Combinatorial Chemistry & High Throughput Screening - Online First

Chenopodium album Linn. is a nutritionally and pharmacologically significant herb that generally grows in the winter season along with other crops. It is rich in fibers, protein, minerals (Mg, Ca, Fe, K, P, and others), vitamins (ascorbic acids, thiamine, riboflavin, and others), and several other biologically active chemical components like flavonoids, saponins, steroids and many more. In this article, the authors briefly describe and assess the chemistry and pharmacology of this nutritionally significant plant.

This study is based on several literature searches conducted via Google Scholar, Research Gate, PubMed, and many other online sources.

Due to its richness with bioactive phytochemicals, it has become a valuable functional food. C. album has several medicinal properties like antioxidant, antimicrobial, anti-arthritic, anti-diabetic, anti-infection, anti-ulcer, and many others. Even after its rich nutritional values, chemical compositions, and a broad spectrum of pharmacological properties, this is a highly ignored herb worldwide. Therefore, extensive research and awareness regarding the functional role of this herb is needed.

Diminished ovarian reserve (DOR) is accompanied by abnormal initiation and development of primordial follicles. Reporting that curcumin can protect the ovarian reserve, we used rats as a model to explore the regulatory mechanism of curcumin on primordial follicle priming.

Curcumin restores the ovarian microenvironment of DOR model rats by AMPK/SIRT 1 signaling pathway, thus regulating the initiation of primordial follicles.

The study used the ovaries of 3-day-old female rats, after replicating the DOR model by triptolide (TP), then used curcumin intervention for 3 days. Histomorphological analysis was counted by H & E staining; ELISA test was used to count ovarian hormone [follicle stimulating hormone (FSH) / luteinizing hormone (LH) ratio and estradiol (E2)] concentration in the culture supernatant. Spectrophotometric measurement was used to count of superoxide dismutase (SOD) and the malondialdehyde (MDA). The protein and mRNA expression of the pathway and key indicators for follicle initiation were determined by Western Blot and Q-PCR (AMPK, SIRT 1, PTEN, PGC-1 α, and AMH).

After curcumin treatment, the number of growing follicles increased (P < 0.05). FSH/LH ratio decreased but the content and expression of E2 and AMH increased (P < 0.05). The protein and mRNA expression of characteristic indicators of inhibiting primordial follicle initiation (PTEN) was decreased (P < 0.05). Oxidation-reduction-related SOD activity increased and the content of MDA decreased (P < 0.05), while the protein and mRNA expression of PGC-1α increased (P < 0.05). The protein and mRNA expression of the pathway (AMPK, SIRT 1) were increased (P < 0.05).

Curcumin restored the ovarian local oxidant-antioxidant balance and promoted primordial follicle priming through AMPK/SIRT 1 signaling pathway in the DOR model rats.

Chronic hyperglycemia in diabetes is a significant contributor to endothelial injury through the induction of oxidative stress. Paeonol is anticipated to address oxidative stress with the aim of ameliorating endothelial injury. Our study delved into the effects of paeonol on endothelial damage induced by diabetes and elucidated the underlying mechanisms.

This research presented a novel endothelial injury model employing advanced glycation end products (AGEs) in human umbilical vein endothelial cells (HUVECs). Additionally, a network analysis was carried out to pinpoint the targets influenced by paeonol, with pivotal targets substantiated via polymerase chain reaction (PCR), western blot analysis, and immunofluorescence staining. Ultimately, the introduction of small interfering RNA transfection validated the involvement of SIRT1 in AGEs-induced HUVECs injury.

Twelve metabolites of paeonol were conclusively detected in vivo. Paeonol demonstrated substantial efficacy in ameliorating and diminishing levels of various cytokines and biochemical indicators, including AGEs, Col IV, ET-1, E-selectin, FN, hs-CRP, ICAM-1, MMP2, and sVCAM-1. Notably, network analysis accentuated the pivotal role of the MAPK signaling pathway. Furthermore, paeonol exhibited significantly elevated mRNA and protein levels of SIRT1 and ERK across varying dosage regimens compared to the model group while displaying relatively decreased mRNA expression levels of p38MAPK.

This research revealed that paeonol inhibited the activation of p38 and ERK within the MAPK signaling pathway. Moreover, the regulatory influence of paeonol over p38 and ERK was compromised subsequent to the silencing of SIRT1, indicating a SIRT1-dependent suppressive action of paeonol on the MAPK pathway. The potential therapeutic utility of SIRT1 in mitigating diabetic endothelial impairment and its concomitant cardiovascular ramifications is underscored by these findings.

