Inflammatory myofibroblastic tumor in the liver: a case report.

Background: Hepatic inflammatory myofibroblastic tumor (IMT) is an infrequent tumor with potential malignancy. However, it lacks specific clinical symptoms and usual imaging features. Case presentation: A 34-year-old woman had a six-month history of fever and on-and-off pain in the upper right part of her abdomen that lasted for two weeks. Imaging tests revealed a liver mass initially thought to be liver malignancy, but subsequent histopathological examination after liver removal confirmed the diagnosis as hepatocellular inflammatory myofibroblastic tumor (HIMT). Conclusion: Hepatic inflammatory myofibroblastic tumor (IMT) is an uncommon growth with vague clinical symptoms and lab results. Surgical removal remains the primary treatment method, resulting in favorable prognostic outcomes.

Rosa roxburghii Tratt Pomace Crude Extract Inactivates Cronobacter sakazakii Isolated from Powdered Infant Formula.

Cronobacter sakazakii is an important foodborne pathogen in powder infant formula (PIF). The objective of this study was to evaluate the inactivation effect of Rosa roxburghii Tratt pomace crude extract (RRPCE) on C. sakazakii isolated from PIF and to reveal the mechanism of action. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were used to evaluate the inhibitory activity of RRPCE against C. sakazakii. The inhibitory mechanism was revealed from the perspective of effects of RRPCE on intracellular adenosine 5'-triphosphate (ATP), reactive oxygen species (ROS), membrane potential, protein and nucleic acid leakage, and cell morphology of C. sakazakii. The inactivation effects of RRPCE on C. sakazakii in biofilms on stainless steel, tinplate, glass, silica gel, polyethylene terephthalate, and polystyrene to evaluate its potential as a natural disinfectant. The results showed that the MIC and MBC of RRPCE against C. sakazakii were 7.5 and 15 mg/mL, respectively. After treatments with RRPCE, intracellular ATP content decreased significantly while intracellular ROS level increased significantly (p < 0.05). The cell membrane depolarization, large leakage of proteins and nucleic acids, and severely damaged cell morphology also occurred in C. sakazakii treated with RRPCE. In addition, a 20-minute treatment with 2 MIC (15 mg/mL) of RRPCE could inactivate all C. sakazakii (from 6.10 to 6.40 CFU/mL) in biofilms on all six contact surfaces. Our findings suggest that RRPCE is ideal for the inactivation of C. sakazakii and has the potential to be used as a natural disinfectant for the inactivation of PIF packaging materials and containers.

Application of 3D printing technology in tumor diagnosis and treatment.

3D printing technology is an increasing approach consisting of material manufacturing through the selective incremental delamination of materials to form a 3D structure to produce products. This technology has different advantages, including low cost, short time, diversification, and high precision. Widely adopted additive manufacturing technologies enable the creation of diagnostic tools and expand treatment options. Coupled with its rapid deployment, 3D printing is endowed with high customizability that enables users to build prototypes in shorts amounts of time which translates into faster adoption in the medical field. This review mainly summarizes the application of 3D printing technology in the diagnosis and treatment of cancer, including the challenges and the prospects combined with other technologies applied to the medical field.

Key enzyme in charge of ketone reabsorption of renal tubular SMCT1 may be a new target in diabetic kidney disease.

