Laryngopharyngeal reflux disease: Updated examination of mechanisms, pathophysiology, treatment, and association with gastroesophageal reflux disease.

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

Pericyte loss leads to microvessel remodeling and nasal polyp formation.

BACKGROUND: Chronic rhinosinusitis (CRS) may be caused by increased vascular permeability and inflammatory cell leakage in the subepithelial tissue. AIMS/OBJECTIVES: The aim of this study is to clarify the role of pericytes in tissue edema, microvessel dysfunction and vascular remodeling mechanisms in patients of CRS with nasal polyps (CRSwNP). MATERIAL AND METHODS: A total of 63 tissue samples were collected, including 42 CRSwNP samples (22 eosinophilic CRSwNP (eCRSwNP) and 20 non-eosinophilic CRSwNP (non-eCRSwNP) samples) and 21 samples of CRS without nasal polyps (CRSsNP). The samples were stained by immunofluorescence to measure microvessel density (MVD) and microvessel pericyte coverage index (MPI). RESULTS: We found that the albumin expression in the eCRSwNP group was significantly increased (p < .05). The MPI was significantly decreased (p <.05). There was a significant negative correlation between the MPI and the plasma albumin level (r=-0.82, p < .05). The MPI was negatively correlated with eosinophilic count (r=-0.77, p < .05). In the eCRSwNP group, the expressions of IL-4, Ang-1 and Ang-2 were increased compared with those in the control group. CONCLUSIONS AND SIGNIFICANCE: Pericyte loss may induce microvessel dysfunction, affect the development of interstitial edema and eosinophilic exosmosis in eCRSwNP, and contribute to the formation and maintenance of nasal polyps.

Blood-letting therapy combined with Master Tung's Five-tiger Point Scraping (Gua Sha) for patients with hematological malignancy and chemotherapy-induced peripheral neuritis.

OBJECTIVE: To investigate the clinical efficacy of Shixuan and Qiduan blood-letting therapy combined with Master Tung's Five-tiger Point (11.27) Scraping for patients with hematological malignancy and peripheral neuritis. METHODS: A total of 70 patients with hematological malignancy who were admitted to Langfang TCM Hospital between January 2020 and December 2022 for treating chemotherapy-induced peripheral neuritis were enrolled retrospectively. The patients were divided into a single treatment group that received western nutritional interventions alone, and a combined treatment group that underwent additional Traditional Chinese Medicine (TCM) Shixuan and Qiduan blood-letting therapy, along with Master Tung's Five-tiger Point (11.27) Scraping. Statistical analyses were carried out to compare the clinical efficacy of the two treatment plans in the patients. Scores of sensory disturbance rating (SDR), numeric rating scale (NRS) for pain, nail fold microcirculation (NFM) of the infected extremity, and the quality of life (QoL), as well as the motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and peroneal nerves of patients in both groups were recorded and compared before and after treatment. The incidence rate of adverse events was compared between the two groups. Furthermore, the clinical outcomes of patients in the two groups were followed up and analyzed for correlated factors using univariate and multivariate analyses. RESULTS: The clinical efficacy rate achieved by the combined therapy was 88.57%, significantly higher than 68.57% for patients undergoing single therapy (P=0.041). Moreover, the scores of SDR, pain NRS, QoL, and NFM of the affected extremity, as well as the MNCV and SNCV of patients in the two groups were all improved after treatment, with better improvements in the combined treatment group than in the single treatment group. The incidence rate of adverse events was higher in the single treatment group compared to that of the combined treatment group (17.14% vs. 11.42%) (P=0.466). In addition, during the six-month follow-up period, a total of 27 patients in both groups developed chronic neural disorders. Logistic regression analysis revealed that the MNCV and SNCV of the median and peroneal nerves, together with the duration of chemotherapy, served as independent influencing factors. CONCLUSION: Shixuan and Qiduan blood-letting therapy combined with Master Tung's Five-tiger Point (11.27) Scraping could improve the SDR and pain NRS scores, facilitate the recovery of neural functions, and advance the QoL of patients with chemotherapy-induced peripheral neuritis without increasing the risk of adverse reactions.

A Decade of Pathogenesis Advances in Non-Type 2 Inflammatory Endotypes in Chronic Rhinosinusitis: 2012-2022.

