Search

Background: In the realm of Gut-Brain axis research, existing evidence points to a complex bidirectional regulatory mechanism between gut microbiota and the brain. However, the question of whether a causal relationship exists between gut microbiota and specific types of brain tumors, such as gliomas, remains unresolved. To address this gap, we employed publicly available Genome-Wide Association Study (GWAS) and MIOBEN databases, conducting an in-depth analysis using Two-Sample Mendelian Randomization (MR). Method: We carried out two sets of MR analyses. The preliminary analysis included fewer instrumental variables due to a high genome-wide statistical significance threshold (5×10−8). To enable a more comprehensive and detailed analysis, we adjusted the significance threshold to 1×10−5. We performed linkage disequilibrium analysis (R2 <0.001, clumping distance = 10,000kb) and detailed screening of palindromic SNPs, followed by MR analysis and validation through sensitivity analysis. Results: Our findings reveal a causal relationship between gut microbiota and gliomas. Further confirmation via Inverse Variance Weighting (IVW) identified eight specific microbial communities related to gliomas. Notably, the Peptostreptococcaceae and Olsenella communities appear to have a protective effect, reducing glioma risk. Conclusion: This study not only confirms the causal link between gut microbiota and gliomas but also suggests a new avenue for future glioma treatment. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. Method: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. Results: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023–1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004–1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006–1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012–1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002–1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. Conclusion: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFU), diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) are common complications of diabetes mellitus, while diabetic peripheral neuropathy and peripheral arterial disease contribute to the pathogenesis of diabetic foot ulcers, and the pathogenic mechanisms between these three diseases still need further investigation. The keywords 'diabetic foot ulcer', 'diabetic peripheral neuropathy' and 'atherosclerosis' were used to search for related gene sets in the GEO database. Differentially expressed genes (DEGs) were screened and analysed for GO, KEGG and enrichR functional enrichment. Potential three disease biomarkers were identified by SVM‐SVM‐RFE and LASSO regression analysis. The results were also validated using external datasets and discriminability was measured by area under the ROC curve (AUC). Finally, biomarkers and co‐upregulated genes were analysed through the GSEA and Attie Laboratories diabetes databases. A total of 11 shared genes (KRT16, CD24, SAMD9L, SRGAP2, FGL2, GPR34, DDIT4, NFE2L3, FBLN5, ANXA3 and CPA3), two biomarkers (SAMD9L and FGL2) and one co‐upregulated gene (CD24) were screened. GO and KEGG pathway analysis of DEGs, enrichr enrichment analysis of shared differential genes and GSEA analysis of biomarkers showed that these significant genes were mainly focused on vasoregulatory, inflammatory‐oxidative stress and immunomodulatory pathways. In this study, we used bioinformatics to investigate the intrinsic relationship and potential mechanisms of three common lower extremity complications of diabetes and identified two pivotal genes using the LASSO model and the SVM‐RFE algorithm, which will further help clinicians to understand the relationship between diabetic complications, improve the diagnosis and treatment of diabetic foot problems and help doctors to identify the potential risk factors of diabetic foot. [ABSTRACT FROM AUTHOR]

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder. The origin and development of CNO involve many complex immune processes, resulting in delayed diagnosis and a lack of effective treatment. Although bioinformatics analysis has been utilized to seek key genes and pathways in CNO, only a few bioinformatics studies that focus on CNO pathogenesis and mechanisms have been reported. This study aimed to identify key biomarkers that could serve as early diagnostic or therapeutic markers for CNO. Two RNA-seq datasets (GSE133378 and GSE187429) were obtained from the Gene Expression Omnibus (GEO). Weighted gene coexpression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to identify the genes associated with CNO. Then, the autoinflammatory genes most associated with CNO were identified based on the GeneCards database and a CNO prediction model, which was created by the LASSO machine learning algorithm. The accuracy of the model and effects of the autoinflammatory genes according to receiver operating characteristic (ROC) curves were verified in external datasets (GSE7014). Finally, we performed clustering analysis with ConsensusClusterPlus. In total, eighty CNO-related genes were identified and were significantly enriched in the biological processes regulation of actin filament organization, cell–cell junction organization and gamma-catenin binding. The main enriched pathways were adherens junctions, viral carcinogenesis and systemic lupus erythematosus. Two autoinflammatory genes with high expression in CNO samples were identified by combining an optimal machine learning algorithm (LASSO) with the GeneCards database. An external validation dataset (GSE187429) was utilized for ROC analysis of the prediction model and two genes, and the results indicated good efficiency. Then, based on consensus clustering analysis, we found that the expression of UTS2 and MPO differed between clusters. Finally, the ceRNA network of lncRNAs and the small molecule compounds targeting the two autoinflammatory genes were predicted. The identification of two autoinflammatory genes, the HCG18/has-mir-147a/UTS2/MPO axis and signalling pathways in this study can help us understand the molecular mechanism of CNO formation and provides candidate targets for the diagnosis and treatment of CNO. [ABSTRACT FROM AUTHOR]

