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Approaches Based on Network Pharmacology and Molecular Docking to Predict the Molecular Mechanism of Plumbago zeylanicas Anti-Inflammatory Action
No full textBackground: The roots of Plumbago zeylanica (P. zeylanica) are widely utilized in the traditional medicine system, i.e., Ayurveda for the treatment of piles, inflammatory diseases, intestinal disorders, abdominal pain, and inflammation of the rectum. Previous experimental studies revealed the anti-inflammatory and antiarthritic activities of P. zeylanica. Because of the experimental and clinical effectiveness of the roots of P. zeylanica root in painful inflammatory conditions and rheumatic diseases, this study aimed to evaluate the network pharmacology to predict the phytoconstituents and signaling pathways of the antiarthritic effect of P. zeylanica. Methods: As per the first step in the network pharmacology analysis, the phytoconstituents were retrieved from the relevant database, and the drug targets as well as the disease targets were downloaded, from the relevant databases. From there, the common targets were obtained, and then, Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis to predict the pathways/processes by which these targets are involved in rheumatoid arthritis (RA). Further, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADME/T), molecular docking, and dynamics studies of the resultant bioactive compounds of P. zeylanica with the regulated proteins were evaluated. Results: At first, using the network pharmacology analysis, the key target proteins in RA were predicted, then the key pathways were predicted using PPI, GO, and KEGG enrichment analysis in the treatment effects of P. zeylanica on RA. These key pathways used to be the responses to oxygen-containing compounds, organic response, and cellular response to a chemical stimulus which are synchronized by cancer, Phosphoinositide 3-kinases/Ak strain transforming (PI3K/AKT) signaling, lipid and atherosclerosis, microRNAs in cancer, calcium signaling and fluid shear stress and atherosclerosis pathways which indicates the involvement of abnormal proliferation of the immune cells and inflammation which are the characteristic features of rheumatoid arthritis. Further, the molecular docking, dynamics, Induced Fit Docking (IFD), and ADME/T studies revealed that the bioactive ingredients of P. zeylanica strongly bind with the essential target proteins in the ambience of rheumatoid arthritis. Conclusion: Hence, this study revealed computationally predicted the key targets of P. zeylanica phytoconstituents specific to its anti-inflammatory action in alleviating rheumatoid arthritis
Bioengineered Grafts and Their Potential Applications in Advancing Knee Anterior Cruciate Ligament Reconstructive Surgery
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Effectiveness of Belimumab in the Treatment of Systemic Lupus Erythematosus and Its Impact on Improving the Quality of Life of Patients
Get PDFObjective: To analyze the efficacy of belimumab in the treatment of systemic lupus erythematosus (SLE) and its effect on improving the quality of life of Chinese patients. Methods: A retrospective study was conducted using the medical records of 52 SLE patients admitted between March 2021 and April 2022. These patients were divided into two groups: the control group and the monoclonal antibody group, with 26 cases in each group. Patients in the control group received standard SLE treatment, while those in the monoclonal antibody group received standard SLE treatment in addition to belimumab therapy. The clinical treatment effect, dosage of hormone drugs, SLE disease activity index (SLEDAI) score, peripheral blood B cell level, 36-item Short Form health survey questionnaire (SF-36) and adverse reactions before and after treatment were compared between the two groups. Results: The routine treatment plus belimumab resulted in higher efficacy than routine treatment alone (p < 0.05). The routine treatment plus belimumab led to a lower B cell as compared to the routine treatment alone (p < 0.05). The routine treatment plus belimumab was associated with higher quality of life (p < 0.05). The safety profiles of the two groups were similar (p > 0.05). Conclusion: Belimumab might be a viable strategy in the treatment of Chinese patients with SLE. Belimumab can significantly reduce the dosage of hormone drugs in patients, and effectively reduce the SLEDAI score and peripheral blood B cell level of patients, and is not linked to adverse reactions. Therefore, it is worth promoting widely
New Gene Markers Regulating the Process of Vascularization in Pig Preovulatory Oocytes during Growth and Maturation
