The Role of Probiotics in Managing Glucose Homeostasis in Adults with Prediabetes: A Systematic Review and Meta-Analysis.

Methods: The Preferred Reporting Items for Systematic Reviews and Analysis checklist was used. A comprehensive literature search of the PubMed, Embase, and Cochrane Library databases was conducted through August 2022 to assess the impact of probiotics on blood glucose, lipid, and inflammatory markers in adults with prediabetes. Data were pooled using a random effects model and were expressed as standardized mean differences (SMDs) and 95% confidence interval (CI). Heterogeneity was evaluated and quantified as I2. Results: Seven publications with a total of 550 patients were included in the meta-analysis. Probiotics were found to significantly reduce the levels of glycosylated hemoglobin (HbA1c) (SMD -0.44; 95% CI -0.84, -0.05; p = 0.03; I2 = 76.13%, p < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (SMD -0.27; 95% CI -0.45, -0.09; p < 0.001; I2 = 0.50%, p = 0.36) and improve the levels of high-density lipoprotein cholesterol (HDL) (SMD -8.94; 95% CI -14.91, -2.97; p = 0.003; I2 = 80.24%, p < 0.001), when compared to the placebo group. However, no significant difference was observed in fasting blood glucose, insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, interleukin-6, tumor necrosis factor-α, and body mass index. Subgroup analyses showed that probiotics significantly reduced HbA1c in adults with prediabetes in Oceania, intervention duration of ≥3 months, and sample size <30. Conclusions: Collectively, our meta-analysis revealed that probiotics had a significant impact on reducing the levels of HbA1c and HOMA-IR and improving the level of HDL in adults with prediabetes, which indicated a potential role in regulating blood glucose homeostasis. However, given the limited number of studies included in this analysis and the potential for bias, further large-scale, higher-quality randomized controlled trials are needed to confirm these findings. This trial is registered with CRD42022358379.

Genome-wide DNA methylation analysis of Astragalus and Danshen on the intervention of myofibroblast activation in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a chronic progressive interstitial lung disease of unknown etiology, is characterized by continuous damage to alveolar epithelial cells, abnormal repair of alveolar tissue, and alveolar wall scar formation. Currently, the recommended treatment for IPF in Western medicine is relatively limited. In contrast, traditional Chinese medicine and compound prescriptions show advantages in the diagnosis and treatment of IPF, which can be attributed to their multi-channel and multi-target characteristics and minimal side-effects. The purpose of this study was to further corroborate the effectiveness and significance of the traditional Chinese medications Astragalus and Danshen in IPF treatment. METHODS: We performed whole-genome methylation analysis on nine rat lung tissue samples to determine the epigenetic variation between IPF and non-fibrotic lungs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and quantitative reverse transcription polymerase chain reactions. RESULTS: We identified differentially methylated regions and 105 associated key functional genes in samples related to IPF and Chinese medicine treatment. Based on the methylation levels and gene expression profiles between the Chinese medicine intervention and pulmonary fibrosis model groups, we speculated that Astragalus and Salvia miltiorrhiza (traditionally known as Danshen) act on the Isl1, forkhead box O3, and Sonic hedgehog genes via regulation at transcriptional and epigenetic levels during IPF. CONCLUSIONS: These findings provide novel insights into the epigenetic regulation of IPF, indicate the effectiveness of Astragalus and Danshen in treating IPF, and suggest several promising therapeutic targets for preventing and treating IPF.

Establishing an evaluation index system of nursing quality for clinical drug trials: A Delphi study.

AIMS: To construct a quality evaluation index system for clinical drug trials nursing management and obtain the weight of all indicators. DESIGN: A mixed-method research design with a quantitative component was used, primarily qualitative. METHODS: Through a literature review and semi-structured interview, an expert consultation questionnaire on the quality of nursing evaluation indicators for clinical drug trials was developed in April 2021. Eighteen experts in clinical drug trial nursing, medical, and pharmacy conducted 2 rounds of consultation according to the Delphi method to determine the indicators for evaluating the quality of clinical drug trial nursing. The weights of each indicator were determined using analytic hierarchical analysis. RESULTS: The established quality evaluation system of clinical drug trial nursing mainly includes 3 first-level indicators, 12 second-level indicators, and 59 third-level indicators. The positive coefficients of the two rounds of expert consultation were 90%-100%, and the authority coefficients were 0.831 and 0.885, respectively; the coordination coefficients were 0.189 and 0.214, respectively. The consulting results and weight settings are reliable. The evaluation index system we constructed is in line with the characteristics of the clinical drug trial nursing profession, with clear index levels and strong clinical operability, which can provide a reference for the assessment, monitoring and improvement of nursing quality in clinical drug trials. It will also clarify how nurses contribute to subjects' safety.