Renal interstitial fibrosis (RIF) is the primary pathological progression in chronic kidney disease (CKD). Given the constraints related to cost and adverse effects of current treatments, it is crucial to explore novel and efficacious therapeutic strategies. The purpose of this study was to elucidate the potential of Jiawei Danggui Buxue Decoction (JDBD) to reduce apoptosis and epithelial-mesenchymal transition (EMT) in RIF by regulating the Janus kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) pathway.

An angiotensin II (Ang II)-induced HK-2 cells model and a unilateral ureteral obstruction (UUO) animal model were employed to replicate the RIF model. A total of 48 male Wistar rats (weighing 200-220g) were acclimated for 1 week and then randomly divided into 6 groups (sham operation, UUO, Losartan potassium tablets, and three JDBD dosage groups: high, medium, and low, n=8). After the acclimatization period, UUO models were established in 40 rats through surgery, excluding the sham operation group. Each group received the corresponding drug via gavage for 2 weeks. After 2 weeks, rats were anesthetized, and tissues were collected for subsequent analysis. Renal function tests and histological stains were used to evaluate renal damage and histopathological alterations in rats. Cell viability was examined using the CCK-8 assay. Apoptosis was identified through the utilization of flow cytometry and assessment of mitochondrial membrane potential, along with other techniques. We identified and examined the expression of EMT and extracellular matrix (ECM)-related factors, as well as the JAK2/STAT3 pathway.

In vivo experiments indicated that JDBD effectively reduced renal dysfunction in UUO rats, ameliorated pathological changes in renal tissues, and significantly modulated the JAK2/STAT3 signaling pathway to inhibit EMT and apoptosis, thereby reducing ECM deposition. Furthermore, JDBD markedly increased the survival rate of Ang II-treated HK-2 cells and reduced apoptosis. The in vitro experimental results further confirmed that JDBD ameliorates RIF by regulating the JAK2/STAT3 pathway.

JDBD exhibits anti-apoptotic and EMT-inhibiting functions in RIF, potentially mediated by targeting and inhibiting JAK2/STAT3 signaling transduction.

Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae, is responsible for acute diarrhea, vomiting, and dehydration, which can lead to high mortality in neonatal piglets. Previous research has indicated the antiviral potential of forsythia essential oil (FEO); however, its active components and mechanisms of action remain inadequately defined. This study aims to investigate the antiviral effects of FEO and elucidate its potential mechanisms for treating PEDV.

The primary components of FEO were identified using gas chromatography-mass spectrometry (GC/MS) in conjunction with the National Institute of Standards and Technology Standard Spectrum (NIST) Database. Network pharmacology and weighting coefficients were employed to determine the key signaling pathways associated with PEDV-related diseases. Molecular docking simulations were conducted to explore the interactions between the active ingredients and their corresponding targets. The safety profile of FEO was assessed through cell viability assays utilizing the CCK8 method. Subsequently, immunofluorescence assays (IFA) and reverse transcription-quantitative polymerase chain reaction (RT-Q-PCR) were performed to provide evidence of the anti-PEDV effects. Additionally, the viral replication cycle was analyzed to identify the stages at which FEO exerts its antiviral effects. Finally, key targets were validated through RT-Q-PCR to further investigate the anti-PEDV mechanisms of FEO.

The IL-17 signaling pathway was identified as a critical pathway for the treatment of PEDV with FEO based on network pharmacology and weighting coefficient analyses. Furthermore, results from RT-Q-PCR and IFA demonstrated that FEO influenced the replication of PEDV during the attachment and internalization phases. Specifically, during the viral attachment phase, FEO significantly upregulated the expression of HSP90AA1 while downregulating MAPK14 expression, leading to a reduction in associated inflammatory factors. At the high dose of FEO, the expression of HSP90AA1 was higher than that of the model group by about 5-fold, and the expression of MAPK14 was lower than that of the model group by about 2-fold. Cell viability assay showed no significant cytotoxicity of FEO at 0.63 µL/mL, thus confirming its safety.

The findings of this study suggest that FEO possesses potential antiviral properties against PEDV. Its novel mechanisms of action warrant further investigation, which may contribute to the development of effective therapeutic strategies for managing PEDV infections.

