Asia Pacific Academy of Science Pte. Ltd.
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Kaempferol Protects against D-Galactose-Induced Premature Ovarian Failure and Endoplasmic Reticulum Stress in Ovarian Granulosa Cells by Promoting Estrogen Receptor 1 Expression
No full textBackground: The efficacy of Chinese herbal medicine on premature ovarian failure (POF) and possible targets of kaempferol (KAE) for treating POF are revealed. This study is designed to determine the efficacy of KAE, a major bioactive component of Tu Si Zi (Semen Cuscutae), on POF. Methods: Female C57BL/6 mice were divided into four groups and treated for 42 days as follows: control group (normal saline injection), KAE group (5 mg/kg/day KAE, tail vein injection), D-galactose (D-gal) group (200 mg/kg/day D-gal, subcutaneous injection for POF model), and D-gal + KAE group (both KAE and D-gal treatments). The number of ovarian follicles and the apoptosis of ovarian cells were assessed using Hematoxylin-Eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP Nick-End labeling (TUNEL) assay. Serum hormone levels were quantified using enzyme-linked immunosorbent assay (ELISA). The viability and apoptosis of D-gal-treated ovarian granulosa cells (OGCs) were detected using Cell Counting Kit-8 and flow cytometry assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used for gene expression quantification. Results: Tu Si Zi most probably regulated the genes related to the gamma-aminobutyric acid signaling pathway. D-gal treatment reduced body weight, the number of primordial, primary, secondary, and antral follicles, as well as the serum level of estradiol. It increased the levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and promoted the apoptosis of ovarian cells (p < 0.001). These effects were reversed via KAE (p < 0.001). D-gal repressed the mRNA and protein levels of estrogen receptor 1 (ESR1) in mice and OGCs, which could be reversed by KAE treatment (p < 0.001). Additionally, the effects of KAE on the viability and apoptosis and the protein levels of apoptosis-and endoplasmic reticulum stress-regulated factors in D-gal-treated OGCs were reversed via silencing ESR1 (p < 0.001). Conclusions: KAE has been found to protect against ovarian injury and endoplasmic reticulum (ER) stress by promoting ESR1, suggesting that KAE holds great promise for the treatment of POF
A Long Non-Coding RNA GATA6-AS1 Inhibits Gastric Intestinal Metaplasia through the Wnt/β-Catenin Pathway
No full textObjective: The Correa cascade explains the histopathological process of gastric carcinogenesis, including chronic non-atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia and gastric cancer (GC). IM is considered as a precancerous lesion of gastric cancer. Therefore, we aimed to identify stratification markers from IM that could predict GC occurrence and explore the mechanism of precancerous lesions. Methods: Whole-transcriptome sequencing (RNA-seq) was performed on 18 clinical gastric mucosal specimens from CNAG, CAG, IM, and GC. Based on weighted gene co-expression network analysis (WGCNA), key modules negatively related to the malignant transformation process were identified and hub genes were found. Expression of candidate lncRNAs (long non-coding RNAs) in human gastric tissues was detected by qRT-PCR (quantitative real-time polymerase chain reaction). Human gastric cell lines GES-1 were treated with chenodeoxycholic acid (CDCA). The GATA6-AS1 (GATA6 antisense RNA 1) overexpression vector and antisense oligonucleotides (ASO) were transfected into gastric cell lines and gastric cancer cell lines, respectively, and qRT-PCR and Western blotting evaluated their effects on the expression of IM markers and the Wnt/β-catenin pathway markers. Results: We constructed a hub gene and lncRNAs co-expression network and identified three candidate lncRNAs with the highest connectivity. The expression of GATA6-AS1 was markedly reduced in the IM group and further decreased in the GC group compared with the CNAG group. According to studies in vitro, GATA6-AS1 exhibited negative regulation of intestinal-specific transcription factor CDX2 (Caudal Type Homeobox 2) and its downstream IM marker KLF4 (kruppel-like factor 4) and MUC2 (mouse polyclonal mucin 2), as well as Wnt signaling pathway markers in GES-1 (The human normal gastric epithelial cell line) and SGC7901 cell lines. Furthermore, the overexpressed GATA6-AS1 could reverse CDCA-induced high expression of IM markers and inhibit Wnt signaling pathway marker. Conclusions: GATA6-AS1 possibly serves as the potential marker for IM and could reduce the expression of intestinal metaplasia markers by inhibiting the Wnt signaling pathway, thereby inhibiting the occurrence of IM and intestinal-type gastric cancer
