Excessive Inflammatory Reaction Research Articles

ACY1215 Exerts Anti-inflammatory Effects by Inhibition of NF-κB and STAT3 Signaling Pathway to Repair Spinal Cord Injury.

Spinal cord injury (SCI), a public health problem caused by mechanical injury, leads to secondary excessive inflammatory reactions and long-term damage to neurological function. ACY1215 is a highly selective histone deacetylase 6 (HDAC6) inhibitor and reportedly has anti-inflammatory effects; however, its regulatory role in SCI has not been studied. The purpose of this study was to explore the role of ACY1215 in preventing inflammation, inhibiting astrogliosis, enhancing remyelination and preserving axons after spinal cord injury and further exploring the possible cellular signaling pathways involved. First, lipopolysaccharide (LPS) was utilized to stimulate rat astrocytes in vitro. Quantitative RT (qRT)-PCR and Western blotting showed that ACY1215 inhibited the expression of glial fibrillary acidic protein (GFAP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) in LPS-activated astrocytes. In addition, Western blotting results showed that ACY1215 could inhibit the signal transduction pathway of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3). In vivo, ACY1215 could exert anti-inflammatory effects by inhibiting the expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Moreover, ACY1215 repaired spinal cord injury by reducing the formation of glial scars and promoting remyelination and nerve recovery. In summary, ACY1215 can inhibit the NF-κB and STAT3 signaling pathways in astrocytes, reduce inflammation and ameliorate SCI. Our results provide a novel strategy for the treatment of SCI.

Role and Mechanism of Sialic Acid in Alleviating Acute Lung Injury through In Vivo and In Vitro Models.

Excessive inflammatory reactions are the most important pathological injury factor in acute lung injury (ALI). Our recent study found that sialic acid had an anti-colitis effect. In this study, the effect of sialic acid (SA) on acute lung inflammation was investigated. A lipopolysaccharide (LPS)-induced ALI animal model and LPS-stimulated HUVEC cell model were used to evaluate the anti-inflammatory effect of SA and study its molecular mechanisms. Compared with the LPS group, the lung index of the SA group decreased from 0.79 ± 0.05% to 0.58 ± 0.06% (LPS + 50 SA) and 0.62 ± 0.02% (LPS + 100 SA), with p < 0.01, suggesting that SA could improve the pulmonary edema of mice and alleviate LPS-induced lung injury. Transcriptome research identified 26 upregulated genes and 25 downregulated genes involved in the protection of SA against ALI. These genes are mainly related to the MAPK and NF-κB signaling pathways. Our study also proved that SA markedly downregulated the expression of inflammatory factors and blocked the JNK/p38/PPAR-γ/NF-κB pathway. Meanwhile, SA treatment also upregulated the expression of HO-1 and NQO1 in ALI mice. In vitro, SA obviously repressed the expressions of inflammatory cytokines and the JNK/p38-NF-κB/AP-1 pathway. SA also regulated the expression of oxidative stress-related genes through the Nrf2 pathway. Taken together, SA exhibits a protective role by modulating the anti-inflammatory and anti-oxidation pathways in ALI, and it may be a promising candidate for functional foods to prevent ALI.

Alpha-boswellic acid accelerates acute wound healing via NF-κB signaling pathway.

Boswellic acids (BAs) showed promising effects in cancer treatment, immune response regulation, and anti-inflammatory therapy. We aimed to assess the roles of alpha-BA (α-BA) in treating acute wound healing. In vivo wound-healing models were established to evaluate the therapeutic effects of α-BA. Cell assays were conducted to assess the impact of α-BA on cellular biological functions. Western blot analysis was employed to validate the potential mechanisms of action of α-BA. Animal models indicated that wound healing was notably accelerated in the α-BA group compared to the control group (P < 0.01). Hematoxylin and eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA) assay preliminarily suggested that α-BA may accelerate wound healing by inhibiting excessive inflammatory reactions and increasing the protein levels of growth factors. Cell function experiments demonstrated that α-BA suppressed the proliferation and migration ability of human hypertrophic scar fibroblasts (HSFBs), thereby favoring wound healing. Additionally, α-BA exerted a significant impact on cell cycle progression. Mechanistically, the protein levels of key genes in nuclear factor kappa beta (NF-κB) signaling pathway, including cyclin D1, p65, IκBα, and p-IκBα, were downregulated by α-BA. α-BA demonstrated the ability to counteract the abnormal proliferation of skin scar tissues, consequently expediting wound healing. These findings suggest its potential for development as a new agent for treating acute wound healing.

