Current Molecular Medicine - Online First

Anaerobic and aerobic exercise are known to increase reactive oxygen species (ROS) and cytokines, which may lead to oxidative stress when ROS accumulate. However, the findings are still inconsistent, with most studies focusing on short exercise durations. This study aimed to compare the effects of anaerobic and aerobic exercise on oxidative stress and cellular fitness in healthy trained young men.

A randomized trial was conducted involving 18 young male subjects, divided into two groups: anaerobic (short-distance running) and aerobic (long-distance running), with each group exercising three times per week for one month. Blood samples were collected before and after the intervention. Malondialdehyde (MDA) reflected oxidative stress, ROS (H2O2), and antioxidant levels (total antioxidant capacity, superoxide dismutase/SOD, glutathione peroxidase/GPX) were detected using spectrophotometry, while Interleukin-6 (IL-6) and ATPase Inhibitory Factor 1 (ATPIF1) reflected cellular fitness, were measured using ELISA.

Both anaerobic and aerobic exercise significantly reduced MDA levels. Aerobic exercise significantly increased SOD and total antioxidant capacity, while anaerobic exercise resulted in decreased GPX levels. No significant changes were observed in H2O2, IL-6, or ATPIF1 levels in either group.

The findings suggest that aerobic exercise enhances the body’s antioxidant defense system more effectively than anaerobic exercise, contributing to reduced oxidative stress. The participants’ trained status may have influenced the SOD response. Limitations include a lack of control over lifestyle variables and limited generalizability due to the homogenous sample.

One month of exercise reduces oxidative stress in trained young men, with aerobic exercise showing greater benefits in boosting endogenous antioxidants.

This systematic review assesses the role of the tumor microenvironment (TME) in cancer progression and therapy resistance by defining drug-microenvironment interactions and determining the molecular determinants in the TME that could help improve the efficacy of administered treatments and alleviate existing adverse effects.

This systematic review follows the PRISMA protocol and the PICOS selection framework to retrieve studies from PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library. Only original human-related research published in English between 2008 and 2023 was used to explore the reciprocal relation between tumor cells and TME components. The ROBINS-I tool assessed the risk of bias.

Out of 258 articles initially identified, 15 met the inclusion criteria for this review. The results showed that TMEs significantly influence treatment outcomes in cancer progression, metastasis, and drug resistance. Focusing on TMEs like CAFs, immune cells, and ECM enhances drug efficacy. The study highlighted potential strategies to improve drug delivery, suppress metastatic processes, and restore immune function, ultimately leading to better outcomes for cancer patients.

Original evidence suggests that Cancer-Associated Fibroblasts (CAFs), immune cells, and Extracellular Matrix (ECM) contribute to therapeutic resistance and metastasis within the TME. They also promote metastasis by inducing Epithelial-Mesenchymal Transition (EMT) and affecting Cancer Stem Cell (CSC) populations. Moreover, the immunosuppressive TME consists of regulatory T cells and myeloid-derived suppressor cells that allow tumors to evade the immune system, a concern for immunotherapy.

The TME plays a vital role in cancer development, metastasis formation, and therapy failure. The perspectives for innovative ECM-modulating treatments and interventions targeting the direct interactions between TME and cancer cells can be revolutionary and suggest better outcomes for treatment-naïve and refractory cancers. Future research should use these results as inputs to apply clinical and therapy studies to enhance cancer management outcomes.

This study aimed to explore the mechanism of semaphorin 3F- (Sema3F) induced hippocampal axonal growth cone collapse by studying the effect of Sema3F on vascular endothelial growth factor (VEGF) in vitro primary rat hippocampal neuron culture system.

Hippocampal neurons were taken from Wistar rats within 24 hours after birth for primary culture in vitro. On the third day, Sema3F was added to the experimental group, and fetal bovine serum at the same concentration was added to the control group. The cells were collected at 0, 5, 15, and 30 min. The expression of VEGF messenger ribonucleic acid (mRNA) in the hippocampal neurons was detected by real-time polymerase chain reaction (PCR), while VEGF expression was detected by Western blot. The level of VEGF expression in the hippocampal neuron culture medium was detected by enzyme-linked immunosorbent assay.