No full textBackground: A frequent reason for in vitro fertilization failure is insufficient oocyte competence and difficulties in mimicking optimal in vivo conditions at the stage of in vitro maturation. This study aimed to identify the expression profile of genes associated with “vasculature development”, “circulatory system process”, “hemopoiesis”, “patterning of blood vessels” and “hemopoietic or lymphoid organ development” ontological groups during in vitro maturation of domestic pig oocytes. The goal was also to describe new genetic markers that can be used in assisted reproduction techniques. Methods: Porcine oocytes were subjected to in vitro maturation, and the expression of selected genes was compared before and after maturation. Microarray and reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis were performed on total RNA isolated from the samples. Additionally, immunocytochemical staining was performed and the histological morphology of ovaries was examined. Results: Regardless of the individual processes, the gene expression pattern remained the same and all 32 gene ontology biological process term-genes were represented in down-regulated gene sets. The greatest change in expression was shown by the Vascular Endothelial Growth Factor A (VEGFA) and the smallest by myoferlin (MYOF). Moreover, the expression of VEGFA was confirmed by immunohistochemical analysis of ovaries. Conclusions: The potential contribution of chosen genes to oocyte performance during in vitro maturation can enhance comprehension of the underlying processes in oocytes and their microenvironment. It may also improve the effectiveness of in vitro fertilization
The Role of Mechanically Isolated Stromal Vascular Fraction on Epithelial Proliferation during Burn Healing
No full textBackground: Burn healing consists of four stages, homeostasis, inflammation, proliferation, and remodeling. Burn treatment aims to avoid infection, enhance tissue recovery, and prevent scarring. Recently, regenerative therapy shifted from using fat that contains mesenchymal stem cells to using various types of cells isolated from fat tissue called Stromal Vascular Fraction (SVF). It can be isolated either enzymatically, using collagenase, or mechanically, using emulsification of fat and filtration of cells. Previous research showed that both enzymatical and mechanical isolation of SVF can enhance neovascularization, re-epithelization and reduce inflammation. However, the mechanism behind its therapeutic effect needs to be explored. This study aims to investigate the role of mechanical isolation of SVF on the re-epithelization stage of deep-partial thickness burn in Wistar rats. Methods: Eighteen Wistar rats were used in this experiment. Three rats were used for fat isolation. After burn induction, fifteen rats were grouped randomly as follows: the control group (5 rats) received intradermal injection of 1 mL saline, Silver Sulfadiazine (SSD) Cream group (5 rats) was treated with the cream, and the SVF group (5 rats) received intradermal injection of (1 × 106 cells/mL). All rats were euthanized at day 32 post-treatment. Morphological and histological examination for re-epithelization, measuring epithelial thickness and Ki-67 immunostaining was compared between all groups. Results: Wound contraction and re-epithelization were completed in all experimental groups. However, the epithelial thickness of the epidermis was higher in the SVF group than in the SSD group (p = 0.034). Ki-67 staining was higher in the SVF group than in the SSD group (p = 0.025). Conclusion: Mechanically-isolated SVF showed a positive effect on re-epithelization by increasing cell proliferation via the activation of Ki-67 thus increasing the epidermis thickness in a regulated way
Cinnamaldehyde Delays the Senescence of Mesenchymal Stem Cells by Maintaining Mitochondrial Homeostasis
No full textBackground: Stem cell exhaustion is a primary factor in human aging. The ability to delay aging by maintaining the steady state of stem cells has emerged as a crucial area of concern. However, the regulatory impact of Cinnamaldehyde (Cina) on stem cell senescence remains unknown. Therefore, this study aimed to elucidate the regulatory effect of Cina on the senescence of mesenchymal stem cells (MSCs). Methods: Physiological cell senescence model was established by cell subculture. Cell counting kit-8 (CCK-8) proliferation assay, continuous doubling experiment, Ki67 staining, and cell cycle assay were used to examine the impact of Cina on the proliferation of MSCs. Senescence-associated β-galactosidase (SA-β-gal) staining was used to evaluate the senescence of MSCs. Histone H3 trimethylated at lysine 9 (H3K9me3) staining was used to assess the stability of MSCs chromatin. Osteogenic and adipogenic induction tests were used to evaluate the differentiation potential of MSCs, and 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) staining