Total synthesis and anti-inflammatory evaluation of violacin A and its analogues.

A concise total synthesis of an exceedingly potent anti-inflammatory agent violacin A as well as the preparation of thirty analogues of this lead from commercially available orcinol are described. Highlights of our synthetic efforts involve Friedel-Crafts acylation, the regioselective etherification and esterification of phenolic hydroxyl groups, and Baker-Venkatamaran rearrangement to form basic skeleton of violacin A. The deprotection reaction with Pd-catalytic was involved to avoid the elimination of the hemiacetal hydroxyl at C2. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO) production using lipopolysaccharide (LPS)-induced Raw264.7 cells. A range of violacin A derivatives 11b, 11d, 11f, 12e, 12g, 13g, 17d-g exhibited stronger anti-inflammatory effect than that of violacin A. Notably, halogeno-benzyloxy substituent at C-7 were favourable for anti-inflammatory activities of violacin A derivatives. Additionally, Western blot results indicated halogeno-benzyloxy derivatives inhibited pro-inflammatory cytokines releases correlated with the suppression of NF-κB signaling pathway.

Design, synthesis and antifungal evaluation of borrelidin derivatives.

Borrelidin, a nitrile containing 18-membered polyketide macrolide, display potent antifungal activity. In this study, a library of borrelidin derivatives were synthesized. Their structures were elucidated by detailed spectroscopic data analysis. The antifungal activity and cytotoxicity of these target compounds were evaluated by broth microdilution and 3-(4,5-dimethylthiazol-2-yl)-3,5-phenytetrazoliumromide (MTT) methods. Among forty-seven prepared analogues, compound 3b had the inhibitory effect on Candida albicans and Candida parapsilosis (MIC: 50 and 12.5 µg/mL, respectively). Furthermore, compounds 4n and 4r presented better antifungal activity against Aspergillus fumigatus with 12.5 µg/mL MIC value, which were insensitive to borrelidin. Preliminary structure-activity relationships (SAR) revealed that the ester analogues containing fragment -OCH2CH2N- had an important effect on the antifungal activity. Meanwhile, the molecular docking study indicated the carboxyl substituents in BN could provide extra interaction with pathogenic fungal threonyl-tRNA synthetase (ThrRS).

The semi-synthesis of novel andrographolide analogues and anti-influenza virus activity evaluation of their derivatives.

Two novel andrographolide analogues with the structural motif of Δ(8,17)-alkene exo-to-endo isomerization, AI78 and AI89, were semi-synthesized firstly. Two series of derivatives were designed and synthesized based on the synthetic pathway (including series I: olefin isomerizing to endocyclic Δ(8,9) and series II: olefin isomerizing to endocyclic Δ(7,8)). The anti-influenza virus activity in vitro for all derivatives was evaluated. Among the compounds synthesized, compound 38 with benzyl amino group showed the greatest potency against H3N2 and was approximately 1.5-fold more potent than that of Lianbizhi, andrographolide analogue used clinically in China. Adamantyl derivative, 43, presented the lowest toxicity, with a higher TC50 and TI values than Lianbizhi. The structure-activity relationships studies of the synthetic analogues indicated that the endocyclic Δ(7,8)-double bond is preferable for anti-viral effect. Furthermore, the introduction of the fatty amino attached to the rigid skeleton at C-17 is beneficial for activity.

Design, synthesis and biological evaluation of novel asperphenamate derivatives.

A series of novel asperphenamate derivatives were designed and synthesized, including series I (the A-phenyl group replaced with various aromatic heterocycles) and series II (the acyl group substituted by sulfonyl group). All compounds have been screened for their antiproliferative activity in vitro against MCF-7, HeLa, and BEL-7402 cell lines by the standard MTT method. Structure-activity relationship studies displayed the heterocycle type played an important role in activity. Six-membered ring derivatives displayed more potency than five-membered ring and the sulfonyl group in A-ring region made an important contribution to activity. Among all derivatives, tosyl derivative 8c exhibited the greatest potency in three human cancer cell lines. Especially in MCF-7 cells, the cellular potency of 8c was approximately 3.0-fold more potent than that of cisplatin. Firstly, the mechanism of cell death induced by 8c in MCF-7 cells was investigated. The results showed that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. Further studies indicated that 8c might induce autophagic cell death in HeLa and BEL-7402 cell lines.

Comparative serum proteomic analysis of serum diagnosis proteins of colorectal cancer based on magnetic bead separation and maldi-tof mass spectrometry.

