Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

A positive association between BMI and kidney stones among the diabetic population: a cross-sectional study from NHANES.

BACKGROUND: In the past, research has shown that a higher body mass index (BMI) is one of the variables that increase the likelihood of kidney stones; however, no studies have found a connection between the two in the type II diabetic population. The purpose of this research is to reveal the association between BMI and kidney stones in the type II diabetic population. METHODS: We selected demographic data, laboratory data, lifestyle, and medical history from the NHANES. Specifically includes age, gender, systemic immune-inflammation index (SII), poverty income rate (PIR), body mass index (BMI), kidney stones, education, coronary artery disease, smoking, and drinking. RESULTS: BMI and kidney stones were shown to have a positive association in type II diabetics (blood sugar level > 7.0 mmol/L or diagnosed by a doctor) (OR = 1.021, 95% CI 1.008-1.033, P = 0.001), even after controlling for factors, such as age, gender, race, education level, coronary heart disease, smoking, and drinking. The subgroup analysis revealed a more significant positive association among the 67-80 years, female and Non-Hispanic White population. CONCLUSIONS: There is a positive correlation between BMI and kidney stones among the type II diabetic population.

Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 -/- mice.

Background: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks associated with miR-147, and the regulation of lncRNAs and miRNAs in this setting remains poorly understood. Methods: After establishing a miR-147-/- model mouse, samples of lung tissue were harvested for RNA-sequencing, and differentially expressed lncRNAs, miRNAs, and mRNAs were identified. The miRNA targets of these lncRNAs and the identified miRNAs were first overlapped to facilitate the prediction of target mRNAs, with analyses then examining the overlap between these targets and mRNAs that were differentially expressed. Then, these target mRNAs were subjected to pathway enrichment analyses. These results were ultimately used to establish a miR-147-related ceRNA network. Results: Relative to wild-type mice, the lungs of miR-147-/- mice exhibited 91, 43, and 71 significantly upregulated lncRNAs, miRNAs, and mRNAs, respectively, together with 114, 31, and 156 that were significantly downregulated. The lncRNA-miRNA-mRNA network established based on these results led to the identification of Kcnh6 as a differentially expressed hub gene candidate and enabled the identification of a range of regulatory relationships. KEGG pathway enrichment showed that the mRNA targets of differentially expressed lncRNAs and miRNAs in the mice were associated with tumor-related signaling, endometrial cancer, bladder cancer, and ErbB signaling. Conclusion: These results suggest that the identified ceRNA network in miR-147-/- mice shapes tumor-associated signaling activity, with miR-147 potentially regulating various lncRNAs and miRNAs through Kcnh6, ultimately influencing tumorigenesis. Future studies of the lncRNA, miRNA, and mRNA regulatory targets shown to be associated with miR-147 in the present study may ultimately lead to the identification of novel clinically relevant targets through which miR-147 shapes the pathogenesis of cancer and other diseases.

MRI- and DWI-Based Radiomics Features for Preoperatively Predicting Meningioma Sinus Invasion.

The aim of this study was to use multimodal imaging (contrast-enhanced T1-weighted (T1C), T2-weighted (T2), and diffusion-weighted imaging (DWI)) to develop a radiomics model for preoperatively predicting venous sinus invasion in meningiomas. This prediction would assist in selecting the appropriate surgical approach and forecasting the prognosis of meningiomas. A retrospective analysis was conducted on 331 participants who had been pathologically diagnosed with meningiomas. For each participant, 3948 radiomics features were acquired from the T1C, T2, and DWI images. Minimum redundancy maximum correlation, rank sum test, and multi-factor recursive elimination were used to extract the most significant features of different models. Then, multivariate logistic regression was used to build classification models to predict meningioma venous sinus invasion. The diagnostic capabilities were assessed using receiver operating characteristic (ROC) analysis. In addition, a nomogram was constructed by incorporating clinical and radiological characteristics and a radiomics signature. To assess the clinical usefulness of the nomogram, a decision curve analysis (DCA) was performed. Tumor shape, boundary, and enhancement features were independent predictors of meningioma venous sinus invasion (p = 0.013, p = 0.013, p = 0.005, respectively). Eleven (T2:1, T1C:4, DWI:6) of the 3948 radiomics features were screened for strong association with meningioma sinus invasion. The areas under the ROC curves for the training and external test sets were 0.946 and 0.874, respectively. The clinicoradiomic model showed excellent predictive performance for invasive meningioma, which may help to guide surgical approaches and predict prognosis.