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by localized inflammation of the upper airways. CRS includes two main phenotypes, namely, CRS with nasal polyps and CRS without nasal polyps. The phenotype-based classification method cannot reflect the pathological mechanism. The endotype-based classification method has been paid more and more attention by researchers. It is mainly divided into type 2 and non-type 2 endotypes. The mechanism driving the pathogenesis of non-type 2 inflammation is currently unknown. In this review, the PubMed and Web of Science databases were searched to conduct a critical analysis of representative literature works on the pathogenesis of non-type 2 inflammation in CRS published in the past decade. This review summarizes the latest evidence that may lead to the pathogenesis of non-type 2 inflammation. It is the main method that analyzing the pathogenesis from the perspective of immunology. Genomics and proteomics technique provide new approaches to the study of the pathogenesis. Due to differences in race, environment, geography, and living habits, there are differences in the occurrence of non-type 2 inflammation, which increase the difficulty of understanding the pathogenesis of non-type 2 inflammation in CRS. Studies have confirmed that non-type 2 endotype is more common in Asian patients. The emergence of overlap and unclassified endotypes has promoted the study of heterogeneity in CRS. In addition, as the source of inflammatory cells and the initiation site of the inflammatory response, microvessels and microlymphatic vessels in the nasal mucosal subepithelial tissue participate in the inflammatory response and tissue remodeling. It is uncertain whether CRS patients affect the risk of infection with SARS-CoV-2. In addition, the pathophysiological mechanism of non-type 2 CRS combined with COVID-19 remains to be further studied, and it is worth considering how to select the befitting biologics for CRS patients with non-type 2 inflammation.

A Comprehensive Insight into Mamaki (Pipturus albidus): Its Ethnomedicinal Heritage, Human Health Research, and Phytochemical Properties.

In Hawaii, the plants P. albidus, P. forbesii, P. kauaiensis, and P. ruber are collectively known as mamaki in ethnomedicine, where P. albidus predominates. Farmed mamaki is becoming increasingly popular in Hawaii and the United States. Mamaki teas (such as bottled Shaka tea) are the dominant product. Historically, mamaki has been utilized for its medicinal properties, promoting well-being and good health through consuming tea made from its leaves, ingesting its fruit, and incorporating it into ointments. Mamaki holds cultural significance among Native Hawaiians and is widely used in ethnic medicine, having been incorporated into traditional practices for centuries. However, the scientific mechanisms behind its effects remain unclear. This review consolidates current knowledge of mamaki, shedding light on its potential therapeutic properties, physical properties, nutritional and mineral composition, and active phytochemicals. We also highlight recent research advances in mamaki's antibacterial, anti-viral, chemopreventive, anti-inflammatory, and antioxidant activities. Additionally, we discuss future prospects in this field.

An Analysis of Linker-Dependent Effects on the APC Activation and In Vivo Immunogenicity of an R848-Conjugated Influenza Vaccine.

Subunit or inactivated vaccines comprise the majority of vaccines used against viral and bacterial pathogens. However, compared to their live/attenuated counterparts, these vaccines often demonstrate reduced immunogenicity, requiring multiple boosters and or adjuvants to elicit protective immune responses. For this reason, studies of adjuvants and the mechanism through which they can improve inactivated vaccine responses are critical for the development of vaccines with increased efficacy. Studies have shown that the direct conjugation of adjuvant to antigen promotes vaccine immunogenicity, with the advantage of both the adjuvant and antigen targeting the same cell. Using this strategy of direct linkage, we developed an inactivated influenza A (IAV) vaccine that is directly conjugated with the Toll-like receptor 7/8 agonist resiquimod (R848) through a heterobifunctional crosslinker. Previously, we showed that this vaccine resulted in improved protection and viral clearance in newborn nonhuman primates compared to a non-adjuvanted vaccine. We subsequently discovered that the choice of linker used to conjugate R848 to the virus alters the stimulatory activity of the vaccine, promoting increased maturation and proinflammatory cytokine production from DC differentiated in vitro. With this knowledge, we explored how the choice of crosslinker impacts the stimulatory activity of these vaccines. We found that the linker choice alters signaling through the NF-κB pathway in human monocyte-derived dendritic cells (moDCs). Further, we extended our analyses to in vivo differentiated APC present in human peripheral blood, replicating the linker-dependent differences found in in vitro differentiated cells. Finally, we demonstrated in a mouse model that the choice of linker impacts the amount of IAV-specific IgG antibody produced in response to vaccination. These data enhance our understanding of conjugation approaches for improving vaccine immunogenicity.

