Biomedical reports最新文献

Most patients with active pulmonary tuberculosis (TB) are difficult to be differentiated from pneumonia (PN), especially those with acid-fast bacillus smear-negative (AFB^-) and interferon-γ release assay-positive (IGRA⁺) results. Thus, the aim of the present study was to develop a risk model of low-cost and rapid test for the diagnosis of AFB^- IGRA⁺ TB from PN. A total of 41 laboratory variables of 204 AFB^- IGRA⁺ TB and 156 PN participants were retrospectively analyzed. Candidate variables were identified by t-statistic test and univariate logistic model. The logistic regression analysis was used to construct the multivariate risk model and nomogram with internal and external validation. A total of 13 statistically differential variables were compared between AFB^- IGRA⁺ TB and PN by false discovery rate (FDR) and odds ratio (OR). By integrating five variables, including age, uric acid (UA), albumin (ALB), hemoglobin (Hb) and white blood cell counts (WBC), a multivariate risk model with a concordance index (C-index) of 0.7 (95% CI: 0.61, 0.8) was constructed. The nomogram showed that UA and Hb acted as protective factors with an OR <1, while age, WBC and ALB were risk factors for TB occurrence. Internal and external validation revealed that nomogram prediction was consistent with the actual observations. Collectively, it was revealed that an integration of five biomarkers (age, UA, ALB, Hb and WBC) may be used to quickly predict TB in AFB^- IGRA⁺ clinical samples from PN.

Systemic chemotherapy, the standard first-line treatment option for patients with advanced oesophageal squamous cell carcinoma (OSCC), results in a median survival of ~1 year. Immune checkpoint inhibitors are a breakthrough oncology treatment option; however, most patients with advanced OSCC develop primary and acquired resistance to programmed death receptor-1 (PD-1) monoclonal antibody, severely affecting their prognosis. Therefore, there is an urgent need to investigate the molecular mechanism underlying resistance to treatment. The present study aimed to explore the mechanism of resistance to PD-1 monoclonal antibody. Plasma samples were collected from patients with OSCC treated with immunotherapy, who achieved pathological response/partial response (CR/PR) or stable disease/progressive disease (SD/PD) after the fourth treatment cycle. TM-widely targeted metabolomics, widely targeted lipidomics, and DIA proteomics assays were performed. Differential metabolites were screened based on fold change (FC) ≥1.5 or ≤0.67 and a VIP ≥1; differential proteins were screened based on FC >1.5 or <0.67 and P<0.05. The identified metabolites were annotated and mapped using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases. The differential proteins were annotated to the Gene Ontology and KEGG pathway databases. A correlation network diagram was drawn using differential expressed proteins and metabolites with (Pearson correlation coefficient) r>0.80 and P<0.05. Finally, 197 and 113 differential metabolites and proteins were screened, respectively, in patients with CR/PR and SD/PD groups. The KEGG enrichment analysis revealed that all of these metabolites and proteins were enriched in cholesterol metabolism and in the NF-κB and phospholipase D signalling pathways. The present study is the first to demonstrate that PD-1 inhibitor resistance may be attributed to cholesterol metabolism or NF-κB and phospholipase D signalling pathway activation. This finding suggests that targeting these signalling pathways may be a promising novel therapeutic approach in OSCC which may improve prognosis in patients undergoing immunotherapy.

Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease with rapid development to end stage renal disease, requiring renal replacement therapy. Genome-wide studies suggest geographical variations in genetic susceptibility to IgAN and disease progression. Specific 'candidate genes' were indicated to correlate with different functions that are involved in the pathogenesis of renal conditions. MicroRNAs (miRNAs/miRs) have a major role in mRNA degradation or translation repression, thereby regulating the expression of their target proteins. Previously, a small number of miRNAs were reported to have direct associations with IgAN. In the present study, new miRNAs linked to IgAN were identified in the Indian population. The miRNA was isolated from kidney biopsies of patients with IgAN (n=6) and healthy control tissue from patients with renal cell carcinoma (n=6). The sequencing results indicated that the miRNA percentage acquired from controls and patients with IgAN was 5.61 and 4.35%, respectively. From the results, 10 upregulated and 15 downregulated miRNAs were identified. Of the 25 differentially expressed miRNAs (DEMs), miR-181a-5p, miR-28-3p, let-7g-5p, miR-92a-3p and miR-30c-5p were not reported previously. Furthermore, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses suggested that the target genes of the DEMs were mainly enriched in pathways such as cancer, ErbB signalling, proteoglycans in cancer, Hippo signalling and MAPK pathways. The newly identified miRNAs may impact the behaviour of tissues or IgA deposition by regulating signalling pathways, which forms a basis for future studies aimed at improving the diagnosis and care of patients with IgAN in the Indian community.

