Discovery of 1,3-disubstituted prop-2-en-1-one derivatives as inhibitors of neutrophilic inflammation via modulation of MAPK and Akt pathways.

Targeting neutrophil function has gained attention as a propitious therapeutic strategy for diverse inflammatory diseases. Accordingly, a series of enone-based derivatives were developed to inhibit neutrophil-mediated inflammation, showing promise for treating inflammatory diseases. These compounds fall into two clusters with distinct effects: one inhibits neutrophilic superoxide (SO) anion production and elastase release triggered by N-formyl-Met-Leu-Phe (fMLF), with compound being most effective (IC values of 1.

Dihydrophenanthropyrans derived from the pseudobulbs of Pholidota chinensis alleviates neutrophilic inflammation by inhibiting MAPKs and calcium.

Five dihydrophenanthropyrans (1-5) were isolated from the pseudobulbs of Pholidota chinensis, among which 1,3-di(4'-hydroxybenzy)-imbricatin (3) was isolated from the nature for the first time. Their structures were elucidated and established through various spectroscopic methods. These compounds exhibited a potent inhibition effect on both N-formyl-methionyl-leucyl-phenylalanine (fMLF)-induced superoxide anion generation and elastase release with IC values ranging from 0.

PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly.

Purinosomes serve as metabolons to enhance de novo purine synthesis (DNPS) efficiency through compartmentalizing DNPS enzymes during stressed conditions. However, the mechanism underpinning purinosome assembly and its pathophysiological functions remains elusive. Here, we show that K6-polyubiquitination of the DNPS enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (PAICS) by cullin-5/ankyrin repeat and SOCS box containing 11 (Cul5/ASB11)-based ubiquitin ligase plays a driving role in purinosome assembly.

Triggering the Vapochromic Behavior in C via the Supramolecular Wrapping of -PMMA.

Understanding the physicochemical modulation of functional molecules is the primary step in exploring novel stimuli-responsive materials, and preventing the π-π stacking configuration of π-conjugated molecules has been an effective strategy of vapochromic material development, such as of nanoporous frameworks. Nevertheless, the more complicated synthetic strategy should in fact be applied in many circumstances. In this study, we explore a facile supramolecular strategy where the commodity plastic, syndiotactic-poly(methyl methacrylate) (-PMMA), is utilized to wrap C to form the inclusion complex.

Peripheral Nerve Denervation in Streptozotocin-Induced Diabetic Rats Is Reduced by Cilostazol.

Our previous study demonstrated that consistent treatment of oral cilostazol was effective in reducing levels of painful peripheral neuropathy in streptozotocin-induced type I diabetic rats. As diabetic neuropathy is characterized by hyperglycemia-induced nerve damage in the periphery, this study aims to examine the neuropathology as well as the effects of cilostazol treatments on the integrity of peripheral small nerve fibers in type I diabetic rats. A total of ninety adult male Sprague-Dawley rats were divided into the following groups: (1) naïve (control) group; (2) diabetic rats (DM) group for 8 weeks; DM rats receiving either (3) 10 mg/kg oral cilostazol (Cilo10), (4) 30 mg/kg oral cilostazol (Cilo30), or (5) 100 mg/kg oral cilostazol (Cilo100) for 6 weeks.

Palbociclib blocks neutrophilic phosphatidylinositol 3-kinase activity to alleviate psoriasiform dermatitis.

Background And Purpose: Neutrophilic inflammation is a critical pathogenic factor in psoriasis. The therapeutic applicability of palbociclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor clinically used to treat cancer, in the treatment of neutrophil-associated psoriasis remains undefined. In this study, we evaluated the therapeutic potential and pharmacological effect of palbociclib on neutrophil-associated psoriasiform dermatitis.

Targeting formyl peptide receptor 1 with anteiso-C13-surfactin for neutrophil-dominant acute respiratory distress syndrome.

Background And Purpose: Acute respiratory distress syndrome (ARDS) is a catastrophic pulmonary inflammatory dysfunction with a high mortality rate. An overwhelming immune response by neutrophils is a key feature in infective or sterile ARDS. The formyl peptide receptor 1 (FPR1) is a crucial damage-sensing receptor for inflammatory reactions in the initiation and progression of neutrophil-mediated ARDS.