OBJECTIVE: A ketogenic diet or mildly increased ketone body levels are beneficial for diabetic kidney disease (DKD) patients. Our previous study has found that sodium-coupled monocarboxylate transporter 1 (SMCT1), a key enzyme in charge of ketone reabsorption, possesses beneficial effects on the function of renal tubular epithelial cells (TECs) in energy crisis. Our present study is to investigate whether SMCT1 is important in maintaining the physiological function of renal tubular and plays a role in DKD. METHODS: We tested the expression of SMCT1 in kidney tissues from DKD patients receiving kidney biopsy as well as diabetes mice. We compared the difference of ß-hydroxybutyrate (ß-HB) levels in serum, urine and kidney tissues between diabetic mice and control. Using recombinant adeno-associated viral vector containing SMCT1 (encoded by Slc5a8 gene), we tested the effect of SMCT1 upregulation on microalbuminuria as well as its effects on mitochondrial energy metabolism in diabetic mice. Then we investigated the role of SMCT1 and its ß-HB reabsorption function in maintaining the physiological function of renal tubular using renal tubule-specific Slc5a8 gene knockout mice. Transcriptomes and proteomics analysis were used to explore the underlying mechanism. RESULTS: SMCT1 downregulation was found in DKD patients as well as in diabetic mice. Moreover, diabetic mice had a decreased renal ß-HB level compared with control, and SMCT1 upregulation could improve microalbuminuria and mitochondrial energy metabolism. In renal tubule-specific Slc5a8 gene knockout mice, microalbuminuria occurred early at 24 weeks of age, accompanied by ATP shortage and metabolic reprogramming in the kidney; however, supplementation with ß-HB precursor substance 1,3-butanediol in food alleviated kidney damage as well as energy metabolic reprogramming. CONCLUSIONS: Decreased SMCT1 expression and its ketone reabsorption function play an important role in the occurrence of DKD. SMCT1 may be a new promising target in treating DKD.

Hyperinsulinemia impairs the metabolic switch to ketone body utilization in proximal renal tubular epithelial cells under energy crisis via the inhibition of the SIRT3/SMCT1 pathway.

Objective: To investigate the effects and mechanism of hyperinsulinemia on the metabolic switch to ß-hydroxybutyrate (BHB) absorption and utilization under a starvation or hypoxic environment in proximal tubular epithelial cells. Methods: A high-fat diet-induced hyperinsulinemia model in ZDF rats was used to test the expression of key enzymes/proteins of ketone body metabolism in the kidney. Notably, 12-week-old renal tubule SMCT1 specific knockout mice (SMCT1 flox/floxCre+) and control mice (SMCT1 flox/floxCre-) were used to confirm the roles of SMCT1 in kidney protection under starvation. The changes of key enzymes/proteins of energy metabolism, mitochondrial function, and albumin endocytosis in HK2 cells under low glucose/hypoxic environments with or without 50 ng/mL insulin were studied. Silent information regulation 2 homolog 3 (SIRT3) was overexpressed to evaluate the effect of hyperinsulinemia on the metabolic switch to BHB absorption and utilization through the SIRT3/SMCT1 pathway in HK2 cells. Results: In ZDF rats, the expression of HMGCS2 increased, the SMCT1 expression decreased, while SCOT remained unchanged. In renal tubule SMCT1 gene-specific knockout mice, starvation for 48 h induced an increase in the levels of urine retinol-binding protein, N-acetyl-ß-glucosaminidase, and transferrin, which reflected tubular damages. In HK2 cells under an environment of starvation and hypoxia, the levels of key enzymes related to fatty acid oxidation and ketone body metabolism were increased, whereas glucose glycolysis did not change. The addition of 2 mmol/l BHB improved ATP production, mitochondrial biosynthesis, and endocytic albumin function, while cell apoptosis was reduced in HK2 cells. The addition of 50 ng/ml insulin resulted in the decreased expression of SMCT1 along with an impaired mitochondrial function, decreased ATP production, and increased apoptosis. The overexpression of SIRT3 or SMCT1 reversed these alterations induced by a high level of insulin both in low-glucose and hypoxic environments. Conclusions: The increased absorption and utilization of BHB is part of the metabolic flexibility of renal tubular epithelial cells under starvation and hypoxic environments, which exhibits a protective effect on renal tubular epithelial cells by improving the mitochondrial function and cell survival. Moreover, hyperinsulinemia inhibits the absorption of BHB through the inhibition of the SIRT3/SMCT1 pathway.

Sugarcane Root Transcriptome Analysis Revealed the Role of Plant Hormones in the Colonization of an Endophytic Diazotroph.

