Low molecular weight 35 kDa hyaluronan fragment HA35 in the treatment of bone metastasis pain: A case report.

Rationale: Late-stage cancer patients often experience severe pain due to bone metastasis, caused by structural damage and cancer-induced inflammation. Hyaluronan, known to alleviate pain by blocking the TRVP1 calcium channel, faces limitations due to its high molecular weight. However, 35 kDa low molecular weight hyaluronan fragment (HA35) have shown promise in relieving various pains, including cancer-related pain.

A clinical study of the local injection of a freshly manufactured 35 kDa hyaluronan fragment for treating chronic wounds.

This study manufactured a 35 kDa hyaluronan fragment (HA35) by enzymatically degrading high-molecular-weight HA using hyaluronidase PH20 derived from bovine testis. The research then examined the therapeutic efficacy of locally administered, tissue-permeable HA35 in alleviating chronic wounds and their associated neuropathic pain. For 20 patients with nonhealing wounds and associated pain lasting over three months, 100 mg of HA35 was injected daily into the healthy skin surrounding the chronic wound for 10 days.

Characterization, Bioactivity, and Biodistribution of 35 kDa Hyaluronan Fragment.

It has been reported that hyaluronic acid (HA) with a 35 kDa molecular weight (HA35) acts biologically to protect tissue from injury, but its biological properties are not yet fully characterized. This study aimed to evaluate the cellular effects and biodistribution of HA35 compared to HA with a 1600 kDa molecular weight (HA1600). We assessed the effects of HA35 and HA1600 on cell migration, NO and ROS generation, and gene expression in cultured macrophages, microglia, and lymphocytes.

Protective Properties of Intestinal Alkaline Phosphatase Supplementation on the Intestinal Barrier: Interactions and Effects.

The intestinal barrier is critical for maintaining intestinal homeostasis, and its dysfunction is associated with various diseases. Recent findings have revealed the multifunctional role of intestinal alkaline phosphatase (IAP) in diverse biological processes, including gut health maintenance and function. This review summarizes the protective effects of IAP on intestinal barrier integrity, encompassing the physical, chemical, microbial, and immune barriers.

Anti-Inflammatory Effects of the 35kDa Hyaluronic Acid Fragment (B-HA/HA35).

Background: Hyaluronic acid (HA) and HA fragments interact with a variety of human body receptors and are involved in the regulation of various physiological functions and leukocyte trafficking in the body. Accordingly, the development of an injectable HA fragment with good tissue permeability, the identification of its indications, and molecular mechanisms are of great significance for its clinical application. The previous studies showed that the clinical effects of injectable 35kDa B-HA result from B-HA binding to multiple receptors in different cells, tissues, and organs.

Anti-Inflammatory and Antioxidant Effects of Liposoluble C60 at the Cellular, Molecular, and Whole-Animal Levels.

Introduction: Liposoluble carbon-60 (C60) has potential applications in many fields, including cosmetics, medical devices, and medicine, but its specific mechanism of action remains unclear. This study explored whether liposoluble C60 could be delivered to human organs, tissues, and cells through blood, extracellular fluid, and cell culture fluid and whether it exerts anti-inflammatory and antioxidant effects at the molecular, cellular, and whole-animal levels.

Methods: At the cellular level, we mixed C60 dissolved in grape seed oil with cell culture medium containing 10% serum and investigated its effects on tumor necrosis factor-α (TNF-α) release, migration, phagocytosis, respiratory burst, and apoptosis in freshly isolated human neutrophils.

A replication-deficient H9N2 influenza virus carrying H5 hemagglutinin conferred protection against H9N2 and H5N1 influenza viruses in mice.

H5N1 and H9N2 influenza viruses have been reported to cause human infections and are believed to have pandemic potential. The vaccine is an effective tool to prevent influenza virus infection. However, inactivated influenza vaccines sometimes result in low antigenicity as result leads to generating of incomplete immune protection in the form of low cellular and humoral immunity.

Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance.

In this study, we investigated the effects of intestinal alkaline phosphatase (IAP) in controlled intestinal inflammation and alleviated associated insulin resistance (IR). We also explored the possible underlying molecular mechanisms, showed the preventive effect of IAP on IR , and verified the dephosphorylation of IAP for the inhibition of intestinal inflammation . Furthermore, we examined the preventive role of IAP in IR induced by a high-fat diet in mice.

Carbon 60 Dissolved in Grapeseed Oil Inhibits Dextran Sodium Sulfate-Induced Experimental Colitis.

Introduction: Carbon 60 (C60) and its derivatives have various biological applications. In our laboratory, we have demonstrated that C60 dissolved in grape seed oil (C60-Oil) has antioxidant and anti-inflammatory properties; however, the effectiveness of this formulation to treat diseases of the intestinal tract and specifically ulcerative colitis has not been studied. In this study, we intend to explore the effects of C60-Oil against experimental ulcerative colitis induced by Dextran Sulfate Sodium (DSS) in rats and a human colorectal cell line, HT-29.