Glycyrrhizin is a saponin glycoside of the liquorice plant. It is commonly used to treat respiratory problems. Inhalable glycyrrhizin formulation in asthma can be a good alternative for widely used inhaled corticosteroids that exhibit side effects upon long-term use.

Asthma is a major and prevalent respiratory disease. However, the rate of drug development in this arena is quite slow, as indicated by merely four new drugs approved by the USFDA in the last 6 years for respiratory diseases.

We herein propose to design and develop Glycyrrhizin-inhalable microspheres for the treatment of asthma.

A 3² full factorial design was applied to show the effect of the two independent variables (polycaprolactone, and polyvinyl alcohol concentration) on each of the selected dependent variables (drug loading and entrapment efficiency).

The optimized microspheres were spherical and 1-5 µm in size. The formulation showed a fine particle fraction of 78%, indicating that the powders were suitable for inhalation. The Drug loading and encapsulation efficiency of the optimized formulation were found to be 9.8% and 40.98%, respectively. The aerosolization study on the Anderson cascade impactor showed that deposition of particles of formulation blended with lactose was better than nonblended formulation and drug in the lungs.

In comparison to the pure drug, optimized formulation prolonged drug residency in the lung for more than 12 hrs after inhalation. Inhalable microparticles of glycyrrhizin provide sustained and prolonged drug release in the lungs along with protection of drugs against pulmonary degradation.

Ferroptosis is a recently identified iron-dependent programmed cell death closely linked to the progression of diffuse large B-cell lymphoma (DLBCL). While studies have shown that FA-2-b-β extracted from Agaricus blazei Murill affects various malignancies, its specific role in modulating ferroptosis in DLBCL and the underlying mechanisms are not yet clear. Objectives: This study aims to elucidate the anticancer properties and mechanisms of FA-2-b-β in inducing ferroptosis in DLBCL cells.

The cell counting kit 8 assay was carried out to evaluate the inhibition of cellular proliferation. Ferroptosis was evaluated using the ferrous colorimetric method, together with kits for measuring malondialdehyde (MDA), reduced glutathione (GSH), reactive oxygen species (ROS), western blotting, JC-1 assays, and transmission electron microscopy. Reverse transcription-quantitative polymerase chain reaction and western blot were conducted to determine whether FA-2-b-β affected nuclear factor erythroid 2- related factor 2 (Nrf2) and heme oxygenase 1 (HO-1).

FA-2-b-β induced ferroptosis in DLBCL cells by elevating the ROS and MDA levels, facilitating the accretion of Fe²⁺, diminishing GSH, upregulating the expression of PTGS2, and downregulating the expression of FTH1, SLC7A11, and GPX4. Furthermore, FA-2-b-β caused structural damage to mitochondria and diminished the mitochondrial membrane potential. The ferroptosis triggered by FA-2-b-β also led to the downregulation of Nrf2 and HO-1, thereby regulating the Nrf2/HO-1 pathway.

FA-2-b-β suppressed DLBCL cell growth by inducing ferroptosis through the Nrf2/HO-1 pathway, making it an attractive potential therapeutic option.

Quantitative Structure–Property Relationship (QSPR) models play a crucial role in predicting the chemical and physical characteristics of molecules.

This study introduces Zagreb rho indices derived from graph theory to assess the physico-chemical properties of benzenes. The rho degree of vertices in connected graphs was formulated and used to compute these indices.

Strong correlations (R> 0.94) were observed between Zagreb rho indices and various molecular properties such as boiling point, molecular weight, and electron energy.

The findings demonstrate that Zagreb rho indices can serve as reliable predictors within QSPR frameworks, offering structural sensitivity and outperforming traditional topological indices in several aspects.

Osteosarcoma (OS), a malignant tumor originating in bone or cartilage, primarily affects children and adolescents. Notably, substantial alterations in mitochondrial energy metabolism have been observed in OS; however, the specific contribution of mitochondrial-related genes (MRGs) to OS pathogenesis and prognosis remains unclear. Herein, we identified novel diagnostic biomarkers associated with mitochondrial-related processes in OS via comprehensive bioinformatics analysis.

