Urea Cycle of Bacillus thuringiensis Affects Its Survival under UV Stress.

Bacillus thuringiensis (Bt) is widely used to produce biological pesticides. However, its persistence is limited because of ultraviolet (UV) rays. In our previous study, we found that exogenous intermediates of the urea cycle were beneficial to Bt for survival under UV stress. To further explore the effect of the urea cycle on the resistance mechanism of Bt, the rocF/argG gene, encoding arginase and argininosuccinate synthase, respectively, were knocked out and recovered in this study. After the target genes were removed, respectively, the urea cycle in the tested Bt was inhibited to varying degrees. The UV stress test showed that the urea cycle disorder could reduce the resistance of Bt under UV stress. Meanwhile, the antioxidant enzyme activities of Bt were also decreased to varying degrees due to the knockout of the target genes. All of these results revealed that the urea cycle can metabolically regulate the stress resistance of Bt.

Bioelectricity in dental medicine: a narrative review.

BACKGROUND: Bioelectric signals, whether exogenous or endogenous, play crucial roles in the life processes of organisms. Recently, the significance of bioelectricity in the field of dentistry is steadily gaining greater attention. OBJECTIVE: This narrative review aims to comprehensively outline the theory, physiological effects, and practical applications of bioelectricity in dental medicine and to offer insights into its potential future direction. It attempts to provide dental clinicians and researchers with an electrophysiological perspective to enhance their clinical practice or fundamental research endeavors. METHODS: An online computer search for relevant literature was performed in PubMed, Web of Science and Cochrane Library, with the keywords "bioelectricity, endogenous electric signal, electric stimulation, dental medicine." RESULTS: Eventually, 288 documents were included for review. The variance in ion concentration between the interior and exterior of the cell membrane, referred to as transmembrane potential, forms the fundamental basis of bioelectricity. Transmembrane potential has been established as an essential regulator of intercellular communication, mechanotransduction, migration, proliferation, and immune responses. Thus, exogenous electric stimulation can significantly alter cellular action by affecting transmembrane potential. In the field of dental medicine, electric stimulation has proven useful for assessing pulp condition, locating root apices, improving the properties of dental biomaterials, expediting orthodontic tooth movement, facilitating implant osteointegration, addressing maxillofacial malignancies, and managing neuromuscular dysfunction. Furthermore, the reprogramming of bioelectric signals holds promise as a means to guide organism development and intervene in disease processes. Besides, the development of high-throughput electrophysiological tools will be imperative for identifying ion channel targets and precisely modulating bioelectricity in the future. CONCLUSIONS: Bioelectricity has found application in various concepts of dental medicine but large-scale, standardized, randomized controlled clinical trials are still necessary in the future. In addition, the precise, repeatable and predictable measurement and modulation methods of bioelectric signal patterns are essential research direction.

Immune System Acts on Orthodontic Tooth Movement: Cellular and Molecular Mechanisms.

Orthodontic tooth movement (OTM) is a tissue remodeling process based on orthodontic force loading. Compressed periodontal tissues have a complicated aseptic inflammatory cascade, which are considered the initial factor of alveolar bone remodeling. Since skeletal and immune systems shared a wide variety of molecules, osteoimmunology has been generally accepted as an interdisciplinary field to investigate their interactions. Unsurprisingly, OTM is considered a good mirror of osteoimmunology since it involves immune reaction and bone remolding. In fact, besides bone remodeling, OTM involves cementum resorption, soft tissue remodeling, orthodontic pain, and relapse, all correlated with immune cells and/or immunologically active substance. The aim of this paper is to review the interaction of immune system with orthodontic tooth movement, which helps gain insights into mechanisms of OTM and search novel method to short treatment period and control complications.

Reconstruction and Analysis of the Immune-Related LINC00987/A2M Axis in Lung Adenocarcinoma.

Enhancer RNAs (eRNAs) participate in tumor growth and immune regulation through complex signaling pathways. However, the immune-related function of the eRNA-mRNA axis in lung adenocarcinoma (LUAD) is unclear. Data on the expression of eRNAs and mRNAs were downloaded from The Cancer Genome Atlas, GEO, and UCSC Xena, including LUAD, and pan-cancer clinical data and mutational information. Immune gene files were obtained from ImmLnc and ImmPort databases. Survival indices, including relapse-free and overall survival, were analyzed using the Kaplan-Meier and log-rank methods. The level of immune cell infiltration, degree of tumor hypoxia, and tumor cell stemness characteristics were quantified using the single-sample gene set enrichment analysis algorithm. The immune infiltration score and infiltration degree were evaluated using the ESTIMATE and CIBERSORT algorithms. The tumor mutation burden and microsatellite instability were examined using the Spearman test. The LUAD-associated immune-related LINC00987/A2M axis was down-regulated in most cancer types, indicating poor survival and cancer progression. Immune cell infiltration was closely related to abnormal expression of the LINC00987/A2M axis, linking its expression to a possible evaluation of sensitivity to checkpoint inhibitors and response to chemotherapy. Abnormal expression of the LINC00987/A2M axis was characterized by heterogeneity in the degree of tumor hypoxia and stemness characteristics. The abnormal distribution of immune cells in LUAD was also verified through pan-cancer analysis. Comprehensive bioinformatic analysis showed that the LINC00987/A2M axis is a functional and effective tumor suppressor and biomarker for assessing the immune microenvironment and prognostic and therapeutic evaluations of LUAD.

