Investigating the therapeutic potential of Bifidobacterium breve and Lactobacillus rhamnosus postbiotics through apoptosis induction in colorectal HT-29 cancer cells.

Background and Objectives: Colorectal cancer (CRC) is a prevalent form of cancer worldwide. Recent studies suggest that postbiotics derived from probiotic bacteria have the potential as an adjunct therapy for CRC. This study investigates the anti-cancer effects of Bifidobacterium breve (B. breve) and Lactobacillus rhamnosus (L. rhamnosus) postbiotics on the HT-29 cell line. Materials and Methods: Through MTT and scratch assay, we investigated the anti-proliferation and anti-migration effects of B. breve and L. rhamnosus postbiotics on HT-29 cells. Furthermore, postbiotic-mediated apoptosis was assessed by analyzing the expression of Bax, Bcl-2, and caspase-3. We also investigated the effects of B. breve postbiotics on the expression of three important genes involved in metastasis, including RSPO2, NGF, and MMP7. Consequently, we validated the expression of selected genes in twelve adenocarcinoma tissues. Results: The results demonstrated the significant impact of postbiotics on HT-29 cells, highlighting their ability to induce anti-proliferation, anti-migration, and apoptosis-related effects. Notably, these effects were more pronounced using B. breve postbiotics than L. rhamnosus. Additionally, B. breve postbiotics could inhibit metastasis through upregulation of RSPO2 while downregulating NGF and MMP7 expression in HT-29 cells. Conclusion: Our research suggests that postbiotic metabolites may be effective biological products for the prevention and treatment of cancer.

CTLA-4 expression and polymorphisms in Schizophrenia; a systematic review of literature.

Schizophrenia constitutes a severe psychiatric disorder with detrimental impacts on individuals, their support systems, and the broader economy. Extensive research has revealed a notable association between variations in the Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene and an increased susceptibility to schizophrenia.This study represents the first systematic review of the literature investigating the impact of CTLA-4 polymorphisms and expression on the development and progression of schizophrenia.Our investigation involved a comprehensive search strategy, using a combination of title, abstract, and MESH terms in four databases, including PubMed, Scopus, Web of Science, and Google Scholar, until August 29th, 2023. The complete texts of the identified records were obtained and rigorously assessed based on predefined exclusion and inclusion criteria. Out of the numerous records, a total of 88 were identified through the databases. 10 studies met the criteria; therefore, their quality was assessed and included in this systematic study. The records were then categorized into polymorphism and expression groups. Our investigation emphasizes an association between rs3087243, rs231779, rs231777, rs16840252, rs5742909, and rs231775 polymorphisms and the development of schizophrenia. The results demonstrate a correlation between CTLA-4 polymorphisms and schizophrenia, compelling the need for further research to thoroughly examine the role of CTLA-4 in schizophrenia and other psychiatric disorders.

Evaluation of the local and systemic pattern of sensitization to allergens in patients with adenotonsillar hypertrophy.

PURPOSE: Adenotonsillar hypertrophy (ATH) is a medical condition characterized by the enlargement or swelling of the tonsils. The role of allergy in ATH has not been persuasively evidenced. Therefore, we investigated the state of humoral immunity and the presence of specific immunoglobulin E (sIgE) in tissues and sera in children suffering from TH. METHODS: According to the skin prick test (SPT) result, 44 ATH children were divided into the atopic and non-atopic groups. The level of sIgE against 30 inhalants and food allergens in the sera and tissue homogenates was measured by a commercial allergy immunoblotting kit. In addition, we evaluated the following variables in both tonsillar tissue homogenates and serum: total IgE, IgA, IgM, IgG, and tissue eosinophil counts. RESULTS: Our results showed that 21 (47.7%) of patients with ATH were sensitized to at least one allergen in the adenotonsillar sample and/or sera. Only two patients were negative for sIgE in the atopic group, but in the non-atopic group, only one had positive sIgE results. In the atopic group, 19 (86.4%) patients had positive sIgE in tonsillar tissues, and 18 (81.8%) had sensitized serum. There were no statistical differences in the case of other antibodies except IgE levels between the two groups. The average eosinophilic count was significantly higher in atopic patients than in the non-atopic group. CONCLUSION: The results of this study support the role of allergy in the pathogenesis of ATH and confirmed local allergic inflammation in tonsillar tissue.

Holistic exploration of CHGA and hsa-miR-137 in colorectal cancer via multi-omic data Integration.