Bis(4-glycosyloxybenzyl) 2-isobutyltartrate and dihydrophenanthrene derivatives from the pseudobulbs of Pholidota chinensis and their anti-inflammatory activity.

Six previously undescribed components, bis(4-glycosyloxybenzyl) 2-isobutyltartrate derivatives (pholidotoside A-E) and phenolic glycoside (pholidotosin A), together with twenty known compounds were isolated from the pseudobulbs of Pholidota chinensis. Their structures and absolute configuration were elucidated and established through various spectroscopic and chemical methods. The anti-inflammatory potential of selected compounds was examined using a human neutrophil cell model activated by N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB).

Sciatic Nerve Intrafascicular Injection Induces Neuropathy by Activating the Matrix Modulators MMP-9 and TIMP-1.

Peripheral nerve block (PNB) under echo guidance may not prevent intrafascicular anesthetic injection-induced nerve injury. This study investigated whether unintended needle piercing alone, or the intrafascicular nerve injectant could induce neuropathy. 120 adult male Sprague-Dawley rats were divided into four groups: 1) group S, only the left sciatic nerve was exposed; 2) group InF-P, the left sciatic nerve was exposed and pierced with a 30 G needle; 3) group InF-S, left sciatic nerve was exposed and injected with saline (0.

Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats.

Cilostazol is an antiplatelet agent with vasodilating, endothelial function restoration, and anti-inflammatory effects. This study aims to investigate the efficacy of oral cilostazol for preventing the development of diabetic peripheral neuropathy (DPN). Ninety adult male Sprague-Dawley rats were divided into five groups: 1) naïve (control); 2) diabetic (DM); 3) DM receiving 10 mg/kg cilostazol (cilo-10); 4) DM receiving 30 mg/kg cilostazol (cilo-30); and 5) DM receiving 100 mg/kg cilostazol (cilo-100).

-Dihydroguaiaretic Acid Ameliorates Acute Respiratory Distress Syndrome through Inhibiting Neutrophilic Inflammation and Scavenging Free Radical.

The pathogenesis of acute respiratory distress syndrome (ARDS) is very complex. Patients with ARDS still suffer high mortality rates. Infiltration and activation of neutrophils in lungs are critical pathogenic factors in ARDS.

Decoding Multiple Biofunctions of Maca on Its Anti-allergic, Anti-inflammatory, Anti-thrombotic, and Pro-angiogenic Activities.

Four active partition layers and ten isolates, including (5)- and (5)-macapyrrolidone A (, ), and four new alkaloids, (5)- and (5)-macapyrrolidone B (, ) and macapyrrolins D, E (, ), were isolated from maca ( Walp.), an indigenous food plant from Peru. Derived from the -hexane layer, the macamide-rich fraction exhibited pro-angiogenic activity on EPC and HUVEC cells.

Anti-Inflammatory, Antiallergic, and COVID-19 Main Protease (M) Inhibitory Activities of Butenolides from a Marine-Derived Fungus .

In December 2020, the U.K. authorities reported to the World Health Organization (WHO) that a new COVID-19 variant, considered to be a variant under investigation from December 2020 (VUI-202012/01), was identified through viral genomic sequencing.

Bletinib ameliorates neutrophilic inflammation and lung injury by inhibiting Src family kinase phosphorylation and activity.

Background And Purpose: Neutrophil overactivation is crucial in the pathogenesis of acute lung injury (ALI). Bletinib (3,3'-dihydroxy-2',6'-bis(p-hydroxybenzyl)-5-methoxybibenzyl), a natural bibenzyl, extracted from the Bletilla plant, exhibits anti-inflammatory, antibacterial, and antimitotic effects. In this study, we evaluated the therapeutic effects of bletinib in human neutrophilic inflammation and LPS-mediated ALI in mice.

Design and synthesis of β-carboline and combretastatin derivatives as anti-neutrophilic inflammatory agents.