The expression of both VEGF mRNA and VEGF protein in the rats’ hippocampal neurons decreased at different times. The VEGF concentration in the culture medium initially increased before decreasing over time.

Sema3F is known to induce growth cone collapse in hippocampal neurons, and this study provides evidence that this effect may be mediated by downregulating VEGF expression and secretion. The initial increase in VEGF concentration in the culture medium could be a compensatory response to the collapse of growth cones, while the subsequent decrease suggests a sustained effect of Sema3F on VEGF regulation. The findings highlight the complex interplay between Sema3F and VEGF in neuronal development and repair. Future research should explore the underlying signaling pathways and potential therapeutic applications of these interactions.

Sema3F inhibited the synthesis of VEGF in hippocampal neurons at transcription and translation levels in a time-dependent manner. Sema3F may also affect the secretion level of VEGF, initially increasing its extracellular expression before decreasing it over time.

Genistein is an isoflavone primarily extracted from soybeans and the Dyer’s broom (Genista tinctora L.). It has been extensively studied using various extraction methods and characterized via NMR for structural elucidation. Its pharmacological potential, mediated through interactions with multiple receptors and signalling pathways, has been validated through numerous preclinical studies globally.

To analyze the pharmaceutical profile of genistein using PASS software, we correlated it with existing literature, and evaluated its efficacy against various diseases. The study aims to explore the broad-spectrum potential of genistein as a lead compound against the various diseases such as cancer, cardiovascular disease (CVD), neurodegenerative and viral diseases.

It is a broad-spectrum drug that is effective against – cancer, heart associated diseases, neurodegenerative diseases and viral diseases. It is a potential anticancer drug that modulates apoptosis, cell cycle, metastasis, and regulates the cancer signalling pathways. Based on the compilation of reports from the literature reviews, it is effective against breast cancer (23%), neuroblastoma (12.77%), prostate and lung cancer (10.64%). Secondly, it has cardio protectant properties and supports cardiovascular health by improving endothelial function and lowering cholesterol. It is reported to be effective against cardiac dysfunction (38.46%), atherosclerosis (26.92%), and cardiotoxicity (15.39%). Thirdly, it offers various neuroprotective benefits in neurodegenerative diseases like Alzheimer's (69.84%) and Parkinson's (19.05%). Lastly, it was also reported to be effective against HSV (23.08%), HIV (23.08%) and HPV (15.39%) viral infections.

Genistein exhibits a wide range of therapeutic properties, including anticancer, cardioprotective, neuroprotective, and antiviral effects. It has shown notable efficacy in treating cancers such as breast, prostate, and lung, as well as neurodegenerative conditions like Alzheimer's and Parkinson's. Additionally, its benefits in improving cardiovascular health and combating viral infections further support its potential as a multifunctional therapeutic agent. Although genistein has a broad pharmacological spectrum, its clinical relevance is hampered by a suboptimal pharmacokinetic profile, such as poor bioavailability, rapid systemic clearance, extensive first-pass metabolism, and low aqueous solubility, which limit its therapeutic efficacy.

This systematic review highlights genistein’s pharmacological profile, demonstrating its efficacy against various diseases and its potential as a lead candidate for drug development in oncology, cardiovascular health, and neurodegenerative therapies. Thus, underscoring its potential, Genistein can be considered a versatile therapeutic agent.

Obesity is a major risk factor for metabolic and cardiovascular disorders. Recently, emerging biomarkers, such as the Visceral Adiposity Index (VAI) and Lipid Accumulation Product (LAP), have garnered attention for their utility in assessing visceral obesity. Bilirubin, a potent endogenous antioxidant, has been associated with protective effects against various diseases. This study aims to investigate the relationship between serum total bilirubin (STB) levels and VAI/LAP in adults.

This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2003 and 2020. The calculation of VAI and LAP was performed computationally. Weighted multivariate regression models were used to explore the potential correlation between STB levels and VAI or LAP. RCS curves were used to identify the potential non-linear relationship. Moreover, subgroup analyses were conducted to examine heterogeneity across different populations.

The analysis included a cohort of 10,625 individuals aged 20 to 85 years. Both unadjusted and adjusted statistical models revealed a significant negative association between STB levels and VAI or LAP (all P< 0.001). RCS indicates that these relationships are linear. Subgroup analyses identified particularly strong associations in non-smokers aged 20-59 without hypertension/diabetes (P < 0.05).