Clinical and upper airway characteristics of 3715 patients with the Omicron variant of SARS-Cov-2 in Changchun, China.

OBJECTIVE: The spread of the novel SARS-Cov-2 variant Omicron created a challenging public health situation in a number of countries. In March 2022, Omicron emerged in Changchun, China, and the number of patients infected rapidly increased. The prevalence of Omicron infection symptoms differs from that of Delta, with more upper airway clinical symptoms apparent. This study aimed to investigate the clinical and upper airway characteristics of the Omicron variant. MATERIALS AND METHODS: In this retrospective study, we collected data from participants in Changchun who had tested positive for Omicron with quantitative polymerase chain reaction between 10 March and 30 May 2022 using telephone interviews. The questionnaire was designed by the research team based on the number of upper airway symptoms using the visual analogue scale. We also considered age, sex, vaccination status, general symptoms, and cure period. RESULTS: A total of 3715 patients (2056 males and 1659 females) with mild COVID-19 from the Omicron variant were included. The patients had a mean age of 38.63 ( ± 13.97) years (range 2-86 years). The vaccine uptake rate was 91.33 % (8.66 %, 4.58 %, 65.33 %, and 21.43 % had received zero, one, two, and three doses, respectively). The incidence of upper airway symptoms, including throat and nasal symptoms, was 54.21 %. Throat symptoms were the most common during Omicron infection (49.12 %). Nasal symptoms were also common (20.08 %). The incidence of lower airway symptoms was 25.60 %, and gastrointestinal symptoms was 10.87 %. The incidence of general symptoms was 55.26 %. The cure period ranged from three to 37 days, with a mean of 10.24 ± 4.69 days. We compared the upper airway symptom severity for Omicron among different vaccination statuses and found no differences. CONCLUSIONS: The main clinical characteristics of the SARS-Cov-2 Omicron variant are upper airway symptoms and general symptoms. Fever remains the most common symptom, followed by mild dry cough. There was no association between Omicron infection and COVID-19 vaccines, and the vaccination status might have been ineffective against upper airway symptom severity by Omicron.

Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.

Activating the macrophage NLRP3 inflammasome can promote excessive inflammation with severe cell and tissue damage and organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenuates NLRP3 inflammasome activation in murine and human macrophages and septic mice by lowering caspase-1 cleavage and interleukin-1ß (IL-1ß) secretion. Inhibiting PDHK reverses NLRP3 inflammasome-induced metabolic reprogramming, enhances autophagy, promotes mitochondrial fusion over fission, preserves crista ultrastructure, and attenuates mitochondrial reactive oxygen species (ROS) production. The suppressive effect of PDHK inhibition on the NLRP3 inflammasome is independent of its canonical role as a pyruvate dehydrogenase regulator. Our study suggests a non-canonical role of mitochondrial PDHK in promoting mitochondrial stress and supporting NLRP3 inflammasome activation during acute inflammation.

Eicosapentaenoic Acid Ameliorates Cardiac Fibrosis and Tissue Inflammation in Spontaneously Hypertensive Rats.