OS mRNA expression profiles were retrieved from GSE16088 and GSE19276 databases. Mitochondrial-related differentially expressed genes (MitoDEGs) were identified by integrating differentially expressed analysis with mitochondrial-localized genes. A protein-protein interaction network was constructed, and machine learning algorithms (LASSO regression analysis and SVM-RFE) identified characteristic MitoDEGs. Subsequently, immune cell infiltration, microenvironment analysis, and single-cell RNA sequencing (scRNA-seq) analyzed differences in characteristic MitoDEGs, and RT-PCR was used for in vitro verification of characteristic MitoDEGs.

MitoDEGs in OS were significantly enriched in the pathways associated with mitochondrial function and immune regulation. Two MitoDEGs, UCP2 and PRDX4, were identified via LASSO and SVM-RFE. Correlation analysis demonstrated a close association between UCP2 and PRDX4 expression levels and immune cell infiltration, particularly in CD8+ T and native CD4+ T cells, as observed in both immune cell and scRNA-seq analyses. Furthermore, RT-PCR confirmed the expression levels of UCP and PRDX4 at the cellular level, which was consistent with the bioinformatics results.

This study identified UCP2 and PRDX4 as characteristic MitoDEGs and potential diagnostic biomarkers for OS using machine learning algorithms. These findings provide novel insights into the clinical applications of these biomarkers for OS diagnosis.

This study aimed to assess the safety and effectiveness of carbamazepine in treating trigeminal neuralgia in contrast to gabapentin. Hence, a systematic review and meta-analysis of randomised controlled trials had been carried out.

The relevant studies were searched in PubMed and filtered according to the inclusion and exclusion criteria. Independently, two reviewers chose the studies, evaluated the quality of the investigations, and retrieved the data. RevMan was used for analysis when the data were collected and entered into the data extraction sheet. In addition to heterogeneity, the overall estimate measures were computed as mean differences with a 95% confidence interval for continuous data and relative risk for dichotomous data. To investigate the impact of outliers on the result, a sensitivity analysis was performed. A funnel plot was used to qualitatively evaluate the publishing bias. A total of 1,650 participants from 19 randomised controlled trials were evaluated.

The meta-analysis revealed that the group receiving gabapentin therapy had a similar overall effective rate to the group receiving carbamazepine therapy (OR = 1.94, 95% CI 1.46, 2.57, P = 0.32). Additionally, our meta-analysis revealed that the group receiving gabapentin therapy witnessed a significantly lower risk of adverse reactions than the group receiving carbamazepine therapy (OR= 0.29, 95% CI 0.22, 0.387, P<0.00001).

In summary, the current trials comparing carbamazepine and gabapentin have had inadequate methodological quality. It is not possible to conclude that gabapentin is more effective than carbamazepine in terms of adverse effects based on the evidence that is currently available.

This study aimed to examine the impact of quercetin on a mouse model of endometriosis and elucidate its underlying mechanisms.

An endometriosis model was established using C57BL/6 mice, which were divided into three groups: 1) sham group, 2) model group, and 3) model group treated with daily gavage administration of 100 mg/kg/d quercetin. Histopathological examination was performed using hematoxylin and eosin (HE) staining. The microstructure of the lesions was examined using electron microscopy. The expressions levels of related proteins, such as the peroxisome proliferator-activated receptor-γ (PPARγ), methionine adenosyl-transferase 2A (MAT2A), Ki67 and VEGF was measured using Western blotting or Immunohistochemistry.

Compared to the model group, the medication group showed sparse endometrial stromal cells, irregular morphology, and numerous vacuoles, indicating apoptosis. Compared to the sham group, SAM expression was unchanged (P > 0.05), while PPARγ decreased. MAT2A, PRMT5, cyclin D1, and C-MYC increased, and vimentin, Ki67, VEGF, and caspase-1 were strongly positive (P < 0.05). Quercetin intervention reduced ectopic lesion weights, increased PPARγ, and decreased MAT2A, PRMT5, SAM, cyclin D1, and C-MYC. Vimentin, Ki67, VEGF, and caspase-1 were weakly positive (P < 0.05).

These results indicate that quercetin effectively reduced endometriosis lesions by modulating key protein expressions and promoting apoptosis.

Quercetin modulated the transcription of the MAT2A/PRMT5 gene by activating PPARγ activity, thereby influencing the ectopic implantation and growth of endometrial cells.

Age-related Macular Degeneration (AMD) is a predominant cause of blindness in the elderly. The present study is the first to investigate the alteration of lncRNAs and mRNAs in neovascular AMD.