Therapeutic effect of oxidized bletilla striata polysaccharide-natamycin eye drops on fungal keratitis.

Fungal keratitis (FK) usually develops to a poor clinical prognosis due to the fungal invasion and excessive inflammatory reaction. In order to enhance the therapeutic effect of natamycin (NAT), we used the anti-inflammatory biological polysaccharide bletilla striata polysaccharide (BSP) combined with NAT to prepare a new eye drop -- oxidized bletilla striata polysaccharide-natamycin (OBN). UV-vis, FT-IR, and fluorescence spectroscopy were used to identify the synthesis of OBN. Biocompatibility of OBN was determined by CCK-8, scratch assay, and corneal toxicity test. RAW264.7 cells and C57BL/6 mice were stimulated with A. fumigatus and treated with PBS, OBN, or NAT. The anti-inflammatory activity of OBN was detected by RT-PCR and ELISA. In mice with FK, the clinical scores were used to evaluate the effect of OBN; HE staining was performed to assess the corneal pathological changes; MPO assay and immunofluorescence staining were used to investigate neutrophil infiltration. OBN was synthesized by combining oxidized bletilla striata polysaccharide (OBSP) with NAT through Schiff base reaction. OBN did not affect cell viability at a concentration of 160μg/mL in HCECs, RAW264.7 cells, and mouse corneas. OBN versus NAT significantly improved the prognosis of A. fumigatus keratitis by reducing disease severity, neutrophil infiltration, and expression of inflammatory factors in vivo. Additionally, OBN treatment down-regulated the mRNA and protein expression levels of inflammatory factors IL-1β, TNF-α, and IL-6 in RAW264.7 and mouse models. OBN is a compound prepared by covalently linking OBSP to the imino group of NAT through Schiff base reaction. OBN treatment down-regulated inflammation and improved the prognosis of mice with A. fumigatus keratitis.

Effects of different doses of glucose and fructose on central carbon metabolic pathways and intercellular wireless communication networks in humans

Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases. To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication, volunteers were given low, medium, and high doses of glucose and fructose. Serum cytokines, glucose, lactate, nicotinamide adenine dinucleotide (NADH) and metabolic enzymes were assayed, and central carbon metabolic pathway networks and cytokine communication networks were constructed. The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose. Compared with glucose, low-dose fructose decreased catabolism and increased anabolism, significantly enhanced the expression of the inflammatory cytokine interferon-γ (IFN-γ), macrophage-derived chemokine (MDC), induced protein-10 (IP-10), and eotaxin, and significantly reduced the activity of isocitrate dehydrogenase (ICDH) and pyruvate dehydrogenase complexes (PDHC). Both medium and high doses of fructose increase catabolism and anabolism, and there are more cytokines and enzymes with significant changes. Furthermore, multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways. Therefore, excessive intake of fructose should be reduced to avoid excessive inflammatory responses, allergic reactions and autoimmune diseases.

Electrospun nanofiber mats caged the mammalian macrophages on their surfaces and prevented their inflammatory responses independent of the fiber diameter

Poly-ε-caprolactone (PCL) has been widely used as biocompatible materials in tissue engineering. They have been used in mammalian cell proliferation to polarization and differentiation. Their modified versions had regulatory activities on mammalian macrophages in vitro. There are also studies suggesting different nanofiber diameters might alter the biological activities of these materials. Based on these cues, we examined the inflammatory activities and adherence properties of mammalian macrophages on electrospun PCL nanofibrous scaffolds formed with PCL having different nanofiber diameters. Our results suggest that macrophages could easily attach and get dispersed on the scaffolds. Macrophages lost their inflammatory cytokine TNF and IL6 production capacity in the presence of LPS when they were incubated on nanofibers. These effects were independent of the mean fiber diameters. Overall, the scaffolds have potential to be used as biocompatible materials to suppress excessive inflammatory reactions during tissue and organ transplantation by caging and suppressing the inflammatory cells.

