Severe pneumonia with pleural effusion caused by co-infection of Paecilomyces variotii and Penicillium oxalicum in a diabetic patient.

BACKGROUND PAECILOMYCES: and Penicillium are considered as rare opportunistic pathogens in immunocompromised hosts, and pneumonia caused by Paecilomyces and Penicillium is rare. In this study, we present first case of severe pneumonia with pleural effusion caused by co-infection of Paecilomyces variotii (P. variotii) and Penicillium oxalicum (P. oxalicum) in a 66-year-old female with poorly controlled type 2 diabetes. CASE PRESENTATION: A 56-year-old woman patient presented to hospital for nausea, poor appetite, and vomiting for one day. On the second day of admission, blood culture and renal puncture fluid culture grew multidrug-resistant Escherichia coli (imipenem/cilastatin sensitive), and she received combination therapy with imipenem/cilastatin (1 g, every 8 h) and vancomycin (0.5 g, every 12 h). On the fourth day, she developed symptoms of respiratory failure. Pulmonary computed tomography (CT) showed an increase in pneumonia compared to before, with minor pleural effusion on both sides. Two fungi were isolated repeatedly from BALF culture, which were confirmed as P. variotii and P. oxalicum by Internal transcribed spacer (ITS) sequencing. Her pleural effusion was completely absorbed, pneumonia symptoms have significantly improved and discharged with receiving liposomal amphotericin B treatment for four weeks. CONCLUSIONS: It is worth noting that clinicians and laboratory personnel should not simply consider Paecilomyces and Penicillium species as contaminants, especially in immunocompromised patients. Early fungal identification and antifungal drug sensitivity are crucial for clinical drug selection and patient prognosis.

Potential Risk Factors of Disorders of Gut-Brain Interaction in Undergraduates and Postgraduates: Partially Mediated by Life Stress and Lifestyle.

INTRODUCTION: This study aimed to investigate the prevalence of disorders of gut-brain interaction (DGBI) and life stress in college students, and explore risk factors of DGBI in college students and the role of life stress. METHODS: A total of 2,578 college students filled up validated questionnaires assessing GI symptoms, lifestyle, and life stress. Participants were diagnosed as DGBI based on the Rome III criteria. Multivariate ordinal logistic regression analysis and mediation effect model were employed to explore potential risk factors of DGBI and the mediating role of life stress and lifestyle in DGBI. RESULTS: A total of 437 of 2,578 (17.0%) college students were diagnosed with DGBI. College students with DGBI had higher levels of life stress, including eight specific categories. Females (1.709 [1.437, 2.033]), staying up late (1.519 [1.300, 1.776]), and life stress (1.008 [1.006, 1.010]) were risk factors for DGBI, while postgraduates (0.751 [0.578, 0.976]) and regular diet (0.751 [0.685, 0.947]) were protective factors. Males and poor family economic were associated with a higher risk of DGBI after controlling stress, while an association between grade and DGBI was mediated by stress, regular diet, and sleep habits. CONCLUSION: DGBI was common among college students. Life stress and lifestyle were associated with DGBI and mediated partial association between grade and DGBI in college students. More attention should be paid to undergraduates.

Nardosinone relieves metabolic-associated fatty liver disease and promotes energy metabolism through targeting CYP2D6.

BACKGROUND: Nardosinone, a major extract of Rhizoma nardostachyos, plays a vital role in sedation, neural stem cell proliferation, and protection of the heart muscle. However, the huge potential of nardosinone in regulating lipid metabolism and gut microbiota has not been reported, and its potential mechanism has not been studied. PURPOSE: To explore the regulation of nardosinone on liver lipid metabolism and gut microbiota. METHODS: In this study, the role of nardosinone in lipid metabolism was investigated in vitro and in vivo by adding it to mouse feed and HepG2 cell culture medium. And 16S rRNA gene sequencing was used to explore its regulatory effect on gut microbiota. RESULTS: Results showed that nardosinone could improve HFD-induced liver injury and abnormal lipid metabolism by promoting mitochondrial energy metabolism in hepatocytes, alleviating oxidative stress damage, and regulating the composition of the gut microbiota. Mechanistically, combined with network pharmacology and reverse docking analysis, it was predicted that CYP2D6 was the target of nardosinone, and the binding was verified by cellular thermal shift assay (CETSA). CONCLUSIONS: This study highlights a novel mechanism function of nardosinone in regulating lipid metabolism and gut microbiota. It also predicts and validates CYP2D6 as a previously unknown regulatory target, which provides new possibilities for the application of nardosinone and the treatment of metabolic-associated fatty liver disease.