Nine patients with neovascular AMD were included in the study. The control group comprised seven patients with epiretinal membranes. RNA sequencing was performed to obtain the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs). Then, the DElncRNA-DEmRNA co-expression network, ceRNA network, and immune-related ceRNA subnetwork were constructed. Functional annotation of DEmRNAs between the two groups and DEmRNAs in networks was conducted. The immune cell distribution in neovascular AMD was also evaluated. Real-time qPCR (RT-qPCR) was used to validate the expression levels of key markers.

A total of 342 DEmRNAs and 157 DElncRNAs were obtained in neovascular AMD. Functional annotation indicated that these DEmRNAs significantly enriched immune system-related processes, such as positive regulation of B cell activation, immunoglobulin receptor binding, complement activation, and classical pathway. The DElncRNA-DEmRNA co-expression network, including 185 DElncRNA-DEmRNA co-expression pairs, and the ceRNA (DElncRNA-miRNA-DEmRNA) network, containing 45 lncRNA-miRNA pairs and 73 miRNA-mRNA pairs, were constructed. The immune-related ceRNA subnetwork, including 2 lncRNAs, 5 miRNAs, and 3 mRNAs, was constructed. In addition, the distribution of immune cells was slightly different between the neovascular AMD group and the control group. RT-qPCR validation indicated the consistency between the RT-qPCR results and RNA sequencing results.

In conclusion, STC1, S100A1, MEG3, MEG3-hsa-miR-608-S100A1, and MEG3-hsa-miR-130b-3p/hsa-miR-149-3p-STC1 may be related to the occurrence and development of neovascular AMD.

Atherosclerosis, a leading cause of death globally, is characterized by the buildup of immune cells and lipids in medium to large-sized arteries. However, its precise mechanism remains unclear. The purpose of this study is to explore innovative and reliable biomarkers as a viable approach for the identification and management of atherosclerosis.

The atherosclerosis-related datasets GSE100927 and GSE66360 were retrieved from the Gene Expression Omnibus (GEO) database. The Limma package in the R programming language was utilized, applying the criteria of |logFC| > 1 and P < 0.05. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the 127 identified DEGs using R. Machine learning techniques were then applied to these data to explore and pinpoint potential biomarkers. The diagnostic potential of these markers was assessed via Receiver Operating Characteristic (ROC) curve analysis. Finally, western blot, real-time quantitative PCR (qRT-PCR), and immunohistochemistry (IHC) were employed to confirm the key biomarkers.

Our research indicated that a total of 127 DEGs linked to atherosclerosis were successfully identified. Through the application of machine learning methods, eight critical genes were highlighted. Among these, Nuclear Receptor Subfamily 4 Group A Member-2 (NR4A2) emerged as the most promising marker for further investigation. CIBERSORT analysis revealed that NR4A2 expression levels were significantly correlated with multiple immune cell types, including B cells, plasma cells, and macrophages. Additional validation experiments confirmed that NR4A2 expression was indeed elevated in atherosclerotic plaques, supporting its potential as a biomarker for atherosclerosis.

Our study identified NR4A2 as a potential immune-related biomarker for the diagnosis and treatment of atherosclerosis.

The phylum Thermotogae is composed of five families: Fervidobacteriaceae, Thermatogaceae, Kosmotogaceae, Petrotogaceae, and Mesoaciditogaceae; one class: Thermotogae; and four orders: Kosmotogales, Petrotogales, and Mesoaciditogales. There are thirteen genera in all. The physical and metabolic characteristics of the Thermotogae species reflect the extreme heat from which they were separated. Thermotogae members have a broad spectrum of metabolic capacities, resulting in a pool of valuable chemicals with potential uses in many different sectors.

A 1.5-liter operating capacity bioreactor with a 2.3-liter double-jacket glass volume was utilised to culture Thermotoga maritima in both oxic and anoxic conditions. In addition to temperature, pH, and redox potential, sensors that were installed within the fermentor monitored additional parameters. RNA extraction and cDNA synthesis A total of RNAs was extracted utilising Roche's High Pure RNA reagent. Analysis of glycolysis pathways in T. maritima was performed by NMR spectroscopy

Based on NMR analysis, our findings demonstrate that T. maritima uses the EM route to metabolize 90% of glucose in anoxia and the ED pathway for 10%. On the other hand, T. maritima continues to employ the EM and ED glycolysis routes concurrently when exposed to extended oxidative stress; however, the ED pathway's contribution drops from 10% to around 5%.