BACKGROUND: At present, the diagnosis of colorectal cancer (CRC) requires a colorectal biopsy which is an invasive procedure. We undertook this pilot study to develop an alternative method and potential new biomarkers for diagnosis, and validated a set of well-integrated tools called ClinProt to investigate the serum peptidome in CRC patients. METHODS: Fasting blood samples from 67 patients diagnosed with CRC by histological diagnosis, 55 patients diagnosed with colorectal adenoma by biopsy, and 65 healthy volunteers were collected. Division was into a model construction group and an external validation group randomly. The present work focused on serum proteomic analysis of model construction group by ClinProt Kit combined with mass spectrometry. This approach allowed construction of a peptide pattern able to differentiate the studied populations. An external validation group was used to verify the diagnostic capability of the peptidome pattern blindly. An immunoassay method was used to determine serum CEA of CRC and controls. RESULTS: The results showed 59 differential peptide peaks in CRC, colorectal adenoma and health volunteers. A genetic algorithm was used to set up the classification models. Four of the identified peaks at m/z 797, 810, 4078 and 5343 were used to construct peptidome patterns, achieving an accuracy of 100% (> CEA, P < 0. 05). Furthermore, the peptidome patterns could differentiate the validation group with high accuracy close to 100%. CONCLUSIONS: Our results showed that proteomic analysis of serum with MALDI-TOF MS is a fast and reproducible approach, which may provide a novel approach to screening for CRC.

Identification of cancer stem cells from hepatocellular carcinoma cell lines and their related microRNAs.

The aim of this study was to identify cancer stem cells (CSC) from three hepatocellular carcinoma (HCC) cell lines and to screen for specific microRNAs (miRNAs) regulating CSCs. Side population (SP) phenotype analysis was used. Four factors in the staining process, the incubation time, shaking interval, culture time and Hoechst 33342 concentration were explored, respectively, to define the SP subtype. CSC characteristics of SP cells were verified by sphere-forming assay and tumorigenic ability in NOD/SCID mice. QPCR assay for 370 miRNAs was performed to identify the differential miRNA expression between SP and Non-SP (NSP) cells in the PLC/PRF/5 cell line. The selected miRNAs were tested again in SP and NSP cells from Huh-7 and Hep-3B cell lines by qPCR assay. All four factors influenced SP percentage, when the other three conditions were fixed, the optimal Hoechst 33342 concentrations determined were 11 µg/ml for PLC/PRF/5 cells, 4 µg/ml for Huh-7 and 5 µg/ml for Hep-3B cells. The resultant SP percentage was 0.73±0.12%, 0.49±0.04% and 0.63±0.08%, respectively. The purity of sorted SP cells was >85%. Floating spheres were formed by SP cells from all three cell lines, while NSP cells did not form a single floating sphere. Mice injected with SP cells on the right side formed more tumor masses compared to their counterpart NSP at the same injection dosage; qPCR profiling identified 27 differentially expressed miRNAs in PLC/PRF/5 cells. Subsequent qPCR assay showed that miR-9* and miR-194 were also downregulated in SP cells from Huh-7 and Hep-3B. The present study identified CSCs via SP and sphere-forming assay from three liver cancer cell lines. Altogether, 27 CSC-specific miRNAs were determined in PLC/PRF/5; miR-9* and miR-194 were identified as the common CSC-specific miRNAs across the three HCC cell lines.

Identification of tubulin beta chain, thymosin beta-4-like protein 3, and cytochrome b-c1 complex subunit 1 as serological diagnostic biomarkers of gastric cancer.

OBJECTIVE: Despite major advances in its diagnosis and treatment, gastric cancer (GC) remains a major life-threatening disease. Treatment of the disease is further aggravated by the lack of diagnostic biomarkers that can aid in the early detection of GC and promote its favorable prognosis. The present work aims to identify novel diagnostic biomarkers for GC. DESIGN AND METHODS: The present work is a case-control study that focuses on proteomic analysis of serum from healthy volunteers and GC patients using ClinProt profiling technology based on mass spectrometry. A pattern of proteins/peptides with the ability to differentiate the studied populations was identified. Deregulated proteins/peptides differentially expressed in the serum of patients compared with healthy volunteers were identified by mass spectroscopy. RESULTS: A pattern of proteins/peptides consisting of four protein/peptide peaks at m/z 1467, 1867, 2701, and 2094 was identified. These protein/peptide peaks were able to differentiate the studied populations with close to 100% sensitivity and specificity. Three of the deregulated proteins/peptides at m/z 1867, 2701, and 2094 were identified by mass spectroscopy (LTQ Orbitrap XL) as tubulin beta chain, thymosin beta-4-like protein 3, and cytochrome b-c1 complex subunit 1, respectively. CONCLUSIONS: The pattern of proteins/peptides identified in the present work shows great potential for GC diagnosis. Deregulated proteins of tubulin beta chain, thymosin beta-4-like protein 3, and cytochrome b-c1 complex subunit 1 may be involved in the pathogenesis of GC and serve as potential serological diagnostic biomarkers.