Huai’er Qinggao Inhibits Hepatocellular Carcinoma Progression by Increasing LINC02154 Expression
No full textBackground: Aberrant expression of long non-coding RNAs (lncRNAs) is associated with various malignant tumors, including hepatocellular carcinoma (HCC). Huaier Qinggao is a traditional Chinese herbal medicine that exerts anti-cancer effects. In this study, we aimed to determine the roles and underlying molecular mechanisms of Huaier Qinggao in HCC via lncRNA sequencing. Methods: We determined the viability of the human HCC cell line, SMMC-7721, treated with Huaier Qinggao using the cell counting kit-8 assay. We also screened the differentially expressed (DE)-lncRNAs in Huaier Qinggao-treated HCC cells using lncRNA sequencing. Expression levels of four selected DElncRNAs and several markers associated with cell growth were determined using quantitative reverse transcription-polymerase chain reaction. Long intergenic non-protein coding RNA 2154 (LINC02154) was knocked down to determine its roles in apoptosis, migration, proliferation, and invasion of SMMC-7721 cells. Results: Huaier Qinggao significantly inhibited SMMC-7721 cell proliferation. Moreover, treatment with Huaier Qinggao (half-maximal inhibitory concentration) resulted in 341 upregulated and 359 downregulated DElncRNAs. LINC02154 expression levels were significantly increased in treated cells than in control cells. Moreover, inhibition of LINC02154 expression significantly rescued the effects of Huaier Qinggao on cell proliferation, clone formation, apoptosis, invasion, and expression of cell growth-related markers, such as cyclin B1, phosphatase and tensin homolog, (B cell lymphoma-2) Bcl-2, ras homolog family member A, and small mothers against decapentaplegic (SMAD) family member 2, in SMMC-7721 cells. Conclusions: Our results indicate that Huaier Qinggao inhibits HCC progression by upregulating LINC02154 expression
Natural Products for Omicron BA.1, BA.1.1 and BA.2 Therapy: Application of Medicinal Plants for Drug Delivery: A DFT & QM/MM Simulation
No full textBackground: Omicron currently accounts for over 85% of the pandemic cases in the world. Recently, the results of researches have exhibited that Omicron sub-lineages and B lineage (BA).4 and BA.5, evaluated to BA.1, BA.1.1 and BA.2, deserted neutralization from sera of triple vaccinated particulars to a bigger extension. The purpose of this study is because the Omicron variant is the most recent variant of concern (VOC) to emerge and was recognized by the World Health Organization (WHO). The Omicron lineage is phylogenetically distinct from earlier variants. These variants of Omicron threaten many lives, particularly among the unvaccinated, due to its higher transmissibility, pathogenicity. This study helps to realize the essential concepts of the Omicron variant, including its history, genome, transmissibility, clinical manifestations, diagnosis, management, and the effectiveness of existing vaccines against this VOC. Asafoetida (Ferula asafoetida) is known to possess antifungal, anti-diabetic, anti-inflammatory, anti-mutagenic and antiviral activities particularly anti coronavirus. Several studies investigated the effects of F. Asafoetida extract on the contractile responses induced by acetylcholine, methacholine, histamine and potassium chloride (KCl) on different smooth muscles. Methods: The method of this work basically is based on molecular mechanics with quantum approach which is known as quantum mechanics/molecular mechanics (QM/MM) method. In addition, for calculating the interaction energies between ligands and enzymes in the Nano-carriers systems containing carbon nanotubes with