Compared to the EM route, the ED pathway has more strongly repressed transcripts that encode its unique enzymes.

Zhishi decoction (ZSD) is one of the most common herb decoctions in traditional Chinese medicine (TCM), and it is used for the treatment of FC. However, its main therapeutic mechanism is not yet clear. This study aims to explore the possible pharmacodynamic material basis and potential molecular mechanism from network pharmacology and molecular docking and verify them through animal experiments.

Firstly, the effective ingredients, potential targets, and key targets of ZSD in the treatment of FC were screened through network pharmacology. Go and KEGG analyses were performed for potential targets. Secondly, molecular docking was used to link the main active components of ZSD with target genes to predict their possible molecular mechanisms. Finally, 30 male BALB/c mice (20±2g) were randomly divided into five groups (n=6), including the blank group, ZSD groups with two dosages (7.15, 14.3g/kg), FC model group, and positive group (lactulose group). All the mice were given difenoxate tablets for 14 days to establish FC model except the blank group. Moreover, the mice in the blank group were given the same volume of normal saline. After admination for 14 days, the whole colon tissues were obtained for the analysis of small intestinal propulsion rate, and the expression of P38MAPK in colon tissues of mice was observed via immunohistochemistry and WesterBlot.

In this study, 43 active ingredients in ZSD were identified. Four hundred and thirty potential therapeutic targets were selected, among which AKT1, MAPK12, and MAPK14 were key targets. 164 GO biological processes and 123 KEGG signaling pathways were identified after analysis, such as MAPK signaling pathway, TNF signaling pathway etc. The molecular docking results showed that Prangenin, 4-Hydroxyhomopterocarpin, isoponcimarin, and AKT1, MAPK12, MAPK14 had good binding degree. Additionally, ZSD could relieve the symptoms of FC in mice significantly. Compared with the model group, p38/MAPK positive expression cells and protein expression levels in the colon tissues of ZSD groups significantly increased in a dose-dependent manner (p<0.01).

This study confirmed that ZSD could act on AKT1, MAPK12, and MAPK14 targets to activate the p38/MAPK signaling pathway to relieve FC induced by defenoxate tablets. The further development of ZSD provided a theoretical basis.

Natural products are a rich source of diverse chemical compounds with interesting therapeutic properties. There is a need for in-depth investigation of this reservoir with in-silico tools to assert the molecular diversity with respect to clinical significance. Although studies have been reported on plants such as Nyctanthes arbor-tristis(NAT) and its medicinal importance. A comprehensive study on comparative analysis of all phyto-constituents has not been carried out.

n the present work, we have carried out a comparative study of compounds obtained from the ethanolic extracts of various parts such as calyx, corolla, leaf, and bark of the NAT plant.

The extracted compounds were characterized by LCMS and GCMS studies. This was further corroborated by the network analysis, docking, and dynamic simulation studies with validated anti-arthritic targets.

The most significant observation from LCMS and GCMS was that the compounds from calyx and corolla were closer in chemical space to the anti-arthritic compounds. To further expand and explore chemical space, the common scaffolds were seeded to enumerate a virtual library. The virtual molecules were prioritized based on the drug-like, leadlike scores and docked against anti-arthritic targets to reveal identical interactions in the pocket region.

The comprehensive study will be of immense value to medicinal chemists for the rational synthesis of molecules as well as bioinformatics professionals for getting useful insight into identifying rich diverse molecules from plant sources.

Prostaglandin D2 (PGD2) can inhibit the development of gastric cancer (GC); however, its role in the autophagic death of GC stem cells (GCSCs) remains elusive. Therefore, this study aims to evaluate the mechanisms by which PGD2 regulates the stemness in GCSCs.

In this study, HGC27-derived GCSCs were employed to knock down PGD2 receptor 2 (PTGDR2). Subsequently, cell stemness and autophagic activity in these GCSCs were assessed via sphere-forming capacity, transmission electron microscopy, and western blot analyses.

The results revealed that PGD2 suppressed the stemness of GCSCs and induced GCSCs autophagy, whereas the downregulation of PTGDR2 had the opposite effect. Furthermore, PGD2 was also found to inhibit the expression of stemness-associated proteins CD44 and OCT4, which were blocked by 3-MA and enhanced by RAPA. Moreover, the shPTGDR2 + PGD2 group indicated higher stemness than the PGD2 group, with 3-MA enhancing this effect and RAPA reducing this change.