Transplantace jater pro ACLF

Summary: Acute-on-chronic liver failure (ACLF) occurs in about one third of patients hospitalized for decmopensation of liver cirrhosis. It is defined as a failure of at least one organ, mostly the kidneys and/or liver, and very high short-term mortality. The most common trigger, precipitating event, is an infection or alcohol abuse. ACLF is caused by an excessive inflammatory reaction to the presence od microbial or sterile molecular structures in the blood circulation, and a disturbed immune response. ACLF is a very dynamic process and the condition must be reevaluated continuously according to the available scoring systems, early contact the transplant center and consider the possibility of this only curative treatment. We should be aware of renal function, nutrition, antimicrobial treatment and in patients with alcoholic hepatitis, it is necessary to consider the administration of corticosteroids. Liver transplantation for ACLF has somewhat worse one-year survival compared to other transplant groups, but long-term survival is comparable. Key words: ACLF – precipitating event – alcohol hepatitis – infection – liver transplantation

Research progress in autophagy in the development of pulp inflammation and dental pulp injury reparation and regeneration

Pulpitis is an infectious disease characterized by persistent inflammation of dental pulp and severe pain of patients, root canal treatment increases the risk of tooth fracture, discoloration and reinfection. Therefore, pulp injury repair and pulp regeneration become the new targets of pulpitis treatment. Autophagy is considered as an important defense and protective mechanism, thus plays an important role in preventing the host from excessive inflammatory reaction. There are few reports on the regulative mechanisms and therapeutic strategies of autophagy on pulp inflammation progression, therefore, this paper reviewed the role of autophagy on the progression of pulpitis, also reviewed the research progress of autophagy on dental pulp injury repair and regeneration, aiming to provide theoretical support for further research and clinical application.

P80 natural essence spray and lozenges provide respiratory protection against Influenza A, B, and SARS-CoV-2

Seasonally circulating viruses, such as Influenza, as well as newly emerging viruses and variants thereof, and waning immunity urge the need for safe, easy-to-use and inexpensive drugs to protect from these challenges. To prevent transmission of these viruses and subsequent excessive inflammatory reactions on mucous membranes, we tested the efficacy of the natural essence P80 as spray and in form of lozenges against respiratory infections caused by SARS-CoV-2 variants of concern (VoCs), influenza A (H3N2) and influenza B (Victoria). P80 natural essence, a Dimocarpus longan extract, shielded highly differentiated human airway epithelia from SARS-CoV-2 wildtype and Omicron variant as well as Influenza A and B infection and dampened inflammation by down-modulating pro-inflammatory cytokine and anaphylatoxin secretion. A single application of P80 natural essence spray maintained tissue integrity long-term. This also significantly reduced the release of infectious viral particles and the secretion of IP10, MCP1, RANTES and C3a, all of which mediate the migration of immune cells to the sites of infection. Even P80 lozenges dissolved in distilled water or non-neutralizing saliva efficiently prevented SARS-CoV-2 and Influenza-induced tissue destruction. Consequently, our in vitro data suggest that P80 natural essence can act as antiviral prophylactic, both in form of nasal or oral spray and in form of lozenges, independent of circulating respiratory challenges.

Cell polarization in ischemic stroke: molecular mechanisms and advances.

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as 'cell polarization.' There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations (microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

Efficacy of pantoprazole plus perforation repair for peptic ulcer and its effect on the stress response.

Peptic ulcer (PU) is an abnormal phenomenon in which there is rupture of the mucosa of the digestive tract, which not only affects patients' normal life but also causes an economic burden due to its high medical costs. To investigate the efficacy of pantoprazole (PPZ) plus perforation repair in patients with PU and its effect on the stress response. The study subjects were 108 PU patients admitted between July 2018 and July 2022, including 58 patients receiving PPZ plus perforation repair [research group (RG)] and 50 patients given simple perforation repair [control group (CG)]. The efficacy, somatostatin (SS) concentration, stress reaction [malondialdehyde (MDA), lipid peroxide (LPO)], inflammatory indices [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-1β], recurrence, and complications (perforation, hemorrhage, and pyloric obstruction) were compared. The overall response rate was higher in the RG than in the CG. Patients in the RG had markedly elevated SS after treatment, which was higher than that of the CG, while MDA, LPO, TNF-, CRP, and IL-1β were significantly reduced to lower levels than those in the CG. Lower recurrence and complication rates were identified in the RG group. Therefore, PPZ plus perforation repair is conducive to enhancing treatment outcomes in PU patients, reducing oxidative stress injury and excessive inflammatory reactions, and contributing to low recurrence and complication rates.