The aim of the present study was to investigate the protective effect of Gastrodia elata Blume (GEB) against Caenorhabditis elegans (C. elegans) in Alzheimer's disease (AD) through network pharmacology. Firstly, the active constituents of GEB through ETCM and BATMAN-TCM databases were collected and its potential AD-related targets in Swiss Target Prediction were predicted. The potential targets related to AD were collected from the GeneCards, OMIM, CTD and DisGeNET databases, and the differential genes (DEGs) between the normal population and the AD patient population in GSE5281 chip of the Gene Expression Omnibus database were collected at the same time. The intersection of the three targets yielded 59 key targets of GEB for the treatment of AD. The drug-active ingredient-target-AD network diagram was constructed and visualized with Cytoscape software to obtain the core components. Subsequently, protein-protein interaction analysis (PPI) was performed on 59 key targets through STRING database, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses was performed on 59 key targets. Finally, molecular docking was conducted between core components and core targets using AutoDock software, and the C. elegans AD model was used for experimental verification to explore the regulatory paralysis effect of core components on the C. elegans model, β-amyloid (Aβ) plaque deposition, and quantitative polymerase chain reaction verification of the regulatory effect of components on targets. The GEB components 4,4'-dihydroxydiphenyl methane (DM) and protocatechuic aldehyde (PA) were found to be most strongly associated with AD, and five core targets were identified in the PPI network, including GAPDH, EP300, HSP90AB1, KDM6B, and CREBBP. In addition to GAPDH, the other four targets were successfully docked with DM and PA using AutoDock software. Compared with the control group, 0.5 mM DM and 0.25 mM PA significantly delayed C. elegans paralysis (P<0.01), and inhibited the aggregation of Aβ plaques in C. elegans. Both DM and PA could upregulate the expression level of core target gene HSP90AB1 (P<0.01), and DM upregulated the expression of KDM6B (P<0.01), suggesting that DM and PA may be potential active components of GEB in the treatment of AD.

Honey is a natural product derived from the insect Apis mellifera. Approximately 200 different compounds are included, making it a complex mixture with antimicrobial, antioxidant, and antidiabetic activity. Flavonoids and phenolic acids contained in honey are associated with its antioxidant capacity via mechanisms such as hydrogen donation and metallic ion chelation, although the exact antioxidant mechanism remains unknown. The aim of the present study was to: i) Estimate the antioxidant activity of a natural honey-based gel, commercially available under the trade name of 'Bear Strength honey gel' and to ii) assess the physiological and redox adjustments obtained after its consumption in healthy adult participants. For this purpose, 20 healthy participants (10 men and 10 women) included in their habitual diet 70 g of the honey-based gel for 14 days in a row. Pre- and post-consumption, physiological [weight, height, body mass index, body fat, waist-to-hip ratio, resting heart rate and blood pressure (BP)] and hematological (complete blood count) data were evaluated, along with the levels of five redox biomarkers: Glutathione (GSH), catalase (CAT), total antioxidant capacity (TAC), protein carbonyls (PCARBS) and thiobarbituric reactive substances (TBARS). The results revealed that the honey-based gel decreased the diastolic and mean arterial BP, especially in women, without affecting the rest of the physiological and hematological variables. Regarding the changes observed in antioxidant status variables, GSH was increased both in the total and women's group, while TAC was increased in all groups post-consumption. No changes were detected in the levels of CAT. Regarding oxidative stress, a decrease in the levels of TBARS in the total and women's group, was observed. PCARBS levels were decreased post-consumption only in the women's group. In conclusion, the present study demonstrated the potential positive effects of a honey-based gel on BP and redox status of healthy adults in a sex-specific manner.

Tyrosine kinase inhibitors are a clinically standard treatment option for non-small cell lung cancers (NSCLCs), the leading cause of cancer-related deaths in the US. These targeted agents include first, second and third generation tyrosine kinase inhibitors; however, these lack clinical efficacy in the treatment of NSCLC due to intrinsic and acquired resistance. This resistance may be a result of genetic aberrations in oncogenic signaling mediators of divergent pathways. The present study aimed to investigate a novel dual tyrosine kinase and PI3K inhibitor, PP121, as a targeted agent in NSCLC cell lines. The present study co-cultured PP121 with healthy human astrocytes, a prevalent cell type located in the brain of NSCLC brain metastases. To date, few preclinical studies have examined the efficacy of PP121 as an anticancer agent, and to the best of my knowledge, no previous studies have previously evaluated its therapeutic potential in the treatment of NSCLC. To investigate the clinical heterogeneity of NSCLC, patient-derived adenocarcinoma (ADC) and squamous cell carcinoma (SCC) xenograft models were used, which exhibited epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) factor amplifications. Notably, both EGFR and MET are known contributors to tyrosine kinase inhibitor resistance; thus, the aforementioned mutations and amplifications enabled the effects of PP121 to be evaluated in these solid tumors. In addition, a co-cultured model system using both NSCLC cells and astrocytes was employed to assess the effects of PP121 on the invasion of ADC and SCC cells in a multicellular environment. Results of the present study demonstrated that PP121 exerted an antitumorigenic effect in the aforementioned model systems via downregulation of pharmacodynamic targets.