was used to evaluate the mitochondrial membrane potential. Glutathione (GSH) assay was used to assess the intracellular redox status. Adenosine triphosphate (ATP) detection and the Seahorse test were used to detect the energy metabolism of cells. Additionally, real-time quantitative PCR (RT-PCR) was used to quantify the indexes associated with senescence, proliferation, and differentiation of MSCs. Moreover, changes in MSCs senescence-related signaling pathways were analyzed using transcriptome. Results: Cina significantly promoted the proliferation of MSCs, maintained their proliferation rate in prolonged exposure, and delayed their senescence (p < 0.05). Cina reduced the number of SA-β-gal posit mycoplasmaive cells, decreased the levels of senescence markers such as cyclin dependent kinase inhibitor 2A (P16), cyclin dependent kinase inhibitor 1A (P21), interleukin 6 (IL-6), and IL-8, and increased the level of Recombinant lamin B1 (LMNB1). Furthermore, Cina treatment increased the expression of H3K9me3, increased the number of Ki67 positive cells, and reversed cell cycle arrest (p < 0.05). Additionally, Cina upregulated the expression of pluripotency-related genes and downregulated senescence-related signaling pathways, such as P53 and RAS-associated protein 1 (RAP1). In osteogenic and adipogenic experiments, Cina was found to promote the differentiation of MSCs (p < 0.05). Furthermore, we observed that Cina substantially protected mitochondrial membrane potential from damage caused by passage replication, maintained intracellular redox balance, and promoted mitochondrial ATP production (p < 0.05). Conclusions: This study indicates that Cinnamaldehyde (Cina) can delay the senescence of MSCs by maintaining mitochondrial homeostasis, suggesting that Cina has a potential anti-aging effect
M1 Macrophage-Derived Exosomes Convert TAMs into an Anti-Tumor M1 Phenotype to Inhibit the Progression of Prostate Cancer
No full textBackground: Prostate cancer is the most common and solid malignancy among male tumors worldwide. Converting tumor-associated macrophages (TAMs) into anti-tumor M1 macrophages holds a promising potential for cancer treatment. Therefore, this study investigated whether M1 macrophage-derived exosomes affect prostate cancer progression by inducing TAM reprogramming into M1-like macrophages. Methods: LPS-induced RAW264.7 cells were polarized into M1-type macrophages. Exosomes isolated from the M1 macrophages (M1-exos) were observed using transmission electron microscopy (TEM), tracked by nanoparticle tracking analysis (NTA), and identified through western blot analysis. After this, M1-exos were co-cultured with human prostate cancer (PC-3) cells and interleukin-4 (IL-4)-induced M2-like macrophages. The effects of M1-exos on prostate cancer progression and TAM polarization were evaluated using cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, Transwell, and wound healing assays. Furthermore, to analyze the impact of M1-exos on prostate cancer progression by inducing TAM polarization, in vivo xenograft tumor models were constructed, followed by H&E staining, immunohistochemistry, and TdT-mediated dUTP nick end labeling (TUNEL) assays. Results: We successfully polarized immature M0 macrophages into an M1 phenotype using RAW264.7 cells and obtained M1-exos from these cells. Moreover, findings from both in vivo and in vitro experiments unveiled that M1-exos inhibited the proliferation (p < 0.05), invasion (p < 0.05), and migration of prostate cancer cells (p < 0.05). Additionally, M1-exos promoted apoptosis (p < 0.05) and induced the polarization of TAM into M1-type macrophages. Conclusion: M1-exos induced the polarization of TAM into the M1 phenotype with anti-tumor potential, thereby suppressing prostate cancer growth and metastasis. Therefore, M1-exos hold promising potential for treating prostate cancer
Probiotics and Recurrent Respiratory Infections in Children
No full textRecurrent respiratory infections (RRIs) represent a significant health concern among children, affecting 6% within their first six years and 25% before reaching one year old. Despite often presenting mild symptoms, these infections persist to varying degrees, typically decreasing in frequency until complete resolution by the age of twelve. However, the transient nature of RRIs disguises the considerable medical and social burdens they impose, notably diminishing the quality of life for affected children and their families. This comprehensive review aims to distil and synthesize findings from extensive research conducted over the past seventeen years, with a particular focus on understanding the role of probiotics in both preventing and treating RRIs. By compiling key insights from these studies, the review sheds light on the complex