UHPLC-HRMS-based Multiomics to Explore the Potential Mechanisms and Biomarkers for Colorectal Cancer.

BACKGROUND: Understanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum. METHODS: Ultrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards. RESULTS: Metabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00). CONCLUSIONS: To our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention.

Value of quantitative microsurface structure analysis for evaluating the invasion depth of type 0-II early gastric cancer.

Background and Aim: The microsurface structure reflects the degree of damage to the glands, which is related to the invasion depth of early gastric cancer. To evaluate the diagnostic value of quantitative microsurface structure analysis for estimating the invasion depth of early gastric cancer. Methods: White-light imaging and narrow-band imaging (NBI) endoscopy were used to visualize the lesions of the included patients. The area ratio and depth-predicting score (DPS) of each patient were calculated; meanwhile, each lesion was examined by endoscopic ultrasonography (EUS). Results: Ninety-three patients were included between 2016 and 2019. Microsurface structure is related to the histological differentiation and progression of early gastric cancer. The receiver operating characteristic curve showed that when an area ratio of 80.3% was used as a cut-off value for distinguishing mucosal (M) and submucosal (SM) type 0-II gastric cancers, the sensitivity, specificity, and accuracy were 82.9%, 80.2%, and 91.6%, respectively. The accuracies for distinguishing M/SM differentiated and undifferentiated early gastric cancers were 87.4% and 84.8%, respectively. The accuracy of EUS for distinguishing M/SM early gastric cancer was 74.9%. DPS can only distinguish M-SM1 (SM infiltration <500 µm)/SM (SM infiltration ≥500 µm) with an accuracy of 83.8%. The accuracy of using area ratio for distinguishing 0-II early gastric cancers was better than those of using DPS and EUS (P < 0.05). Conclusion: Quantitative analysis of microsurface structure can be performed to assess M/SM type 0-II gastric cancer and is expected to be effective for judging the invasion depth of gastric cancer.

Integrating artificial intelligence in osteosarcoma prognosis: the prognostic significance of SERPINE2 and CPT1B biomarkers.

The principal aim of this investigation is to identify pivotal biomarkers linked to the prognosis of osteosarcoma (OS) through the application of artificial intelligence (AI), with an ultimate goal to enhance prognostic prediction. Expression profiles from 88 OS cases and 396 normal samples were procured from accessible public databases. Prognostic models were established using univariate COX regression analysis and an array of AI methodologies including the XGB method, RF method, GLM method, SVM method, and LASSO regression analysis. Multivariate COX regression analysis was also employed. Immune cell variations in OS were examined using the CIBERSORT software, and a differential analysis was conducted. Routine blood data from 20,679 normal samples and 437 OS cases were analyzed to validate lymphocyte disparity. Histological assessments of the study's postulates were performed through immunohistochemistry and hematoxylin and eosin (HE) staining. AI facilitated the identification of differentially expressed genes, which were utilized to construct a prognostic model. This model discerned that the survival rate in the high-risk category was significantly inferior compared to the low-risk cohort (p < 0.05). SERPINE2 was found to be positively associated with memory B cells, while CPT1B correlated positively with CD8 T cells. Immunohistochemical assessments indicated that SERPINE2 was more prominently expressed in OS tissues relative to adjacent non-tumorous tissues. Conversely, CPT1B expression was elevated in the adjacent non-tumorous tissues compared to OS tissues. Lymphocyte counts from routine blood evaluations exhibited marked differences between normal and OS groups (p < 0.001). The study highlights SERPINE2 and CPT1B as crucial biomarkers for OS prognosis and suggests that dysregulation of lymphocytes plays a significant role in OS pathogenesis. Both SERPINE2 and CPT1B have potential utility as prognostic biomarkers for OS.

The landscape of super-enhancer regulates remote target gene transcription through loop domains in adipose tissue of pig.