Neutrophil Extracellular Traps (NETs) in Kidney Disease: Role in Pathogenesis and Possibilities of NET Regulatory Therapy

Excessive uncontrolled inflammatory and immune reactions often lead to the development of acute and chronic forms of damage to various organs, including the kidneys. Neutrophils are the cells of the innate immune system, which are the first cellular effectors in protecting the host from a variety of pathogens, including bacteria, fungi and protozoa. As the most numerous leukocytes present in human blood, neutrophils migrate early to the foci of inflammation or tissue damage, where they play a significant role in the development of inflammation, recruitment of immune cells, removal of pathogens and tissue repair. Neutrophils also produce pro-inflammatory cytokines and release, in a process called netosis, a network of DNA and granular proteins known as neutrophil extracellular traps (NETs). NETs are potentially toxic, contribute to glomerular damage, activate autoimmune processes, cause vascular damage, and promote renal fibrosis. Numerous studies show that an imbalance between NET production and clearance is detrimental to kidney function. Therefore, strategies aimed at modulating the processes associated with NET may have a favorable prognostic effect. The review discusses the role of the netosis in the pathogenesis of kidney diseases, describes the mechanisms of tissue damage associated with NET, and the therapeutic potential of NET regulatory therapy.

The recent research progress of polyphenol‐derived biomaterials in wound repair

AbstractThe clinical requirements for wound care are increasing daily, and the global wound dressing market is expanding; however, the research and development of new wound dressings are imminent. Natural biomolecules such as polyphenols, have been widely used in this field of vision. Owing to their unique anti‐oxidative, adhesive, antibacterial and other bioactive functions, researchers have developed a series of wound dressings with excellent performance and applied them to a variety of biomaterials, such as hydrogels, nanofibers, films and scaffolds. They can effectively promote angiogenesis and fibroblast migration and proliferation, scavenge active oxygen free radicals, inhibit excessive inflammatory reactions at wound sites and ultimately accelerate wound healing. The authors summarise the latest progress in polyphenol‐derived biomaterials in skin wound repair to provide inspiration for future wound dressing research.

Application of dual-frequency ultrasound for reduction of perilesional edema and ecchymosis after rhinoseptoplasty.

Biological aspect and clinical research demonstrated that dual-frequency ultrasound (local dynamic micro-massage, LDM) waves of very high frequency can significantly modify cellular signaling providing anti-inflammatory and anti-fibrotic effects. During the recent past, these waves were successfully applied for the treatment of various inflammatory skin conditions, hypertrophic scars, and chronical wounds. Since the main complications after rhinoseptoplasty are caused by excessive inflammatory reactions and development of fibrosis along nasal implants which can lead to a revision rhinoseptoplasty, in this retrospective multicenter blinded study we have evaluated the efficacy of LDM ultrasound for the treatment of the postoperative perilesional ecchymosis and edema in patients after rhinoseptoplasty. Twenty-four patients received daily LDM treatment (study group) for 5 days starting from the first day postoperative, whereas 24 patients (control group) were treated with conventional ice packs. Dynamic reduction of the postoperative perilesional ecchymosis and edema was followed up, and the total duration of these side effects was determined within specific paranasal anatomical areas. Post-rhinoseptoplasty ecchymosis and edema were observed in the areas of anterior cheek, lower eyelids, and upper eyelids. Duration of the postoperative perilesional edema was significantly reduced in the group treated with LDM (1.9 ± 0.9 days) compared with control group (4.5 ± 2.1 days). Duration of the ecchymosis was also significantly reduced in LDM group (2.8 ± 1.4 days) compared with controls (7.4 ± 2.8 days). Postoperative patient satisfaction in LDM-treated and control groups was 3.1 ± 1.3 and 1.5 ± 0.7, respectively, demonstrating significantly higher satisfaction in LDM-treated group. This study proved that the post-rhinoseptoplasty group treated with LDM ultrasound showed a significantly shorter duration of the postsurgical perilesional ecchymosis and edema, with no substantial adverse effects other than those observed in the control group. It can be suggested that ultrasound treatment can serve as an alternative option for the noninvasive management of postoperative perilesional ecchymosis and edema.