Hypertension affects 1 in 3 adults in the United States and leads to left ventricular (LV) concentric hypertrophy, interstitial fibrosis, and increased stiffness. The treatment of cardiac fibrosis remains challenging and empiric. Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that is highly effective in reducing cardiovascular events in patients and cardiac fibrosis and hypertrophy in animals when administered before pressure overload by promoting the increase of anti-inflammatory M1 macrophages. In this study, we investigated whether EPA mitigates the exacerbation of cardiac remodeling and fibrosis induced by established hypertension, a situation that closely recapitulates a clinical scenario. Twelve-week-old spontaneously hypertensive rats were randomized to eat an EPA-enriched or control diet for 20 weeks. We report that rats eating the EPA-enriched diet exhibited a reduction of interstitial cardiac fibrosis and ameliorated LV diastolic dysfunction despite the continuous increase in blood pressure. However, we found that EPA did not have an impact on cardiac hypertrophy. Interestingly, the EPA diet increased mRNA expression of M2 macrophage marker Mrc1 and interleukin-10 in cardiac tissue. These findings indicated that the antifibrotic effects of EPA are mediated in part by phenotypic polarization of macrophages toward anti-inflammatory M2 macrophages and increases of the anti-inflammatory cytokine, interleukin-10. In summary, EPA prevents the exacerbation of cardiac fibrosis and LV diastolic dysfunction during sustained pressure overload. EPA could represent a novel treatment strategy for hypertensive cardiomyopathy.

SMGR: a joint statistical method for integrative analysis of single-cell multi-omics data.

Unravelling the regulatory programs from single-cell multi-omics data has long been one of the major challenges in genomics, especially in the current emerging single-cell field. Currently there is a huge gap between fast-growing single-cell multi-omics data and effective methods for the integrative analysis of these inherent sparse and heterogeneous data. In this study, we have developed a novel method, Single-cell Multi-omics Gene co-Regulatory algorithm (SMGR), to detect coherent functional regulatory signals and target genes from the joint single-cell RNA-sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) data obtained from different samples. Given that scRNA-seq and scATAC-seq data can be captured by zero-inflated Negative Binomial distribution, we utilize a generalized linear regression model to identify the latent representation of consistently expressed genes and peaks, thus enables the identification of co-regulatory programs and the elucidation of regulating mechanisms. Results from both simulation and experimental data demonstrate that SMGR outperforms the existing methods with considerably improved accuracy. To illustrate the biological insights of SMGR, we apply SMGR to mixed-phenotype acute leukemia (MPAL) and identify the MPAL-specific regulatory program with significant peak-gene links, which greatly enhance our understanding of the regulatory mechanisms and potential targets of this complex tumor.

Sepsis, pyruvate, and mitochondria energy supply chain shortage.

Balancing high energy-consuming danger resistance and low energy supply of disease tolerance is a universal survival principle that often fails during sepsis. Our research supports the concept that sepsis phosphorylates and deactivates mitochondrial pyruvate dehydrogenase complex control over the tricarboxylic cycle and the electron transport chain. StimulatIng mitochondrial energetics in septic mice and human sepsis cell models can be achieved by inhibiting pyruvate dehydrogenase kinases with the pyruvate structural analog dichloroacetate. Stimulating the pyruvate dehydrogenase complex by dichloroacetate reverses a disruption in the tricarboxylic cycle that induces itaconate, a key mediator of the disease tolerance pathway. Dichloroacetate treatment increases mitochondrial respiration and ATP synthesis, decreases oxidant stress, overcomes metabolic paralysis, regenerates tissue, organ, and innate and adaptive immune cells, and doubles the survival rate in a murine model of sepsis.

Effect of swallowing training combined with nutritional intervention on the nutritional status and quality of life of laryngeal cancer patients with dysphagia after operation and radiotherapy.

BACKGROUND: Dysphagia is a common complication in patients with laryngeal cancer after surgery and radiotherapy. OBJECTIVES: To explore the effect of swallowing training administered in combination with nutritional intervention on the nutritional status and quality of life of laryngeal cancer patients with dysphagia after surgery and radiotherapy. METHODS: Sixty-six patients with laryngeal cancer who developed dysphagia were randomly divided into control group and intervention group (n = 33 in each group). Patients in both groups received total laryngectomy and prophylactic radiotherapy and were provided routine health counseling and swallowing training. Patients in the intervention group were additionally provided with nutritional intervention. All patients were evaluated using video fluoroscopic swallowing examination (VFSE), Patient-Generated Subjective Global Assessment on nutritional status (PG-SGA) score, and Quality of Life Questionnaire-core 30 (QLQ-c30) score immediately after radiotherapy and 3 months later. RESULTS: Prior to swallowing training, there was no significant between-group difference with respect to VFSE evaluation, PG-SGA score, or QLQ-c30 score. Both groups showed improvement in these measures at 3 months after radiotherapy; however, the improvement in the intervention group was significantly better than that in the control group. CONCLUSIONS: Swallowing training combined with nutritional intervention can improve swallowing function, nutritional status and the quality of life of laryngeal cancer patients with dysphagia after operation and radiotherapy.