Background: A super-enhancer (SE) is a huge cluster of multiple enhancers that control the key genes for cell identity and function. The rise of advanced chromatin immunoprecipitation sequencing (ChIP-seq) technology such as Cleavage Under Targets and Tagmentation (CUT&Tag) allows more SEs to be discovered. However, SE studies in Luchuan and Duroc pigs are very rare in animal husbandry. Results: We used the CUT&Tag technique to identify 145 and 378 SEs from the adipose tissues of Luchuan and Duroc pigs, respectively. There were significant differences in the peak coverage ratio of SE peaks in the gene promoter region between the two breeds. Not only that, peak signals at the start and end point of the SE peak profile showed obvious spikes. The proximal target genes of SE were highly expressed compared with the background genes and the typical enhancer target genes. Subsequently, in conjoint analysis with high-throughput chromosome conformation capture sequencing (Hi-C seq) data, we predicted the remote regulatory genes of SE and found that their expression level was related to the distance of SE extended to the loop's anchor, but not the length of loops. According to our prediction model, SEs can maintain promoter accessibility of partial remote target genes through loop domains. Finally, a batch of SEs closely related to fat metabolism traits were obtained by performing a coalition analysis of quantitative trait loci and SE data. Conclusions: This work enabled us to obtain hundreds of SEs from Luchuan and Duroc pigs. Our model provides a new method for predicting the SE remote target genes based on loop domains, and to further explore the potential role of super-enhancer in the regulation of fat metabolism.

Identifying CTH and MAP1LC3B as ferroptosis biomarkers for prognostic indication in gastric cancer decoding.

Gastric cancer (GC), known for its high incidence and poor prognosis, urgently necessitates the identification of reliable prognostic biomarkers to enhance patient outcomes. We scrutinized data from 375 GC patients alongside 32 non-cancer controls, sourced from the TCGA database. A univariate Cox Proportional Hazards Model (COX) regression was employed to evaluate expressions of ferroptosis-related genes. This was followed by the application of Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate COX regression for the development of prognostic models. The composition of immune cell subtypes was quantified utilizing CIBERSORT, with their distribution in GC versus control samples being comparatively analyzed. Furthermore, the correlation between the expressions of Cystathionine Gamma-Lyase (CTH) and Microtubule Associated Protein 1 Light Chain 3 Beta (MAP1LC3B) and the abundance of immune cell subtypes was explored. Our bioinformatics findings underwent validation through immunohistochemical analysis. Our prognostic models integrated CTH and MAP1LC3B. Survival analysis indicated that patients categorized as high-risk, as defined by the model, exhibited significantly lower survival rates compared to their low-risk counterparts. Notably, CTH expression inversely correlated with monocyte levels, while MAP1LC3B expression showed an inverse relationship with the abundance of M2 macrophages. Immunohistochemical validation corroborated lower expressions of CTH and MAP1LC3B in GC tissues relative to control samples, in concordance with our bioinformatics predictions. Our study suggests that the dysregulation of CTH, MAP1LC3B, and the accompanying monocyte-macrophage dynamics could be pivotal in the prognosis of GC. These elements present potential targets for prognostic assessment and therapeutic intervention.

Deletion of the mitochondrial calcium uniporter in adipose tissue promotes energy expenditure and alleviates diet-induced obesity.

OBJECTIVE: Studies have shown a correlation between obesity and mitochondrial calcium homeostasis, yet it is unclear whether and how Mcu regulates adipocyte lipid deposition. This study aims to provide new potential target for the treatment of obesity and related metabolic diseases, and to explore the function of Mcu in adipose tissue. METHODS: We firstly investigated the role of mitoxantrone, an Mcu inhibitor, in the regulation of glucose and lipid metabolism in mouse adipocytes (3T3-L1 cells). Secondly, C57BL/6J mice were used as a research model to investigate the effects of Mcu inhibitors on fat accumulation and glucose metabolism in mice on a high-fat diet (HFD), and by using CRISPR/Cas9 technology, adipose tissue-specific Mcu knockdown mice (Mcufl/+ AKO) and Mcu knockout of mice (Mcufl/fl AKO) were obtained, to further investigate the direct effects of Mcu on fat deposition, glucose tolerance and insulin sensitivity in mice on a high-fat diet. RESULTS: We found the Mcu inhibitor reduced adipocytes lipid accumulation and adipose tissues mass in mice fed an HFD. Both Mcufl/+ AKO mice and Mcufl/fl AKO mice were resistant to HFD-induced obesity, compared to control mice. Mice with Mcufl/fl AKO showed improved glucose tolerance and insulin sensitivity as well as reduced hepatic lipid accumulation. Mechanistically, inhibition of Mcu promoted mitochondrial biogenesis and adipocyte browning, increase energy expenditure and alleviates diet-induced obesity. CONCLUSIONS: Our study demonstrates a link between adipocyte lipid accumulation and mCa2+ levels, suggesting that adipose-specific Mcu deficiency alleviates HFD-induced obesity and ameliorates metabolic disorders such as insulin resistance and hepatic steatosis. These effects may be achieved by increasing mitochondrial biosynthesis, promoting white fat browning and enhancing energy metabolism.