Our study's strengths include the use of nationally representative data with appropriate weighting, comprehensive adjustment for confounding variables, and pioneering research on the link between serum bilirubin levels and visceral fat indices, which may indicate early metabolic risk markers. This finding highlights the significant role of bilirubin in body fat distribution and lipid metabolism.

This study revealed that STB was associated with VAI or LAP among the specific general American population aged 20-59 without hypertension/diabetes. Further prospective investigations are warranted to clarify the temporal relationship between STB and novel obesity indices.

Observational studies suggest the potential association between sleep traits and vertigo; however, causal evidence remains limited.

This study aimed to explore the relationship between genetically predicted sleep traits and vertigo with the Mendelian randomization (MR) method.

Instrumental variables for sleep traits (snoring, sleep duration, insomnia, daytime sleepiness, daytime napping, and chronotype) were adopted from genome-wide association studies (GWAS) data of European ancestry from UK Biobank. The summary-level datasets of vertigo were retrieved from the GWAS of FinnGen. Inverse-variance weighted (IVW) method was adopted as the main analysis.

IVW analysis revealed a significant association between genetically predicted daytime napping (OR = 1.51, 95% CI =1.08-2.12, P = 0.016) and chronotype (OR = 1.13, 95% CI =1.01-1.26, P = 0.033), both of which were associated with an increased risk of vertigo. However, we did not find evidence for a causal effect of snoring, overall sleep duration, long sleep duration, short sleep duration, insomnia, and excessive daytime sleepiness on vertigo. No reverse causality was detected.

Our findings suggest that abnormal sleep patterns may serve as risk factors for vertigo disorders and offer opportunities for the prevention and management of vertigo disorders.

Prior studies established associations between gut microbiota and myocardial interstitial fibrosis. Nevertheless, the causal relationships and potential intermediaries remain unknown. Thus, we employed a Mendelian randomization strategy to explore whether gut microbiota causally influence myocardial interstitial fibrosis and to assess whether plasma metabolites serve as potential intermediaries in this pathway.

A two-sample Mendelian randomization approach was performed, utilizing genome-wide association studies to examine the causal relationship between gut microbiota (n= 18,340) and myocardial interstitial fibrosis (n=41,505). Additionally, an investigation was conducted to determine the potential mediation by four plasma metabolites (n=8,299) via a two-step Mendelian randomization analysis. Inverse variance weighted method was the primary method employed in Mendelian randomization, and complementary analyses were conducted alongside to enhance the robustness of the results.

Mendelian randomization analysis indicated suggestive associations of three microbial taxa with myocardial interstitial fibrosis. The most significant taxon was the genus Faecalibacterium (β [SE], -0.1272 [0.0347], P = 0.0002). Reverse Mendelian randomization analyses revealed no evidence of myocardial interstitial fibrosis affecting these three microbial taxa. In the two-step Mendelian randomization analysis involving four plasma metabolites, it was found that plasma sphingomyelin levels mediated the causal effects of genus Faecalibacterium on myocardial interstitial fibrosis (proportion mediated = 14.2%, 95% CI = 1.4-27.0%).

The study validates the causality between particular gut microbial taxa and myocardial interstitial fibrosis, and suggests that plasma sphingomyelin might mediate this association. These findings offer a novel perspective on myocardial interstitial fibrosis prevention, and underscore the significance of plasma sphingomyelin in human health and disease.

Obliterative bronchiolitis (OB) is a severe and progressive complication characterized by the fibrotic obliteration of small airways, leading to significant morbidity and mortality, particularly in lung transplant recipients. The pathogenesis of OB involves complex cellular processes, among which epithelial-to-mesenchymal transition (EMT) plays a crucial role. This study investigates the role of mechanosensitive ion channel Piezo1 in promoting OB through Yes-associated protein (YAP)-dependent EMT.

Piezo1-induced signal pathway alterations, fibrosis, and EMT-related features were examined in the mouse OB model and BEAS-2B cells. The efficacy of Piezo1 in EMT and OB was explored and validated both in vitro and in vivo.