Research Progress of Artificial Intelligence in the Grading and Classification of Meningiomas.

A meningioma is a common primary central nervous system tumor. The histological features of meningiomas vary significantly depending on the grade and subtype, leading to differences in treatment and prognosis. Therefore, early diagnosis, grading, and typing of meningiomas are crucial for developing comprehensive and individualized diagnosis and treatment plans. The advancement of artificial intelligence (AI) in medical imaging, particularly radiomics and deep learning (DL), has contributed to the increasing research on meningioma grading and classification. These techniques are fast and accurate, involve fully automated learning, are non-invasive and objective, enable the efficient and non-invasive prediction of meningioma grades and classifications, and provide valuable assistance in clinical treatment and prognosis. This article provides a summary and analysis of the research progress in radiomics and DL for meningioma grading and classification. It also highlights the existing research findings, limitations, and suggestions for future improvement, aiming to facilitate the future application of AI in the diagnosis and treatment of meningioma.

A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

Integrated bioinformatics and network pharmacology to explore the therapeutic target and molecular mechanisms of Bailing capsule on polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that is common in women of reproductive age. The clinical features of PCOS include hyperandrogenemia and polycystic ovarian changes. Bailing capsule (BL), a proprietary Chinese medicine that contains fermented Cordyceps sinensis powder, has been applied to treat PCOS. However, the specific active ingredients of BL and its mechanisms of action are yet to be elucidated. METHODS: Initially, the effectiveness of BL on PCOS model mice was evaluated. Subsequently, the active ingredients of BL were searched in the TCMSP and TCM Systems Pharmacology databases, and their targets were predicted using Swiss Target Prediction and SEA databases. Furthermore, the GEO gene database was used to screen for differentially expressed genes (DEGs) related to PCOS. Data from Gene Card, OMIM, DDT, and Drugbank databases were then combined to establish a PCOS disease gene library. Cross targets were imported into the STRING database to construct a protein-protein interaction network. In addition, GO and KEGG pathway enrichment analyses were performed using Metascape and DAVID databases and visualized using Cytoscape software and R 4.2.3. The core targets were docked with SYBYL-X software, and their expressions in PCOS mice were further verified using qPCR. RESULTS: The core active ingredients of BL were identified to be linoleyl acetate, cholesteryl palmitate, arachidonic acid, among others. Microarray data sets from four groups containing disease and normal samples were obtained from the GEO database. A total of 491 DEGs and 106 drug-disease cross genes were selected. Estrous cycle and ovarian lesions were found to be improved in PCOS model mice following BL treatment. While the levels of testosterone, progesterone, and prolactin decreased, that of estradiol increased. qPCR findings indicated that the expressions of JAK2, PPARG, PI3K, and AKT1 were upregulated, whereas those of ESR1 and IRS1 were downregulated in PCOS model mice. After the administration of BL, the expressions of associated genes were regulated. This study demonstrated that BL exerted anti-PCOS effects via PIK3CA, ESR1, AKT, PPARG, and IRS1 targets affecting PI3K-Akt signaling pathways. DISCUSSION: This research clarified the multicomponent, multitarget, and multichannel action of BL and provided a theoretical reference for further investigations on its pharmacological basis and molecular mechanisms against PCOS.

Calponin 2 regulates ketogenesis to mitigate acute kidney injury.