Abdominal Abscesses Caused by Nocardia farcinica in an Immunocompromised Patient: A Case Report and Literature Review.

Nocardiosis is mainly an opportunistic infection that affects immunosuppressed individuals, with the most common manifestation being the pulmonary infection and cerebral abscesses. Abdominal abscesses caused by Nocardia is rare in diabetes patients. Here, we report a rare case of abdominal abscesses caused by Nocardia farcinica (N. farcinica) in a 56-year-old man with poorly controlled type 2 diabetes and prolonged use of corticosteroids for the treatment of secondary adrenal insufficiency. Abdominal CT suggested abdominal abscesses, and the culture of the abscess puncture fluid identified it as N. farcinica by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Treatment with a combination of trimethoprim-sulfamethoxazole (TMP-SMX) and imipenem/cilastatin (IPM/CS), along with surgical drainage and reduction in corticosteroid dosage, achieved successful outcomes in treating disseminated abdominal abscesses. Immunocompromised patients with unexplained fever, abdominal pain, and abdominal abscess should be suspected of Nocardia infection.

Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health. However, to date, no safe, effective and appropriate treatment modalities are available. In recent years, ferroptosis has emerged as a significant mode of cell death and has been found to play a key regulatory role in the development of NAFLD. In this study, we found that arbutin (ARB), a natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits the onset of ferroptosis and ameliorates high-fat diet-induced NAFLD in vivo and in vitro. Using reverse docking, we identified the demethylase fat mass and obesity-related protein (FTO) as a potential target of ARB. Subsequent mechanistic studies revealed that ARB plays a role in controlling methylation of the SLC7A11 gene through inhibition of FTO. In addition, we demonstrated that SLC7A11 could alleviate the development of NAFLD in vivo and in vitro. Our findings identify the FTO/SLC7A11 axis as a potential therapeutic target for the treatment of NAFLD. Specifically, we show that ARB alleviates NAFLD by acting on the FTO/SLC7A11 pathway to inhibit ferroptosis.

Adipose-Derived Stem Cell Exosomes Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicle Growth by Activating Wnt/ß-Catenin Pathway.

The most prevalent type of alopecia is androgenetic alopecia (AGA), which has a high prevalence but no effective treatment. Elevated dihydrotestosterone (DHT) level in the balding area was usually thought to be critical in the pathophysiology of AGA. The canonical Wnt/ß-catenin signaling pathway plays a key role in promoting hair follicle development and sustaining the hair follicle cycle. Adipose-derived stem cell exosomes (ADSC-Exos) are widely used in the field of regenerative medicine due to the advantages of being cell free and immune privileged. Still, few studies have reported the therapeutic effect on hair disorders. As a result, we sought to understand how ADSC-Exos affected hair growth and explore the possibility that ADSC-Exos could counteract the hair-growth-inhibiting effects of DHT. This research using human hair follicle organs, in vitro dermal papilla cells, and in vivo animal models showed that ADSC-Exos not only encouraged healthy hair growth but also counteracted the inhibitory effects of DHT on hair growth. Additionally, we discovered that ADSC-Exos increased Ser9 phosphorylated glycogen synthase kinase-3ß levels and facilitated nuclear translocation of ß-catenin, which may have been blocked by the specific Wnt/ß-catenin signaling pathway inhibitor dickkopf-related protein 1. Our findings suggested that ADSC-Exos are essential for hair regeneration, which is anticipated to open up new therapeutic possibilities for clinical alopecia, particularly for the treatment of AGA.

BATF relieves hepatic steatosis by inhibiting PD1 and promoting energy metabolism.

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) has become a global health threat that needs to be addressed urgently. Basic leucine zipper ATF-like transcription factor (BATF) is commonly thought to be involved in immunity, but its effect on lipid metabolism is not clear. Here, we investigated the function of BATF in hepatic lipid metabolism. BATF alleviated high-fat diet (HFD)-induced hepatic steatosis and inhibited elevated programmed cell death protein (PD)1 expression induced by HFD. A mechanistic study confirmed that BATF regulated fat accumulation by inhibiting PD1 expression and promoting energy metabolism. PD1 antibodies alleviated hepatic lipid deposition. In conclusion, we identified the regulatory role of BATF in hepatic lipid metabolism and that PD1 is a target for alleviation of NAFLD. This study provides new insights into the relationship between BATF, PD1, and NAFLD.