Colorectal cancer (CRC) ranks among the most widespread malignancies globally, with early detection significantly influencing prognosis. Employing a systems biology approach, we aimed to unravel the intricate mRNA-miRNA network linked to CRC pathogenesis, potentially yielding diagnostic biomarkers. Through an integrative analysis of microarray, Bulk RNA-seq, and single-cell RNA-seq data, we explored CRC-related transcriptomes comprehensively. Differential gene expression analysis uncovered crucial genes, while Weighted Gene Co-expression Network Analysis (WGCNA) identified key modules closely linked to CRC. Remarkably, CRC manifested its strongest correlation with the turquoise module, signifying its pivotal role. From the cohort of genes showing high Gene Significance (GS) and Module Membership (MM), and Differential Expression Genes (DEGs), we highlighted the downregulated Chromogranin A (CHGA) as a notable hub gene in CRC. This finding was corroborated by the Human Protein Atlas database, which illustrated decreased CHGA expression in CRC tissues. Additionally, CHGA displayed elevated expression in primary versus metastatic cell lines, as evidenced by the CCLE database. Subsequent RT-qPCR validation substantiated the marked downregulation of CHGA in CRC tissues, reinforcing the significance of our differential expression analysis. Analyzing the Space-Time Gut Cell Atlas dataset underscored specific CHGA expression in epithelial cell subclusters, a trend persisting across developmental stages. Furthermore, our scrutiny of colon and small intestine Enteroendocrine cells uncovered distinct CHGA expression patterns, accentuating its role in CRC pathogenesis. Utilizing the WGCNA algorithm and TargetScan database, we validated the downregulation of hsa-miR-137 in CRC, and integrated assessment highlighted its interplay with CHGA. Our findings advocate hsa-miR-137 and CHGA as promising CRC biomarkers, offering valuable insights into diagnosis and prognosis. Despite proteomic analysis yielding no direct correlation, our multifaceted approach contributes comprehensive understanding of CRC's intricate regulatory mechanisms. In conclusion, this study advances hsa-miR-137 and CHGA as promising CRC biomarkers through an integrated analysis of diverse datasets and network interactions.

Characterization of Wnt signaling pathway under treatment of Lactobacillus acidophilus postbiotic in colorectal cancer using an integrated in silico and in vitro analysis.

Colorectal cancer (CRC) is a prevalent and life-threatening cancer closely associated with the gut microbiota. Probiotics, as a vital microbiota group, interact with the host's colonic epithelia and immune cells by releasing a diverse range of metabolites named postbiotics. The present study examined the effects of postbiotics on CRC's prominent differentially expressed genes (DEGs) using in silico and in vitro analysis. Through single-cell RNA sequencing (scRNA-seq), we identified four DEGs in CRC, including secreted frizzled-related protein 1 (SFRP1), secreted frizzled-related protein 2 (SFRP2), secreted frizzled-related protein 4 (SFRP4), and matrix metallopeptidase 7 (MMP7). Enrichment analysis and ExpiMap, a novel deep learning-based method, determined that these DEGs are involved in the Wnt signaling pathway as a primary cascade in CRC. Also, spatial transcriptome analysis showed specific expression patterns of the SFRP2 gene in fibroblast cell type. The expression of selected DEGs was confirmed on CRC and normal adjacent tissues using Real-Time quantitative PCR (RT-qPCR). Moreover, we examined the effects of postbiotics extracted from Lactobacillus acidophilus (L. acidophilus) on the proliferation, migration, and cell cycle distribution of HT-29 cells using MTT, scratch, and flow cytometry assays. Our results showed that L. acidophilus postbiotics induce cell cycle arrest at G1 phase and also had anti-proliferative and anti-migration effects on HT-29 cells, while it did not exert anti-proliferative activity on control fibroblasts. Finally, we revealed that treating HT-29 cells with postbiotics can affect the expression of selected DEGs. We suggested that L. acidophilus postbiotics have therapeutic potential in CRC by modulating key genes in the Wnt pathway.

Deep learning applications in single-cell genomics and transcriptomics data analysis.

