2'-FL and cross-feeding bifidobacteria reshaped the gut microbiota of infants with atopic dermatitis ex vivo and prevented dermatitis in mice post-microbiota transplantation through retinol metabolism activation.

2'-Fucosyllactose (2'-FL), a predominant human milk oligosaccharide, plays a crucial role in the development of the infant gut microbiota and immune system. However, the microbiota of infants with atopic dermatitis (AD) often has difficulty utilizing 2'-FL. Here, we found that strains from human milk, FN120 and subsp.

Discovery of highly potent dual GSPT1/BRD4 degraders with anti-AML activity.

Translational readthrough (TR) regulation has emerged as a promising therapeutic strategy for cancer treatment. Utilizing a constructed monoclonal cell line AG-9, designed for screening compounds that induce TR, we identified a BRD4-targeted PROTAC molecule, dBET57, that promotes TR by degrading GSPT1. Notably, dBET57 exhibited significant antiproliferative activity against acute myeloid leukemia (AML) and non-Hodgkin lymphoma (NHL) cells across a diverse panel of tumor cell lines.

Harnessing the power of breast milk: how FN029 from rural western China mitigates severe atopic dermatitis in mice through retinol metabolism activation.

Tongwei and Wuxi represent a rural county in western China and an industrialized city in the east, respectively. The study compared breast milk and the corresponding infant gut microbiota from 35 healthy mothers in Tongwei and 28 in Wuxi, uncovering significant differences in microbial alpha and beta diversity. A unique strain, FN029, characteristically transmitted from breast milk to the infant gut in Tongwei, was identified.

Quercetin regulates pulmonary vascular remodeling in pulmonary hypertension by downregulating TGF-β1-Smad2/3 pathway.

Background: Pulmonary arterial hypertension (PAH) is a worldwide challenging disease characterized by progressive elevation of pulmonary artery pressure. The proliferation, migration and phenotypic transformation of pulmonary smooth muscle cells are the key steps of pulmonary vascular remodeling. Quercetin (3,3', 4', 5, 6-pentahydroxyflavone, Que) is a natural flavonol compound that has antioxidant, anti-inflammatory, anti-tumor and other biological activities.

A Nerve-Fibroblast Axis in Mammalian Lung Fibrosis.

Fibrosis contributes to incurable pathologies in vital organs including the lung. Myofibroblasts are fibrogenic effector cells that accumulate via incompletely understood mechanisms. We discovered that α1-adrenoreceptor expressing myofibroblasts receive sympathetic nerve-derived noradrenergic inputs in fibrotic mouse and human lungs.

A new TROP2-targeting antibody-drug conjugate shows potent antitumor efficacy in breast and lung cancers.

Trophoblast cell surface antigen 2 (Trop2) is considered to be an attractive therapeutic target in cancer treatments. We previously generated a new humanized anti-Trop2 antibody named hIMB1636, and designated it as an ideal targeting carrier for cancer therapy. Lidamycin (LDM) is a new antitumor antibiotic, containing an active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP).

Microbial diversity of ticks and a novel typhus group Rickettsia species (Rickettsiales bacterium Ac37b) in Inner Mongolia, China.

Ticks can carry multiple pathogens, and Inner Mongolia's animal husbandry provides excellent environmental conditions for ticks. This study characterized the microbiome of ticks from different geographical locations in Inner Mongolia; 905 Dermacentor nuttalli and 36 Ixodes persulcatus were collected from sheep in three main pasture areas and from bushes within the forested area. Mixed DNA samples were prepared from three specimens from each region and tick species.

hIMB1636-MMAE, a Novel TROP2-Targeting Antibody-Drug Conjugate Exerting Potent Antitumor Efficacy in Pancreatic Cancer.

Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen ( ∼ 0.

Elucidating the development, characterization, and antitumor potential of a novel humanized antibody against Trop2.

Trophoblast cell surface antigen 2 (Trop2) has emerged as a potential target for effective cancer therapy. In this study, we report a novel anti-Trop2 antibody IMB1636, developed using hybridoma technology. It exhibited high affinity and specificity (K = 0.

[Effects of probenecid on the migration and proliferation ability of platelet derived growth factor-BB induced pulmonary artery smooth muscle cells in rats].