Background: Sepsis is one of the most lethal diseases worldwide. Pyroptosis is a unique form of cell death, and the mechanism of interaction with sepsis is not yet clear. The aim of this study was to uncover pyroptosis genes associated with sepsis and to provide early therapeutic targets for the treatment of sepsis. Methods: Based on the GSE134347 dataset, sepsis-related genes were mined by differential expression analysis and weighted gene coexpression network analysis (WGCNA). Subsequently, the sepsis-related genes were analysed for enrichment, and a protein‒protein interaction (PPI) network was constructed. We performed unsupervised consensus clustering of sepsis patients based on 33 pyroptosis-related genes (PRGs) provided by prior reviews. We finally obtained the PRGs mostly associated with sepsis by machine learning prediction models combined with prior reviews. The GSE32707 dataset served as an external validation dataset to validate the model and PRGs via receiver operating characteristic (ROC) curves. The NetworkAnalyst online tool was utilized to create a ceRNA network of lncRNAs and miRNAs around PRGs mostly associated with sepsis. Results: A total of 170 genes associated with sepsis and 13 hub genes were acquired by WGCNA and PPI network analysis. The results of the enrichment analysis implied that these genes were mainly involved in the regulation of the inflammatory response and the positive regulation of bacterial and fungal defence responses. The prolactin signalling pathway and IL-17 signalling pathway were the primary enrichment pathways. Thirty-three PRGs can effectively classify septic patients into two subtypes, implying that there is a reciprocal relationship between sepsis and pyroptosis. Eventually, NLRC4 was considered the PRG most strongly associated with sepsis. The validation results of the prediction model and NLRC4 based on ROC curves were 0.74 and 0.67, respectively, both of which showed better predictive values. Meanwhile, the ceRNA network consisting of 6 lncRNAs and 2 miRNAs was constructed around NLRC4. Conclusion: NLRC4, as the PRG mostly associated with sepsis, could be considered a potential target for treatment. The 6 lncRNAs and 2 miRNAs centred on NLRC4 could serve as a further research direction to uncover the deeper pathogenesis of sepsis. [ABSTRACT FROM AUTHOR]

Background: In hospitalized patients, drug side effects usually trigger intestinal mucositis (IM), which in turn damages intestinal absorption and reduces the efficacy of treatment. It has been discovered that natural polysaccharides can relieve IM. In this study, we extracted and purified homogenous polysaccharides of Wuguchong (HPW), a traditional Chinese medicine, and explored the protective effect of HPW on 5-fluorouracil (5-FU)-induced IM. Methods and results: First, we identified the physical and chemical properties of the extracted homogeneous polysaccharides. The molecular weight of HPW was 616 kDa, and it was composed of 14 monosaccharides. Then, a model of small IM induced by 5-FU (50 mg/kg) was established in mice to explore the effect and mechanism of HPW. The results showed that HPW effectively increased histological indicators such as villus height, crypt depth and goblet cell count. Moreover, HPW relieved intestinal barrier indicators such as D-Lac and diamine oxidase (DAO). Subsequently, western blotting was used to measure the expression of Claudin-1, Occludin, proliferating cell nuclear antigen, and inflammatory proteins such as NF-κB (P65), tumour necrosis factor-α (TNF-α), and COX-2. The results also indicated that HPW could reduce inflammation and protect the barrier at the molecular level. Finally, we investigated the influence of HPW on the levels of short-chain fatty acids, a metabolite of intestinal flora, in the faeces of mice. Conclusions: HPW, which is a bioactive polysaccharide derived from insects, has protective effects on the intestinal mucosa, can relieve intestinal inflammation caused by drug side effects, and deserves further development and research. [ABSTRACT FROM AUTHOR]

