GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice.

BACKGROUND: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro. METHODS: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 µg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway. RESULTS: The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway. CONCLUSIONS: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway.

The C1q and gC1qR axis as a novel checkpoint inhibitor in cancer.

Understanding at the molecular level of the cell biology of tumors has led to significant treatment advances in the past. Despite such advances however, development of therapy resistance and tumor recurrence are still unresolved major challenges. This therefore underscores the need to identify novel tumor targets and develop corresponding therapies to supplement existing biologic and cytotoxic approaches so that a deeper and more sustained treatment responses could be achieved. The complement system is emerging as a potential novel target for cancer therapy. Data accumulated to date show that complement proteins, and in particular C1q and its receptors cC1qR/CR and gC1qR/p33/HABP1, are overexpressed in most cancer cells and together are involved not only in shaping the inflammatory tumor microenvironment, but also in the regulation of angiogenesis, metastasis, and cell proliferation. In addition to the soluble form of C1q that is found in plasma, the C1q molecule is also found anchored on the cell membrane of monocytes, macrophages, dendritic cells, and cancer cells, via a 22aa long leader peptide found only in the A-chain. This orientation leaves its 6 globular heads exposed outwardly and thus available for high affinity binding to a wide range of molecular ligands that enhance tumor cell survival, migration, and proliferation. Similarly, the gC1qR molecule is not only overexpressed in most cancer types but is also released into the microenvironment where it has been shown to be associated with cancer cell proliferation and metastasis by activation of the complement and kinin systems. Co-culture of either T cells or cancer cells with purified C1q or anti-gC1qR has been shown to induce an anti-proliferative response. It is therefore postulated that in the tumor microenvironment, the interaction between C1q expressing cancer cells and gC1qR bearing cytotoxic T cells results in T cell suppression in a manner akin to the PD-L1 and PD-1 interaction.

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

The effect of illness perception on psychosocial adjustment of patients with breast cancer and their spouses: actor-partner independence model.

OBJECTIVE: With the increase in the prevalence rate and improvements in the survival of breast cancer patients, there is a growing interest in understanding the level of psychosocial adjustment in these patients. The study aimed to describe the illness perception and psychosocial adjustment levels of both breast cancer patients and their spouses, to use the Actor-Partner Interdependence Model (APIM) to clarify the actor-partner relationships between spouses, and to explore the impact of illness perception on psychosocial adjustment to the disease within the joint actions of both spouses. METHODS: A total of 216 female patients with breast cancer and their spouses participated in the study. They were selected from two tertiary hospitals in Guangdong Province, China from October 2022 to May 2023 using a convenience sampling method. The participants were assessed using the Brief Illness Perception Questionnaire and the Psychosocial Adjustment to Illness Scale to examine the relationship between illness perception and psychosocial adjustment. AMOS24.0 was used to test and analyze the actor-partner interdependence model. RESULTS: The illness perception score (57.75 ± 10.91) was slightly higher than that of the spouse (57.10 ± 11.00), and the psychosocial adjustment score (64.67 ± 6.33) was slightly lower than that of the spouse (64.76 ± 7.49). The results of the actor-partner interdependence model indicated that there was a couple partner between breast cancer patients and their spouses: the spouse's illness perception significantly affected the patient's psychosocial adjustment (ß = 0.095, p = 0.015); the patient's illness perception also significantly affected the spouse's psychosocial adjustment (ß = 0.106, p = 0.033). Among them, the patient's psychosocial adjustment was found to be related to the patient's illness comprehensibility or coherence of illness (ß = 0.433, p = 0.009), the spouse's emotional illness representation (ß = 0.218, p = 0.037), and the spouse's illness comprehensibility or coherence of illness (ß = 0.416, p = 0.007), while the spouse's psychosocial adjustment was only related to the spouse's illness comprehensibility or coherence of illness (ß = 0.528, p = 0.007). CONCLUSIONS: The psychosocial adjustment of breast cancer patients is affected by both their own and spouse's illness perception. Therefore, in the future, the healthcare staff can implement early psychological interventions for patients diagnosed with breast cancer and their spouses as a unit to promote the psychosocial adjustment of them.