Piezo1 was found to be upregulated in OB, and pharmacological inhibition of Piezo1 effectively alleviated EMT and fibrotic deposition. Piezo1 activation stimulated the Ca2+ influx and nuclear translocation of YAP that triggered the transition of epithelial cells into a mesenchymal phenotype, which contributed to airway fibrosis and obstruction. Furthermore, inhibition of YAP or calcium chelation significantly attenuated Piezo1 activation-induced EMT and OB, indicating that YAP and Ca2+ are critical mediators in this process.

Piezo1 expression was found to be upregulated in OB, and its activation induced the epithelial-to-mesenchymal transition (EMT) process via a YAP-dependent pathway. Piezo1 could accelerate EMT and the occlusion rate of grafts via Ca2+ influx-dependent YAP activation in OB, suggesting a direct role in facilitating EMT and subsequent fibrotic remodeling in OB.

The present results highlight that Piezo1 promotes OB through a YAP-dependent EMT pathway, suggesting Piezo1 as a novel therapeutic strategy for treating OB and potentially improving outcomes of lung transplant recipients.

This study aimed to investigate the role of JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) signaling in liver injury during severe acute pancreatitis (SAP), focusing on pancreatic elastase- and lipopolysaccharide (LPS)-induced Kupffer cell (KC) activation.

A rat SAP model was established via retrograde taurocholic acid infusion into the biliopancreatic duct. Inflammatory cytokine levels and JAK2/STAT3 pathway activity were quantified in liver tissues. KCs were treated with elastase/LPS ± AG490 (JAK2 inhibitor). Proinflammatory cytokines, RNA, and protein expression were analyzed.

SAP rats exhibited elevated TNF-α, IL-6, and IL-18 levels in both serum and liver tissues, with JAK2/STAT3 pathway activation. AG490 administration suppressed JAK2/STAT3 activation, reduced inflammation, and alleviated liver injury. Similarly, KCs treated with elastase and LPS showed increased proinflammatory cytokine levels and JAK2/STAT3 upregulation, which were mitigated by AG490 treatment.

The findings highlighted the pivotal role of the JAK2/STAT3 signaling pathway in SAP-induced liver injury. Selective inhibition of this pathway by AG490 could reduce inflammation and protect against liver damage, suggesting its potential as a therapeutic target for inflammatory liver diseases.

The pathogenesis of diabetic kidney disease (DKD) is complex, and the specific biomarkers for detecting early diagnosis and monitoring kidney function deterioration are insufficient, which affects the prognosis of patients. The complement activation in glomeruli and renal interstitium contributes to the aggravation of DKD. Several key complement proteins, such as complement factor 3 (C3), CD59, and complement factor H-related protein 2 (CFHR2) were reported to be potential biomarkers for early diagnosis and prognosis for DKD.

In the current study, we focus on CFHR2, to investigate its capability and sensitivity as a DKD biomarker. As a non-invasive detection sample, urine has the characteristic of convenient sampling. In the current study, the urine samples were collected from three groups: diabetic patients without albuminuria, with micro-albuminuria, and macroalbuminuria, to analyze whether CFHR2 was associated with albuminuria concentration and declined renal function. Meanwhile, the urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and C3 were also examined by enzyme-linked immunosorbent assay (ELISA) to compare with CFHR2 to determine whether CFHR2 had an advantage in predicting the early detection and progression of DKD. The Spearman correlation analysis was performed for the correlation analysis. The receiver operating characteristic curve was used to analyze the diagnostic efficacy.

CFHR2 had superior diagnostic power to predict the early occurrence of DKD and disease progression, compared with NGAL, microalbumin, and C3 in urine.

CFHR2 has satisfactory potential to be a biomarker for early diagnosis and risk of progression of DKD.

The antiviral effects of type I interferons [IFNs] on respiratory syncytial virus [RSV]-infected airway epithelial cells have been identified. We aim to further reveal the mechanism of stat3 and kruppel-associated box-associated protein 1 [KAP1] in RSV-infected airway epithelial cells.