Lactoferrin Alleviates the Progression of Atherosclerosis in ApoE-/- Mice Fed with High-Fat/Cholesterol Diet Through Cholesterol Homeostasis.

Lactoferrin (LF) is a multifunctional glycoprotein and has beneficial effects on the regulation of lipid metabolism. However, whether LF supplementation alleviates the development of atherosclerosis (AS) remains unclear. In the present study, all of 48 male Apolipoprotein E-/- mice were fed with high-fat diet with 1.25% added cholesterol and divided to four treatment groups with either distilled water (HFCD), LF solutions at 2 mg/mL (low LF), 10 mg/mL (middle LF or MLF), or 20 mg/mL (high LF or HLF) for 12 weeks. Oral glucose tolerance tests (OGTT) were performed at weeks 0, 4, 8, and 12. At the end of the experiment, lipids in serum, liver, and feces were determined. The livers, whole aortas, and aortic sinuses were pathologically examined. The protein expression of factors related to cholesterol synthesis, absorption, and excretion were detected through western blot. No significant difference in body weight, food intake, and OGTT was observed among the four groups. Compared with the HFCD group, the MLF and HLF groups had significantly decreased serum and hepatic cholesterol levels and significantly increased fecal cholesterol contents. LF alleviated the hepatic steatosis and lipid droplet, especially in the MLF group. LF also significantly decreased the average lesion areas in the whole aorta, especially in the MLF group. On the other hand, LF downregulated hepatic protein expression of HMG-CoA reductase (the rate-limiting enzyme in cholesterol synthesis) and upregulated cholesterol 7-alpha hydroxylase (the rate-limiting enzyme in bile acid synthesis from cholesterol). LF also downregulated the intestinal expression of Niemann-Pick C1-like 1 protein, which is known to bind to a critical mediator of cholesterol absorption. In conclusion, LF supplementation alleviates the AS in mice on HFCD likely by reducing the synthesis and absorption of cholesterol and increasing cholesterol excretion.

Holo-Lactoferrin Modified Liposome for Relieving Tumor Hypoxia and Enhancing Radiochemotherapy of Cancer.

Hypoxic microenvironments in the solid tumor play a negative role in radiotherapy. Holo-lactoferrin (holo-Lf) is a natural protein, which acts as a potential ligand of transferrin receptor (TfR). In this work, an anticancer drug, doxorubicin (Dox)-loaded liposome-holo-Lf nanocomposites, is developed for tumor targeting and imaging guided combined radiochemotherapy. Dox-loaded liposome-holo-Lf (Lf-Liposome-Dox) nanocomposites exhibit significant cellular uptake likely owing to the TfR receptor-mediated targeting accumulation of Lf-Liposome-Dox nanocomposites. Additionally, the nanocomposites exhibit high accumulation in the tumor site after intravenous injection as evidenced from in vivo fluorescence imaging. More importantly, it is found that the holo-Lf has the ability to catalyze the conversion of hydrogen peroxide (H2 O2 ) to oxygen for relieving the tumor hypoxic microenvironment. Photoacoustic imaging further confirms the abundant generation of oxygen in the presence of Lf-Liposome-Dox nanocomposites. Based on these findings, in vivo combined radiochemotherapy is performed using Lf-Liposome-Dox as therapeutic agent, achieving excellent cancer treatment effect. The study further promotes the potential biomedical application of holo-Lf in cancer treatment.

Effects of Metformin Combined with Lactoferrin on Lipid Accumulation and Metabolism in Mice Fed with High-Fat Diet.

Metformin (Met) and lactoferrin (Lf) both exhibit beneficial effects on body weight management and lipid accumulation. However, the synergistical action of Met and Lf remains unclear. In this study, 64 mice were divided into five groups, namely, the control group, high-fat diet (HFD group), HFD with Met (Met group), Lf (Lf group), and a combination of Met and Lf (Met + Lf group). Met (200 mg/kg body weight) and Lf (2 g/100 mL) were administrated in drinking water. The experiment lasted for 12 weeks. Body weight, serum, and hepatic lipids were determined. Histology of the liver and perirenal fat was observed. Protein expression related to hepatic lipid metabolism was also measured. HFD significantly increased body weight, visceral fat weight, and lipid profiles, which lead to obesity and dyslipidemia in mice. Compared with the HFD group, the treatments significantly decreased body weight and Lee's index (body mass index of mice) with the lowest values in the Met + Lf group. The treatments also decreased the weight of visceral fat, and improved circulating lipid profile and the ability for regulating glucose intake. The adipocyte size and serum TC level were significantly lower in the Met + Lf group as compared with those in the Met or Lf group. The treatments alleviated hepatic lipid accumulation, especially in the Met + Lf group. For protein expression, the p-AMPK/AMPK ratio, a key kinase-regulating cellular energy homeostasis, was significantly higher in the Met + Lf group than the ratio in the HFD group. Similarly, the treatments significantly downregulated the protein expression of lipogenic enzymes (FAS, ACC, and SREBP-1) and upregulated the protein expression of lipolytic enzyme (ATGL). The protein expression of HMGCoAR, which is an important rate limiting enzyme in cholesterol biosynthesis, was only significantly lower in the Met + Lf group than in the HFD group. In conclusion, Met and Lf, either alone or in combination, prevented HFD-induced obesity and improved lipid metabolism.