Reprogramming Of Energy Metabolism Research Articles

IRAP Drives Ribosomal Degradation to Refuel Energy for Platelet Activation during Septic Thrombosis.

Platelets play crucial roles in multiple pathophysiological processes after energy-dependent activation. It is puzzling how such a small cellular debris has abundant energy supply. In this study, it is shown that insulin-regulated aminopeptidase (IRAP), a type II transmembrane protein, is a key regulator for platelet activation by promoting energy regeneration during septic thrombosis. Through interaction with certain endosome membrane proteins, IRAP can not only promote granule release, but also facilitate lysosomal degradation of theoretically discarded ribosomes in an mTORC1- and S-acylation-dependent manner in activated platelets. Plentiful amino acids obtained from IRAP-mediated ribophagy are recruited to aerobic glycolysis and then promote energy metabolism reprogramming, thereby producing abundant energy for platelet life extension and prolonged activation. Consequently, targeted blocking IRAP can dramatically alleviate platelet hyperactivation and septic thrombosis.

SNHG17 Reprograms Energy Metabolism of Breast Cancer by Activating Mitochondrial DNAs Transcription.

In most solid tumors, cellular energy metabolism is primarily dominated by aerobic glycolysis, which fulfills the high demand for biomacromolecules at the expense of reduced ATP production efficiency. Elucidation of the mechanisms by which rapidly proliferating malignant cells acquire sufficient energy in this state of inefficient ATP production from glycolysis could enable development of metabolism targeted therapeutic strategies. In this study, we observed a significant association between elevated expression levels of the long non-coding RNA (lncRNA) SNHG17 and unfavorable prognosis in breast cancer (BCa). SNHG17 promoted BCa cell proliferation by augmenting mitochondrial ATP production. Mechanistically, SNHG17 directly interacted with the p65 subunit of NF-κB and phosphorylated p65 at the threonine 505 site. SNHG17 bound to p65 at its truncated loop2 site, recruited p65 to mitochondria, and co-regulated the transcriptional activation of mitochondrial DNA to promote ATP production. Accordingly, targeting SNHG17 with an anti-sense oligonucleotide (ASO) significantly reduced BCa tumor growth both in vitro and in vivo. Overall, these results established a role for SNHG17 in promoting BCa progression by increasing ATP production and provided insight into the reprogramming of energy metabolism in solid tumors.

Comprehensive Overview of Ketone Bodies in Cancer Metabolism: Mechanisms and Application.

Reprogramming energy metabolism is pivotal to tumor development. Ketone bodies (KBs), which are generated during lipid metabolism, are fundamental bioactive molecules that can be modulated to satisfy the escalating metabolic needs of cancer cells. At present, a burgeoning body of research is concentrating on the metabolism of KBs within tumors, investigating their roles as signaling mediators, drivers of post-translational modifications, and regulators of inflammation and oxidative stress. The ketogenic diet (KD) may enhance the sensitivity of various cancers to standard therapies, such as chemotherapy and radiotherapy, by exploiting the reprogrammed metabolism of cancer cells and shifting the metabolic state from glucose reliance to KB utilization, rendering it a promising candidate for adjunct cancer therapy. Nonetheless, numerous questions remain regarding the expression of key metabolic genes across different tumors, the regulation of their activities, and the impact of individual KBs on various tumor types. Further investigation is imperative to resolve the conflicting data concerning KB synthesis and functionality within tumors. This review aims to encapsulate the intricate roles of KBs in cancer metabolism, elucidating a comprehensive grasp of their mechanisms and highlighting emerging clinical applications, thereby setting the stage for future investigations into their therapeutic potential.

Energy Metabolism and Stemness and the Role of Lauric Acid in Reversing 5-Fluorouracil Resistance in Colorectal Cancer Cells.