Calponin 2 (CNN2) is a prominent actin stabilizer. It regulates fatty acid oxidation (FAO) by interacting with estrogen receptor 2 (ESR2) to determine kidney fibrosis. However, whether CNN2 is actively involved in acute kidney injury (AKI) remains unclear. Here, we report that CNN2 was induced in human and animal kidneys after AKI. Knockdown of CNN2 preserved kidney function, mitigated tubular cell death and inflammation, and promoted cell proliferation. Distinct from kidney fibrosis, proteomics showed that the key elements in the FAO pathway had few changes during AKI, but we identified that 3-hydroxymethylglutaryl-CoA synthase 2 (Hmgcs2), a rate-limiting enzyme of endogenous ketogenesis that promotes cell self-renewal, was markedly increased in CNN2-knockdown kidneys. The production of ketone body ß-hydroxybutyrate and ATP was increased in CNN2-knockdown mice. Mechanistically, CNN2 interacted with ESR2 to negatively regulate the activities of mitochondrial sirtuin 5. Activated sirtuin 5 subsequently desuccinylated Hmgcs2 to produce energy for mitigating AKI. Understanding CNN2-mediated discrete fine-tuning of protein posttranslational modification is critical to optimize organ performance after AKI.

PARP-1: a critical regulator in radioprotection and radiotherapy-mechanisms, challenges, and therapeutic opportunities.

Background: Since its discovery, poly (ADP-ribose) polymerase 1 (PARP-1) has been extensively studied due to its regulatory role in numerous biologically crucial pathways. PARP inhibitors have opened new therapeutic avenues for cancer patients and have gained approval as standalone treatments for certain types of cancer. With continued advancements in the research of PARP inhibitors, we can fully realize their potential as therapeutic targets for various diseases. Purpose: To assess the current understanding of PARP-1 mechanisms in radioprotection and radiotherapy based on the literature. Methods: We searched the PubMed database and summarized information on PARP inhibitors, the interaction of PARP-1 with DNA, and the relationships between PARP-1 and p53/ROS, NF-κB/DNA-PK, and caspase3/AIF, respectively. Results: The enzyme PARP-1 plays a crucial role in repairing DNA damage and modifying proteins. Cells exposed to radiation can experience DNA damage, such as single-, intra-, or inter-strand damage. This damage, associated with replication fork stagnation, triggers DNA repair mechanisms, including those involving PARP-1. The activity of PARP-1 increases 500-fold on DNA binding. Studies on PARP-1-knockdown mice have shown that the protein regulates the response to radiation. A lack of PARP-1 also increases the organism's sensitivity to radiation injury. PARP-1 has been found positively or negatively regulate the expression of specific genes through its modulation of key transcription factors and other molecules, including NF-κB, p53, Caspase 3, reactive oxygen species (ROS), and apoptosis-inducing factor (AIF). Conclusion: This review provides a comprehensive analysis of the physiological and pathological roles of PARP-1 and examines the impact of PARP-1 inhibitors under conditions of ionizing radiation exposure. The review also emphasizes the challenges and opportunities for developing PARP-1 inhibitors to improve the clinical outcomes of ionizing radiation damage.

Analysis of lncRNA-miRNA-mRNA Expression in the Troxerutin-Mediated Prevention of Radiation-Induced Lung Injury in Mice.

Background: Radiation-induced lung injury (RILI) is a critical factor that leads to pulmonary fibrosis and other diseases. LncRNAs and miRNAs contribute to normal tissue damage caused by ionizing radiation. Troxerutin offers protection against radiation; however, its underlying mechanism remains largely undetermined. Methods: We established a model of RILI in mice pretreated with troxerutin. The lung tissue was extracted for RNA sequencing, and an RNA library was constructed. Next, we estimated the target miRNAs of differentially expressed (DE) lncRNAs, and the target mRNAs of DE miRNAs. Then, functional annotations of these target mRNAs were performed using GO and KEGG. Results: Compared to the control group, 150 lncRNA, 43 miRNA, and 184 mRNA were significantly up-regulated, whereas, 189 lncRNA, 15 miRNA, and 146 mRNA were markedly down-regulated following troxerutin pretreatment. Our results revealed that the Wnt, cAMP, and tumor-related signaling pathways played an essential role in RILI prevention via troxerutin using lncRNA-miRNA-mRNA network. Conclusion: These evidences revealed that the abnormal regulation of RNA potentially leads to pulmonary fibrosis. Therefore, targeting lncRNA and miRNA, along with a closer examination of competitive endogenous RNA (ceRNA) networks are of great significance to the identification of troxerutin targets that can protect against RILI.

Calponin 2 harnesses metabolic reprogramming to determine kidney fibrosis.