At present, the pedicle screw is the most commonly used internal fixation device. However, there are many kinds of common posterior pedicle screw insertion techniques performed to reconstruct the lumbar stability. Therefore, spinal surgeons often face a difficult choice. The stress distribution of internal fixation system is an important index for evaluating safety. Unfortunately, little had been known about the difference of stress distribution of screw-rod systems that established by Roy-Camille, Magerl and Krag insertion techniques. Here, combination of finite element analysis and model measurement research was adopted to evaluate the difference of stress. Following different pedicle screw insertion techniques, three lumbar posterior surgery models were established after modeling and validation of the L1–S1 vertebrae finite element model. By analyzing the data, we found that stress concentration phenomenon was in all the postoperative models. Roy-Camille and Magerl insertion techniques led to the great stress on screw-rod systems. Then, fresh frozen calf spines were selected as a model for subsequent measurements. Fitted with a specially designed test pedicle screw, L5–L6 vertebrae were selected to repeat and verify the results of the finite element analysis. With the aid of universal testing machine and digital torque wrench, models simulated flexion, extension, lateral bending and rotation. Finally, the strain value was captured by the strain gauge and was then calculated as the stress value. Krag and Magerl were found to be the safer choice for pedicle screw insertion. Overall, our combination method obtained the reliable result that Krag insertion technique was the safer approach for pedicle screw implantation due to its relatively dispersive stress. Therefore, without the consideration of screw size, pedicle fill, bone density, and bone structures, we recommend the Krag insertion technique as the first choice to reconstruction of lumbar stability. Additionally, the combination method of finite element analysis and strain gauge measurement can provide a feasible way to study the stress distribution of spinal internal fixation. [ABSTRACT FROM AUTHOR]

Development of new effective antimicrobial drugs is still a big challenge to date due to microbial infection remains an inevitable problem against human health. In this study, fatty acids extract of Lucilia sericata larvae (LFAs) was obtained and evaluated by gas chromatograph-mass spectrometry (GC-MS), and its antibacterial activity against Staphylococcus aureus (S. aureus) and Streptococcus pneumoniae (S. pneumoniae) was investigated. We found that LFAs exhibited effective antibacterial activity against S. aureus and S. pneumoniae with minimal inhibitory concentrations (MICs) of 125 μg/mL and 100 μg/mL, respectively. The bacterial wall and membrane were the main targets, which was confirmed by fluorescence microscopy, scanning electron microscopy and transmission electron microscopy. Furthermore, a notable anti-biofilm activity against S. aureus and S. pneumoniae was also observed, which was able to both prevent biofilm formation and eradicate mature biofilms of these bacteria. As a promising antibacterial agent, LFAs showed good application prospects in clinical practice. [ABSTRACT FROM AUTHOR]