While 5-fluorouracil (5FU) plays a central role in chemotherapy for colorectal cancer (CRC), resistance to 5FU remains a major challenge in CRC treatment, and its underlying mechanisms remain unclear. In this study, we investigated the relationship between 5FU resistance acquisition, stemness, and energy metabolism. Among the two CRC cell lines, HT29 cells exhibited glycolytic and quiescent properties, while CT26 cells relied on oxidative phosphorylation (OXPHOS) for energy. In contrast, the 5FU-resistant sublines (HT29R and CT26R), developed through continuous exposure to low concentrations of 5FU, demonstrated enhanced stemness. This was associated with glycolytic dominance, low proliferation, and reduced reactive oxygen species (ROS) production. However, treatment with the medium-chain fatty acid lauric acid shifted the cells to OXPHOS, reducing stemness, increasing ROS levels, and inducing cell death, therefore reversing 5FU resistance. These findings suggest that an enhancement in stemness and the reprogramming of energy metabolism play key roles in acquiring 5FU resistance in CRC. While lauric acid reversed 5FU resistance, further clinical studies are required.

Exercise-induced extracellular vesicles in reprogramming energy metabolism in cancer.

Cancer is caused by complex interactions between genetic, environmental, and lifestyle factors, making prevention strategies, including exercise, a promising avenue for intervention. Physical activity is associated with reduced cancer incidence and progression and systemic anti-cancer effects, including improved tumor suppression and prolonged survival in preclinical models. Exercise impacts the body's nutrient balance and stimulates the release of several exercise-induced factors into circulation. The mechanisms of how exercise modulates cancer energy metabolism and the tumor microenvironment through systemic effects mediated, in part, by extracellular vesicles (EVs) are still unknown. By transferring bioactive cargo such as miRNAs, proteins and metabolites, exercise-induced EVs may influence cancer cells by altering glycolysis and oxidative phosphorylation, potentially shifting metabolic plasticity - a hallmark of cancer. This short review explores the roles of EVs in cancer as mediators to reprogram cellular energy metabolism through exchanging information inside the tumor microenvironment, influencing immune cells, fibroblast and distant cells. Considering this knowledge, further functional studies into exercise-induced EVs and cellular energy production pathways could inform more specific exercise interventions to enhance cancer therapy and improve patient outcomes.

Targeting Asparagine Metabolism in Solid Tumors.

Reprogramming of energy metabolism to support cellular growth is a "hallmark" of cancer, allowing cancer cells to balance the catabolic demands with the anabolic needs of producing the nucleotides, amino acids, and lipids necessary for tumor growth. Metabolic alterations, or "addiction", are promising therapeutic targets and the focus of many drug discovery programs. Asparagine metabolism has gained much attention in recent years as a novel target for cancer therapy. Asparagine is widely used in the production of other nutrients and plays an important role in cancer development. Nutritional inhibition therapy targeting asparagine has been used as an anticancer strategy and has shown success in the treatment of leukemia. However, in solid tumors, asparagine restriction alone does not provide ideal therapeutic efficacy. Tumor cells initiate reprogramming processes in response to asparagine deprivation. This review provides a comprehensive overview of asparagine metabolism in cancers. We highlight the physiological role of asparagine and current advances in improving survival and overcoming therapeutic resistance.

Effects of Supplementing Yeast Fermentation Products on Growth Performance, Colonic Metabolism, and Microbiota of Pigs Challenged with Salmonella Typhimurium.

