The wide variety of phenolic compounds, along with their similar structural features and physicochemical properties, poses significant challenges for reliable identification and detection. This article develops a novel photoelectrochemical (PEC) sensor array based on three metal-organic framework (MOF) nanozymes with substrate diversity and an efficient PEC sensing platform, achieving accurate identification and detection of six phenolic compounds. MOF nanozymes (ZIF-8, D-ZIF-67 and MIL-88B) catalyze the oxidation of phenolic compounds, yielding distinct quinone derivatives. These quinone derivatives are coupled to the surface of the PEC sensing platform with chitosan (CS) as the recognition element and BiOI as the signal transduction element, generating unique PEC response fingerprints for recognition and detection. This sensor array is the first report of a phenolic compound sensor array based on MOF nanozymes integrated with a PEC sensing platform, avoiding the limitations of sample color and turbidity on detection. In addition, inheriting the high sensitivity advantage of PEC technology, the developed sensor array can accurately identify phenolic compounds with concentrations as low as 1 μM, and achieve quantitative detection of two model targets, catechol and dopamine, with a linear range of 1-100 μM. This study provides a new approach for the identification and detection of phenolic compounds, and contributes to the advancement of PEC sensor arrays.

This study investigates the effects of high-altitude hypoxia on cardiac function and explores underlying mechanisms. The results demonstrate that exposure to high-altitude hypoxia induces structural and functional damage to the heart, leading to myocardial cell injury and oxidative stress, which are accompanied by ferroptosis. Inhibition of ferroptosis with Fer-1 significantly enhances hypoxia-induced expression of GPX4 and SLC7A11, reduces ROS levels, restores the GSH/GSSG ratio, and improves viability of hypoxia-damaged myocardial cells. Further investigation revealed that hypoxia induces mitochondrial damage and disrupts FAO, accompanied by downregulation of PPARα. Activation of PPARα with WY14643 enhances FAO, suppresses ferroptosis, and boosts cell viability and ATP levels under hypoxic conditions. Overexpression of SIRT1 upregulates PPARα, enhances FAO, and mitigates ferroptosis, these effects are reversed by the PPARα inhibitor GW6471. Resveratrol, a natural SIRT1 activator, improves cardiac function and mitochondrial structure, enhances FAO, and reduces ferroptosis in high-altitude hypoxia-induced cardiac injury through the SIRT1-PPARα-GPX4 pathway. These findings identify the SIRT1-PPARα-GPX4 pathway as a potential therapeutic target for high-altitude-induced cardiac injury.

Astragaloside IV (AS-IV), a bioactive compound renowned for its anti-inflammatory, antioxidant, and anti-apoptotic properties, has not yet been investigated for its potential role in modulating cardiac function under high-altitude conditions. This study elucidates the cardioprotective effects of AS-IV against high-altitude-induced cardiac injury and explores the underlying molecular mechanisms. Under hypobaric hypoxia, we observed significant cardiac dysfunction, hypertrophy, and fibrosis, as confirmed by comprehensive echocardiographic, histopathological, and molecular analyses. Remarkably, AS-IV administration effectively attenuated these pathological changes, restoring cardiac architecture and function while mitigating oxidative stress and apoptosis. Further in vivo and in vitro experiments revealed that AS-IV preserves mitochondrial integrity by enhancing membrane potential, ameliorating mitochondrial impairment, and modulating calcium homeostasis through the calcium-sensing receptor (CaSR)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling axis. Network pharmacology-based screening identified key molecular targets, including epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mouse double minute 2 (MDM2), which were subsequently validated via molecular docking studies demonstrating strong binding affinities between AS-IV and these core proteins. Mechanistic investigations further revealed that siRNA-mediated EGFR knockdown or pharmacological activation of CaSR abolished AS-IV's cardioprotective effects, including its anti-apoptotic, antioxidant, and mitochondrial-stabilizing properties. Taken together, our findings demonstrate that AS-IV exerts its therapeutic effects through a dual-pathway mechanism involving (1) the EGFR-PI3K-AKT-MDM2 axis and (2) CaSR-NF-κB signaling. These insights position AS-IV as a promising candidate for the prevention and treatment of high-altitude-related cardiovascular diseases.