Metabolic Regulation-Mediated Reversion of the Tumor Immunosuppressive Microenvironment for Potentiating Cooperative Metabolic Therapy and Immunotherapy.

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.

In Situ Formed Microalgae-Integrated Living Hydrogel for Enhanced Tumor Starvation Therapy and Immunotherapy through Photosynthetic Oxygenation.

The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) is developed to concurrently enhance hypoxia-constrained tumor starvation therapy and immunotherapy. The ACG gel is formed in situ following intratumoral injection of a biohybrid fluid composed of alginate, Chlorella sorokiniana, and glucose oxidase, facilitated by the crossing-linking between divalent ions within tumors and alginate. The microalgae Chlorella sorokiniana embedded in ACG gel generate abundant oxygen through photosynthesis, enhancing glucose oxidase-catalyzed glucose consumption and shifting the TME from immunosuppressive to immunopermissive status, thus reducing the tumor cell energy supply and boosting antitumor immunity. In murine 4T1 tumor models, the ACG gel significantly suppresses tumor growth and effectively prevents postoperative tumor recurrence. This study, leveraging microalgae as natural oxygenerators, provides a versatile and universal strategy for the development of oxygen-dependent tumor therapies.

Screening and functional analysis of StMYB transcription factors in pigmented potato under low-temperature treatment.

MYB transcription factors play an extremely important regulatory role in plant responses to stress and anthocyanin synthesis. Cloning of potato StMYB-related genes can provide a theoretical basis for the genetic improvement of pigmented potatoes. In this study, two MYB transcription factors, StMYB113 and StMYB308, possibly related to anthocyanin synthesis, were screened under low-temperature conditions based on the low-temperature-responsive potato StMYB genes family analysis obtained by transcriptome sequencing. By analyzed the protein properties and promoters of StMYB113 and StMYB308 and their relative expression levels at different low-temperature treatment periods, it is speculated that StMYB113 and StMYB308 can be expressed in response to low temperature and can promote anthocyanin synthesis. The overexpression vectors of StMYB113 and StMYB308 were constructed for transient transformation tobacco. Color changes were observed, and the expression levels of the structural genes of tobacco anthocyanin synthesis were determined. The results showed that StMYB113 lacking the complete MYB domain could not promote the accumulation of tobacco anthocyanins, while StMYB308 could significantly promote the accumulation involved in tobacco anthocyanins. This study provides a theoretical reference for further study of the mechanism of StMYB113 and StMYB308 transcription factors in potato anthocyanin synthesis.

Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis.

Tumor antigen-specific CD8+ T cells from draining lymph nodes gain an accumulating importance in mounting anti-tumor immune response during tumorigenesis. However, in many cases, cancer cells form metastatic loci in lymph nodes before further metastasizing to distant organs. To what extent the local and systematic CD8+ T cell responses were influenced by LN metastasis remains obscure. To this end, we set up a murine LN metastasis model combined with a B16F10-GP melanoma cell line expressing the surrogate neoantigen derived from lymphocytic choriomeningitis virus (LCMV), glycoprotein (GP), and P14 transgenic mice harboring T cell receptors (TCRs) specific to GP-derived peptide GP33-41 presented by the class I major histocompatibility complex (MHC) molecule H-2Db. This protocol enables the study of antigen-specific CD8+ T cell responses during LN metastasis. In this protocol, C57BL/6J mice were subcutaneously implanted with B16F10-GP cells, followed by adoptive transfer with naive P14 cells. When the subcutaneous tumor grew to approximately 5 mm in diameter, the primary tumor was excised, and B16F10-GP cells were directly injected into the tumor draining lymph node (TdLN). Then, the dynamics of CD8+ T cells were monitored during the process of LN metastasis. Collectively, this model has provided an approach to precisely investigate the antigen-specific CD8+ T cell immune responses during LN metastasis.