Hematopoietic Cell-Specific SLC37A2 Deficiency Accelerates Atherosclerosis in LDL Receptor-Deficient Mice.

Macrophages play a central role in the pathogenesis of atherosclerosis. Our previous study demonstrated that solute carrier family 37 member 2 (SLC37A2), an endoplasmic reticulum-anchored phosphate-linked glucose-6-phosphate transporter, negatively regulates macrophage Toll-like receptor activation by fine-tuning glycolytic reprogramming in vitro. Whether macrophage SLC37A2 impacts in vivo macrophage inflammation and atherosclerosis under hyperlipidemic conditions is unknown. We generated hematopoietic cell-specific SLC37A2 knockout and control mice in C57Bl/6 Ldlr-/- background by bone marrow transplantation. Hematopoietic cell-specific SLC37A2 deletion in Ldlr-/- mice increased plasma lipid concentrations after 12-16 wks of Western diet induction, attenuated macrophage anti-inflammatory responses, and resulted in more atherosclerosis compared to Ldlr-/- mice transplanted with wild type bone marrow. Aortic root intimal area was inversely correlated with plasma IL-10 levels, but not total cholesterol concentrations, suggesting inflammation but not plasma cholesterol was responsible for increased atherosclerosis in bone marrow SLC37A2-deficient mice. Our in vitro study demonstrated that SLC37A2 deficiency impaired IL-4-induced macrophage activation, independently of glycolysis or mitochondrial respiration. Importantly, SLC37A2 deficiency impaired apoptotic cell-induced glycolysis, subsequently attenuating IL-10 production. Our study suggests that SLC37A2 expression is required to support alternative macrophage activation in vitro and in vivo. In vivo disruption of hematopoietic SLC37A2 accelerates atherosclerosis under hyperlipidemic pro-atherogenic conditions.

Carbon Nanodots Inhibit Oxidized Low Density Lipoprotein-Induced Injury and Monocyte Adhesion to Endothelial Cells Through Scavenging Reactive Oxygen Species.

Oxidized low density lipoprotein (Ox-LDL) is a known biomarker of inflammation and atherosclerosis, a leading cause of death worldwide. As a new class of nanomaterials, carbon nanodots (CNDs) are widely used in bioimaging, diagnostics, and drug delivery. However, there is no current report on how these CNDs affect the cardiovascular system, particularly their potential in mediating endothelial inflammatory dysfunction. This study examined effects of CNDs on Ox-LDL-mediated endothelial dysfunction. CNDs significantly inhibited Ox-LDL-mediated adhesion of monocytes to human microvascular endothelial cells (HMEC-1), in human microvascular endothelial cells (HMEC-1). CNDs significantly inhibited Ox-LDL-mediated adhesion of monocytes to endothelial cells, which is an essential step in the development of atherosclerosis. Further, CNDs significantly inhibited OxLDL-induced expression of interleukin-8 (IL-8), a vital cytokine on monocyte adhesion to the endothelial cells. These results demonstrate CNDs possess anti-inflammatory properties. CNDs also protect cells against Ox-LDL-induced cytotoxicity. Electron paramagnetic resonance (EPR) spectroscopy studies demonstrated direct reactive oxygen species-scavenging by CNDs. This result indicates that the anti-inflammatory properties of CNDs are most likely due to their direct scavenging of reactive oxygen species. Animal studies involving mice did not show any morphological or physical changes between the CNDs and control groups. Our study provides evidence of potential of CNDs in reducing Ox-LDL-mediated inflammation and cytotoxicity in HMEC-1.

lncRNA MIAT/HMGB1 Axis Is Involved in Cisplatin Resistance via Regulating IL6-Mediated Activation of the JAK2/STAT3 Pathway in Nasopharyngeal Carcinoma.