OBJECTIVE: In the fibrotic kidneys, the extent of a formed deleterious microenvironment is determined by cellular mechanical forces. This process requires metabolism for energy. However, how cellular mechanics and metabolism are connected remains unclear. METHODS: A multi-disciplinary approach was employed: the fibrotic kidney disease models were induced by renal ischemia-reperfusion injury and unilateral ureteral obstruction in Calponin 2 (CNN2) knockdown mice. Proteomics, bioinformatics, and in vivo and in vitro molecular experimental pathology studies were performed. RESULT: Our proteomics revealed that actin filament binding and cell metabolism are the two most dysregulated events in the fibrotic kidneys. As a prominent actin stabilizer, CNN2 was predominantly expressed in fibroblasts and pericytes. In CKD patients, CNN2 levels was markedly induced in blood. In mice, CNN2 knockdown preserves kidney function and alleviates fibrosis. Global proteomics profiled that CNN2 knockdown enhanced the activities of the key rate-limiting enzymes and regulators of fatty acid oxidation (FAO) in the diseased kidneys. Inhibiting carnitine palmitoyltransferase 1α in the FAO pathway resulted in lipid accumulation and extracellular matrix deposition in the fibrotic kidneys, which were restored after CNN2 knockdown. Bioinformatics and chromatin immunoprecipitation showed that CNN2 interactor, estrogen receptor 2 (ESR2), binds peroxisome proliferator-activated receptor-α (PPARα) to transcriptionally regulate FAO downstream target genes expression amid kidney fibrosis. In vitro, ESR2 knockdown repressed the mRNA levels of PPARα and the key genes in the FAO pathway. Conversely, activation of PPARα reduced CNN2-induced matrix inductions. CONCLUSIONS: Our results suggest that balancing cell mechanics and metabolism is crucial to develop therapeutic strategies to halt kidney fibrosis.

Construction and validation of a competing endogenous RNA network in the thymus of miR-147-/- mice.

BACKGROUND: Prior evidence has demonstrated that miR-147 can regulate cellular proliferation, migration, apoptotic death, inflammatory responses, and the replication of viruses through its interactions with specific mRNA targets. LncRNA-miRNA-mRNA interactions are often found in various biological processes. No studies have documented lncRNA-miRNA-mRNA regulatory interactions in miR-147-/- mice. METHODS: Thymus tissue samples from miR-147-/- mice were systematically analyzed to detect patterns of lncRNA, miRNA, and mRNA dysregulation in the absence of this biologically important miRNA. Briefly, RNA-sequencing was used to analyze samples of thymus tissue from wild-type (WT) and miR-147-/- mice. Radiation damage models of miR-147-/- mice were prepared and prophylactic intervention with the drug trt was performed. The validation of miR-47, PDPK1,AKT and JNK were carried out by qRT-PCR, western blot and fluorescence in situ hybridization. Apoptosis was detected by Hoechst staining, and histopathological changes were detected by HE staining. RESULTS: We showed the identification of 235 mRNAs, 63 lncRNAs, and 14 miRNAs that were significantly upregulated in miR-147-/- mice as compared to WT controls, as well as 267 mRNAs, 66 lncRNAs and 12 miRNAs exhibiting significant downregulation. Predictive analyses of the miRNAs targeted by dysregulated lncRNAs and their associated mRNAs were further performed, highlighting the dysregulation of pathways including the Wnt signaling pathway, Thyroid cancer, Endometrial cancer (include PI3K/AKT) and Acute myeloid leukemia pathway(include PI3K/AKT) pathways. Troxerutin (TRT) upregulated PDPK1 via targeting miR-147 to promote AKT activation and inhibit JNK activation in the lungs of mice in radioprotection. CONCLUSION: Together, these results highlight the potentially important role of miR-147 as a key regulator of complex lncRNA-miRNA-mRNA interacting networks. Further research focusing on PI3K/AKT pathways in miR-147-/- mice in radioprotection will thus benefit current knowledge of miR-147 while also informing efforts to improve radioprotection.

Calponin 2 harnesses metabolic reprogramming to determine kidney fibrosis.

