Exploring the Conformational Dynamics and Key Amino Acids in the CD26-Caveolin-1 Interaction and Potential Therapeutic Interventions DOI Creative Commons
Xiao Hu, Chunmei Jiang,

Yanli Gu

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Авг. 29, 2023

Abstract The study focused on the interaction between CD26 and caveolin-1, employed zDOCK to identify two binding conformations, con1 con4. Molecular dynamics simulations alanine scanning were performed analyze contribution of key amino acids in caveolin-1 interaction. 100ns simulation trajectories revealed that exhibited smaller fluctuations displayed more stable thermodynamic characteristics compared In con1, specific interactions observed, including CD26's GLU237 forming a hydrogen bond with F chain's TYR151, TYR24 engaging π-π PHE160, TYR248 G H chains' ARG147 I TYR148, GLY99 participating cation-π J PHE98 TYR151. con4, ARG253 formed THR95, LYS250 interacted PHE99 through bonding interactions, engaged TRP98. Based information about involved interaction, high-throughput virtual screening small molecule compounds was conducted using Traditional Chinese Medicine Library Anti-diabetic Compound Library. Crocin, Poliumoside, Canagliflozin identified as high docking scores favorable modes caveolin-1. These primarily hydrophobic interactions. Interestingly, also found interact sites. This represents first elucidation preferred conformations identification these contributes better understanding structure-function relationship protein provides important insights for further research drug design. Additionally, potential (Crocin, Canagliflozin) have inhibit tumor growth metastasis, alleviate inflammatory responses, regulate metabolic processes by targeting However, vitro vivo experiments are required validate findings before can progress into clinical translation. conclusion, comprehensive pathological mechanisms underlying relevant diseases new targets strategies disease treatment intervention.

Язык: Английский

Identification of Novel Biomarkers of Spinal Muscular Atrophy and Therapeutic Response by Proteomic and Metabolomic Profiling of Human Biological Fluid Samples DOI Creative Commons
Megi Meneri, Elena Abati, Delia Gagliardi

и другие.

Biomedicines, Год журнала: 2023, Номер 11(5), С. 1254 - 1254

Опубликована: Апрель 23, 2023

Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations or deletions in SMN1 that lead to progressive death of alpha motor neurons, ultimately leading severe muscle weakness and atrophy, as well premature the absence treatment. Recent approval SMN-increasing medications SMA therapy has altered natural course disease. Thus, accurate biomarkers are needed predict severity, prognosis, drug response, overall treatment efficacy. This article reviews novel non-targeted omics strategies could become useful clinical tools for patients with SMA. Proteomics metabolomics can provide insights into molecular events underlying progression response. High-throughput data have shown untreated different profiles than controls. In addition, who clinically improved after profile those did not. These results glimpse on potential markers assist identifying responders, tracing disease, predicting its outcome. studies been restricted by limited number patients, but approaches feasible unravel severity-specific neuro-proteomic metabolic signatures.

Язык: Английский

Процитировано

16
Intestinal Immune Imbalance is an Alarm in the Development of IBD DOI Creative Commons
C.C. Hu, Shengtao Liao, Lin Lv

и другие.

Mediators of Inflammation, Год журнала: 2023, Номер 2023, С. 1 - 17

Опубликована: Июль 31, 2023

Immune regulation plays a crucial role in human health and disease. Inflammatory bowel disease (IBD) is chronic relapse with an increasing incidence worldwide. Clinical treatments for IBD are limited inefficient. However, the pathogenesis of immune-mediated remains unclear. This review describes activation innate adaptive immune functions by intestinal cells to regulate balance maintain mucosal integrity. Changes susceptible genes, autophagy, energy metabolism, other factors interact complex manner system, eventually leading imbalance onset IBD. These events indicate that alarm development, further opening new possibilities unprecedented development immunotherapy

Язык: Английский

Процитировано

16
Effect of DPP4/CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives m62A and CD) regulations on patients with cancer and healthy individuals DOI Creative Commons

Jiaman Du,

Jiewen Fu, Wenqian Zhang

и другие.