The present study aimed to investigate the therapeutic potential of Osmundacetone (Osu), a natural plant product, for the treatment of rheumatoid arthritis (RA). The study revealed that Osu effectively reduced arthritis-induced swelling and bone destruction, as well as alleviating inflammation-related factors and oxidative stress in animal models. We focused the mechanism exploration on its regulatory mechanism on osteoclastogenesis in the next investigation. In vitro experiments demonstrated a dose-dependent inhibition of osteoclastic differentiation by Osu, as evidenced by tartrate resistant acid phosphatase (TRAP) staining and a reduction in osteoclastic differentiation markers observed through Western blotting analysis. And three different approaches Osu inhibiting osteoclastogenesis were found in our researches: (1) The binding of Receptor Activator of Nuclear Factor Kappa B (RANK) and Osu was revealed by the in-silico analysis. (2) According to 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining, Osu attenuated the level of reactive oxygen species (ROS), and western blotting studies revealed this effect was modulated by the regulation of Kelch-like ECH-associated protein 1 / Nuclear Factor erythroid 2-Related Factor 2 (Keap1/Nrf2) pathway. (3) Interestingly, we found that Osu increased the lipid peroxidation via downregulating the expression of glutathione peroxidase 4 (GPX4) at the same time as reducing the ROS, leading to the reduction of the fluidity of the membrane and the fusion of osteoclasts which could be reversed by using the ferroptosis inhibitor- Ferrostatin-1 (Fer-1). Overall, a natural compound to the existing therapeutics for rheumatoid arthritis was confirmed and a new strategy for inhibiting osteoclastogenesis was added.

As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.

Hypobaric hypoxia-induced hyperuricemia (HUA) is a major health challenge for high-altitude populations, yet its molecular mechanisms remain poorly understood. This study employed metabolomic and proteomic profiling of a high-altitude cohort (10 HUA patients and 10 matched controls) to address this gap. HUA patients exhibited significantly elevated uric acid (UA), creatine kinase, and lactate dehydrogenase levels alongside reduced platelet counts. Metabolomic analysis identified 79 significantly altered metabolites, which were associated with amino acids, lipids, and other pathways, including glycerophospholipid and riboflavin metabolism. Notably, l-cystathionine and serine emerged as potential discriminatory biomarkers for HUA. Parallel proteomics revealed 46 differentially expressed proteins, predominantly linked to complement activation and immune response pathways. Functional enrichment analysis indicated upregulated immune signaling and downregulated hemostasis-related proteins in HUA patients. A machine learning model identified 30 molecular signatures, including both proteins and metabolites, that could distinguish HUA from the control subjects. The resulting signature demonstrated a high discriminatory power. Furthermore, protein-metabolite interaction networks unveiled key regulators and potential therapeutic targets for HUA. These findings provide novel insights into the underlying molecular mechanisms of high-altitude HUA and highlight potential diagnostic and therapeutic strategies for hypobaric hypoxia conditions.

Grape seed proanthocyanidins (GSPs) have been receiving extensive attention due to their outstanding brain protection role in various disease models. This study aimed to explore the therapeutic effects of GSPs against acute high-altitude hypoxia-induced brain injury (AHHBI) and elucidate the underlying mechanism. SD rats and PC12 cells were employed in this study to establish in vivo and in vitro models of acute high-altitude hypoxia, respectively. In compared to mode group rats with hypobaric hypoxia exposure, GSP treatment significantly restored spatial learning and memory abilities of rats, reduced hippocampal inflammatory factor levels and NRLP3 inflammasome, and also enhanced hippocampal autophagy. In hypoxic PC12 cells, GSP treatment increased the survival rate of cells, improved cell morphology, reduced cell cycle arrest and apoptosis, and inhibited the activation of the NLRP3 inflammasome. Furthermore, GSP treatment enhanced autophagy and suppressed the PI3K/Akt/mTOR signaling pathway in hypoxic PC12 cells. However, autophagy inhibitor 3-MA compromised inhibitory effect of GSPs on NLRP3 inflammasome and the protective effects on hypoxic PC12 cells. Our study demonstrated neuroprotective effects of GSPs on rat model with high-altitude hypoxia exposure and PC12 cells experiencing hypoxic damage. The mechanism is related to the increase of autophagic flux promoted by GSPs, and the subsequent attenuation of NLRP3 inflammasome-mediated neuroinflammation. More effects and mechanisms of GSPs on the high-altitude hypoxia-induced brain injury are worthy to be explored in the future.