In the fibrotic kidneys, the extent of a formed deleterious microenvironment is determined by cellular mechanical forces. This process requires metabolism for energy; however, how cellular mechanics and metabolism are connected remains unclear. Our proteomics revealed that actin filament binding and cell metabolism are the two most dysregulated events in the fibrotic kidneys. As a prominent actin stabilizer, Calponin 2 (CNN2) is predominantly expressed in fibroblasts and pericytes. CNN2 knockdown preserves kidney function and alleviates fibrosis. Global proteomics profiled that CNN2 knockdown enhanced the activities of the key rate-limiting enzymes and regulators of fatty acid oxidation (FAO) in diseased kidneys. Inhibiting carnitine palmitoyltransferase 1α in the FAO pathway results in lipid accumulation and extracellular matrix deposition in the fibrotic kidneys, which were restored after CNN2 knockdown. In patients, increased serum CNN2 levels are correlated with lipid content. Bioinformatics and chromatin immunoprecipitation showed that CNN2 interactor, estrogen receptor 2 (ESR2) binds peroxisome proliferator-activated receptor-α (PPARα) to transcriptionally regulate FAO downstream target genes expression amid kidney fibrosis. In vitro , ESR2 knockdown repressed the mRNA levels of PPARα and the key genes in the FAO pathway. Conversely, activation of PPARα reduced CNN2-induced matrix inductions. Our results suggest that balancing cell mechanics and metabolism is crucial to develop therapeutic strategies to halt kidney fibrosis.

Effects of a Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Anthropomorphic Unhealthy Lifestyle.

Aim: Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods: Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results: DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion: DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

Activation of long-non-coding RNA NEAT1 sponging microRNA-147 inhibits radiation damage by targeting PDPK1 in troxerutin radioprotection.

A better understanding of the molecular mechanism involving the lncRNA-miRNA-mRNA network underlying radiation damage can be beneficial for radioprotection. This study was designed to investigate the potential role of lncRNA NEAT1, miR-147 and Phosphoinositide Dependent Protein Kinase 1 (PDPK1) interaction in radioprotection by troxerutin (TRT). We first demonstrated that NEAT1 sponged miR-147, and PDPK1 mRNA was the primary target of miR-147. In the cells, the NEAT1 and PDPK1 levels were downregulated after the radiation but increased after the treatment with TRT. The miR-147 level was significantly induced by radiation and inhibited by TRT. NEAT1 negatively regulated the expression of miR-147, whereas miR-47 targeted PDPK1 to downregulate its expression. In radioprotection, TRT effectively upregulated NEAT1 to inhibit miR-147 and to upregulate PDPK1. We concluded that TRT could promote radioprotection by stimulating NEAT1 to upregulate PDPK1 expression by suppressing miR-147. NEAT1 could be a critical therapeutic target of radiation damage.

An intelligent peptide recognizes and traps Mycobacterium tuberculosis to inhibit macrophage phagocytosis.

Tuberculosis is a major public health concern worldwide, and it is a serious threat to human health for a long period. Macrophage phagocytosis of Mycobacterium tuberculosis (M. tuberculosis) is a crucial process for granuloma formation, which shelters the bacteria and gives them an opportunity for re-activation and spread. Herein, we report an intelligent anti-microbial peptide that can recognize and trap the M. tuberculosis, inhibiting the macrophage phagocytosis process. The peptide (Bis-Pyrene-KLVFF-WHSGTPH, in abbreviation as BFH) first self-assembles into nanoparticles, and then forms nanofibers upon recognizing and binding M. tuberculosis. Subsequently, BFH traps M. tuberculosis by the in situ formed nanofibrous networks and the trapped M. tuberculosis are unable to invade host cells (macrophages). The intelligent anti-microbial peptide can significantly inhibit the phagocytosis of M. tuberculosis by macrophages, thereby providing a favorable theoretical basis for inhibiting the formation of tuberculosis granulomas.

High Throughput Isolation and Data Independent Acquisition Mass Spectrometry (DIA-MS) of Urinary Extracellular Vesicles to Improve Prostate Cancer Diagnosis.