The multiple endocrine neoplasia type 1 gene coding the protein menin was originally identified in patients with multiple endocrine tumors, and is mainly expressed in the cell nucleus. Multiple lines of evidence have indicated that menin acts as a tumor suppressor protein interacting with other various proteins. The mechanism of menin inhibiting tumorigenesis remains unclear. The present study analyzed the expression of menin and IQ motif-containing GTPase-activating protein 1 (IQGAP1) proteins in gastric cancer tissues and cell lines, and investigated the association between these two molecules. Western blotting was used to determine the quantity of target proteins. Cell proliferation was measured using MTT assay. It was found that the protein expression of menin was lower in gastric cancer tissues and AGS cells, while the protein expression of IQGAP1 was higher, compared with the levels observed in normal tissues and GES-1 cells. Ectopic expression of IQGAP1 stimulated the proliferation of gastric cancer cells, but did not affect the expression of menin. However, overexpression of menin inhibited the proliferation of gastric cancer cells. The inhibition was partly achieved through inhibiting the expression of IQGAP1, which was accompanied by inhibition of PI3K and NF-κB expression. Taken together, the present results suggest a novel function for menin and IQGAP1 contributing to suppress the proliferation of gastric cancer cells.

The present study aimed to investigate the effects of combined Phyllanthus emblica Linn. (PE) and simvastatin (SIM) on diabetic wounds in male BALB/C mice. Bilateral full thickness wound excisions were performed in the control and diabetic groups (45 mg/kg streptozotocin, intraperitoneally injected daily for 5 days). The diabetic mice received daily treatment with four different types of cream: Vehicle [diabetes mellitus (DM) + Vehicle group], 100% PE (DM + PE group), 5% SIM (DM + SIM group) and combined 100% PE + 5% SIM (DM + Combination group) for 4, 7 and 14 days. The tissue malondialdehyde (MDA) and IL-6 protein levels, the number of infiltrated neutrophils, and the percentages of wound closure (%WC), capillary vascularity (%CV) and re-epithelialization (%RE) were subsequently measured. The results indicated that in the DM + Combination group, %CV and %WC were significantly increased when compared with the DM + Vehicle group on days 7 and 14. The tissue MDA content on day 14, and the number of infiltrated neutrophils on days 4 and 7 were significantly reduced in the DM + Combination group compared with those in the DM + Vehicle group. Furthermore, a strong positive correlation was revealed between %CV and %WC in the five groups on day 7 (r=0.736; P=0.0003). These findings indicated that topical application of combined PE and SIM could enhance wound healing by upregulating angiogenesis and reducing neutrophil infiltration in mice with diabetic wounds.

Pneumonia is one of the most prevalent infections in the intensive care unit (ICU), where pneumonia may occur during hospitalization in the ICU as a complication. ICU patients with central nervous system (CNS) injuries are not an exception, and they may even be more susceptible to infections such as pneumonia due to issues such as swallowing difficulties, the requirement for mechanical ventilation, and extended hospital stay. Numerous common CNS injuries, such as ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage, can prolong hospital stay and increase the risk of pneumonia. Multidrug-resistant (MDR) microorganisms are a common and significant concern, with increased mortality in nosocomial pneumonia. However, research on pneumonia due to MDR pathogens in patients with CNS injuries is limited. The aim of the present review was to provide the current evidence regarding pneumonia due to MDR pathogens in patients with CNS injuries. The prevalence of pneumonia due to MDR pathogens in CNS injuries differs among different settings, types of CNS injuries, geographical areas, and time periods in which the studies were performed. Specific risk factors for the emergence of pneumonia due to MDR pathogens have been identified in ICUs and neurological rehabilitation units. Antimicrobial resistance is currently a global issue, although using preventive measures, early diagnosis, and close monitoring of MDR strains may lessen its impact. Since there is a lack of information on these topics, more multicenter prospective studies are required to offer insights into the clinical features and outcomes of these patients.