Tumor microenvironment characterization in colorectal cancer to identify prognostic and immunotherapy genes signature.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in tumorigenesis, progression, and therapeutic response in many cancers. This study aimed to comprehensively investigate the role of TME in colorectal cancer (CRC) by generating a TMEscore based on gene expression. METHODS: The TME patterns of CRC datasets were investigated, and the TMEscores were calculated. An unsupervised clustering method was used to divide samples into clusters. The associations between TMEscores and clinical features, prognosis, immune score, gene mutations, and immune checkpoint inhibitors were analyzed. A TME signature was constructed using the TMEscore-related genes. The results were validated using external and clinical cohorts. RESULTS: The TME pattern landscape was for CRC was examined using 960 samples, and then the TMEscore pattern of CRC datasets was evaluated. Two TMEscore clusters were identified, and the high TMEscore cluster was associated with early-stage CRC and better prognosis in patients with CRC when compared with the low TMEscore clusters. The high TMEscore cluster indicated elevated tumor cell scores and tumor gene mutation burden, and decreased tumor purity, when compared with the low TMEscore cluster. Patients with high TMEscore were more likely to respond to immune checkpoint therapy than those with low TMEscore. A TME signature was constructed using the TMEscore-related genes superimposing the results of two machine learning methods (LASSO and XGBoost algorithms), and a TMEscore-related four-gene signature was established, which had a high predictive value for discriminating patients from different TMEscore clusters. The prognostic value of the TMEscore was validated in two independent cohorts, and the expression of TME signature genes was verified in four external cohorts and clinical samples. CONCLUSION: Our study provides a comprehensive description of TME characteristics in CRC and demonstrates that the TMEscore is a reliable prognostic biomarker and predictive indicator for patients with CRC undergoing immunotherapy.

UHPLC-HRMS-based serum untargeted lipidomics: Phosphatidylcholines and sphingomyelins are the main disturbed lipid markers to distinguish colorectal advanced adenoma from cancer.

Colorectal advanced adenoma (CAA) is a key precancerous lesion of colorectal cancer (CRC), and early diagnosis can lessen CRC morbidity and mortality. Although abnormal lipid metabolism is associated with the development of CRC, there are no studies on the biomarkers and mechanism of lipid metabolism linked to CAA carcinogenesis. Hence, we performed a lipidomics study of serum samples from 46 CAA, and 50 CRC patients by the ultra high-performance liquid chromatography tandem high resolution mass spectrometry (UHPLC-HRMS) in both electrospray ionization (ESI) modes. Differential lipids were selected by univariate and multivariate statistics analysis, and their diagnostic performance was evaluated using a receiver operating characteristic curve (ROC) analysis. Combining P < 0.05 and variable importance in projection (VIP) > 1, 59 differential lipids were obtained totally. Ten of them showed good discriminant ability for CAA and CRC (AUC > 0.900). Especially, the lipid panel consisting of PC 44:5, PC 35:6e, and SM d40:3 showed the highest selection frequency and outperformed (AUC = 0.952). Additionally, phosphatidylcholine (PC) and sphingomyelin (SM) were the main differential and high-performance lipids. In short, this is the first study to explore the biomarkers and mechanism for CAA-CRC sequence with large-scale serum lipidomics. The findings should provide valuable reference and new clues for the development of diagnostic and therapeutic strategies of CRC.

A case report of gastrointestinal hemorrhage caused by small intestinal hemangioma.

RATIONALE: Small intestinal hemangioma is a rare condition and very difficult to diagnose preoperatively. It can occur in all segments of the small intestine, but jejunum is common. Its common symptoms are gastrointestinal bleeding and chronic anemia, while intussusception, intestinal obstruction and perforation are rare. In recent years, the popularization and application of capsule endoscopy, computed tomographic enterography and double-balloon enteroscopy play vital roles in the diagnosis and management of small bowel bleeding. We report a case of gastrointestinal hemorrhage caused by of the small intestine hemangioma. PATIENT CONCERNS: A 56-year-old male complaint of hematochezia for 1 day with dizziness, fatigue, and vomiting of gastric contents. DIAGNOSIS: Based on the clinical, laboratory, imaging tests, endoscopy, laparoscopic approach and pathological examination, the patient was diagnosed with small intestinal hemangioma. INTERVENTIONS: Segmental resection was performed for the small intestinal hemangioma by a laparoscopic approach. OUTCOMES: The patient was discharged without operation complications, and his hemoglobin increased to 130 g/L at the second month after the operation. LESSONS: Small intestinal hemangioma is a rare condition without specific symptoms and can cause gastrointestinal bleeding. The possibility of small intestinal hemangioma should be considered with unexplained gastrointestinal bleeding. Surgical resection is the preferred treatment option for symptomatic hemangiomas. Furthermore, double-balloon enteroscopy can increase the diagnostic yield. Applying endoscopic titanium clip combined with Indian ink marking can obtain an accurate positioning before surgery.