Yeast fermentation products (YFPs) are known to contain bioactive compounds, such as nutritional metabolites and cell wall polysaccharides (specifically glucan and mannan), which have been demonstrated to exert positive effects on the growth performance and immunity of livestock and poultry. However, the impact of YFPs on intestinal inflammation and microflora composition in pigs infected with Salmonella typhimurium remains unclear. To investigate this, a total of 18 weaned pigs were divided into three treatment groups: a non-challenged control group (Con), a group challenged with Salmonella typhimurium (ST), and a group challenged with Salmonella typhimurium and supplemented with 0.4% YFP (YFP). The experiment spanned five weeks, encompassing a period of 21 days prior to and 14 days subsequent to the initial Salmonella typhimurium challenge. The findings indicated that the YFP group exhibited an increase in average daily gain (ADG) and a decrease in the feed-gain ratio (F/G) in comparison to the ST group following the Salmonella challenge. Additionally, the YFP group demonstrated a reduction in the levels of inflammatory cytokines in plasma and a decrease in the expression of inflammatory genes in the colon. Treatment with YFP also resulted in improved colon histomorphology, heightened alpha diversity of the gut microbiota, augmented the abundance of butyrate-producing bacteria, and elevated concentrations of short-chain fatty acids (SCFAs). In addition, YFP reprogrammed energy metabolism in colon epithelial cells by blunting glycolysis. Together, dietary YFP supplementation alleviated colon inflammation in weaned pigs challenged with Salmonella typhimurium, and shaped the beneficial microbiota, thereby maintaining gut homeostasis. The results provided evidence supporting the application of yeast fermentation products in livestock production.

Role of metabolic reprogramming-mediated hepatic stellate cell activation in the pathogenesis of hepatic fibrosis

The activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix are the keys to the occurrence and development of liver fibrosis. Metabolic reprogramming supports the activation process of HSCs, which requires substantial energy to meet the corresponding energy requirements for liver fibrosis formation. This review focuses on the effect of metabolomic changes characterized by metabolic reprogramming on HSC activation and summarizes the characteristics of HSC energy metabolism reprogramming during the formation of liver fibrosis, with the aim to summarize research evidence for exploring the mechanism and developing strategies for the prevention and treatment of liver fibrosis.

Responsive plasmonic hybrid nanorods enables metabolism reprogramming via cuproptosis-photothermal combined cancer therapy

Abnormal tumor metabolism leads to tumor growth, metastasis, and recurrence, reprogramming tumor metabolism and activating potent anti-tumor immune response have been demonstrated to have good therapeutic effects on tumor elimination. Copper-based nanomaterials involved in cuproptosis show great prospects in these two aspects, but their efficiency is restricted by Cu homeostasis and the toxicity of the chelator. Here, the pH-responsive AuNRs@Cu2O core-shell plasmonic hybrid nanorods (ACNRs) have been successfully fabricated to realize microenvironment-controlled release at the tumor site for the combined therapy of cuproptosis and photothermal treatment. The AuNRs core exhibited excellent NIR-II photothermal property, which boost the intracellular concentration of copper to trigger severe cuproptosis and induce immunogenic cell death of tumor cells. In vivo studies demonstrated the ACNR exhibited efficient tumor therapy for primary, metastatic, and recurrent tumors. ACNRs-induced cuproptosis and PTT were capable of reprogramming energy metabolism, leading to a decreased production of lactic acid. This potential of metabolic reprogramming assisted in reshaping the immunosuppressive tumor microenvironment to facilitate the infiltration of immune cells and boost the immune responses triggered by PTT. The therapeutic mechanism was further verified by metabolomics analysis, which indicated that ACNRs + PTT treatment led to the inhibition of the Pentose Phosphate Pathway and Glycolysis pathways in tumor cells. The suppression of glycolytic reduced ATP synthesis, thereby hindering energy-dependent copper efflux, which in turn promoted cuproptosis. Taken together, this study offers promising insights for cuproptosis-based cancer treatment and sheds new light on nanomedicine-mediated metabolic modulation for future tumor therapy.

BHLHE40-mediated transcriptional activation of GRIN2D in gastric cancer is involved in metabolic reprogramming.