Mechanic study based on untargeted metabolomics of Pi-pa-run-fei-tang on pepper combined with ammonia induced chronic cough model mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Pi-pa-run-fei-tang (PPRFT), a traditional Chinese medicine formula with long-standing history, demonstrated beneficial effect on chronic cough. However, the mechanism underlying efficacy unclear. In current research, we explored the impact and molecular mechanism of chronic cough mouse stimulating with capsaicin combined with ammonia. AIM OF THE STUDY: To investigate the metabolic modulating effects, and potential mechanisms underlying the therapeutic effect of PPRFT in chronic cough. MATERIALS AND METHODS: Chronic cough mouse models were created by stimulating mice by capsaicin combined with ammonia. Number of coughs and cough latency within 2 min were recorded. With lung tissue and serum samples collected for histopathology, metabolomics, RT-qPCR, immunohistochemistry, and WB analysis. Lymphocytes were isolated and flow cytometric assays were conducted to evaluate the differentiation between Th17 and Treg cell among CD4+ cells. RESULTS: Results indicated that PPRFT obviously reduced the number of coughs, prolonged cough latency, reduced inflammatory cell infiltration and lung tissues damage, and decreased the serum level of IL-6, IL-1ß, TNF-α, and IL-17 while increasing IL-10 levels. Notably, PPRFT suppressed Th17 cell divergence and promoted Treg cell divergence. Furthermore, serum metabolomic assays showed that 46 metabolites differed significantly between group, with 35 pathways involved. Moreover, mRNA levels of IL-6, NF-κB, IL-17, RORγT, JAK2, STAT3, PI3K and AKT in lung tissues remarkably reduced and mRNA levels of IL-10 and FOXP3 were elevated after PPRFT pretreatment. Additionally, PPRFT treatments decreased the protein levels of IL-6, NF-κB, IL-17, RORγT, p-JAK2, p-STAT3, p-PI3K, and p-AKT and increased the protein levels of IL-10 and FOXP3, but no significantly effects to the levels on JAK2, STAT3, PI3K, and AKT in the lungs. CONCLUSION: Conclusively, our result suggested the effect with PPRFT on chronic cough may be mediated through IL-6/JAK2/STAT3 and PI3K/AKT/NF-κB pathway, which regulate the differentiation between Th17 and Treg cell. This beneficial effect of PPRFT in capsaicin and ammonia-stimulated chronic cough mice indicates its potential application in treating chronic cough.

A study integrated metabolomics and network pharmacology to investigate the effects of Shicao in alleviating acute liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Shicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases. AIM OF STUDY: To explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury. METHODS: A rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network. RESULTS: Compared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao. CONCLUSION: This study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.

Development and external validation of a quantitative diagnostic model for malignant gastric lesions in clinical opportunistic screening: A multicenter real-world study.

BACKGROUND: Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening. METHODS: We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial. RESULTS: This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750-0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570-0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios. CONCLUSION: This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Do patients with cN0 oral squamous cell carcinoma benefit from elective neck dissection? A large-scale population-based study.

BACKGROUND: The neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END. METHODS: Patients with cN0 OSCC were identified in the SEER database from 2000 to 2019. 5-year Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan‒Meier method, and the hazard ratios (HRs) for survival were estimated using the Cox regression model. Multiple subgroup analyses of DSS and OS among different factors, comparing END and No END, were performed. RESULTS: A total of 17,019 patients with cN0 OSCC were included. The basic survival analysis and Cox regression model showed that END increased the probability of 5-year DSS and OS and was an independent prognostic factor. However, among patients who underwent only primary tumor surgery, no significant differences were found between the END and No END groups in 5-year DSS (P = 0. 585) and OS (P = 0.465). Further subgroup analysis showed that primary sites and T stage, but not other factors, might influence the benefit of END. Significant differences were found for T1 (P < 0.001 for OS) and T2 (P = 0.001 for DSS and < 0.001 for OS) tongue squamous cell carcinoma (TSCC) but not for other primary tumor sites. CONCLUSION: This large-scale retrospective population-based cohort study suggests that not all patients with cN0 OSCC could benefit from END. Patients with cN0 TSCC are recommended to undergo END, especially with early-stage tumors.

