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Hidden diversity: Identification and characterisation of compartment-specific testicular macrophage populations.

Two major populations of resident macrophages have been identified in the mouse testis: interstitial tissue macrophages, characterised by high expression of CD206 and low or undetectable MHC class II antigen (MHCII) expression, and peritubular macrophages that generally lack CD206, but exhibit elevated MHCII. A morphometric analysis of macrophage subset marker antigens throughout the entire adult mouse testis was undertaken employing transgenic expression of the green fluorescent protein reporter at the locus of the Cx3cr1 gene (Cx3cr1gfp/+), and immunofluorescence localisation of F4/80, MHCII

Disease-specific signatures of circulating extracellular vesicles detected by the surface plasmon resonance imaging: a pilot study.

Aim: Cells in the human body release extracellular vesicles (EVs) into fluids, such as plasma, urine, and cerebrospinal fluid. EVs express tetraspanin family proteins (e.g., CD63, CD9, and CD81) and cell-specific antigens on their surface as common and specific markers, respectively. In this study, we hypothesized that the profile of blood cell-derived circulating EVs could reveal both common and specific pathophysiology in atherogenic diseases. Methods: Using surface plasmon resonance imaging (SPRi), we analyzed EVs surface molecules and identified circulating EVs in healthy controls (n = 18)

Transcriptional Changes in Cumulus Cells During In Vitro Maturation of Human Oocytes.

This study assessed transcriptional changes in human cumulus cells (CCs) during oocyte maturation In Vitro. CCs were collected from 25 cumulus-oocyte complexes derived from surplus ovarian medulla tissue of eight women (mean age 29 years, range 19-36) undergoing ovarian tissue cryopreservation without ovarian stimulation. Samples included CCs from fresh germinal vesicle (GV) oocytes (n = 5), and from GV (n = 8) and metaphase II (MII) oocytes (n = 12) after 48 h of In Vitro maturation (IVM). Microarray analysis revealed active signaling pathways during IVM, emphasizing LHCGR upregulation as cen

Fibroblast-specific targeting of bone morphogenetic protein signaling molecules does not alter the outcome of alcohol-associated chronic pancreatitis in mice.

AIMS: Prolonged alcohol misuse is a common cause of chronic pancreatitis, a disease characterized by progressive pancreatic fibrosis. Currently, there are no specific therapies due to unclear mechanisms. To explore the molecular mechanisms in chronic pancreatitis, we focused on the bone morphogenetic protein (BMP) signaling pathway and reported an anti-fibrogenic role of BMP signaling and a pro-fibrogenic role of Gremlin1 (Grem1, an endogenous BMP antagonist) using constitutive global knockout (KO) mice of BMP receptor type II (Bmpr2) and Grem1. In this study, we generated fibroblast(f)-specif

A Point Mutation in an Otherwise Dispensable Upstream Fshb Enhancer Moderately Impairs Fertility in Female Mice.

Follicle-stimulating hormone (FSH) is necessary for fertility in both sexes as a regulator of gametogenesis and hormone synthesis. Humans with loss-of-function mutations within the gene encoding the FSH beta subunit (FSHB) are infertile. Similarly, female Fshb knock-out mice are infertile and fail to ovulate, and males are subfertile. We recently reported the discovery and characterization of an upstream enhancer of FSHB located 26 Kb upstream of the transcriptional start site in humans (-17 Kb in mouse) that also amplifies activin and gonadotropin-releasing hormone induction of FSHB. Notably,

Structure and function of therapeutic antibodies approved by the US FDA in 2024.

In 2024, the Food and Drug Administration approved 47 new molecular entities (NMEs), including 15 therapeutic antibody-based molecules, marking the 30th anniversary of the first approved recombinant antibody. Ten of these were recombinant immunoglobulin G antibodies, while the rest comprised three bispecific antibodies, one immunocytokine, and one Fc-fusion protein. Seven antibodies targeted previously approved targets like programmed cell death receptor-1, programmed cell death receptor ligand-1, complement factor C5, interleukin (IL)-13, human epidermal growth factor receptor 2 (HER2) (bipar

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… Three different forms of activins can be formed: the homodimeric β A β A and β B β B activins, or the heterodimeric β A β B activin [ 171 ]. These activins can bind to two Type II receptors, ActRII(A) and ActRIIB, both of which are single-pass, serine/threonine kinase receptors [ 168 , 171 ]. … Once an activin has bound to either Type II receptor, a Type I receptor, ActRIB (aka ALK4), is recruited to the receptor-activin complex, and signaling occurs [ 168 ]. Activins are involved in regulation of FSH synthesis, osteogenesis, immune responses, and hematopoiesis, amongst other functions. …

Hormonal symphony: The dynamic duo of IGF and EGF in gonadotropin-induced fish ovarian development and egg maturation.

Fish oocyte maturation (FOM) is a critical biological process that occurs before ovulation and is influenced by gonadotropins, particularly luteinizing hormone (LH). The release of LH stimulates the ovarian follicle to produce a maturation-inducing hormone (MIH), specifically 17α, 20β-dihydroxy-4-pregnen-3-one (17α, 20β-DP), which initiates the formation of maturation-promoting factor (MPF) through the activation of cyclin B and cdc2 kinase. Insulin-like growth factor I (IGF-I) significantly regulates ovarian functions, including steroidogenesis, by activating its membrane receptors and the ty

Excessive BMP3b suppresses skeletal muscle differentiation.