A series of β-carboline derivatives was synthesized by the Pictet-Spengler reaction with or without the combretastatin skeleton. The structures of these derivatives were elucidated by spectroscopic techniques. All synthesized compounds were evaluated for their anti-inflammatory activity in human neutrophils.

An Anti-Inflammatory 2,4-Cyclized-3,4-Secospongian Diterpenoid and Furanoterpene-Related Metabolites of a Marine Sponge sp. from the Red Sea.

Chemical investigation of a Red Sea sp. led to the isolation of four new compounds, i.e.

Aqueous Extract of Kan-Lu-Hsiao-Tu-Tan Ameliorates Collagen-Induced Arthritis in Mice by Inhibiting Oxidative Stress and Inflammatory Responses.

Background: Kan-Lu-Hsiao-Tu-Tan (KLHTT) exhibits anti-psoriatic effects through anti-inflammatory activity in mice. However, the therapeutic effects of KLHTT on rheumatoid arthritis (RA), another significant autoimmune inflammatory disorder, have not been elucidated. Herein, we explored the anti-arthritic effects of KLHTT on collagen-induced arthritis (CIA) in mice.

Mechanism of Nanoformulated Graphene Oxide-Mediated Human Neutrophil Activation.

Understanding the molecular mechanisms of graphene oxide (GO)-based biomaterials is important for logical biomedical applications. Previous studies have revealed biointeractions between GO and immune effector cells, but the effects on neutrophils, crucial cells in the immune system, have not been thoroughly discussed. In this study, GO nanoformulations were synthesized with different functional groups, including GO, GO-carboxylated (GO-COOH), and PEGylated GO (GO-PEG), with different surface features, which were elucidated using imaging methods and surface-sensitive quantitative spectroscopic techniques, including atomic force microscopy (AFM), transmission electron microscopy (TEM), and X-ray photoemission spectroscopy (XPS).

Lophatherum gracile Brongn. attenuates neutrophilic inflammation through inhibition of JNK and calcium.

Ethnopharmacological Relevance: Lophatherum gracile Brongn. (L. gracile) has been long used in traditional herbal medicine to clinically clear heat, disinhibit dampness, and treat inflammation.

Upregulation of miR-133a-3p in the Sciatic Nerve Contributes to Neuropathic Pain Development.

The micro (mi)RNAs expressed in the sciatic nerve of streptozotocin (STZ)-induced diabetic rats were evaluated in terms of their therapeutic potential in patients with diabetic neuropathic pain (DNP). Relative miRNA expression in sciatic nerve with DNP was analyzed using next-generation sequencing and quantitative PCR. Potential downstream targets of miRNAs were predicted using Ingenuity Pathway Analysis and the TargetScan database.

A synthesized heterocyclic chalcone inhibits neutrophilic inflammation through K -dependent pH regulation.

Human neutrophils have a vital role in host defense and inflammatory responses in innate immune systems. Growing evidence shows that the overproduction of reactive oxygen species and granular proteolytic enzymes from activated neutrophils is linked to the pathogenesis of acute inflammatory diseases. However, adequate therapeutic targets are still lacking to regulate neutrophil functions.

Longitudinal Effects of an Intergenerational mHealth Program for Older Type 2 Diabetes Patients in Rural Taiwan.

Purpose: The purpose of the study is to test the longitudinal efficacy of a mHealth intervention (Intergenerational Mobile Technology Opportunities Program, IMTOP) for older type 2 diabetes mellitus (T2DM) patients in rural Taiwan. Few mHealth programs targeted rural older adults and the longitudinal effects are unknown.

Methods: Ninety-seven T2DM patients aged 55+ were recruited from an outpatient in Hualien, Taiwan.

Bioactive Capnosanes and Cembranes from the Soft Coral .

Two new capnosane-based diterpenoids, flaccidenol A () and 7--pavidolide D (), two new cembranoids, flaccidodioxide () and flaccidodiol (), and three known compounds to were characterized from the marine soft coral , collected off the coast of the island of Pratas. The structures of the new compounds were determined by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and spectroscopic data comparison with related structures. The rare capnosane diterpenoids were isolated herein from the genus for the first time.