In summary, this study indicated that PGD2/PTGDR2 signaling affects stemness and autophagy in GCSCs. The results suggest that PGD2/PTGDR2 signaling may affect the stemness of GCSCs by regulating autophagy.

Pachyman, derived from Poria cocos, has been used to treat gouty arthritis (GA) for thousands of years, although its precise role and mechanisms remain unclear. Herein, we investigate the therapeutic effects of pachyman on GA and explore their underlying mechanisms.

Network pharmacology and experimental methods were employed to investigate the therapeutic mechanisms of pachyman against GA. The protein-protein interaction network of shared targets between pachyman and gout was constructed. Furthermore, we elucidated the functions and mechanisms of pachyman against GA. Subsequently, we validated the predicted mechanisms from an experiment on rats.

The treatment of GA with pachyman primarily related to tumor necrosis factor (TNF), matrix metalloproteinases (MMP), and relaxation factor signaling pathways. In the experimental validation, pachyman were found to regulate the expression of IL-1β, TNF-α, TGF-β, superoxide dismutase, and glutathione peroxidase of hyperuricemic rats.

These collective findings suggest that pachyman holds promise as an alternative treatment for GA.

GBM is an aggressive brain tumor with limited treatment options. Prior research has indicated FOLR1 as a pivotal gene involved in cancer pathogenesis.

This study aimed to explore the involvement of folate receptor alpha (FOLR1) in glioblastoma (GBM) and evaluate its potential as a therapeutic target.

This study investigated the expression pattern of FOLR1 in GBM, its impact on patient prognosis, and its role in GBM cell growth and the SRC/ERK1/2 signaling axis.

Initially, we conducted an expression analysis of FOLR1 based on public databases and examined its expression pattern in GBM and its impact on patient prognosis. Subsequently, cell experiments were carried out to evaluate the regulation of GBM cells by differential FOLR1 expression. We then downloaded 100 FOLR1 co-expressed genes from the Linkedomics data repository and performed an enrichment analysis. Finally, the role of FOLR1 and SRC/ERK1/2 axis in GBM was analyzed again by cell experiments.

FOLR1 was found to be substantially expressed in GBM patients and was linked to a poor prognosis. Cell experiments showed that overexpression of FOLR1 promoted GBM cell growth, while low expression of FOLR1 inhibited cell growth. Additionally, genes related to FOLR1 were enriched in the lysosome, toxoplasmosis, and other pathways. This study further indicated that FOLR1 facilitates the activation of the SRC/ERK1/2 signaling pathway in GBM cells, and the attenuation of these pathways can effectively impede the malignancy-promoting effects triggered by FOLR1 in GBM cells.

We revealed that FOLR1 orchestrates the malignant advancement of GBM by stimulating the SRC/ERK1/2 signaling axis, underscoring its pivotal role in the pathogenesis of GBM.

Thermotoga maritima is an anaerobic hyperthermophilic eubacterium isolated from geothermally heated maritime surfaces. It can grow at temperatures up to 80 degrees Celsius.

A 2.3-L bioreactor was specifically designed to cultivate hyperthermophilic bacteria under carefully regulated pH, redox potential, temperature, and dissolved O2.

Using this bioreactor, which was adjusted at 80°C and pH 7.0, it was found that Thermotoga maritima demonstrated continued growth even after being exposed to oxygen for an extended period. Transcription studies revealed that following prolonged oxygen exposure, the genes encoding ROS-scavenging systems, alkyl hydroperoxide reductase (ahp), thioredoxin-dependent thiol peroxidase (bcp 2), and, to a lesser extent, neelaredoxin (nlr), were upregulated/overexpressed. When oxygen was available, the metabolism of glucose was diverted to make lactate rather than acetate.

Based on the O/R ratio of 1.0 in anaerobiosis and 1.67 in the presence of O2, we may conclude that Thermotoga maritima is capable of semi-oxidative metabolism.

Colorectal Cancer (CRC) has attracted much attention due to its high mortality and morbidity. Cordycepin, also known as 3'-deoxyadenosine (3'-dA), exhibits many biological functions, including antibacterial, anti-inflammatory, antiviral, anti-tumor, and immunomodulatory effects. It has been proven to show anticancer activity in both laboratory research studies and living organisms. However, the molecular mechanism of the effect of cordycepin on CRC remains unclear.