Rheumatoid arthritis (RA) is a chronic autoimmune disease which afflicts about nearly 1

Background: Oral squamous cell carcinoma (OSCC), which accounts for over 90% of all oral malignancies, remains a major global health challenge due to its aggressive clinical course and poor prognosis. Periodontitis, a widespread chronic inflammatory condition affecting the supporting structures of the teeth, has increasingly been implicated as a potential risk factor for the development of various cancers. Emerging evidence suggests that microbial dysbiosis within the oral cavity may contribute to the creation of a pro-tumorigenic microenvironment, thereby promoting tumor initiation and progression. Nevertheless, the precise mechanisms linking periodontitis to OSCC, particularly through alterations in the oral microbiota, remain insufficiently understood. This article seeks to comprehensively analyze the association between periodontitis and OSCC and to elucidate the potential role of oral microbiota dysbiosis in mediating this relationship. Methods: In this study, a ligature-induced periodontitis model was established in C57BL/6J mice, and after two weeks, an OSCC model was introduced by the subcutaneous injection of SCC-7 cells to investigate the impact of periodontitis on OSCC progression. The effects of periodontitis on OSCC cell proliferation and invasion were assessed using scratch wound healing assays and CCK-8 proliferation assays. 16S rDNA high-throughput sequencing was conducted to profile the microbial communities present in the oral cavity and OSCC tissues, with particular emphasis on α-diversity indices (including Pielou’s evenness and Chao1 richness) and taxonomic composition at both the phylum and class levels. Furthermore, qPCR was utilized to assess the expression levels of cytokines in both periodontal and OSCC tissues, thereby elucidating the inflammatory milieu, potentially linking periodontitis to OSCC progression. Results: Our findings demonstrated that periodontitis significantly promoted OSCC growth and enhanced the invasive potential of OSCC cells. Microbial profiling revealed marked alterations in both the oral and OSCC microbiota, characterized by significant shifts in community composition and increased microbial diversity. Notably, these microbial changes exhibited consistent patterns between the oral cavity and the OSCC microenvironment, suggesting a potential mechanistic link between periodontitis-associated dysbiosis and OSCC progression. Consistently, qPCR analysis revealed elevated expression levels of IL-1β, IL-10, and IL-18 in both periodontal and OSCC tissues, providing evidence that the microbial alterations were accompanied by intensified inflammatory responses, which may contribute to OSCC progression. Conclusions: This study underscores the intricate interplay between periodontitis-induced microbial dysbiosis and the development of oral squamous cell carcinoma (OSCC). The findings suggest that periodontal inflammation, together with associated shifts in the oral microbiota, acts synergistically to drive OSCC progression. The elevated expression of cytokines further supports the role of a pro-inflammatory tumor microenvironment in mediating this interaction. These results offer important insights into the microbial and inflammatory mechanisms underlying the connection between periodontitis and OSCC, highlighting the critical role of maintaining periodontal health in the prevention and management of OSCC.

Hypoxia imposes notable stress on organisms and even causes tissue damage; however, the cellular and molecular mechanisms underlying hypoxic adaptation and maladaptation are elusive. Here, we performed single-cell RNA sequencing to analyze hematopoietic stem and progenitor cells (HSPCs) and erythroid cells in a mouse model of high-altitude polycythemia (HAPC) mimicking long-term high-altitude hypoxia exposure. We identified a distinct erythroid-biased multipotent progenitor subset, FOShi MPP, characterized by a unique responsiveness to interferon (IFN) signaling, which expands under hypoxia conditions. This subset rapidly responds to hypoxia during re-ascent by sustaining low methylation of erythroid-priming genes, suggesting a memory function in HSPCs for faster acclimatization. Additionally, erythroid cells in HAPC mice had active metabolic and autophagic activity, as well as abundant CD47 expression that prevented the phagocytosis of erythrocytes. Finally, CD47 blockade and/or IFNα treatments alleviated erythrocytosis in HAPC mice. These approaches might constitute promising therapeutic strategies for HAPC.