Brachial-ankle pulse wave velocity (baPWV) has been shown to correlate with a host of disorders associated with arterial stiffness. Type 2 diabetes is associated with the involvement of both small vessels and large vessels. Studies on the relevance of baPWV to early diabetic nephropathy are scarce. This retrospective observational case-control study enrolled 120 patients with type 2 diabetes from our medical records. We classified patients into two groups depending on the magnitude of albuminuria: 60 patients with microalbuminuria were classified as the early diabetic nephropathy group (EDN group) and 60 patients without albuminuria were classified as the diabetes without nephropathy group (DWN group). An additional 30 nondiabetic age- and sex-matched controls were also enrolled. Data regarding the lipid profile, blood pressure, baPWV, high-sensitivity C reactive protein (hs-CRP) level, anthropometric measurements, urine albumin/creatinine ratio (UACR), serum creatinine level, and glycemic control indices (i.e., fasting plasma glucose (FPG), postprandial glucose (PPG), and glycosylated hemoglobin (hemoglobin A1c, HbA1c)) were recorded for all enrolled participants. baPWV was significantly higher in the EDN group than in the DWN group. Moreover, baPWV was positively correlated with age, duration of diabetes, obesity, poor glycemic control, and high serum levels of triglycerides (TG), hs-CRP, creatinine, and uric acid as well as a high UACR (all P < 0.01). A significant negative correlation was found between baPWV and high-density lipoprotein levels (P < 0.05). Multivariate regression analysis showed that the hs-CRP level and duration of diabetes most strongly influenced baPWV. baPWV may be a convenient, noninvasive, and reproducible method for detecting early diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Aims: The objective is to investigate the effects of liraglutide on nonalcoholic fatty liver disease in type 2 diabetes mellitus. Materials and methods: Thirty-two patients with T2DM and NAFLD admitted to the Third Affiliated Hospital of Dalian Medical University from December 2014 to December 2016 were selected, including 11 females and 21 males, aged 39.34 ± 8.54 years old. The patients were given liraglutide on the basis of their original hypoglycemic regimen. Results: After 3 months treatment of liraglutide, FPG was reduced from 8.54 ± 2.21 mmol/L to 6.90 ± 1.73 mmol/L. HbA1c was reduced from 9.72 ± 1.95 to 7.78 ± 1.99. WC was reduced from 103.27 ± 9.92 kg to 93.97 ± 8.35 kg. BMI was reduced from 30.56 ± 4.06 kg/m2 to 28.01 ± 3.12 kg/m2. FLI was reduced from 79.23 ± 16.56 to 58.83 ± 19.75. The differences were statistically significant (p < 0.001). TG was reduced from 2.95 ± 2.13 mmol/L to 2.27 ± 1.31 mmol/L. The difference was significant (p < 0.01). Meanwhile, HOMA-IR was reduced from 1.504 ± 0.002 to 1.503 ± 0.002. GGT was reduced from 62.63 ± 71.61 U/L to 38.13 ± 30.13 U/L. AST was reduced from 27.25 ± 13.74 U/L to 25.44 ± 16.69 U/L. The differences were statistically significant (p < 0.05). After treatment, FCP, TC, HDL-C, LDL-C, ALT, and HOMA-β were also improved compared with before treatment, but the difference was not statistically significant (p > 0.05). Conclusion: In addition to effectively lowering glucose and improving islet resistance, liraglutide could also improve obesity and adjust blood lipids. However, the improvement of islet function might not be significant after 3 months of treatment. Liraglutide could reduce liver fat accumulation in patients with T2DM and NAFLD. [ABSTRACT FROM AUTHOR]

Background: Obesity is a severe public health threat worldwide. Emerging evidence suggests that gut microbiota dysbiosis is closely associated with obesity and its related metabolic complications. The aim of the present study is to investigate the effects of polysaccharide extracted from WuGuChong (PEW) on high-fat diet (HFD)-induced obesity, and the potential mechanisms involving modulation of the gut microbiota composition. Methods: Mice were fed a normal chow diet and a high-fat diet with or without PEW (300 mg/kg/day) by oral gavage for 8 weeks. Body weight, obesity-related metabolic disorders, and gut microbiota were examined at the end of the experiment. Results: PEW supplementation reduces body weight, adipose hypertrophy, liver steatosis, insulin resistance and systemic inflammation in HFD-fed mice, as well as maintains intestinal epithelium integrity. High-throughput 16S rRNA analysis demonstrates that PEW supplementation alters the composition of gut microbiota. The Firmicutes to Bacteroidetes ratio and the relative abundance of Proteobacteria are increased in HFD-fed mice, which are reversed by PEW supplementation to approximately the control levels. Conclusions: Our results suggest that PEW may be used as a bioactive ingredient to prevent obesity and its related metabolic disorders by modulating the composition of gut microbiota. [ABSTRACT FROM AUTHOR]

The calcaneus is a rare location for the occurrence and development of primary tumour types. Clinicians are unfamiliar with calcaneal tumour types, which may result in a delay in diagnosis or a missed diagnosis, resulting in unnecessary morbidity and amputation. Heel pain and localized swelling of the ankle are the most common symptoms. X‑ray is the first choice for a tentative diagnosis of a calcaneal tumour. The final diagnosis depends on a histological examination. The treatment of calcaneal tumour types varies depending on the Enneking system. The majority of patients with benign tumours heal, except for a few with a palindromia. For malignant tumours, the prognosis is comparatively poor, resulting in disability and a high rate of metastasis. This review describes the spectrum of calcaneal tumour types and specifically illustrates the epidemiology, symptomatology, imagology, histopathology and treatment options that may facilitate diagnosis and improve prognosis. [ABSTRACT FROM AUTHOR]