The genes associated with cordycepin and colorectal cancer have been identified by comparing the toxicogenomics database (CTD) and GeneCards database. The common genes between cordycepin and CRC have been identified using the Venny tool. The Protein-protein Interaction (PPI) network has been drawn using the STRING database. GO and KEGG enrichment analyses of the intersecting genes have been followed by experimental validation, both in vitro and in vivo.

24 drug targets have been screened using the CTD database and 1490 disease targets have been obtained from the GeneCards database and GO and KEGG analyses. The effect of cordycepin on the proliferation of SW480 cells has been assessed using CCK-8. The related results have indicated cordycepin to inhibit the proliferation of SW480 cells, promote apoptosis, and activate the p53 signal pathway. The findings obtained from in vivo experiments have been found to be consistent with those obtained from in vitro studies.

Our findings have elucidated an effective way to search for cordycepin’s potential mechanism of effect on CRC therapy by employing the network pharmacology and experiment. We have predicted that cordycepin can inhibit tumor growth by regulating the apoptosis pathway. This study has offered valuable insights into the potential mechanism of the effect of cordycepin on CRC and provided a theoretical basis for further validation of its clinical application.

Male Wistar rats were randomly assigned to control, CNP, and BSDZG groups. CNP was induced using purified prostaglandin solution and Freund's complete adjuvant, after which the BSDZG group received 1.54 g/kg/d of BSDZG for 30 days. Prostate tissues were used to determine apoptosis and inflammatory cytokines. The herb-composition-target network and functional signaling pathways were built using a network pharmacology approach, which was also confirmed in vivo.

Treatment with BSDZG significantly alleviated the histopathological lesions, inflammation, and apoptosis in the prostate of CNP rats. The herb-composition-target network comprising 42 active compounds and 32 targets of 11 herbs was illustrated, and KEGG pathways analysis identified the Akt and MAPK pathways as related to the effects of BSDZG. Phosphorylation of p38 MAPK, NF-кB, and Bax expression was significantly enhanced and phosphorylated Akt and Bcl-2 levels were decreased in CNP rats, which could be reversed by BSDZG.

This study presented for the first time that BSDZG effectively alleviated CNP symptoms in rats and elucidated the underlying mechanisms mediated by the Akt and MAPK pathways, providing the theoretical basis for the clinical use and promotion of BSDZG.

Qilong capsule (QC) has been used clinically to treat ischemic stroke in China. This study evaluated the therapeutic effects of QC on myocardial ischemia-reperfusion injury (MIRI) and its potential mechanisms.

The components and candidate targets of QC against MIRI were predicted by network pharmacology via relevant databases such as TCMSP, BATMAN-TCM, GeneCards. The potential mechanisms were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and verified by enzyme-linked immunosorbent assay (ELISA) and Western blot.

Network pharmacology analysis indicated that the cardioprotective effect of QC against MIRI was associated with inflammatory pathways. We further confirmed that QC effectively decreased the levels of inflammatory factors, including hs-CRP and MCP-1, and suppressed the expression of TNF-α and the phosphorylation of STAT3.

This study provides evidence for further clinical applications of QC for MIRI therapy.

Observational studies have reported that arm fat, left leg fat, and trunk fat masses have different effects on polycystic ovarian syndrome (PCOS). However, the causal relationship between them remains unknown.

A two-sample Mendelian randomization (MR) study was conducted by utilizing pooled data from the largest Genome-Wide Association Study (GWAS). Random effect inverse variance weighted (IVW) method, weighted median (WM), and MR-Egger regression analysis were the main statistical methods utilized. Finally, a sensitivity assessment was conducted. Cochran’s Q test was used to analyze heterogeneity, whereas MR-Egger regression (intercept term) was used to analyze horizontal pleiotropy. The leave-one-out analysis was performed to assess if MR estimates were impacted by a single nucleotide polymorphism (SNP) exhibiting significant horizontal pleiotropy.

This study discovered a significant positive correlation between left leg fat mass, arm fat mass, and trunk fat mass and genetic factors of PCOS (odds ratio (OR): 4.452, confidence interval (CI): 2.740−7.232, p < 0.001, OR: 3.321, CI: 2.248−4.907, p < 0.001, and OR: 2.518, CI: 1.722−3.682, p < 0.001, respectively).

This study indicates that arm fat, left leg fat, and trunk fat masses may be genetically correlated with PCOS.