Dual Functional Eudragit S100/L30D-55 and PLGA Colon-Targeted Nanoparticles of Iridoid Glycoside for Improved Treatment of Induced Ulcerative Colitis.

Aim: Iridoid glycosides (IG) as the major active fraction of Lindl. has a proven anti-inflammatory effect for ulcerative colitis (UC). However, its current commercial formulations are hampered by low bioavailability and unable to reach inflamed colon.

Inflammation imaging of atherosclerosis in Apo-E-deficient mice using a (99m)Tc-labeled dual-domain cytokine ligand.

Unlabelled: Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) play a critical role in initiating and accelerating atherosclerosis. This study evaluated the imaging properties of (99m)Tc-TNFR2-Fc-IL-1RA ((99m)Tc-TFI), a dual-domain cytokine radioligand that targets TNF-α and IL-1β pathways, in assessing atherosclerosis development in apolipoprotein-E-deficient (ApoE(-)(/)(-)) mice.

Methods: The feasibility and specificity of detecting atherosclerosis with (99m)Tc-TFI SPECT imaging were investigated in ApoE(-)(/)(-) and ApoE(+)(/)(+) mice.

Cross talk between vascular smooth muscle cells and monocytes through interleukin-1β/interleukin-18 signaling promotes vein graft thickening.

Objective: Interleukin (IL)-1β and IL-18 are key proinflammatory cytokines that play important roles in the pathophysiology of vein graft remodeling. However, the mechanism of IL-1β/IL-18 production and its role in the development of graft remodeling remain unclear.

Approach And Results: IL-1β/IL-18 were rapidly expressed in venous interposition grafts.

5TNF-α and IL-1β neutralization ameliorates angiotensin II-induced cardiac damage in male mice.

Inflammation is a key event in hypertensive organ damage, and TNF-α and IL-1β are elevated in hypertension. In this study, we evaluated the effects of TNF-α and IL-1β elevation on hypertensive cardiac damage by treatment with a bifunctional inflammatory inhibitor, TNF receptor 2-fragment crystalization-IL-1 receptor antagonist (TFI), which can neutralize these 2 cytokines simultaneously. A mouse hypertension model of angiotensin II (Ang II) infusion (1500 ng/kg·min for 7 d) was induced in wild-type mice.

SPECT imaging of inflammatory response in ischemic-reperfused rat hearts using a 99mTc-labeled dual-domain cytokine ligand.

Unlabelled: Soluble tumor necrosis factor (TNF) receptor-2 (TNFR2) and interleukin-1 receptor antagonist (IL-1ra) were fused to the Fc portion of IgG1 using recombinant DNA technology. The resulting dual-domain cytokine ligand, TNFR2-Fc-IL-1ra, specifically binds to TNF and to the type I IL-1 receptor (IL-1RI). This study was designed to characterize the kinetic profile of (99m)Tc-labeled TNFR2-Fc-IL-1ra (TFI) for imaging inflammatory response in an ischemic-reperfused (IR) rat heart model.

Characterization of 99mTc-labeled cytokine ligands for inflammation imaging via TNF and IL-1 pathways.

Introduction: TNFR2-Fc and IL-1ra-Fc are recombinant cytokine ligands that target TNF and IL-1. TNFR2-Fc-IL-1ra, a dual-domain agent that incorporates both ligands, allows bifunctional binding of IL-1 receptors and TNF. This study was designed to characterize (99m)Tc-labeled forms of these ligands, (99m)Tc-IL-1ra-Fc (IF), (99m)Tc-TNFR2-Fc (TF), and (99m)Tc-TNFR2-Fc-IL-1ra (TFI), for inflammation imaging.

A novel bifunctional protein TNFR2-Fc-IL-1ra (TFI): expression, purification and its neutralization activity of inflammatory factors.

Tumor necrosis factor receptor (TNF) and internleukin-1 (IL-1) are the most potent proinflammatory cytokines involving in autoimmune and inflammatory human diseases. Many anti-inflammatory agents have been exploited for anti-inflammation treatments by targeting cytokines including TNF and IL-1. Theoretically, simultaneously neutralizing or blocking two important inflammatory mediators may achieve a synergistic therapeutic effect.

A (99m)Tc-labeled dual-domain cytokine ligand for imaging of inflammation.

Introduction: Interleukin (IL)-1 and IL-18 are potent proinflammatory cytokines in inflammation-related diseases. Their actions are regulated by IL-1 receptor antagonist (IL-1ra) and IL-18 binding protein (IL-18bp). This study was designed to (99m)Tc-radiolabel an IL-1ra and IL-18bp dual-domain cytokine ligand, IL-18bp-Fc-IL-1ra, for specific inflammation targeting.

PET imaging of acute and chronic inflammation in living mice.

Purpose: In this study, we evaluated the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced acute and chronic inflammation in living mice by PET imaging of TNF-alpha and integrin alpha(v)beta(3) expression.

Methods: TPA was topically applied to the right ear of BALB/c mice every other day to create the inflammation model. (64)Cu-DOTA-etanercept and (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) were used for PET imaging of TNF-alpha and integrin alpha(v)beta(3) expression in both acute and chronic inflammation.