Some sugarcane germplasms can absorb higher amounts of nitrogen via atmospheric nitrogen fixation through the bacterial diazotrophs. Most endophytic diazotrophs usually penetrate through the root, colonize inside the plant, and fix the nitrogen. To assess the plant's bacterial association during root colonization, strain GXS16 was tagged with a plasmid-bear green fluorescent protein (GFP) gene. The results demonstrated that the strain can colonize roots all the way to the maturation zone. The strain GXS16 showed maximum nitrogenase enzyme activity at pH 8 and 30°C, and nitrogenase activity is less affected by different carbon sources. Further, strain GXS16 colonization response was investigated through plant hormones analysis and RNAseq. The results showed that the bacterial colonization gradually increased with time, and the H2O2 and malondialdehyde (MDA) content significantly increased at 1 day after inoculation. There were no substantial changes noticed in proline content, and the ethylene content was detected initially, but it decreased with time. The abscisic acid (ABA) content showed significant increases of 91.9, 43.9, and 18.7%, but conversely, the gibberellin (GA3) content decreased by 12.9, 28.5, and 45.2% at 1, 3, and 5 days after inoculation, respectively. The GXS16 inoculation significantly increased the activities of catalase (CAT), superoxide dismutase (SOD), polyphenol oxidase (PPO), ascorbate peroxidase (APX), and glutathione reductase (GR) at different timepoint. In contrast, the peroxisome (POD) activity had no changes detected during the treatment. In the case of RNAseq analysis, 2437, 6678, and 4568 differentially expressed genes (DEGs) were identified from 1, 3, and 5 days inoculated root samples, and 601 DEGs were shared in all samples. The number or the expression diversity of DEGs related to ethylene was much higher than that of ABA or GA, which indicated the critical role of ethylene in regulating the sugarcane roots response to GXS16 inoculation.

Magnetic Resonance Imaging Quantification of the Liver Iron Burden and Volume Changes Following Treatment With Thalidomide in Patients With Transfusion-Dependent ß-Thalassemia.

Clinical trials have indicated that thalidomide could be used to treat thalassemia, but evidence of changes in liver iron burden and liver volume during thalidomide treatment is lacking. This study aimed to evaluate the liver iron burden and volume changes following thalidomide treatment in patients with transfusion-dependent ß-thalassemia. A total of 66 participants with transfusion-dependent ß-thalassemia were included in this prospective cohort study between January 2017 and December 2020. Patients were treated with thalidomide (150-200 mg/day) plus conventional therapy. Liver volume, liver R2*, and hepatic muscle signal ratio (SIR)_T1 and SIR_T2 were measured with magnetic resonance imaging (MRI), and serum ferritin, hemoglobin, erythrocyte and platelet counts, and liver function were measured at baseline and at the 3rd and 12th months. Adverse events were also noted. Patients showed progressive increase in hemoglobin, erythrocyte, platelet count, SIR_T1, and SIR_T2 during the 12-months follow up. Serum ferritin, R2*, and liver volume progressively decreased during the follow up. The R2* value had a significantly positive correlation with serum ferritin, and SIR_T1 and SIR_T2 had a significantly negative correlation with serum ferritin. No serious adverse events were observed. This study showed that thalidomide could potentially be used to successfully treat patients with transfusion-dependent ß-thalassemia; the liver iron burden and liver volume could be relieved during treatment, and the MRI-measured R2*, SIR_T1, and SIR_T2 may be used to noninvasively monitor liver iron concentration.

Retinal Neuropathy in IGT Stage of OLETF Rats: Another Characteristic Change of Diabetic Retinopathy.

AIMS: We investigated the changes of retinal structure in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), diabetes mellitus (DM), and diabetic kidney disease (DKD) stages in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: We assigned OLETF rats to four groups based on their OGTT results and 24 h urinary microalbumin (24 h UMA) levels: NGT, IGT, DM, and DKD groups. We observed the structural and the corresponding pathological changes and quantified the expression of HIF-1α, iNOS, NF-κB, VEGF, ICAM-1, and occludin in the retina. RESULTS: Significant damage to the retinal structure, especially in retinal ganglion cells (RGCs), was observed in the IGT stage. The expression of HIF-1α, iNOS, NF-κB, VEGF, and ICAM-1 was significantly upregulated, while that of occludin was downregulated. CONCLUSION: Significant retinal neuropathy occurs in the IGT stage. Inflammation and hypoxia may damage the blood retina barrier (BRB), leading to diabetic retinopathy.