functional nanostructures, we used docking simulation via using the Gaussian, HyperChem, Chemoffice, Charmm, Autodock, and Schrodinger packages. In this research, asafoetida (asafoetida is also known colloquially as “devils dung" in English and similar names in most languages of the other countries) as a medicinal plant can be applied in treatment for Omicron sub-units BA.4 and BA.5 through adsorbing of its effective compound of ferulic acid on the surface of (m, m) armchair single-walled carbon nanotube. In addition, we simulated a drug delivery density functional theory (DFT) calculation (QM/MM methods). Results: In fact, the achieved results have represented that the feasibility of using (m, m) armchair single-walled carbon nanotube (SWCNT) (m = 6, 5) and ferulic acid are suitable in such drug delivery system due to physico-chemical properties of nuclear magnetic resonance (NMR), infrared (IR) and ultraviolet-visible (UV-VIS) spectroscopy. Conclusions: Asafoetida has attracted much attention for the clinical treatment of Omicron subvariants BA.4 and BA.5 through adsorption of its effective compound of ferulic acid on the surface of (6,6) armchair SWCNT which introduces an efficient drug delivery system though charge distribution, NMR and IR spectroscopy on the optimized structure. Moreover, the lowering gap energies (∆E = ELUMO – EHOMO) has illustrated the charge transfer interactions taking place within ferulic acid
Identification and Verification of FABP4 Regulate Ferroptosis in Ulcerative Colitis
No full textBackground: Ferroptosis has garnered increasing attention; however, relevant researches are insufficient. Methods: We incorporated two microarray datasets from Gene Expression Omnibus (GEO) and utilized the FerrDb website to identify ferroptosis genes. Differential expression analysis of ferroptosis-related genes and functional enrichment analysis were performed using R software. Machine learning technique was employed to screen for core genes and evaluate their correlation with immune cells, ultimately identifying core genes with diagnostic value. In vivo and in vitro experiments were conducted to confirm the relationship between the core gene and ulcerative colitis (UC) ferroptosis. We conducted a UC mouse model using 3% dextran sodium sulfate (DSS) free drinking water method. We detected the expression of Fatty Acid Biding Protein-4 (Fabp4), glutathione peroxidase 4 (Gpx4), ferritin heavy chain (Fth), protein kinase B (PKB, also named as Akt), Phosphatidylinositide 3-kinases (Pi3k), and interleukin-1β (IL-1β) in the mouse colon through quantitative real-time PCR (qPCR) and western blot (WB) analysis. Additionally, we performed an in vitro experiment using the THP-1 cell line. The cells were pretreated with Ferrostatin-1 (Fer-1) and FABP4 inhibitor (BMS 3094033) for 1 hour, followed by the addition of Erastin. We then measured the intracellular expression of FABP4, GPX4, FTH, AKT, PI3K, and IL-1β using qPCR and immunofluorescence. Results: FABP4 is a crucial gene in ulcerative colitis (UC). It is associated with the infiltration of immune cells like macrophages, dendritic cells, and neutrophils, as well as Phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway. In vivo experiments have demonstrated that the expressions of Fabp4, Fth, Pi3k, Akt, and Il-1β were elevated in the colon of UC mice, while the Gpx4 was reduced. In vitro experiments found that after adding FABP4 inhibitors, the expressions of FTH, PI3K, AKT, and IL-1β decreased, while GPX4 increased. Conclusions: FABP4 has been identified as a pivotal gene in the ferroptosis process in UC. It is suggested that FABP4 regulates the PI3K/AKT signaling pathway, thereby playing a crucial role in UCs ferroptosis development
Elevated Serum C-Reactive Protein to Lymphocyte Ratio is a Predictor of Pneumonia in Patients with Type 2 Diabetes Mellitus