International Journal of Oncology, Год журнала: 2023, Номер 62(3)

Опубликована: Фев. 16, 2023

The worldwide COVID‑19 pandemic was brought on by a new coronavirus (SARS Cov‑2). A marker/receptor called Dipeptidyl peptidase 4/CD26(DPP4/CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 COVID‑invaded cancer patients its role small molecule compounds remain unclear. present study used Human Protein Atlas, Monaco, Schmiedel databases analyze expression human tissues immune cells. association between survival various tumor compared using GEPIA 2. DNMIVD database correlation promoter methylation tumors. On cBioPortal network, frequency DPP4 DNA mutations cancers analyzed. immunomodulators analyzed TISIDB database. inhibitory effects cordycepin (CD), N6, N6‑dimethyladenosine (m62A) adenosine (AD) cells were evaluated. mainly expressed endocrine tissue, followed gastrointestinal tract, female tissue (mainly placenta), male prostate seminal vesicle), proximal digestive kidney, bladder, liver, gallbladder respiratory system. In cells, mRNA T upregulated esophageal carcinoma, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular (LIHC), lung adenocarcinoma, pancreatic stomach thyroid thymoma. it downregulated breast invasive chromophobe, squamous skin cutaneous melanoma. Thus, is involved viral invasion most types cancer. could inhibited CD, m62A AD different Moreover, CD significantly formation GFP‑positive syncytial In vivo experiments with injection further showed that lymphocyte activating factor 3 expression. These drugs have potential treat targeting DPP4. medically significant for SARS‑CoV‑2‑infected patients, providing prospective novel targets concepts creation against COVID‑19.

Язык: Английский

Процитировано

13
Insights into the Roles of GLP-1, DPP-4, and SGLT2 at the Crossroads of Cardiovascular, Renal, and Metabolic Pathophysiology DOI Creative Commons
Melania Gaggini, Laura Sabatino,

Adrian Florentin Suman

и другие.

Cells, Год журнала: 2025, Номер 14(5), С. 387 - 387

Опубликована: Март 6, 2025

In recent years, new drugs for the treatment of type 2 diabetes (T2D) have been proposed, including glucagon-like peptide 1 (GLP-1) agonists or sodium–glucose cotransporter (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Over time, some these agents (in particular, GLP-1 SGLT2 inhibitors), which were initially developed their glucose-lowering actions, demonstrated significant beneficial pleiotropic effects, thus expanding potential therapeutic applications. This review aims to discuss mechanisms, GLP-1, DPP-4, SGLT2, with a particular focus on cardiorenal benefits beyond glycemic control.

Язык: Английский

Процитировано

0
Dihydromyricetin Promotes Glucagon‐Like Peptide‐1 Secretion and Improves Insulin Resistance by Modulation of the Gut Microbiota‐CDCA Pathway DOI Creative Commons
Pengfei Li,

Yong Zhang,

Hedong Lang

и другие.

Molecular Nutrition & Food Research, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

ABSTRACT Insulin resistance is a common metabolic disease, and its pathogenesis still unclear. The decrease of glucagon‐like peptide‐1 (GLP‐1) level mediated by the alteration gut microbiota may be pathogenesis. study was to investigate regulatory effect dihydromyricetin (DHM) on GLP‐1 insulin induced high‐fat diet (HFD), further explore possible molecular mechanism. Mice were fed an HFD establish model determine whether DHM had protective effect. could improve resistance. increased serum improving intestinal secretion inhibiting decomposition, associated with intraepithelial lymphocytes (IELs) proportions decreased expression CD26 in IELs TCRαβ + CD8αβ HFD‐induced mice. ameliorate modulation metabolites, particularly regulation chenodeoxycholic acid (CDCA) content, followed inhibition farnesoid X receptor (FXR) L cells glucagon gene (Gcg) mRNA secretion. This research demonstrates role “gut microbiota‐CDCA” pathway improvement levels mice administration, providing new target for prevention

Язык: Английский

Процитировано

0
Cation-independent mannose 6-phosphate receptor: From roles and functions to targeted therapies DOI Creative Commons
Corentin Gauthier, Khaled El Cheikh,

Ilaria Basile

и другие.

