinal cancer is the most common and major malignant tumor, and its morbidity and mortality are gradually increasing. Although there are effective treatments such as radiotherapy and chemotherapy for gastrointestinal tumors, they are often accompanied by serious side effects. According to the traditional Chinese medicine and food homology theory, many materials are both food and medicine. Moreover, food is just as capable of preventing and treating diseases as medicine. Medicine and food homologous herbs not only have excellent pharmacological effects and activities but also have few side effects. As a typical medicinal herb with both medicinal and edible uses, some components of ginger have been shown to have good efficacy and safety against cancer. A mass of evidence has also shown that ginger has anti-tumor effects on digestive tract cancers (such as gastric cancer, colorectal cancer, liver cancer, laryngeal cancer, and pancreatic cancer) through a variety of pathways. The aim of this study is to investigate the mechanisms of action of the main components of ginger and their potential clinical applications in treating gastrointestinal tumors.