Traditional bulk sequencing methods are limited to measuring the average signal in a group of cells, potentially masking heterogeneity, and rare populations. The single-cell resolution, however, enhances our understanding of complex biological systems and diseases, such as cancer, the immune system, and chronic diseases. However, the single-cell technologies generate massive amounts of data that are often high-dimensional, sparse, and complex, thus making analysis with traditional computational approaches difficult and unfeasible. To tackle these challenges, many are turning to deep learning (DL) methods as potential alternatives to the conventional machine learning (ML) algorithms for single-cell studies. DL is a branch of ML capable of extracting high-level features from raw inputs in multiple stages. Compared to traditional ML, DL models have provided significant improvements across many domains and applications. In this work, we examine DL applications in genomics, transcriptomics, spatial transcriptomics, and multi-omics integration, and address whether DL techniques will prove to be advantageous or if the single-cell omics domain poses unique challenges. Through a systematic literature review, we have found that DL has not yet revolutionized the most pressing challenges of the single-cell omics field. However, using DL models for single-cell omics has shown promising results (in many cases outperforming the previous state-of-the-art models) in data preprocessing and downstream analysis. Although developments of DL algorithms for single-cell omics have generally been gradual, recent advances reveal that DL can offer valuable resources in fast-tracking and advancing research in single-cell.

Anti-inflammatory Effects of Ziziphus Jujube Mill on LPS-induced Acute Lung Injury in Mice.

Ziziphus Jujuba Mill (Z.J) is a well-known ethnomedical source of biologically active compounds with anti-inflammatory effects. However, its significance in acute lung injury (ALI) has never been studied. The present study aimed to explore whether Z.J could attenuate lipopolysaccharide (LPS)-induced inflammatory responses in an experimental model of ALI. Male BALB/c mice received an intratracheal administration of LPS (n=32) or phosphate buffer saline (PBS) (control, n=8). Within 1, 11, and 23 h post-LPS injection, mice were randomly assigned to receive intraperitoneal treatments of saline, dexamethasone (2 mg/kg), and 100 and 200 mg/kg of Z.J extracts, respectively. 24 h after intratracheal administration of LPS, bronchoalveolar lavage fluid and lung tissues were harvested and assessed for inflammatory cell influx, tumor necrosis factor-α (TNF-α) levels, and histological assessments. Treatment with Z.J extracts (100 and 200 mg/kg) and dexamethasone effectively reduced LPS-induced neutrophil and other inflammatory cell influx into the lung tissue compared to the untreated group. additionally, both doses of Z.J extracts (100 and 200 mg/kg) significantly ameliorated the lung wet-to-dry ratio and histopathological damage. Furthermore, compared to the untreated ALI mice, Z.J extract at the highest dose could significantly reduce the TNF-α level.   The present findings indicated that Z.J could effectively ameliorate LPS-induced ALI inflammatory responses and might be considered a promising alternative therapy for the ALI phenotype.

Immunotherapy of cancer in single-cell RNA sequencing era: A precision medicine perspective.

Immunotherapy has revolutionized cancer treatment and brought new aspects into tumor immunology. Effective immunotherapy will require using the suitable target antigens, optimizing the interaction between the antigenic peptide, the APC, and the T cell, and the simultaneous inhibitor of the negative regulatory process that inhibits immunotherapeutic effects and develop resistance. Tumor heterogeneity and its microenvironment is the leading cause of resistance in patients. Recently by emerging the single-cell RNA sequencing technology and its combination with immunotherapy, now we can specifically evaluate the mechanism of tumors in the face of immunotherapy agents at the single-cell resolution by detecting the transcriptional activity of immune checkpoints, screening neoantigens with high transcription levels, identifying rare cells, and other important processes. This review focuses on scRNA-seq, particularly on its application in cancer immunotherapy.

Anti-proliferative and apoptotic effects of Ziziphus Jujube on cervical and breast cancer cells.

OBJECTIVE: Ziziphus Jujube (Jujube) plant has exhibited numerous medicinal and pharmacological properties including antioxidant and anti-inflammatory effects. This study was carried out to investigate its anti-cancer and pro-apoptotic abilities in human cervical and breast cancer cells in vitro. MATERIALS AND METHODS: The cervical OV2008 and breast MCF-7 cancer cells were incubated with different concentrations of Jujube aqueous extraction (0-3 mg/ml) for various times (0-72 h). Cell viability was assessed by Trypan Blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of two apoptosis-related genes in treated cells evaluated by quantitative Real Time -PCR analysis. RESULTS: Jujube significantly inhibited cancer cell viability in a dose- and time- dependent manner. Herb-induced apoptosis was associated with enhanced expression of Bax and decreased Bcl2 gene leading eventually to a time-dependent six fold increase in the Bax/Bcl-2 ratio. CONCLUSION: These results indicated that Jujube may be a natural potential and promising agent to prevent or treat human cancers.