No full textBackground: Type 2 diabetes mellitus is associated with an increased risk of certain infections, such as pneumonia. Timely diagnosis and treatment of infections is crucial in populations with diabetes. The C-reactive protein to lymphocyte ratio (CLR) has been proposed as a novel marker of inflammation. We studied the role of CLR in subjects with diabetes who had pneumonia. Methods: A total of 426 subjects with pneumonia and type 2 diabetes mellitus who presented to the pulmonology clinics of Hisar Intercontinental Hospital were enrolled in the study, and 161 patients with diabetes who had no pneumonia were enrolled as controls. Overall, 176 (66.4%) of the diabetic pneumonia group and 101 (62.7%) of the control subjects were men. C-reactive protein (CRP) was analyzed using Enzyme-Linked Immunosorbent Assay (ELISA) immune assay, and lymphocytes were counted by an automatic analyzer. The CLR levels of patients with diabetes comorbid with pneumonia were compared to those diabetics without pneumonia in the present cross-sectional study. Results: Median CLR levels of the patients with diabetes comorbid with pneumonia and control subjects were 28.7 (1.1–116)% and 1.9 (0.04–12.2)%, respectively (p < 0.001). The CLR of the participants was significantly and positively correlated with their white blood cell count (r = 0.21, p < 0.001) and serum creatinine levels (r = 0.2, p < 0.001). Receiver operating characteristic (ROC) analysis revealed that CLR (when higher than 5.73%) had 86% sensitivity and 91% specificity in detecting pneumonia in patients with diabetes (AUC (area under the curve): 0.945, p < 0.001, 95% CI (confidence interval): 0.926–0.964). The sensitivity and specificity of CLR was higher than separate values of C-reactive protein (76% sensitivity and 71% specificity when higher than 7.1 mg/L; AUC: 0.813, p < 0.001, 95% CI: 0.774–0.852) and blood leukocyte count (65% sensitivity and 70% specificity when higher than 7.9 k/mm3; AUC: 0.665, p < 0.001, 95% CI: 0.614–0.716). Conclusion: These findings suggest that CLR could be a useful marker in the timely diagnosis of pneumonia in populations with diabetes
Olfactory Marker Protein in the Human Carotid Body
No full textBackground: Transduction mechanisms of the hypoxic chemoreflex elicited by carotid body (CB) chemoreceptor cells remain unclear. Recent studies direct attention to the plausible link between CB and olfactory chemoreceptor functions. Methods: Here we used immunohistochemistry to investigate the distribution and localization of olfactory marker protein (OMP) in human CB. Carotid bodies were collected post-mortem from hospital patients aged 27–76 years who died from reasons unrelated to chronic pulmonary or cardiovascular disorders. We used specific antibodies to selectively identify CB cells and OMP in tissue sections. The binding of antibodies to target antigens was visualized with the Ultra Vision detection system. Results: We show that OMP is abundantly present in the cytoplasm of CB chemoreceptor cells. The presence of OMP in these cells indicates that the olfactory system may participate in shaping the chemosensory CB function. Conclusions: The findings support the notion that the transduction mechanisms of chemoreceptive systems contain a degree of homology, irrespective of the anatomical localization and the functional role these systems fulfill. The ectopic presence of OMP in CB broadens the current understanding of the mechanisms underlying chemosensory responses
Intervention Effect of Benzoylmesaconine on Slow Transit Constipation in Rats
No full textBackground: Slow transit constipation (STC) is a chronic gastrointestinal dysfunction that significantly impairs the quality of life for many individuals. This study aims to explore the role and mechanism of Benzoylmesaconine (BAC) in the treatment of STC. Methods: Rats were treated with loperamide (Lop) hydrochloride for 7 days to build the STC model. After that, they were given BAC concentrated solution and 0.2 g/L Mosapride via intragastric treatment. The rats body weight was monitored, and their intestinal propulsion rate was determined using the intestinal charcoal powder propulsion assay. Pathological symptoms were assessed by hematoxylin-eosin (HE) staining. Additionally, the concentrations of 5-hydroxytryptamine (5-HT) in both serum and colon tissues were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of 5-HT receptor 3 (5-HT3R), 5-HT receptor 4 (5-HT4R) and Chlorogenic acid (CgA) were evaluated using immunohistochemistry (IHC) and immunofluorescence (IF), respectively. Moreover, the gut microbiota profiles of fecal samples were analyzed through 16S rRNA analysis. Results: BAC treatment improved the intestinal propulsion rate and pathological symptoms induced by Lop. In rats treated with Lop, the concentrations of 5-HT in both serum and colon tissues, and the expression levels of 5-HT3R, 5-HT4R (p < 0.05), and CgA were decreased. However, these levels were restored with the BAC and mosapride treatments. Additionally, BAC improved the decrease of intestinal microflora caused by Lop and changed the fecal microbial composition caused by Lop. Conclusions: BAC alleviated the symptoms of STC and improved the composition of intestinal microflora associated with STC. These findings suggest that BAC could be a potential treatment for functional bowel disease
Chitosan Regulates CAV1 to Facilitate M2 Macrophage Differentiation through Activation of Canonical Wnt Signaling Pathway in Diabetic Skin Trauma Model Rats
No full textBackground: Chitosan has the advantage of improving inflammatory response. However, the molecular mechanism by which chitosan derivatives promote macrophage proliferation is not fully illuminated. Here, we focused on the Caveolin 1 (CAV1)/Wnt family member (Wnt) regulatory axis to study the effect of chitosan on wound healing of diabetic skin ulcer. Methods: We prepared Sprague Dawley (SD) rat models of diabetic (DM), DM with chronic refractory wound (CW), and CW with chitosan treatment (CTS). Flow cytometric assay was used to isolate macrophage from epidermis of skin tissues with chronic wound. RNA sequencing was used to study the transcriptome of M0 and M2 macrophages. Immunoprecipitation and western blot were used to study Wnt/β-catenin signaling pathway and the target gene Caveolin 1 (Cav1) of M0 macrophages. Molecular docking was used to mimic the protein-protein interaction between CAV1 and β-catenin. Results: We observed that chitosan was capable of facilitating the differentiation process of M0 to M2 macrophage in wound area. Total 734 differentially expressed genes (318 elevated and 416 reduced) were found compared between CTS and CW. Cav1 was significantly up-regulated in chitosan treated M0 macrophages. Furthermore, we noticed that the delivery of chitosan particle containing with Cav1 shRNA could enhance the phosphorylation of glycogen synthase kinase 3 beta (GSK3β) and the followed activity of canonical Wnt pathway in M0 macrophages in vivo. Both C-terminus of CAV1 and GSK3β shown by protein docking remodeling indicated the interaction of these two proteins. Conclusions: Current study determines that chitosan promotes the expression of Cav1, and enhances the activity of GSK3β function through canonical Wnt/β-catenin signaling pathway
Expression and Clinical Significance of Programmed Death Ligand-1 and Nucleophosmin in Triple-Negative Breast Cancer
No full textObjective: The purpose of this study was to determine the expressions of programmed death ligand-1 (PD-L1) and nucleophosmin (NPM1) in triple-negative breast cancer (TNBC) tissues, and their relevance and clinical significance. Methods: Seventy pathologically-confirmed TNBC tissue specimens were used in this study. The expressions of PD-L1 and NPM1 in TNBC tissues were determined using immunohistochemistry (streptavidin-peroxidase). The association between expressions of PD-L1 and NPM1 and clinicopathological parameters was investigated. The correlation between the two markers was analyzed using Pearson correlation coefficient, and Kaplan-Meier survival curves were generated. Results: The positive expression rates of PD-L1 and NPM1 in 70 TNBC tissue specimens were 54.29 and 51.43%, respectively. Tumor tissue differentiation was positively correlated with positive expressions of PD-L1 and NPM1 (r = 0.248, p = 0.032). Participants with PD-L1-positive, NPM1-positive, and PD-L1 and NPM1 co-positive expressions showed worse prognosis than those with negative expressions. Moreover, PD-L1-positive expression was identified as an independent risk factor for prognosis of TNBC in patients. Conclusions: PD-L1 and NPM1 may be involved in the pathogenesis of TNBC. Therefore, their expressions may be helpful for predicting the prognosis of TNBC in patients