High altitude environment is mainly characterized by low oxygen. Due to persistent hypoxia, nonhealing wounds are common in high-altitude areas. Moreover, Basic fibroblast growth factor (bFGF) is a versatile biologically active substance that has crucial impact on wound healing. Given the limited availability of atmospheric oxygen and reduced blood oxygen saturation in high-altitude area, and the challenge that arises from direct oxygen and bFGF delivery to wounds through the traumatized vascular structure, it necessitates an innovative solution for local and permeable delivery of oxygen and bFGF. In this study, we present a strategy that involves revamping traditional gel-based wound dressings through the incorporation of nanoparticles encapsulating oxygen and bFGF, engineered to facilitate the localized delivery of dissolved oxygen and bFGF to wound surfaces. The prospective evaluation of this delivery technique's therapeutic impacts on epithelial, endothelial and fibroblasts cells can be materialized. Further experiment corroborated these effects on a high-altitude wounds' murine model. Given its biocompatibility, efficacy, and utility, we posit that NOB-Gel exhibits remarkable translational potential for managing and hastening the healing process of an array of clinical wounds, more so for wounds inflicted at high altitudes.

Although direct hepatic stellate cell (HSC) inhibition is considered a promising strategy for alleviating liver fibrosis, traditional therapies struggle with off-target effects due to limited penetration of liver sinusoidal endothelial cell barriers. This study reports on the development of a "Kupffer cell (KC) teleportation" strategy to treat liver fibrosis by fabricating a hybrid polymer-bimetallic sequential delivery system, CF@BPPM (baicalin prodrug polymer [BP]/mannose derivative polymer [PM] encapsulated copper [Cu]-iron [Fe] ultrasmall nanoparticles [CFs]). The nanosystems exhibit KCs targeting and acidic response sequential release properties by a hybrid polymer, which first releases CFs in lysosome after being internalized by KCs through a PM targeting effect. The exposed CFs efficiently scavenge reactive oxygen species in KCs and subsequently degrade Cu2+/ Fe2+ to upregulate the heme oxygenase expression for suppressing interleukin 1 beta, interleukin 6, tumor necrosis factor-alpha, and platelet-derived growth factors. Second, baicalin, released from BP in lysosome, further inhibits transforming growth factor beta secretion. These results suggest that CF@BPPM inhibits the inclusive cytokine secretion of KCs, which play a vital conductive role in liver fibrosis progression. Subsequently, CF@BPPM achieves protection against HSCs activation, migration, and collagen production, enriching anti-liver fibrosis therapeutic methods by exploiting messaging between KCs and HSCs. Ultimate synthesis of CF@BPPM through the self-assembly of BP and PM polymers, encapsulating CF. A " Kupffer Cell Teleportation" strategy analogous to Newton's pendulum for alleviating liver fibrosis, employing CF@BPPM. The mechanism of CF@BPPM sequential release and the treatment of liver fibrosis through inhibition of cytokine secretion from Kupffer cells.image