Journal of Controlled Release, Год журнала: 2023, Номер 365, С. 759 - 772

Опубликована: Дек. 14, 2023

Язык: Английский

Процитировано

9
The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19 DOI Open Access
Adam Drzymała

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9635 - 9635

Опубликована: Сен. 5, 2024

Angiotensin-converting enzyme 2 (ACE2) is considered a severe acute respiratory syndrome coronavirus (SARS-CoV-2) receptor of high importance, but due to its non-ubiquitous expression, studies other proteins that may participate in virus internalisation have been undertaken. To date, many alternative receptors discovered. Their functioning provide an explanation for some the events observed COVID-19 cannot be directly explained by model which ACE2 constitutes central point infection. Diabetes mellitus type (T2D) can induce development. Although mechanisms associated with lead increased SARS-CoV-2 virulence diabetes, such as basigin (CD147), glucose-regulated protein 78 kDa (GRP78), cluster differentiation 4 (CD4), transferrin (TfR), integrins α5β1/αvβ3, or co-receptors neuropilin (NRP2), vimentin, and even syalilated gangliosides also responsible worsening course. On hand, others play protective roles. Understanding how diabetes-associated via modification needs further extensive studies.

Язык: Английский

Процитировано

3
Life of Pi: Exploring functions of Pi16+ fibroblasts DOI Creative Commons
Erika E. McCartney,

Yein Chung,

Matthew B. Buechler

и другие.

F1000Research, Год журнала: 2024, Номер 13, С. 126 - 126

Опубликована: Фев. 20, 2024

Fibroblasts are mesenchymal cells that responsible for creating and maintaining tissue architecture through the production of extracellular matrix. These also play critical roles in processes such as wound repair immune modulation normal tissues various disease states including fibrosis, autoimmunity, cancer. Fibroblasts have a complex repertoire functions vary by organ, inflammatory state, developmental stage an organism. How fibroblasts manage so many context-dependent manner represents gap our understanding these cells. One possibility is tissue-resident precursor cell state exists provides fibroblast lineage with flexibility during growth, inflammation, or other contexts require dynamic changes. Recent work has suggested marked expression Peptidase inhibitor 16 (Pi16). This review aims to concatenate compare studies on express Pi16 clarify this development functions.

Язык: Английский

Процитировано

1
Exploring the conformational dynamics and key amino acids in the CD26-caveolin-1 interaction and potential therapeutic interventions DOI Creative Commons
Xiaopeng Hu, Chunmei Jiang,

Yanli Gu

и другие.

Medicine, Год журнала: 2024, Номер 103(22), С. e38367 - e38367

Опубликована: Май 31, 2024

This study aimed to decipher the interaction between CD26 and caveolin-1, key proteins involved in cell signaling linked various diseases. Using computational methods, we predicted their binding conformations assessed stability through 100 ns molecular dynamics (MD) simulations. We identified two distinct (con1 con4), with con1 exhibiting superior stability. In con1, specific amino acids CD26, namely GLU237, TYR241, TYR248, ARG147, were observed engage interactions F-J chain of Caveolin-1, establishing hydrogen bonds cation or π-π interactions. Meanwhile, con4, ARG253, LYS250, TYR248 interacted J Caveolin-1 via bonds, cation-π interactions, Virtual screening also revealed potential small-molecule modulators, including Crocin, Poliumoside, Canagliflozin, that could impact this interaction. Additionally, predictive analyses conducted on bioactivity, drug-likeness, ADMET properties these three compounds. These findings offer valuable insights into mechanism, paving way for new therapeutic strategies. However, further validation is required before clinical application. summary, provide a detailed understanding caveolin-1 interaction, identifying essential developing targeted therapies.

Язык: Английский

Процитировано

1
New investigational drugs for Steroid-Refractory Acute Graft-versus-Host disease: a review of the literature DOI
Na Hyun Kim, Mehdi Hamadani, Sameem Abedin

и другие.

Expert Opinion on Investigational Drugs, Год журнала: 2024, Номер 33(8), С. 791 - 799

Опубликована: Июль 8, 2024

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a formidable obstacle in the field of allogeneic hematopoietic cell transplantation (allo-HCT), significantly contributing to patient morbidity and mortality. The current therapeutic landscape for SR-aGVHD is limited, often yielding suboptimal results, thereby emphasizing urgent need innovative effective treatments.

Язык: Английский

Процитировано

1