In the last decade, maggot has been hailed as the miraculous “medicinal maggot” for its diverse properties, including antimicrobial, antibiofilm, anti-inflammatory, and wound healing activities. The fact that maggots show so many beneficial properties has increased the interest in these tiny larvae dramatically. Whilst there is relatively abundant clinical evidence to demonstrate the success of maggots as debridement agents, not so much emphasis has been placed on the basic science evidence, which was a combination of physical and biochemical actions. This review differs from those earlier works in that it is undertaken to provide an update of the latest scientific basis published on maggot, particularly active ingredients within maggot excretions/secretions (ES). Further investigations should focus on the isolation, identification, recombination, transgenosis, and mass production of the beneficial molecules within maggots. [ABSTRACT FROM AUTHOR]

Annexins are a group of calcium- and phospholipid-dependent proteins. As a member of the annexin, annexin A2 (Anxa2) is widely distributed in nucleus, cytoplasm and extracellular surface and mainly expressed in human endothelial cells, mononuclear cells, macrophages, marrow cells and some tumor cells. Accumulated evidences indicated that Anxa2 deregulation was associated with the occurrence, invasion and metastasis of cancers. Anxa2 up-regulation was related to the development, invasion, metastasis and drug resistance of hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, acute promyelocytic leukemia and renal cell carcinoma; while Anxa2 down-regulation was associated with prostate cancer, esophageal squamous carcinoma and nasopharyngeal carcinoma and sinonasal adenocarcinoma. The association between Anxa2 and malignant tumors as well as the potential action mechanisms were summarized in current work. Anxa2 might be used as a potential biomarker for the diagnosis, treatment and prognosis of certain tumors. [ABSTRACT FROM AUTHOR]

Lymph node metastasis (LNM) is recognised as an important factor involved in malignant tumour progression by interfering with a favourable prognosis. It is involved in a variety of cancers. Proteins are believed to play important roles in the LNM of cancers. The rapid achievements of state-of-the-art proteomic techniques have emerged as the key technologies successfully applied to identify markers for cancers at high-throughput level by providing novel targets and creating possible therapeutic interventions in cancer research. This review summarises recent progress in proteomic research in hepatocarcinoma, gastric cancer, oesophageal cancer, colorectal cancer, breast cancer, lung cancer and nasopharyngeal cancer. Actin, heat-shock proteins (HSPs), annexins, cytokeratin 10 (CK10), CK19, protein gene product 9.5 (PGP9.5) and protein disulfide isomerase (PDI) are the most common proteins in lymphatic metastases of cancers revealed by proteomic and protein functional studies. Other protein candidates specifically associated with LNMs of certain cancers are also summarised and discussed. [ABSTRACT FROM AUTHOR]

Background: Lateral mass screw fixation (LSF) techniques have been widely used for reconstructing and stabilizing the cervical spine; however, complications may result depending on the choice of surgeon. There are only a few reports related to LSF applications, even though fracture fixation has become a severe complication. This study establishes the three-dimensional finite element model of the lower cervical spine, and compares the stress distribution of the four LSF techniques (Magerl, Roy-Camille, Anderson, and An), following laminectomy -- to explore the risks of rupture after fixation.Method: CT scans were performed on a healthy adult female volunteer, and Digital imaging and communication in medicine (Dicom) data was obtained. Mimics 10.01, Geomagic Studio 12.0, Solidworks 2012, HyperMesh 10.1 and Abaqus 6.12 software programs were used to establish the intact model of the lower cervical spines (C3-C7), a postoperative model after laminectomy, and a reconstructive model after applying the LSF techniques. A compressive preload of 74 N combined with a pure moment of 1.8 Nm was applied to the intact and reconstructive model, simulating normal flexion, extension, lateral bending, and axial rotation. The stress distribution of the four LSF techniques was compared by analyzing the maximum von Mises stress.Result: The three-dimensional finite element model of the intact C3-C7 vertebrae was successfully established. This model consists of 503,911 elements and 93,390 nodes. During flexion, extension, lateral bending, and axial rotation modes, the intact model's angular intersegmental range of motion was in good agreement with the results reported from the literature. The postoperative model after the three-segment laminectomy and the reconstructive model after applying the four LSF techniques were established based on the validated intact model. The stress distribution for the Magerl and Roy-Camille groups were more dispersive, and the maximum von Mises stress levels were lower than the other two groups in various conditions.Conclusion: The LSF techniques of Magerl and Roy-Camille are safer methods for stabilizing the lower cervical spine. Therefore, these methods potentially have a lower risk of fixation fracture. [ABSTRACT FROM AUTHOR]