Local anesthetic levobupivacaine induces ferroptosis and inhibits progression by up-regulating p53 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a common malignancy with high mortality and poor prognosis. Levobupivacaine is a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of levobupivacaine in the NSCLC development remains elusive. Here, we tried to investigate the impact of levobupivacaine on the NSCLC progression and the underlying mechanism. Significantly, we revealed that levobupivacaine could inhibit the proliferation and induce the apoptosis of NSCLC cells. Levobupivacaine was able to attenuate the invasion and migration in the cells. Meanwhile, the treatment of levobupivacaine enhanced the erastin-induced inhibition of cell growth of NSCLC cells. The treatment of levobupivacaine remarkably increased the levels of ROS, iron, and Fe2+ in NSCLC cells. Mechanically, levobupivacaine up-regulated the expression of p53 and induced ferroptosis by regulating p53 in NSCLC cells. Moreover, tumorigenicity analysis in nude mice showed that the treatment of levobupivacaine significantly repressed the tumor growth of NSCLC cells in vivo. In summary, we concluded that the local anesthetic levobupivacaine inhibits the progression and induces ferroptosis of NSCLC by up-regulating p53. Our finding provides new insights into the mechanism by which levobupivacaine attenuates the development of NSCLC. Levobupivacaine may serve as a potential anti-tumor candidate for the therapeutic strategy of NSCLC.

Physiological changes and transcriptome profiling in Saccharum spontaneum L. leaf under water stress and re-watering conditions.

As the polyploidy progenitor of modern sugarcane, Saccharum spontaneum is considered to be a valuable resistance source to various biotic and abiotic stresses. However, little has been reported on the mechanism of drought tolerance in S. spontaneum. Herein, the physiological changes of S. spontaneum GXS87-16 at three water-deficit levels (mild, moderate, and severe) and after re-watering during the elongation stage were investigated. RNA sequencing was utilized for global transcriptome profiling of GXS87-16 under severe drought and re-watered conditions. There were significant alterations in the physiological parameters of GXS87-16 in response to drought stress and then recovered differently after re-watering. A total of 1569 differentially expressed genes (DEGs) associated with water stress and re-watering were identified. Notably, the majority of the DEGs were induced by stress. GO functional annotations and KEGG pathway analysis assigned the DEGs to 47 GO categories and 93 pathway categories. The pathway categories were involved in various processes, such as RNA transport, mRNA surveillance, plant hormone signal transduction, and plant-pathogen interaction. The reliability of the RNA-seq results was confirmed by qRT-PCR. This study shed light on the regulatory processes of drought tolerance in S. spontaneum and identifies useful genes for genetic improvement of drought tolerance in sugarcane.

The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling.

Non-small cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. Bupivacaine serves as a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of bupivacaine in the NSCLC development remains elusive. Here, we tried to investigate the impact of bupivacaine on the NSCLC progression. Significantly, we revealed that bupivacaine was able to reduce the proliferation and induce the apoptosis of NSCLC cells. Bupivacaine could attenuate the invasion and migration in the cells. Mechanically, the treatment of bupivacaine increased the expression ratio of light chain 3B-II (LC3B-II)/LC3B-I and the expression of Beclin-1 in the NSCLC cells. Meanwhile, the expression of the autophagic adaptor protein p62 was decreased by bupivacaine treatment in the cells. The treatment of bupivacaine attenuated the phosphorylation of AKT and mTOR in the NSCLC cells. The AKT activator SC79 and autophagy inhibitor 3-methyladenine (3-MA) reversed the bupivacaine-inhibited phosphorylation of AKT and mTOR and bupivacaine-induced autophagy, as well as the bupivacaine-attenuated NSCLC progression in the cells. Bupivacaine could inhibit the tumor growth in vivo. In conclusion, we discovered that the local anesthetic bupivacaine inhibited the progression of NSCLC by inducing autophagy through Akt/mTOR signaling. Our finding provides new insights into the mechanism by which bupivacaine attenuates the development of NSCLC. Bupivacaine may serve as a potential anti-tumor candidate for the therapeutic strategy of NSCLC.