dynamics of RRIs and explores the potential of probiotics as a promising avenue for reducing the frequency and severity of these infections. Probiotics, defined as live microorganisms conferring health benefits, have garnered attention due to their immunomodulatory properties. Recent studies have investigated the efficacy of probiotics in preventing and treating RRIs, emphasizing their ability to modulate immune responses, enhance mucosal immunity, and maintain a balanced microbial environment within the respiratory tract. Through critical examination of accumulated evidence, this review aims to provide a nuanced understanding of the intricate interplay between RRIs, the evolving immune systems of children, and the potential therapeutic contributions of probiotics. By synthesizing findings from recent research, it seeks to contribute meaningfully to ongoing discussions on effective strategies for alleviating the burden of RRIs in pediatric populations. The insights gleaned from this review are poised to inform future interventions, guiding healthcare practitioners in devising targeted and effective approaches to managing and mitigating the impact of RRIs in children
Diagnostic Assessment of Breast Cancer with a Combination of the 21-Gene Recurrence Score, Clinicopathologic Parameters, and Biomarkers
Get PDFBackground: A chemotherapy regimen based on biomarkers in patients might be more efficient than standard therapy. In this study, we evaluated the extensive correlation between the 21-recurrence score (RS), candidate genes, patient demographics, histopathologic factors, and prognosis. We identified the risk factors that affect breast cancer progression, providing evidence for the breast cancer treatment. Methods: In this study, a total of 150 patients were analyzed, all of whom underwent a 21-gene RS score evaluation. The candidate genes evaluated in this study included thymidylate synthase (TYMS), ribonucleotide reductase M1 (RRM1), tubulin beta 3 class III (TUBB3), topoisomerase II alpha (TOP2A), and phosphatase and tensin homolog (PTEN) deleted on chromosome ten. Subsequently, we collected patient information regarding the types of endocrine therapy they received. Results: The 21-gene RS score was significantly correlated with the sentinel lymph node status (p = 0.045). Further investigations into the TYMS and RRM1 genes revealed that the genes are distinct factors involved in the progression of breast cancer. Additionally, human epidermal growth factor receptor 2 (HER2) staining was found to be a compelling indicator of disease progression. Specifically, grade ≥2 staining implies an advanced risk of disease progression. It was demonstrated that the combination of tumor node metastasis (TNM) stage, sentinel lymph node, and 21-gene RS data provides very convincing evidence for clinical application. Moreover, TYMS, RRM1, and HER2 are all independent factors that separately affect the progression of breast cancer. Conclusions: The 21-gene RS was closely associated with the sentinel lymph nodes status in breast cancer. Besides, TYMS, RRM1, and HER2 were identified as independent factors affecting breast cancer progression
IQGAP3 can Serve as a Promising Biomarker for the Diagnosis of Endometrial Cancer
Get PDFObjective: Endometrial cancer (EC), a prevalent malignancy in womens reproductive system, commonly occurs in uterine tissue. Due to its persistently high incidence despite considerable medical advancements, there is a need for the identification of novel diagnostic and treatment biomarkers. This study aims to investigate the potential of IQ motif-containing GTPase-activating protein 3 (IQGAP3) as a biomarker for early diagnosis of endometrial cancer and explore its significance in cervical cancer. Methods: This study utilized CaSki and Hela cell lines and employed siRNA/shRNA and scrambled control antisense for transfection experiments. However, the expression level of the gene was assessed using qPCR (Quantitative Polymerase Chain Reaction). Additionally, the involvement of IQGAP3 in the cell cycle pathway was elucidated through pathway analysis. Results: Tumor Immune Estimation Resource (TIMER) 2.0 data analysis showed that IQGAP3 exhibited significant overexpression in cancer groups (*p < 0.05), with elevated levels in EC samples compared to normal tissues (***p < 0.001). Furthermore, IQGAP3 showed significantly close association with survival prognosis (p < 0.05). Additionally, we observed that the knockdown of IQGAP3 inhibited cell proliferation in endometrial cancer cells. Conclusion: This study provides valuable insights into the role of IQGAP3 in cancer diagnosis and treatment. The findings suggest that IQGAP3 holds potential as a promising biomarker for endometrial cancer diagnosis and as a therapeutic target for its treatment