To alleviate bone loss, most current drugs target osteoclasts. Saikosaponin A (Ssa), a triterpene saponin derived from Bupleurum falcatum (also known as Radix bupleuri), has immunoregulatory, neuromodulatory, antiviral, anticancer, anti-convulsant, anti-inflammatory, and anti-proliferative effects. Recently, modulation of bone homeostasis was shown to involve ferroptosis. Herein, we aimed to determine Ssa's inhibitory effects on osteoclastogenesis and differentiation, whether ferroptosis is involved, and the underlying mechanisms. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining, and pit formation assays were conducted to confirm Ssa-mediated inhibition of RANKL-induced osteoclastogenesis in vitro. Ssa could promote osteoclast ferroptosis and increase mitochondrial damage by promoting lipid peroxidation, as measured by iron quantification, FerroOrange staining, Dichloro-dihydro-fluorescein diacetate, MitoSOX, malondialdehyde, glutathione, and boron-dipyrromethene 581/591 C11 assays. Pathway analysis showed that Ssa can promote osteoclasts ferroptosis by inhibiting the Nrf2/SCL7A11/GPX4 axis. Notably, we found that the ferroptosis inhibitor ferrostatin-1 and the Nrf2 activator tert-Butylhydroquinone reversed the inhibitory effects of Ssa on RANKL-induced osteoclastogenesis. In vivo, micro-computed tomography, hematoxylin and eosin staining, TRAP staining, enzyme-linked immunosorbent assays, and immunofluorescence confirmed that in rats with periodontitis induced by lipopolysaccharide, treatment with Ssa reduced alveolar bone resorption dose-dependently. The results suggested Ssa as a promising drug to treat osteolytic diseases.

Long-term exposure to high altitudes can induce adaptive or pathological changes in humans; however, the effects of altitude on human serum remain unclear. This study employed untargeted metabolomics and proteomics to examine the differences in serum metabolites and proteins from subjects residing at altitudes of 2900, 3500, 4300, and 4600 m for at least one year compared with those residing in a plain area (altitude of 3 m) under normoxic conditions. The results revealed that long-term high-altitude hypoxia significantly altered human serum metabolites and proteins. Moreover, the pathways of linoleic acid metabolism, arachidonic acid (AA) metabolism, and the complement and coagulation cascades were significantly altered in response to hypoxia. Further analysis revealed that hypoxia at extremely high altitudes (3500–4600 m) promoted the conversion of AA into thromboxane A2, thromboxane B2, 15(S)-hydroxyeicosatetraenoic acid, and 12(S)-hydroxyeicosatetraenoic acid in platelets, resulting in reduced serum AA levels and platelet aggregation. Additionally, the metabolism of AA in platelets further increased with increasing altitude. Exposure to high-altitude areas (2900–4600 meters) increased oxygen transport, glycolysis, coagulation, and inhibits complement activation by increasing the expression of proteins such as globin, glyceraldehyde-3-phosphate dehydrogenase, superoxide dismutase 1, carbonate dehydratase II, and inhibiting complement component 1q. The inhibition of fibrinogen and coagulation factor XI may represent a physiological response to thrombosis and may be associated with liver injury. These findings indicate that high-altitude exposure promotes adaptation to hypoxia by increasing oxygen transport and glycolysis, and promotes thrombosis by interfering with platelet metabolism, and disrupts the complement system by inducing liver damage.

High-altitude exposure has been linked to cardiac dysfunction. Silent information regulator factor 2-related enzyme 1 (sirtuin 1, SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, plays a crucial role in regulating numerous cardiovascular diseases. However, the relationship between SIRT1 and cardiac dysfunction induced by hypobaric hypoxia (HH) remains unexplored. This study aims to assess the impact of SIRT1 on HH-induced cardiac dysfunction and delve into the underlying mechanisms, both in vivo and in vitro. In this study, we have demonstrated that exposure to HH results in cardiomyocyte injury, along with the downregulation of SIRT1 and mitochondrial dysfunction. Upregulating SIRT1 significantly inhibits mitochondrial fission, improves mitochondrial function, reduces cardiomyocyte injury, and consequently enhances cardiac function in HH-exposed rats. Additionally, HH exposure triggers aberrant expression of mitochondrial fission-regulated proteins, with a decrease in PPARγ coactivator 1 alpha (PGC-1α) and mitochondrial fission factor (MFF) and an increase in mitochondrial fission 1 (FIS1) and dynamin-related protein 1 (DRP1), all of which are mitigated by SIRT1 upregulation. Furthermore, inhibiting PGC-1α diminishes the positive effects of SIRT1 regulation on the expression of DRP1, MFF, and FIS1, as well as mitochondrial fission. These findings demonstrate that SIRT1 alleviates HHinduced cardiac dysfunction by preventing mitochondrial fission through the PGC-1α-DRP1/FIS1/MFF pathway.