Using the A549 cell line, we investigated the impact of RSV infection, KAP1 overexpression, and stat3 inhibition with Stattic. Cell counting kit 8 assay was used to determine the viability, and enzyme-linked immunosorbent assay was applied to measure the levels of IL-6, IL-8, IL-1β, IFN-α, and IFN-β. Viral replication was tested via plaque assay. Meanwhile, quantitative real-time reverse transcription polymerase chain reaction or/and western blot were applied to measure the expressions of p-stat3 and KAP1 in the cells.

RSV infection repressed the viability, upregulated p-stat3 and KAP1 expressions, elevated levels of inflammation-related factors [IL-6, IL-8, IL-1β], and type I IFN immune response-associated factors [IFN-α, IFN-β], and promoted viral replication in A549 cells. Stattic attenuated the promoting effect of RSV on inflammation-related factors and viral replication, but enhanced its impact on IFN-α and IFN-β levels in the cells. More importantly, KAP1 overexpression reversed the effects of Stattic on viability, inflammation [IL-6, IL-8, IL-1β], type I IFN immune response [IFN-α, IFN-β], and viral replication in RSV-infected A549 cells.

Our findings unveil the pivotal role of stat3 inhibition in potentiating type I IFN-mediated antiviral responses against RSV in lung epithelial cells, revealing KAP1 as a potential therapeutic target for combating respiratory viral infections.

Gastric cancer (GC) remains one of the most common malignancies and the third cause of cancer-related deaths worldwide. Non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, can contribute to the pathogenesis and progression of GC and therefore could be its potent diagnostic and prognostic biomarkers. The aim of our work was to estimate the expression of PROX1-AS1 (Prospero Homeobox 1 Antisense RNA 1) and miR-647 (microRNA-647) in GC and investigate their potential interaction and clinical significance.

The study included tumor and adjacent non-tumor tissues from 110 GC patients and plasma samples from 65 GC patients; 38 sectional normal gastric tissue samples and 49 plasma samples of healthy donors were included as controls. Expression levels of both ncRNAs were quantified in all samples by using real-time polymerase chain reaction (RT-PCR) and their possible correlations with the clinical and pathological characteristics of patients were analyzed. A potential inverse correlation between PROХ1-AS1 and miR-647 expression was addressed by in vitro experiments in a panel of cancer cell lines.

The expression of PROX1-AS1 and miR-647 was not significantly different in tissues of GC patients and sectional normal gastric tissue samples. However, they have demonstrated a negative correlation both in the tumor and the adjacent non-tumor tissue of GC patients. PROX1-AS1 expression was significantly decreased in GC tissues, whereas the miR-647 expression was increased. The expression of the ncRNAs was associated with clinical and pathological characteristics of GC patients. The overexpression of miR-647 led to a significant decrease in PROX1-AS1 expression in five cancer cell lines, including the GC cell line SNU-1.

We have demonstrated a negative correlation between PROX1-AS1 and miR-647 in both GC tissues and the cancer cell lines. In addition, expression of both ncRNAs was associated with the primary tumor size. Therefore, these ncRNAs might have potential prognostic value.

The relationship between heavy metals, particularly lead (Pb), and diabetic kidney disease (DKD) remains unclear, especially regarding exposure thresholds. This study investigates the association between blood Pb levels and DKD risk using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018.

A total of 1,343 participants were included, with 508 diagnosed with DKD. Baseline characteristics were compared between DKD and non-DKD groups. Multivariate generalized linear models (GLMs) and weighted logistic regression were used to assess correlations between blood Pb levels and DKD risk. A nomogram was developed to evaluate the predictive power of significant clinical characteristics.

Key clinical characteristics, including age, marital status, and serum Pb levels, differed significantly between DKD and non-DKD groups. Serum Pb was identified as a significant risk factor (ORs: 1.18–1.39, p < 0.01). The nomogram demonstrated good predictive accuracy (AUC = 0.717).

Elevated blood Pb levels are significantly associated with DKD, with a non-linear relationship and a defined threshold. These findings highlight the potential role of Pb exposure in DKD pathogenesis and suggest the utility of blood Pb monitoring in diabetic patients.

Chromobox 7 (CBX7) has been implicated in the progression of various malignant tumors, but its clinical relevance in lung adenocarcinoma (LUAD) remains poorly understood. This study aimed to investigate the expression, prognostic value, biological functions, and immunological role of CBX7 in LUAD.