Autophagy and Inflammation: Regulatory Roles in Viral Infections.

Autophagy is a highly conserved intracellular degradation pathway in eukaryotic organisms, playing an adaptive role in various pathophysiological processes throughout evolution. Inflammation is the immune system's response to external stimuli and tissue damage. However, persistent inflammatory reactions can lead to a range of inflammatory diseases and cancers. The interaction between autophagy and inflammation is particularly evident during viral infections. As a crucial regulator of inflammation, autophagy can either promote or inhibit the occurrence of inflammatory responses. In turn, inflammation can establish negative feedback loops by modulating autophagy to suppress excessive inflammatory reactions. This interaction is pivotal in the pathogenesis of viral diseases. Therefore, elucidating the regulatory roles of autophagy and inflammation in viral infections will significantly enhance our understanding of the mechanisms underlying related diseases. Furthermore, it will provide new insights and theoretical foundations for disease prevention, treatment, and drug development.

What General Neurologists Should Know about Autoinflammatory Syndromes?

Autoinflammatory disorders encompass a wide range of conditions with systemic and neurological symptoms, which can be acquired or inherited. These diseases are characterized by an abnormal response of the innate immune system, leading to an excessive inflammatory reaction. On the other hand, autoimmune diseases result from dysregulation of the adaptive immune response. Disease flares are characterized by systemic inflammation affecting the skin, muscles, joints, serosa, and eyes, accompanied by unexplained fever and elevated acute phase reactants. Autoinflammatory syndromes can present with various neurological manifestations, such as aseptic meningitis, meningoencephalitis, sensorineural hearing loss, and others. Early recognition of these manifestations by general neurologists can have a significant impact on the prognosis of patients. Timely and targeted therapy can prevent long-term disability by reducing chronic inflammation. This review provides an overview of recently reported neuroinflammatory phenotypes, with a specific focus on genetic factors, clinical manifestations, and treatment options. General neurologists should have a good understanding of these important diseases.

Revealing the biological mechanism of acupuncture in alleviating excessive inflammatory responses and organ damage in sepsis: a systematic review.

Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even endanger life. Acupuncture is widely accepted and applied in the treatment of sepsis, and breakthroughs have been made regarding its mechanism of action in recent years. In this review, we systematically discuss the current clinical applications of acupuncture in the treatment of sepsis and focus on the mechanisms of acupuncture in animal models of systemic inflammation. In clinical research, acupuncture can not only effectively inhibit excessive inflammatory reactions but also improve the immunosuppressive state of patients with sepsis, thus maintaining immune homeostasis. Mechanistically, a change in the acupoint microenvironment is the initial response link for acupuncture to take effect, whereas PROKR2 neurons, high-threshold thin nerve fibres, cannabinoid CB2 receptor (CB2R) activation, and Ca2+ influx are the key material bases. The cholinergic anti-inflammatory pathway of the vagus nervous system, the adrenal dopamine anti-inflammatory pathway, and the sympathetic nervous system are key to the transmission of acupuncture information and the inhibition of systemic inflammation. In MODS, acupuncture protects against septic organ damage by inhibiting excessive inflammatory reactions, resisting oxidative stress, protecting mitochondrial function, and reducing apoptosis and tissue or organ damage.

Autoinflammatory syndromes

The concept of autoinflammation includes aheterogeneous group of monogenic and polygenic diseases. These are characterized by excessive activation of the innate immune system without antigen-specific Tcells or autoantibodies. The diseases are characterized by periodic episodes of fever and increased inflammation parameters. Monogenic diseases include familial Mediterranean fever (FMF) and the newly described VEXAS (vacuoles, E1 enzyme, X‑linked, autoinflammatory, somatic) syndrome. Heterogeneous diseases include adult-onset Still's disease and Schnitzler syndrome. Treatment is aimed at preventing the excessive inflammatory reaction in order to avoid long-term damage, such as amyloidA (AA) amyloidosis.