Chronic restraint stress promotes oral squamous cell carcinoma development by inhibiting ALDH3A1 via stress response hormone.

BACKGROUND: Chronic restraint stress (CRS) has iteratively been reported to be possibly implicated in the development of numerous cancer types. However, its role in oral squamous cell carcinoma (OSCC) has not been well elucidated. Here we intended to evaluate the role and mechanism. METHODS: The effects of CRS were investigated in xenograft models of OSCC by using transcriptome sequencing, LC-MS, ELISA and RT-PCR. Moreover, the role of CRS and ALDH3A1 on OSCC cells was researched by using Trans-well, flow cytometry, western blotting, immunofluorescence, ATP activity and OCR assay. Furthermore, immunohistochemical staining was employed to observe the cell proliferation and invasion of OSCC in xenotransplantation models. RESULTS: CRS promoted the progression of OSCC in xenograft models, stimulated the secretion of norepinephrine and the expression of ADRB2, but decreased the expression of ALDH3A1. Moreover, CRS changed energy metabolism and increased mitochondrial metabolism markers. However, ALDH3A1 overexpression suppressed proliferation, EMT and mitochondrial metabolism of OSCC cells. CONCLUSION: Inhibition of ALDH3A1 expression plays a pivotal role in CRS promoting tumorigenic potential of OSCC cells, and the regulatory of ALDH3A1 on mitochondrial metabolism may be involved in this process.

Dendritic Cell-Based In Situ Nanovaccine for Reprogramming Lipid Metabolism to Boost Tumor Immunotherapy.

Cancer vaccines have been considered to be an alternative therapeutic strategy for tumor therapy in the past decade. However, the popularity and efficacy of cancer vaccines were hampered by tumor antigen heterogeneity and the impaired function of cross-presentation in the tumor-infiltrating dendritic cells (TIDCs). To overcome these challenges, we engineered an in situ nanovaccine (named as TPOP) based on lipid metabolism-regulating and innate immune-stimulated nanoparticles. TPOP could capture tumor antigens and induce specific recognition by TIDCs to be taken up. Meanwhile, TPOP could manipulate TIDC lipid metabolism and inhibit de novo synthesis of fatty acids, thus improving the ability of TIDCs to cross-present by reducing their lipid accumulation. Significantly, intratumoral injection of TPOP combined with pretreatment with doxorubicin showed a considerable therapeutic effect in the subcutaneous mouse colorectal cancer model and melanoma model. Moreover, in combination with immune checkpoint inhibitors, such TPOP could markedly inhibit the growth of distant tumors by systemic antitumor immune responses. This work provides a safe and promising strategy for improving the function of immune cells by manipulating their metabolism and activating the immune system effectively for in situ cancer vaccines.

Metabolic Patterns of High-Invasive and Low-Invasive Oral Squamous Cell Carcinoma Cells Using Quantitative Metabolomics and 13C-Glucose Tracing.

Most current metabolomics studies of oral squamous cell carcinoma (OSCC) are mainly focused on identifying potential biomarkers for early screening and diagnosis, while few studies have investigated the metabolic profiles promoting metastasis. In this study, we aimed to explore the altered metabolic pathways associated with metastasis of OSCC. Here, we identified four OSCC cell models (CAL27, HN6, HSC-3, SAS) that possess different invasive heterogeneity via the transwell invasion assay and divided them into high-invasive (HN6, SAS) and low-invasive (CAL27, HSC-3) cells. Quantitative analysis and stable isotope tracing using [U-13C6] glucose were performed to detect the altered metabolites in high-invasive OSCC cells, low-invasive OSCC cells and normal human oral keratinocytes (HOK). The metabolic changes in the high-invasive and low-invasive cells included elevated glycolysis, increased fatty acid metabolism and an impaired TCA cycle compared with HOK. Moreover, pathway analysis demonstrated significant differences in fatty acid biosynthesis; arachidonic acid (AA) metabolism; and glycine, serine and threonine metabolism between the high-invasive and low-invasive cells. Furthermore, the high-invasive cells displayed a significant increase in the percentages of 13C-glycine, 13C-palmitate, 13C-stearic acid, 13C-oleic acid, 13C-AA and estimated FADS1/2 activities compared with the low-invasive cells. Overall, this exploratory study suggested that the metabolic differences related to the metastatic phenotypes of OSCC cells were concentrated in glycine metabolism, de novo fatty acid synthesis and polyunsaturated fatty acid (PUFA) metabolism, providing a comprehensive understanding of the metabolic alterations and a basis for studying related molecular mechanisms in metastatic OSCC cells.