Oxaliplatin related lncRNAs prognostic models predict the prognosis of patients given oxaliplatin-based chemotherapy.

BACKGROUND: Oxaliplatin-based chemotherapy is the first-line treatment for colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) have been implicated in chemotherapy sensitivity. This study aimed to identify lncRNAs related to oxaliplatin sensitivity and predict the prognosis of CRC patients underwent oxaliplatin-based chemotherapy. METHODS: Data from the Genomics of Drug Sensitivity in Cancer (GDSC) was used to screen for lncRNAs related to oxaliplatin sensitivity. Four machine learning algorithms (LASSO, Decision tree, Random-forest, and support vector machine) were applied to identify the key lncRNAs. A predictive model for oxaliplatin sensitivity and a prognostic model based on key lncRNAs were established. The published datasets, and cell experiments were used to verify the predictive value. RESULTS: A total of 805 tumor cell lines from GDSC were divided into oxaliplatin sensitive (top 1/3) and resistant (bottom 1/3) groups based on their IC50 values, and 113 lncRNAs, which were differentially expressed between the two groups, were selected and incorporated into four machine learning algorithms, and seven key lncRNAs were identified. The predictive model exhibited good predictions for oxaliplatin sensitivity. The prognostic model exhibited high performance in patients with CRC who underwent oxaliplatin-based chemotherapies. Four lncRNAs, including C20orf197, UCA1, MIR17HG, and MIR22HG, displayed consistent responses to oxaliplatin treatment in the validation analysis. CONCLUSION: Certain lncRNAs were associated with oxaliplatin sensitivity and predicted the response to oxaliplatin treatment. The prognostic models established based on the key lncRNAs could predict the prognosis of patients given oxaliplatin-based chemotherapy.

Echinocystic acid prevents obesity and fatty liver via interacting with FABP1.

Long-term high-fat diet (HFD) will lead to obesity and their complications. Echinocystic acid (EA), a triterpene, shows anti-inflammatory and antioxidant effects. We predict that EA supplementation can prevent obesity, diabetes, and nonalcoholic steatohepatitis. To test our hypothesis, we investigated the effects of EA supplementation on mice with HFD-induced obesity in vivo and in vitro by adding EA to the diet of mice and the medium of HepG2 cells, the protein target of EA was analyzed by molecular docking. The results showed that EA ameliorated obesity and inhibited blood triglyceride and liver triglyceride concentrations than those in the HFD groups. The data on molecular docking indicated that FABP1 was a potential target of EA. Further experimental results confirmed that EA affected the triglyceride level by regulating the function of FABP1. This study may provide a new potential inhibitor for FABP1 and a new strategy for the treatment of obesity.

Tussilagone ameliorates high-fat diet-induced hepatic steatosis by enhancing energy metabolism and antioxidant activity.

Non-alcoholic fatty liver disease (NAFLD) is a major health problem. However, no effective treatments are currently available. Thus, there is a critical need to develop novel drugs that can prevent and treat NAFLD with few side effects. In this study, Tussilagone (TUS), a natural sesquiterpene isolated from Tussilago farfara L, was explored in vitro and in vivo for its potential to treat NAFLD. Our results showed that in vitro TUS reduced oleic acid palmitate acid-induced triglyceride and cholesterol synthesis in HepG2 cells, reduced intracellular lipid droplet accumulation, improved glucose metabolism disorders and increased energy metabolism and reduced oxidative stress levels. In vivo, TUS significantly reduced fat accumulation and improved liver injury in high-fat diet (HFD)-induced mice. TUS treatment significantly increased liver mitochondrial counts and antioxidant levels compared to the HFD group of mice. In addition, TUS was found to reduce the expression of genes involved in lipid synthesis sterol regulatory element binding protein-1 (SREBP1), fatty acid synthase (FASN), and stearoy-CoA desaturase 1 (SCD1) in vitro and in vivo. Our results suggest that TUS may be helpful in the treatment of NAFLD, suggesting that TUS is a promising compound for the treatment of NAFLD. Our findings provided novel insights into the application of TUS in regulating lipid metabolism.