Gastric cancer (GC) is the third leading cause of death in developed countries. The reprogramming of energy metabolism represents a hallmark of cancer, particularly amplified dependence on aerobic glycolysis. Here, we aimed to illustrate the functional role of glutamate ionotropic receptor N-methyl-D-aspartate type subunit 2D (GRIN2D) in the regulation of glycolysis in GC and the mechanisms involved. Differentially expressed genes were analyzed using the GEO and GEPIA databases, followed by prognostic value prediction using the Kaplan-Meier Plotter database. The effect of GRIN2D knockdown on the malignant behavior and glycolysis of GC cells was explored. GRIN2D expression was upregulated in GC cells and promoted the malignant behavior of GC cells by activating glycolysis. Class E basic helix-loop-helix protein 40 (BHLHE40) was overexpressed in GC cells and mediated transcriptional activation of GRIN2D. The anti-tumor effects of BHLHE40 knockdown on GC cells in vitro and in vivo were reversed by GRIN2D overexpression. Knockdown of GRIN2D or BHLHE40 downregulated the expression of mRNA of electron transport chain subunits and phosphorylation of p38 MARK and inhibited calcium efflux in GC cells. Overexpression of GRIN2D promoted calcium efflux, phosphorylation of p38 MARK protein, and proliferation of GES1 cells. Altogether, the findings derived from this study suggest that BHLHE40 knockdown suppresses the growth, mobility, and glycolysis of GC cells by inhibiting GRIN2D transcription and disrupting the BHLHE40/GRIN2D axis may be an attractive therapeutic strategy for GC.

Dracocephalum Moldavica L.-derived carbon dots for effective periodontitis treatment via reprogramming energy metabolism in macrophages

Dracocephalum Moldavica L. (DML), a Chinese traditional medicine rich in flavone compounds (e.g., tilianin), has shown antioxidant and anti-inflammatory potential for alleviating inflammatory disorders. However, the extraction of active ingredients of DML is complex, and these extracts usually act synergistically to treat inflammatory diseases. In this study, the carbon dots derived from DML (T-CDs) were rapidly prepared via the one-pot method and showed good performance in biocompatibility and free radical scavenging capacity. Then, the T-CDs were loaded into the hydrogel and applied to treat periodontitis. The in vivo experiments demonstrated that T-CDs could promote the inflammation resolution of and the alveolar bone reparation in the periodontitis model after periodontal injection. With further investigation, it could be found that T-CDs involved the alternative polarization of macrophage by rebalancing glycolysis and mitochondrial respiration. Overall, it was the first time DML had been used to prepare carbon dots with anti-inflammation. This study provided an effective drug candidate for the treatment of periodontitis and offered an in-depth understanding of the therapeutic mechanism of T-CDs in periodontitis through macrophage immunomodulation.

Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets.

Energy metabolic reprogramming is frequently observed during tumor progression as tumor cells necessitate adequate energy production for rapid proliferation. Although current medical research shows promising prospects in studying the characteristics of tumor energy metabolism and developing anti-tumor drugs targeting energy metabolism, there is a lack of systematic compendiums and comprehensive reviews in this field. The objective of this study is to conduct a systematic review on the characteristics of tumor cells' energy metabolism, with a specific focus on comparing abnormalities between tumor and normal cells, as well as summarizing potential targets for tumor therapy. Additionally, this review also elucidates the aberrant mechanisms underlying four major energy metabolic pathways (glucose, lipid, glutamine, and mitochondria-dependent) during carcinogenesis and tumor progression. Through the utilization of graphical representations, we have identified anomalies in crucial energy metabolism pathways, encompassing transporter proteins (glucose transporter, CD36, and ASCT2), signaling molecules (Ras, AMPK, and PTEN), as well as transcription factors (Myc, HIF-1α, CREB-1, and p53). The key molecules responsible for aberrant energy metabolism in tumors may serve as potential targets for cancer therapy. Therefore, this review provides an overview of the distinct energy-generating pathways within tumor cells, laying the groundwork for developing innovative strategies for precise cancer treatment.

The Role of the CPT Family in Cancer: Searching for New Therapeutic Strategies.