Objective: To investigate whether probenecid (PROB) could improve the proliferation and migration ability of rats' pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB (PDGF-BB).

Methods: Primary pulmonary artery smooth muscle cells (PASMCs) of SD rats were cultured , and were randomly divided into control group (CON group), PDGF-BB group (10 ng/ml PDGF-BB treatment for 24 h) and PDGF-BB+PROB group (10 ng/ml PDGF-BB and 200 μmol/L PROB treatment for 24 h, PROB is a specific blocker of pannexin-1). CCK-8 method was used to select the suitable intervention concentrations of PROB and PDGF-BB, and to detect the proliferation of PASMCs in each group.

[Capsaicin inhibits proliferation and migration of cerebral basilar artery smooth muscle cells in spontaneously hypertensive rats].

Objective To investigate whether capsaicin (CAP) can improve the proliferation and migration of cerebral basilar artery smooth muscle cells (BASMCs) in spontaneously hypertensive rats (SHR). Methods Primary BASMCs of SHR and Wistar-Kyoto (WKY) rats were cultured in vitro, randomly divided into control group (WKY group), SHR group and capsaicin treatment group (CAP group). The intervention concentration of CAP was determined by CCK-8 assay; Transwell chamber assay and scratch test were used to detect the migration ability of BASMCs; the expression and distribution of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) in BASMCs were detected by immunofluorescence assay, and Western blot analysis was used to detect the protein levels of OPN and PCNA in BASMCs.

Inhibition of KIR2.1 decreases pulmonary artery smooth muscle cell proliferation and migration.

The investigation of effective therapeutic drugs for pulmonary hypertension (PH) is critical. KIR2.1 plays crucial roles in regulating cell proliferation and migration, and vascular remodeling.

[Emodin inhibits the proliferation and migration of human pulmonary artery smooth muscle cells by blocking SMAD2/3 signaling pathway].

Objective To investigate the effect of emodin on the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMCs) induced by transforming growth factor β1 (TGF-β1). Methods HPASMCs were cultured in vitro, and HPASMCs in logarithmic growth phase were divided into control group, TGF-β1 group, and TGF-β1 combined with emodin group. The activity of HPASMCs was detected by CCK-8 assay, the migration ability of HPASMCs was detected by Transwell chamber assay and scratch assay, and the expressions of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) were detected by immunofluorescence assay.

Polysaccharides of Brassica rapa L. attenuate tumor growth via shifting macrophages to M1-like phenotype.

Macrophages are the major tumor-infiltrating leukocytes, and tumor-associated macrophages (TAM) play a critical role in cancer-related inflammation since they show alternative polarization to M1 (tumor-inhibited macrophages) or M2 (tumor-promoted macrophages) phenotype. Brassica rapa L. (B.

The Probiotic Ameliorates Diarrhea Cause by O Gut Microbiota Modulation.

Introduction: Koumiss is a fermented horse milk food containing abundant probiotics. is a bacterial strain isolated from koumiss that helps regulate the intestinal microbiota. One of the major cause of diarrhea is an imbalance of the intestinal flora.

A recombinant scFv antibody-based fusion protein that targets EGFR associated with IMPDH2 downregulation and its drug conjugate show therapeutic efficacy against esophageal cancer.

The present study aimed to evaluate the anti-tumor efficacy of the epidermal growth factor receptor (EGFR)-targeting recombinant fusion protein Fv-LDP-D3 and its antibody-drug conjugate Fv-LDP-D3-AE against esophageal cancer. Fv-LDP-D3, consisting of the fragment variable (Fv) of an anti-EGFR antibody, the apoprotein of lidamycin (LDP), and the third domain of human serum albumin (D3), exhibited a high binding affinity for EGFR-overexpressing esophageal cancer cells, inhibited EGFR phosphorylation and down-regulated inosine monophosphate dehydrogenase type II (IMPDH2) expression. Fv-LDP-D3 was taken up by cancer cells through intensive macropinocytosis; it inhibited the proliferation and induced the apoptosis of esophageal cancer cells.

Emodin Improves Intestinal Health and Immunity through Modulation of Gut Microbiota in Mice Infected by Pathogenic O.