Cisplatin-based chemotherapy and radiotherapy are the main first-line treatment strategies for nasopharyngeal carcinoma (NPC) patients. Unfortunately, resistance is a major obstacle in the clinical management of NPC patients. We prove that the expression level of high-mobility group box 1 (HMGB1) is dramatically increased in resistant NPC cells than that in sensitive cells. HMGB1 induces the expression and secretion of IL6, which leads to constitutive autocrine activation of the JAK2/STAT3 pathway and eventually contributes to chemoresistance in NPC cells. Long non-coding RNAs (lncRNAs) have been identified as key regulators involved in drug resistance. In this study, using GO analysis of the biological process and differential expression analysis, we find 12 significantly altered IncRNAs in NPC cell lines, which may be involved in regulating gene expression. Furthermore, we determine that elevated lncRNA MIAT level upregulates HMGB1 expression, contributing to cisplatin resistance in NPC cells. We find that the deficiency of the lncRNA MIAT/HMGB1 axis, inhibition of JAK2/STAT3, or neutralization of IL6 by antibodies significantly re-sensitizes resistant NPC cells to cisplatin in resistant NPC cells. Moreover, we provide the in vivo evidence that the deficiency of HMGB1 reduces cisplatin-resistant tumor growth. Most importantly, we provide clinical evidence showing that the expression level of the lncRNA MIAT/HMGB1/IL6 axis is elevated in resistant NPC tumors, which is highly correlated with poor clinical outcome. Our findings identify a novel chemoresistance mechanism regulated by the lncRNA MIAT/HMGB1/IL6 axis, which indicates the possibilities for lncRNA MIAT, HMGB1, and IL6 as biomarkers for chemoresistance and targets for developing novel strategies to overcome resistance in NPC patients.

Modulation of Macrophage Polarization by Carbon Nanodots and Elucidation of Carbon Nanodot Uptake Routes in Macrophages.

Atherosclerosis represents an ever-present global concern, as it is a leading cause of cardiovascular disease and an immense public welfare issue. Macrophages play a key role in the onset of the disease state and are popular targets in vascular research and therapeutic treatment. Carbon nanodots (CNDs) represent a type of carbon-based nanomaterial and have garnered attention in recent years for potential in biomedical applications. This investigation serves as a foremost attempt at characterizing the interplay between macrophages and CNDs. We have employed THP-1 monocyte-derived macrophages as our target cell line representing primary macrophages in the human body. Our results showcase that CNDs are non-toxic at a variety of doses. THP-1 monocytes were differentiated into macrophages by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) and co-treatment with 0.1 mg/mL CNDs. This co-treatment significantly increased the expression of CD 206 and CD 68 (key receptors involved in phagocytosis) and increased the expression of CCL2 (a monocyte chemoattractant and pro-inflammatory cytokine). The phagocytic activity of THP-1 monocyte-derived macrophages co-treated with 0.1 mg/mL CNDs also showed a significant increase. Furthermore, this study also examined potential entrance routes of CNDs into macrophages. We have demonstrated an inhibition in the uptake of CNDs in macrophages treated with nocodazole (microtubule disruptor), N-phenylanthranilic acid (chloride channel blocker), and mercury chloride (aquaporin channel inhibitor). Collectively, this research provides evidence that CNDs cause functional changes in macrophages and indicates a variety of potential entrance routes.

Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction.

Metabolic reprogramming between resistance and tolerance occurs within the immune system in response to sepsis. While metabolic tissues such as the liver are subjected to damage during sepsis, how their metabolic and energy reprogramming ensures survival is unclear. Employing comprehensive metabolomic, lipidomic, and transcriptional profiling in a mouse model of sepsis, we show that hepatocyte lipid metabolism, mitochondrial tricarboxylic acid (TCA) energetics, and redox balance are significantly reprogrammed after cecal ligation and puncture (CLP). We identify increases in TCA cycle metabolites citrate, cis-aconitate, and itaconate with reduced fumarate and triglyceride accumulation in septic hepatocytes. Transcriptomic analysis of liver tissue supports and extends the hepatocyte findings. Strikingly, the administration of the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate reverses dysregulated hepatocyte metabolism and mitochondrial dysfunction. In summary, our data indicate that sepsis promotes hepatic metabolic dysfunction and that targeting the mitochondrial PDC/PDK energy homeostat rebalances transcriptional and metabolic manifestations of sepsis within the liver.