Along with abnormalities in glucose metabolism, disturbances in the balance of lipid catabolism and synthesis have emerged as a new area of cancer metabolism that needs to be studied in depth. Disturbances in lipid metabolic homeostasis, represented by fatty acid oxidation (FAO) imbalance, leading to activation of pro-cancer signals and abnormalities in the expression and activity of related metabolically critical rate-limiting enzymes, have become an important part of metabolic remodeling in cancer. The FAO process is a metabolic pathway that facilitates the breakdown of fatty acids into CO2 and H2O and releases large amounts of energy in the body under aerobic conditions. More and more studies have shown that FAO provides an important energy supply for the development of cancer cells. At the same time, the CPT family, including carnitine palmitoyltransferase 1 (CPT1) and carnitine palmitoyltransferase 2 (CPT2), are key rate-limiting enzymes for FAO that exert a pivotal influence on the genesis and progression of neoplastic growth. Therefore, we look at molecular structural properties of the CPT family, the roles they play in tumorigenesis and development, the target drugs, and the possible regulatory roles of CPTs in energy metabolism reprogramming to help understand the current state of CPT family research and to search for new therapeutic strategies.

Integrated multi-omics analysis of the microbial profile characteristics associated with pulmonary arterial hypertension in congenital heart disease.

Dysregulation of immune and inflammatory cells around blood vessels and metabolic dysfunction are key mechanisms in the development of pulmonary arterial hypertension (PAH). The homeostasis of the human microbiome plays a crucial role in regulating immune responses and the progression of diseases. For pulmonary arterial hypertension associated with congenital heart disease involving body-lung shunt (PAH-CHD), the potential impact of the microbiome on the "gut-lung axis" remains underexplored. This study recruited 15 healthy individuals and 15 patients with pulmonary arterial hypertension due to congenital heart disease from Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, and Kunming Children's Hospital. We performed differential analyses of metabolites and microbiota from both the gut and lower respiratory tract for these two groups. The goal was to investigate the "gut-lung axis" microbiome and metabolome profiles in children with PAH-CHD and to analyze the interrelationships between these profiles. Ultimately, we aim to propose the potential value of these profiles in aiding diagnosis. The results indicated that the gut and pulmonary microbiota of children with PAH-CHD are characterized by an increased abundance of beneficial symbionts, which are closely linked to changes in the metabolome. Metabolite functional enrichment analysis revealed energy metabolism reprogramming in the PAH-CHD group, with active metabolic pathways associated with bile acid secretion and carnitine homeostasis. Moreover, the differential expression of metabolites was correlated with right heart function and growth development.IMPORTANCEPrevious studies have primarily focused on the relationship between the gut microbiome and PAH. However, the impact of microbial homeostasis on the progression of PAH-CHD from the perspective of the gut-lung axis has not been adequately elucidated. Our study utilizes an integrated multi-omics approach to report on the differential characteristics of gut and lung microbiota between children with PAH-CHD and reference subjects. We found that microbiota influence the pathological changes and disease manifestations of PAH-CHD through their metabolic activity. Additionally, alterations in metabolites impact the microbial ecological structure. Our findings suggest that modulating the microbiome composition may have positive implications for maintaining and regulating the immune environment and pathological progression of PAH-CHD.

The contribution of the novel CLTC-VMP1 fusion gene to autophagy regulation and energy metabolism in cisplatin-resistant osteosarcoma.