Unmasking the Silent Invader: A Rare Case of Follicular Thyroid Carcinoma With Skull Metastasis and an Uncommon KRAS Q61R Mutation.

Follicular thyroid carcinoma (FTC) is a noteworthy subtype of thyroid cancer known for its tendency to metastasize through the bloodstream, usually to the lungs and bones. This case report examines an exceptionally rare instance involving an 81-year-old female presenting with an unusual metastatic scalp lesion. Remarkably, this aggressive metastasis originated from a thyroid lesion as small as 0.7 cm. Lab findings, including suppressed TSH and elevated T3 levels, revealed subclinical hyperthyroidism, adding another layer of rarity to this FTC case. Molecular profiling identified a rare KRAS Q61R mutation, providing potential insight into the case's aggressive behavior and underscoring the importance of genetic assessment in FTC. This report emphasizes the critical role of comprehensive diagnostic evaluations, including histopathological assessments, in properly diagnosing and managing FTC, especially when clinical presentations defy conventional paradigms.

Immune pathway activation in neurons triggers neural damage after stroke.

Ischemic brain injury is a severe medical condition with high incidences in elderly people without effective treatment for the resulting neural damages. Using a unilateral mouse stroke model, we analyze single-cell transcriptomes of ipsilateral and contralateral cortical penumbra regions to objectively reveal molecular events with single-cell resolution at 4 h and 1, 3, and 7 days post-injury. Here, we report that neurons are among the first cells that sense the lack of blood supplies by elevated expression of CCAAT/enhancer-binding protein ß (C/EBPß). To our surprise, the canonical inflammatory cytokine gene targets for C/EBPß, including interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α), are subsequently induced also in neuronal cells. Neuronal-specific silencing of C/EBPß or IL-1ß and TNF-α substantially alleviates downstream inflammatory injury responses and is profoundly neural protective. Taken together, our findings reveal a neuronal inflammatory mechanism underlying early pathological triggers of ischemic brain injury.

Macrophage-hitchhiked arsenic/AB bionic preparations for liver cancer.

Macrophage-hitchhiked arsenic/AB bionic preparations were developed to improve the therapeutic effect on liver cancer by means of the tumor-targeting ability of macrophages in vivo. In vitro and in vivo cellular uptake assays demonstrated that arsenic/AB, with negatively charged particles of around 100-200 nm size, could hitchhike to macrophages. Dissolution experiments of arsenic/AB showed that arsenic/AB could delay the release of arsenic and ensure the safety of macrophages during its transport. Histological examination confirmed the safety of the preparations for major organs. In vivo distribution experiment showed that the arsenic/AB bionic preparations could rapidly accumulate in tumors, and in vivo treatment experiment showed a significant tumor inhibition of arsenic/AB. The therapeutic mechanism of liver cancer might be that the arsenic/AB bionic preparations could inhibit tumor growth by reducing inflammatory response and inhibiting CSF1 secretion to block CSF1R activation to induce more differentiation of tumor-associated macrophages (TAMs) towards the anti-tumor M1 phenotype. Therefore, we concluded that the arsenic/AB bionic preparations could improve the distribution of arsenic in vivo by hitchhiking on macrophages as well as make it have tumor targeting and deep penetration abilities, thus increasing the therapeutic effect of arsenic on liver cancer with reduced side effects.