Inflammatory reaction and immune response of half-smooth tongue sole (Cynoglossus semilaevis) after infection with Vibrio anguillarum

Frequently occurred bacterial diseases have seriously affected the aquaculture industry of half-smooth tongue sole (Cynoglossus semilaevis). Notably, vibriosis, with Vibrio anguillarum as one of the causative pathogens, is the most severe bacterial disease with severe inflammatory response of the host, leading to high mortality rates. In the present study, we explored the relationship between bacterial concentrations and host mortality, inflammatory reaction, and immune response in half-smooth tongue sole after infection with V. anguillarum at different concentrations (Treatment 1, 6.4 × 105 CFU/mL; Treatment 2, 6.4 × 106 CFU/mL). The mortality of Treatment 2 (77.5%) was significantly higher than that of Treatment 1 (10%), corresponding with bacterial concentrations. Although the number of deaths varies, intensive deaths were observed within 24 h post infection (hpi) in both bacterial concentration groups. Histopathological analyses revealed that fish tissues were most severely damaged at 24 or 48 hpi, and Treatment 2 was more severe than Treatment 1. A qRT-PCR-based detection method with virulence factor gene empA was established to quantify the bacterial loads in various tissues, and the bacterial loads were the highest at 24 hpi in Treatment 2, and at 48 hpi in Treatment 1. Additionally, the expression levels of complement genes (C5a, C3, C5, and C6), inflammatory factors (IL-1β, TNF-α, and IL-10), and other immune-related genes (jak2, NF-κB1, stat3, and tlr3) were increased in various tissues after infection in both treatment groups, with most genes being most expressed at 24 or 48 hpi, and expression levels of inflammatory factors in Treatment 2 were higher than those in Treatment 1. Moreover, the expression of C5a was positively correlated with that of proinflammatory cytokines in both bacterial concentration groups. According to the results of this study, 24–48 hpi was a key node for early vibriosis detection and intervention. Compared with the low mortality of Treatment 1, the mass death of fish in Treatment 2 was suggested to be caused by uncontrolled excessive inflammatory reaction induced by the overactivation of complement system, especially C5a. We believe these results could provide theoretical basis for prevention, evaluation, and treatment of vibrio disease in tongue sole aquaculture, and lay a solid foundation for future functional analyses.

A paintable and adhesive hydrogel cardiac patch with sustained release of ANGPTL4 for infarcted heart repair

The infarcted heart undergoes irreversible pathological remodeling after reperfusion involving left ventricle dilation and excessive inflammatory reactions in the infarcted heart, frequently leading to fatal functional damage. Extensive attempts have been made to attenuate pathological remodeling in infarcted hearts using cardiac patches and anti-inflammatory drug delivery. In this study, we developed a paintable and adhesive hydrogel patch using dextran-aldehyde (dex-ald) and gelatin, incorporating the anti-inflammatory protein, ANGPTL4, into the hydrogel for sustained release directly to the infarcted heart to alleviate inflammation. We optimized the material composition, including polymer concentration and molecular weight, to achieve a paintable, adhesive hydrogel using 10% gelatin and 5% dex-ald, which displayed in-situ gel formation within 135 s, cardiac tissue-like modulus (40.5 kPa), suitable tissue adhesiveness (4.3 kPa), and excellent mechanical stability. ANGPTL4 was continuously released from the gelatin/dex-ald hydrogel without substantial burst release. The gelatin/dex-ald hydrogel could be conveniently painted onto the beating heart and degraded in vivo. Moreover, in vivo studies using animal models of acute myocardial infarction revealed that our hydrogel cardiac patch containing ANGPTL4 significantly improved heart tissue repair, evaluated by echocardiography and histological evaluation. The heart tissues treated with ANGPTL4-loaded hydrogel patches exhibited increased vascularization, reduced inflammatory macrophages, and structural maturation of cardiac cells. Our novel hydrogel system, which allows for facile paintability, appropriate tissue adhesiveness, and sustained release of anti-inflammatory drugs, will serve as an effective platform for the repair of various tissues, including heart, muscle, and cartilage.