Bone defects have serious economic and clinical impacts; however, despite improvements in bone defect management, the range of clinical outcomes remains limited. A variety of biomaterials have been used to treat complex bone defects. However, final bone repair outcomes may be adversely affected by poor osteogenic capacity and risk of infection. Consequently, therapeutic methods are required that reduce bacterial contamination and increase the use of osteogenic biomaterials. Herein, we report the preparation of poly(lactic acid-coglycolic acid) (PLGA) microspheres coloaded with magnesium (Mg2+) and gallium (Ga3+) ions (Mg-Ga@PLGA), which can fill irregular bone defects and show good biosafety. During in vitro testing, Mg-Ga@PLGA not only showed a synergistic effect on promoting osteogenic differentiation but also inhibited osteoclastic differentiation. Moreover, we found that Mg-Ga@PLGA demonstrated an antibacterial effect. During in vivo testing, Mg-Ga@PLGA exhibited strong in situ osteogenic ability. In conclusion, Mg-Ga@PLGA has good potential for treating bone defects at risk of infection.

Accurate prognosis prediction of head and neck squamous cell carcinoma (HNSCC) is vital for guiding clinical decision-making. DNA methylation (DNAm) plays important roles in the regulation of gene expression and abnormal DNAm is a hallmark of cancers. This study aimed to develop a prognostic model for HNSCC based on DNAm changes that can regulate gene expression. Based on The Cancer Genome Atlas HNSCC dataset, we constructed a novel four-CpG (cg02409878, cg01984743, cg23867673, and cg01995815) prognostic risk score (FCPRscore) model. The FCPRscore showed good generalizability on both TCGA and independent validation datasets, and achieved better performance compared with nine existing RNA/DNAm-based prognostic models. Furthermore, the FCPRscore is an independent prognostic factor and can enhance the predictive power of established clinical predictors. The low-risk group showed a more immune-active tumor microenvironment (TME) and more sensitive to immune checkpoint inhibitor therapy, while the high-risk group benefited more from chemotherapy. In addition, STK3, a gene regulated by cg02409878, significantly reduced proliferation and migration ability of SCC15 cells after belumosudil-mediated inhibition or shRNA-mediated knockdown. Our study proposed a robust prognostic model of HNSCC, FCPRscore, which could serve a prognostic factor and a promising tool to guide therapy decisions for HNSCC.

About 140 million people worldwide live at an altitude above 2500 m. Studies have showed an increase of the incidence of hyperuricemia among plateau populations, but little is known about the possible mechanisms. This study aims to assess the effects of high altitude on hyperuricemia and explore the corresponding mechanisms at the histological, inflammatory and molecular levels. This study finds that intermittent hypobaric hypoxia (IHH) exposure results in an increase of serum uric acid level and a decrease of uric acid clearance rate. Compared with the control group, the IHH group shows significant increases in hemoglobin concentration (HGB) and red blood cell counts (RBC), indicating that high altitude hyperuricemia is associated with polycythemia. This study also shows that IHH exposure induces oxidative stress, which causes the injury of liver and renal structures and functions. Additionally, altered expressions of organic anion transporter 1 (OAT1) and organic cation transporter 1 (OCT1) of kidney have been detected in the IHH exposed rats. The adenosine deaminase (ADA) expression levels and the xanthione oxidase (XOD) and ADA activity of liver of the IHH exposure group have significantly increased compared with those of the control group. Furthermore, the spleen coefficients, IL-2, IL-1β and IL-8, have seen significant increases among the IHH exposure group. TLR/MyD88/NF-κB pathway is activated in the process of IHH induced inflammatory response in joints. Importantly, these results jointly show that IHH exposure causes hyperuricemia. IHH induced oxidative stress along with liver and kidney injury, unusual expression of the uric acid synthesis/excretion regulator and inflammatory response, thus suggesting a potential mechanism underlying IHH-induced hyperuricemia.