Proteomic profiling of extracellular vesicles (EVs) represents a promising approach for early detection and therapeutic monitoring of diseases such as cancer. The focus of this study was to apply robust EV isolation and subsequent data-independent acquisition mass spectrometry (DIA-MS) for urinary EV proteomics of prostate cancer and prostate inflammation patients. Urinary EVs were isolated by functionalized magnetic beads through chemical affinity on an automatic station, and EV proteins were analyzed by integrating three library-base analyses (Direct-DIA, GPF-DIA, and Fractionated DDA-base DIA) to improve the coverage and quantitation. We assessed the levels of urinary EV-associated proteins based on 40 samples consisting of 20 cases and 20 controls, where 18 EV proteins were identified to be differentiated in prostate cancer outcome, of which three (i.e., SERPINA3, LRG1, and SCGB3A1) were shown to be consistently upregulated. We also observed 6 out of the 18 (33%) EV proteins that had been developed as drug targets, while some of them showed protein-protein interactions. Moreover, the potential mechanistic pathways of 18 significantly different EV proteins were enriched in metabolic, immune, and inflammatory activities. These results showed consistency in an independent cohort with 20 participants. Using a random forest algorithm for classification assessment, including the identified EV proteins, we found that SERPINA3, LRG1, or SCGB3A1 add predictable value in addition to age, prostate size, body mass index (BMI), and prostate-specific antigen (PSA). In summary, the current study demonstrates a translational workflow to identify EV proteins as molecular markers to improve the clinical diagnosis of prostate cancer.

Tripeptide Leu-Pro-Phe from Corn Protein Hydrolysates Attenuates Hyperglycemia-Induced Neural Tube Defect in Chicken Embryos.

Neural tube defect (NTD) is the most common and severe embryopathy causing embryonic malformation and even death associated with gestational diabetes mellitus (GDM). Leu-Pro-Phe (LPF) is an antioxidative tripeptide isolated from hydrolysates of corn protein. However, the biological activity of LPF in vivo and in vitro remains unclear. This study is aimed at investigating the protective effects of tripeptide LPF against NTD in the high glucose exposure condition and delineate the underlying biological mechanism. We found that LPF alleviated NTD in the high glucose-exposed chicken embryo model. In addition, DF-1 chicken embryo fibroblast was loaded with high glucose for induction of oxidative stress and abnormal O-GlcNAcylation in vitro. LPF significantly decreased accumulation of reactive oxygen species and content of malondialdehyde in DF-1 cells but increased the ratio of reduced glutathione and oxidized glutathione in chick embryo. Oxygen radical absorbance capacity results showed that LPF itself had good free radical scavenging capacity and could enhance antioxidant activity of the cell content. Mechanistic studies suggested that the resistance of LPF to oxidative damage may be related to promotion of NRF2 expression and nuclear translocation. LPF alleviated the overall O-GlcNAcylation level of cellular proteins under high glucose conditions and restored the level of Pax3 protein. Collectively, our findings indicate that LPF peptide could act as a nutritional supplement for the protection of development of embryonic neural tube affected by GDM.

G-CSF/GM-CSF-induced hematopoietic dysregulation in the progression of solid tumors.

There are two types of abnormal hematopoiesis in solid tumor occurrence and treatment: pathological hematopoiesis, and myelosuppression induced by radiotherapy and chemotherapy. In this review we primarily focus on the abnormal pathological hematopoietic differentiation in cancer induced by tumor-released granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). As key factors in hematopoietic development, G-CSF/GM-CSF are well-known facilitators of myelopoiesis and mobilization of hematopoietic stem cells (HSCs). In addition, these two cytokines can also promote or inhibit tumors, dependent on tumor type. In multiple cancer types, hematopoiesis is greatly enhanced and abnormal lineage differentiation is induced by these two cytokines. Here, dysregulated hematopoiesis induced by G-CSF/GM-CSF in solid tumors and its mechanism are summarized, and the prognostic value of G-CSF/GM-CSF-associated dysregulated hematopoiesis for tumor metastasis is also briefly highlighted.

[Effects of different extracts of Dendrobium officinale on rats with chronic pharyngitis induced by pepper water combined with ammonia].

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1ß(IL-1ß), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor ß1(TGF-ß1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1ß, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.