Osteosarcoma (OS) is a highly malignant tumor, and chemotherapy resistance is a major challenge in the treatment of this disease. This study aims to explore the role of the CLTC-VMP1 gene fusion in the mechanism of chemotherapy resistance in OS and investigate its molecular mechanisms in mediating energy metabolism reprogramming by regulating autophagy and apoptosis balance. Using single-cell transcriptome analysis, the heterogeneity of OS cells and their correlation with resistance to platinum drugs were revealed. Cisplatin-resistant cell lines were established in human OS cell lines for subsequent experiments. Based on transcriptomic analysis, the importance of VMP1 in chemotherapy resistance was confirmed. Lentiviral vectors overexpressing or interfering with VMP1 were used, and it was observed that inhibiting VMP1 could reverse cisplatin resistance, promote cell apoptosis, and inhibit autophagy, and mitochondrial respiration and glycolysis. Furthermore, the presence of CLTC-VMP1 gene fusion was validated, and its ability to regulate autophagy and apoptosis balance, promote mitochondrial respiration, and glycolysis was demonstrated. Mouse model experiments further confirmed the promoting effect of CLTC-VMP1 on tumor growth and chemotherapy resistance. In summary, the CLTC-VMP1 gene fusion mediates energy metabolism reprogramming by regulating autophagy and apoptosis balance, which promotes chemotherapy resistance in OS.NEW & NOTEWORTHY This study identifies the CLTC-VMP1 gene fusion as a key driver of chemotherapy resistance in osteosarcoma by regulating autophagy and reprogramming cellular energy metabolism. Through single-cell transcriptomics, the research reveals the heterogeneity of tumor cells and the role of VMP1 in promoting resistance to cisplatin. The findings suggest that targeting the CLTC-VMP1 fusion gene may offer new therapeutic strategies to overcome chemotherapy resistance in osteosarcoma.

A lactate metabolism-related gene signature to diagnose osteoarthritis based on machine learning combined with experimental validation.

Lactate is gradually proved as the essential regulator in intercellular signal transduction, energy metabolism reprogramming, and histone modification. This study aims to clarify the diagnosis value of lactate metabolism-related genes in osteoarthritis (OA). Lactate metabolism-related genes were retrieved from the MSigDB. GSE51588 was downloaded from the Gene Expression Omnibus (GEO) as the training dataset. GSE114007, GSE117999, and GSE82107 datasets were adopted for external validation. Genomic difference detection, protein-protein interaction network analysis, LASSO, SVM-RFE, Boruta, and univariate logistic regression (LR) analyses were used for feature selection. Multivariate LR, Random Forest (RF), Support Vector Machine (SVM), and XGBoost (XGB) were used to develop the multiple-gene diagnosis models. 12 control and 12 OA samples were collected from the local hospital for re-verification. The transfection assays were conducted to explore the regulatory ability of the gene to the apoptosis and vitality of chondrocytes. Through the bioinformatical analyses and machine learning algorithms, SLC2A1 and NDUFB9 of the 273 lactate metabolism-related genes were identified as the significant diagnosis biomarkers. The LR, RF, SVM, and XGB models performed impressively in the cohorts (AUC > 0.7). The local clinical samples indicated that SLC2A1 and NDUFB9 were both down-regulated in the OA samples (both P < 0.05). The knockdown of NDUFB9 inhibited the viability and promoted the apoptosis of the CHON-001 cells treated with IL-1beta (both P < 0.05). A lactate metabolism-related gene signature was constructed to diagnose OA, which was validated in multiple independent cohorts, local clinical samples, and cellular functional experiments.

SMYD2 Promotes Calcium Oxalate-Induced Glycolysis in Renal Tubular Epithelial Cells via PTEN Methylation.

Background/Objectives: Damage to renal tubular cells (RTCs) represents a critical pathological manifestation in calcium oxalate (CaOx) stone disease, but the underlying mechanism remains elusive. Energy metabolism reprogramming is a vital influencer of RTC survival, and SMYD2 is a histone methylation transferase that has been extensively implicated in various metabolic disorders. Hence, this research aimed to identify whether SMYD2 induces the reprogramming of energy metabolism in RTCs exposed to CaOx nephrolithiasis. Methods: Kidney samples were obtained from patients who underwent laparoscopic nephrectomy for non-functioning kidneys caused by nephrolithiasis. The glyoxylate-induced CaOx stone mice model was established and treated with AZ505. The SMYD2-knockout HK-2 cell line was constructed. Histological changes were evaluated by HE, VK, Tunel, Masson stainings. The molecular mechanism was explored through co-immunoprecipitation and western blotting. Results: The results found that SMYD2 upregulation led to energy reprogramming to glycolysis in human kidney tissue samples and in mice with CaOx nephrolithiasis. We also identified the substantial involvement of glycolysis in the induction of apoptosis, inflammation, and epithelial-mesenchymal transition (EMT) in HK-2 cells caused by calcium oxalate monohydrate (COM). In vivo and in vitro results demonstrated that SMYD2 inhibition reduces glycolysis, kidney injury, and fibrosis. Mechanistically, SMYD2 was found to promote metabolic reprogramming of RTCs toward glycolysis by activating the AKT/mTOR pathway via methylated PTEN, which mediates CaOx-induced renal injury and fibrosis. Conclusions: Our findings reveal an epigenetic regulatory role of SMYD2 in metabolic reprogramming in CaOx nephrolithiasis and associated kidney injury, suggesting that targeting SMYD2 and glycolysis may represent a potential therapeutic strategy for CaOx-induced kidney injury and fibrosis.