Serum peptidome patterns of colorectal cancer based on magnetic bead separation and MALDI-TOF mass spectrometry analysis.

Background. Colorectal cancer (CRC) is one of the most common cancers in the world, identification of biomarkers for early detection of CRC represents a relevant target. The present study aims to determine serum peptidome patterns for CRC diagnosis. Methods. The present work focused on serum proteomic analysis of 32 health volunteers and 38 CRC by ClinProt Kit combined with mass spectrometry. This approach allowed the construction of a peptide patterns able to differentiate the studied populations. An independent group of serum (including 33 health volunteers, 34 CRC, 16 colorectal adenoma, 36 esophageal carcinoma, and 31 gastric carcinoma samples) was used to verify the diagnostic and differential diagnostic capability of the peptidome patterns blindly. An immunoassay method was used to determine serum CEA of CRC and controls. Results. A quick classifier algorithm was used to construct the peptidome patterns for identification of CRC from controls. Two of the identified peaks at m/z 741 and 7772 were used to construct peptidome patterns, achieving an accuracy close to 100% (>CEA, P < 0.05). Furthermore, the peptidome patterns could differentiate validation group with high accuracy. Conclusions. These results suggest that the ClinProt Kit combined with mass spectrometry yields significantly higher accuracy for the diagnosis and differential diagnosis of CRC.

Serum peptidome patterns of breast cancer based on magnetic bead separation and mass spectrometry analysis.

BACKGROUND: Breast cancer is one of the most common cancers in the world, and the identification of biomarkers for the early detection of breast cancer is a relevant target. The present study aims to determine serum peptidome patterns for screening of breast cancer. METHODS: The present work focused on the serum proteomic analysis of 36 healthy volunteers and 37 breast cancer patients using a ClinProt Kit combined with mass spectrometry (MS). This approach allows the determination of peptidome patterns that are able to differentiate the studied populations. An independent group of sera (36 healthy volunteers and 37 breast cancer patients) was used to verify the diagnostic capabilities of the peptidome patterns blindly. An immunoassay method was used to determine the serum mucin 1 (CA15-3) of validation group samples. RESULTS: Support Vector Machine (SVM) Algorithm was used to construct the peptidome patterns for the identification of breast cancer from the healthy volunteers. Three of the identified peaks at m/z 698, 720 and 1866 were used to construct the peptidome patterns with 91.78% accuracy. Furthermore, the peptidome patterns could differentiate the validation group achieving a sensitivity of 91.89% (34/37) and a specitivity of 91.67% (33/36) (> CA 15-3, P < 0.05). CONCLUSIONS: These results suggest that the ClinProt Kit combined with MS shows great potentiality for the diagnosis of breast cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1501556838687844.

Discovery and verification of gelsolin as a potential biomarker of colorectal adenocarcinoma in the Chinese population: Examining differential protein expression using an iTRAQ labelling-based proteomics approach.

OBJECTIVE: To identify and validate potential biomarkers of colorectal adenocarcinoma using a proteomic approach. METHODS: Multidimensional liquid chromatography/mass spectrometry was used to analyze biological samples labelled with isobaric mass tags for relative and absolute quantitation to identify differentially expressed proteins in human colorectal adenocarcinoma and paired normal mucosa for the discovery of cancerous biomarkers. Cancerous and noncancerous samples were compared using online and offline separation. Protein identification was performed using mass spectrometry. The downregulation of gelsolin protein in colorectal adenocarcinoma samples was confirmed by Western blot analysis and validated using immunohistochemistry. RESULTS: A total of 802 nonredundant proteins were identified in colorectal adenocarcinoma samples, 82 of which fell outside the expression range of 0.8 to 1.2, and were considered to be potential cancer-specific proteins. Immunohistochemistry revealed a complete absence of gelsolin expression in 86.89% of samples and a reduction of expression in 13.11% of samples, yielding a sensitivity of 86.89% and a specificity of 100% for distinguishing colorectal adenocarcinoma from normal tissue. CONCLUSIONS: These findings suggest that decreased expression of gelsolin is a potential biomarker of colorectal adenocarcinoma.