The effect of emodin on the intestinal mucosal barrier of a mouse O-induced diarrhea model was observed. Following successful establishment of a diarrhea model, the mice were treated with drugs for seven days. Intestinal lesions and the shape and the number of goblet cells were assessed via hematoxylin-eosin and periodic-acid-Schiff staining, while changes in inflammatory factors, ultrastructure of the small intestine, expression of MUC-2, and changes in the intestinal microbiota were analyzed via RT-PCR, electron microscopy, immunofluorescence, and 16S rRNA sequencing.

The promoting role of Cx43 on the proliferation and migration of arterial smooth muscle cells for angiotensin II-dependent hypertension.

Background: Recent studies have shown that endothelin-1 and angiotensin II (AngII) can increase gap junctional intercellular communication (GJIC) by activating Mitogen-activated protein kinases (MAPKs) pathway. However, not only the precise interaction of AngII with Connexin43(Cx43) and the associated functions remain unclear, but also the regulatory role of Cx43 on the AngII-mediated promotion proliferation and migration of VSMCs is poorly understood.

Material And Methods: Our research applicated pressure myography measurements, immunofluorescence and Western blot analyses to investigate the changes in physiological indicators in spontaneously hypertensive rats (SHRs) and AngII-stimulated proliferation and migration of A7r5 SMCs(Rat vascular smooth muscle cells).

The Role of TMEM16A/ERK/NK-1 Signaling in Dorsal Root Ganglia Neurons in the Development of Neuropathic Pain Induced by Spared Nerve Injury (SNI).

Increasing evidence suggests that transmembrane protein 16A (TMEM16A) in nociceptive neurons is an important molecular component contributing to peripheral pain transduction. The present study aimed to evaluate the role and mechanism of TMEM16A in chronic nociceptive responses elicited by spared nerve injury (SNI). In this study, SNI was used to induce neuropathic pain.

Comparative Analysis of Fecal Microbiota of Grazing Mongolian Cattle from Different Regions in Inner Mongolia, China.

Mongolian cattle from China have strong adaptability and disease resistance. We aimed to compare the gut microbiota community structure and diversity in grazing Mongolian cattle from different regions in Inner Mongolia and to elucidate the influence of geographical factors on the intestinal microbial community structure. We used high throughput 16S rRNA sequencing to analyze the fecal microbial community and diversity in samples from 60 grazing Mongolian cattle from Hulunbuir Grassland, Xilingol Grassland, and Alxa Desert.

Galectin-3 participates in PASMC migration and proliferation by interacting with TGF-β1.

Pulmonary vascular remodelling is one of the most important factors for pulmonary hypertension (PH). Galectin-3 (Gal-3) is a β-galactoside-binding lectin. In the latest literature, Gal-3 has been reported to be involved in pulmonary vascular remodelling, and its underlying mechanism is unclear.

Macrophage-derived netrin-1 drives adrenergic nerve-associated lung fibrosis.

Fibrosis is a macrophage-driven process of uncontrolled extracellular matrix accumulation. Neuronal guidance proteins such as netrin-1 promote inflammatory scarring. We found that macrophage-derived netrin-1 stimulates fibrosis through its neuronal guidance functions.

Intrabody against prolyl hydroxylase 2 ameliorates acetaminophen-induced acute liver injury in mice via concomitant promotion of angiogenesis and redox homeostasis.

Acetaminophen (APAP) overdose has become the most common cause of drug-induced acute liver failure. Angiogenesis and redox homeostasis play an important role in liver protection and repair of APAP-induced acute liver injury (AILI). Hypoxia inducible factor-1 (HIF-1) is a transcription factor that plays a crucial role in regulating the expression of genes associated with angiogenesis, redox homeostasis and energy balance.

Regulation of Hedgehog signaling Offers A Novel Perspective for Bone Homeostasis Disorder Treatment.

The hedgehog (HH) signaling pathway is central to the regulation of bone development and homeostasis. HH signaling is not only involved in osteoblast differentiation from bone marrow mesenchymal stem cells (BM-MSCs), but also acts upstream within osteoblasts via the OPG/RANK/RANKL axis to control the expression of RANKL. HH signaling has been found to up-regulate parathyroid hormone related protein (PTHrP) expression in osteoblasts, which in turn activates its downstream targets nuclear factor of activated T cells (NFAT) and cAMP responsive element binding protein (CREB), and as a result CREB and NFAT cooperatively increase RANKL expression and osteoclastogenesis.