SLC45A4 is involved in malignant progression of ovarian cancer through glycolytic metabolic reprogramming

Tumor cells promote malignant behaviors such as proliferation, invasion, and metastasis of cancer cells through glucose metabolic reprogramming, but the role of the H-dependent sugar cotransporter SLC45A4 in regulating metabolic reprogramming in ovarian cancer (OC) remains largely unknown. This study aimed to investigate the effects of SLC45A4 silencing on the transcriptome spectrum of ovarian cancer cells (OCC), glucose uptake, lactic acid production, intracellular ATP levels, and the expression and activity of HIF-α glycolysis signaling pathway. The results showed that SLC45A4 is overexpressed in OC and its elevated expression correlates with adverse clinical outcomes in OC patients. Silencing of SLC45A4 significantly inhibited the proliferation, invasion, and metastasis of OCC by suppressing glucose uptake and glycolysis, and it also reduced the expression of HIF-α glycolysis signaling pathway in OC tissues. In vivo experiments using shRNA to knock down SLC45A4 in xenograft models in nude mice demonstrated a significant inhibition of tumor growth. These findings suggest that SLC45A4 silencing can restrain the malignant progression of OC by inhibiting glucose uptake in OCC and affecting the reprogramming of glycolytic energy metabolism, indicating that SLC45A4 may serve as a potential therapeutic target for OC intervention.

Empagliflozin Reduces Progressive Proteinuria by Potentially Reprogramming Energy Metabolism in Proximal Tubules in Young, Nondiabetic, Obese, Dahl Salt-Sensitive Rats

Empagliflozin Reduces Progressive Proteinuria by Potentially Reprogramming Energy Metabolism in Proximal Tubules in Young, Nondiabetic, Obese, Dahl Salt-Sensitive Rats

Synergistic regulation of chassis cell growth and screening of promoters, signal peptides and fusion protein linkers for enhanced recombinant protein expression in Bacillus subtilis

Growth-advantageous microbial chassis cells are beneficial for shortening fermentation period and boosting biomolecule productivity. This study focused on enhancing recombinant proteins synthesis efficiency in Bacillus subtilis by CRISPRi-mediated metabolism regulation for improved cell growth and screening expression elements. Specifically, by repressing odhA gene expression to reallocate cellular resource and overexpressing atpC, atpD and atpG genes to reprogram energy metabolism, the growth-advantageous chassis cell with high specific growth rate of 0.63 h−1 and biomass yield of 0.41 g DCW/g glucose in minimum medium was developed, representing 61.54 % and 46.43 % increasements compared to B. subtilis 168. Subsequently, using screened optimal P566 promoter and (EAAAK)3 protein linker, secretory bovine alpha-lactalbumin (α-LA) titer reached 1.02 mg/L. Finally, to test protein synthesis capability of cells, intracellular GFP, secretory α-LA and α-amylase were expressed with P566 promoter, representing 43.76 %, 75.49 % and 82.98 % increasements. The growth-advantageous B. subtilis chassis cells exhibit their potential to boost bioproduction productivity.