CBX7 expression in LUAD and adjacent normal tissues was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier curves and Cox risk regression evaluated prognostic significance. Various algorithms assessed the correlation between CBX7 and immune micro-environment. The expression of CBX7 in LUAD tissues was detected by RT-qPCR, western blotting, and immunohistochemistry. The function of CBX7 in LUAD was further investigated by in vitro and in vivo experiments.

CBX7 expression significantly downregulated LUAD, which was associated with aberrant DNA methylation. Decreased CBX7 expression correlated with advanced tumor stage and poor prognosis. Notably, CBX7 is associated with immune cell infiltration and immune checkpoints, highlighting its potential role in guiding immunotherapy. Functional experiments demonstrated that CBX7 overexpression suppressed the malignant phenotype of LUAD cells, while CBX7 knockdown promoted tumor progression.

We conducted a systematic analysis of the diagnostic, prognostic, and immunological significance of CBX7 in LUAD, and found that it might serve as a diagnostic marker and therapeutic target in the future.

Alternative splicing (AS) events significantly affect melanoma progression. Therefore, understanding their effect on prognosis is important for developing new treatments.

Univariate Cox regression analysis and LASSO regression were carried out to identify key AS events, build an AS risk model, and classify sample risk levels. Pearson correlation analysis was also performed to analyze the relationship between AS events and RNA-binding protein (RBP) genes or indicators of immune infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using gene expression data from patients with varying risk levels. Univariate and multivariable Cox regression analyses were also carried out to examine the association between immune cell infiltration and prognosis.

A total of 41446 AS events were identified; among them, 446 AS events were identified as significantly associated with melanoma prognosis. An AS risk model for prognosis was established using seven key AS events. A close correlation was found between 137 AS events and 1013 RBP genes, suggesting that these genes may participate in the regulation of AS events. KEGG enrichment analysis revealed that the genes involved in AS were closely associated with immune system functions, which may explain why AS events affect the prognosis of melanoma. Finally, by combining the AS risk score and clinical indicators, we developed a nomogram model that could effectively predict melanoma prognosis.

This analysis of AS events and regulation may aid in developing novel prognostic biomarkers and therapeutic targets for melanoma.

Platinum-based drugs like cisplatin are key in treating ovarian cancer, but resistance frequently leads to treatment failure. The TGF-β1/β-catenin signaling pathway has been implicated in tumor resistance. This study investigates whether hyperthermiaenhances ovarian cancer cell sensitivity to platinum-based drugs by activating the TGF-β1/β-catenin pathway.

In vitro and in vivo models of ovarian cancer were treated with hyperthermia and cisplatin. Changes in TGF-β1 and β-catenin expression were measured using Western blotting, qPCR, immunohistochemistry, and cell viability assays to determine the impact of hyperthermia on drug sensitivity.

Hyperthermia significantly reduced TGF-β1 and β-catenin expression in ovarian cancer cells and tumor tissues, suppressing the pathway. This led to increased cisplatin sensitivity and higher apoptosis rates in vitro, while in vivo, tumor growth was significantly suppressed, and cisplatin's antitumor effects were enhanced.

Hyperthermia boosts the effectiveness of platinum-based drugs in ovarian cancer by suppressing the TGF-β1/β-catenin pathway, presenting a potential strategy to overcome chemoresistance and improve patient outcomes.

The prognosis of patients with stage III colorectal cancer (CRC) shows significant variations. The purpose of this study was to investigate the role of key regulatory proteins in glycolysis and lipid metabolism for the prognostic evaluation of stage III CRC patients.

Utilizing the Cancer Genome Atlas (TCGA) database, we analyzed the expression of various key regulatory genes in glycolysis and lipid metabolism pathways in CRC, as well as the relationship between gene expression levels and overall survival. We selected the top two key genes exhibiting differential expression patterns in glycolysis and lipid metabolism, namely, glucose transporter type 1 (GLUT1), pyruvate kinase M2 (PKM2), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1), as targets for subsequent exploration. We analyzed the effects of GLUT1, PKM2, FASN, and SCD1 on the proliferation, migration, and drug sensitivity of CRC cells in vitro. These proteins were detected by immunohistochemistry (IHC) in the clinical tissues of stage III CRC patients. Based on the intensity of IHC staining for GLUT1, PKM2, FASN and SCD1, the cumulative score from these 4 target proteins for each sample was calculated (score range from 0 to 8). The relationships between high (scores of 6-8) or low (scores of 0-5) expression of glycolysis and lipid metabolism molecules and the clinicopathological characteristics, and survival of patients were analyzed.

The expression disparities of the GLUT1, PKM2, FASN, and SCD1 genes were the most prominent between tumor and normal tissues. Overexpression of GLUT1, PKM2, FASN, or SCD1 significantly promoted CRC cell growth and migration, as evidenced by CCK-8, colony formation, and Transwell assays. Exogenous introduction of GLUT1, PKM2, FASN, or SCD1 increased oxaliplatin IC50 values, enhanced cell survival, and reduced early apoptosis in CRC cells exposed to oxaliplatin. High glycolysis and lipid metabolism status were associated with poor tumor differentiation, vascular or nerve invasion, and shorter overall survival. The status of glycolysis and lipid metabolism was an independent prognostic factor for stage III CRC patients.

High glycolysis and lipid metabolism status are correlated with a poor prognosis in patients with stage III colorectal cancer.

This study aimed to examine the molecular mechanisms involved in transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma (LUAD) A549 cells.

Proteins were extracted from cultured human LUAD A549 cells cultured under two conditions: untreated and treated with TGF-β (5 ng/ml) for 48 hours. The expression levels of EMT-related proteins, including E-cadherin, Vimentin, and α-smooth muscle actin, were assessed using western blotting. Proteomic analysis was performed using isobaric tags for relative and absolute quantification combined with two-dimensional liquid chromatography-tandem mass spectrometry. Differentially expressed proteins were subjected to bioinformatics analysis, including functional annotation and interaction network studies.

A total of 122 proteins were identified as differentially expressed between the untreated and TGF-β-treated A549 cells. Of these, 55 proteins were upregulated, while 67 were downregulated following TGF-β treatment. Bioinformatics and interaction network analyses highlighted six proteins—GAPDH, TP53, MAPK1, IGF1, SRC, and MYC—as being closely associated with the EMT in human LUAD.

This study provides new insights into the processes of invasion and metastasis in LUAD by examining the molecular mechanisms underlying TGF-β-induced EMT in A549 cells.

Hippo signaling regulates the behavior and fate of mesenchymal stem cells (MSCs), which are crucial for the repair and cure of acute respiratory distress syndrome (ARDS). However, whether 2-deoxy-D-glucose (2-DG), a specific activator of Hippo signaling, would further enhance the reparative effect of MSCs in ARDS remains unclarified.

This study aimed to determine whether 2-DG could promote the proliferation, differentiation, migration, and resistance to oxidative stress of mouse bone marrow-derived MSCs (mBMSCs).

mBMSCs were isolated from C57BL/6 mice and differentiated into alveolar type II epithelial (ATII) cells by noncontact coculture. The specific activator and inhibitor 2-DG and 4-[(5,10-dimethyl-6-Oxo-6,10-dihydro-5h-pyrimido[5,4-B]thieno[3,2-E][1,4]diazepin-2-Yl)amino]benzenesulfonamide (XMU-MP-1) were used to activate and inhibit Hippo signaling, respectively. Oxidative stress-induced injuries were induced by H2O2 treatment.

We observed that 2-DG activated Hippo signaling and promoted mBMSC proliferation in a dose-dependent manner. 2-DG also promoted the differentiation of mBMSCs into ATII cells and enhanced not only the horizontal and vertical migration of mBMSCs but also mBMSC homing to injured lung tissue. H2O2 treatment inhibited Hippo signaling and reduced the viability of mBMSCs by decreasing the Bcl-2/Bax ratio, but 2-DG activated Hippo signaling and conferred mBMSCs with resistance to oxidative stress by increasing the Bcl-2/Bax ratio. However, XMU-MP-1 suppressed these effects to some extent.

Through Hippo signaling, 2-DG promoted the proliferation, migration, differentiation, and resistance to oxidative stress of mBMSCs, suggesting a novel strategy for enhancing the reparative effects of MSCs in ARDS.