Bone morphogenetic protein (BMP)-3b, also known as growth differentiation factor (GDF)-10, belongs to the transforming growth factor (TGF)-β superfamily. Despite being named a BMP, BMP3b is considered as an intermediate between the TGFβ/activin/myostatin and BMP/GDF subgroups of the TGFβ superfamily. Myoblast differentiation is tightly regulated by various cytokines, including the TGFβ superfamily members. However, despite BMP3b supporting the maintenance of skeletal myofibers, myoblast differentiation induced by BMP3b remains unclear. In this study, BMP3 expression levels in isolated satellit

Activated THP-1 Macrophage-Derived Factors Increase the Cytokine, Fractalkine, and EGF Secretions, the Invasion-Related MMP Production, and Antioxidant Activity of HEC-1A Endometrium Cells.

Endometrium receptivity is a multifactor-regulated process involving progesterone receptor-regulated signaling, cytokines and chemokines, and additional growth regulatory factors. In the female reproductive system, macrophages have distinct roles in the regulation of receptivity, embryo implantation, immune tolerance, and angiogenesis or oxidative stress. In the present study, we investigated the effects of PMA-activated THP-1 macrophages on the receptivity-related genes, cytokines and chemokines, growth regulators, and oxidative stress-related molecules of HEC-1A endometrium cells. We establi

Effects of ECM protein-coated surfaces on the generation of retinal pigment epithelium cells differentiated from human pluripotent stem cells.

Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical app

Synergistically Acting on Myostatin and Agrin Pathways Increases Neuromuscular Junction Stability and Endurance in Old Mice.

Sarcopenia is the primary cause of impaired motor performance in the elderly. The current prevailing approach to counteract such condition is increasing the muscle mass through inhibition of the myostatin system: however, this strategy only moderately improves muscular strength, not being able to sustain the innervation of the hypertrophic muscle per se, leading to a progressive worsening of motor performances. Thus, we proposed the administration of ActR-Fc-nLG3, a protein that combines the soluble activin receptor, a strong myostatin inhibitor, with the C-terminal agrin nLG3 domain. This com

Trigonelline Chloride Ameliorated Triphenyltin-Induced Testicular Autophagy, Inflammation, and Apoptosis: Role of Recovery.

Triphenyltin chloride (TPT-Cl) is an organometallic organotin. This study aimed to investigate the role of trigonelline (TG) along with the impact of TPT withdrawal on the testicular toxicity induced by TPT-Cl. Thirty-six adult male albino rats were divided into control, TG (40 mg/kg/day), TPT-Cl (0.5 mg/kg/day), TG + TPT-Cl, and recovery groups. Animals were daily gavaged for 12 weeks. Both TG and TPT-Cl withdrawal improved TPT-Cl-induced testicular toxicity features involving testis and relative testis weight reduction, luteinizing hormone, follicular stimulating hormone, and sex hormone-bin

Validation of a multiple marker test for early pregnancy outcome prediction.

PURPOSE: To validate the use of a multiple biomarker test panel for predicting first trimester pregnancy outcome in a multi-center cohort. METHODS: A case-control study of women presenting with pain and bleeding in early pregnancy at 5-10 weeks gestational age was performed at three academic centers. Sera from women with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage (SAB) were analyzed via immunoassay for Activin A (AA), Progesterone (P4), A Disintegrin And Metalloprotease-12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), glycodelin (Glyc), and human

A new shortened protocol to obtain islet-like cells from hESC-derived ductal cells.

Conventional methods for obtaining pancreatic β cells are based on simulating the embryonic development phase of endocrine cells via hierarchical differentiation of pluripotent stem cells (PSCs). Accordingly, we attempted to modify the protocols for obtaining insulin-secreting cells (ISCs) by sequential differentiation of a human embryonic stem cell (hESC), using the HS181 cell line. Furthermore, we hypothesize that actual pancreatic endocrine cells may arise from trans-differentiation of mature ductal cells after the embryonic developmental stage and throughout the rest of life. According to

Adenosine A2A receptor antagonism protects against hyperoxia-induced retinal vascular loss via cellular proliferation.

Retinopathy of prematurity (ROP) remains one of the major causes of blindness in children worldwide. While current ROP treatments are mostly disruptive to reduce proliferative neovascularization by targeting the hypoxic phase, protection against early hyperoxia-induced retinal vascular loss represents an effective therapeutic window, but no such therapeutic strategy is available. Built upon our recent demonstration that the protection against oxygen-induced retinopathy by adenosine A2A receptor (A2A R) antagonists is most effective when administered at the hyperoxia (not hypoxic) phase, we her

Treatment of α-1 antitrypsin deficiency using hepatic-specified cells derived from human-induced pluripotent stem cells.

OBJECTIVE: α-1 antitrypsin deficiency (AATD) is an inherited liver disease characterized by the "Z" mutations, which can cause pulmonary emphysema and liver fibrosis. Transplantation of the organ (i.e., the lung/liver) is the best treatment method, however, the scarcity of suitable donors limits its application. The cell transplantation technique poses an alternative way of combating liver failure. METHODS: Hepatic specific differentiation of the human induced pluripotent stem cells (iPSCs) was initiated with 100 ng/mL activin A, followed by 20 ng/mL of BMP-4 and 10 ng/mL of FGF-2. The cells

SOHO State of the Art Updates and Next Questions: Identifying and Treating "Progression" in Myelofibrosis.

Over the last decade, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib has become widely established as the cornerstone of pharmacologic therapy for most patients with myelofibrosis (MF), providing dramatic and durable benefits in terms of splenomegaly and symptoms, and prolonging survival. Ruxolitinib does not address all aspects of the disease, however; notably cytopenias, and its ability to modify the underlying biology of the disease remains in question. Furthermore, patients eventually lose response to ruxolitinib. Multiple groups have reported the median overall survival of MF patients a

Innovative Treatments for Rare Anemias.

Rare anemias (RA) are mostly hereditary disorders with low prevalence and a broad spectrum of clinical severity, affecting different stages of erythropoiesis or red blood cell components. RA often remains underdiagnosed or misdiagnosed, and treatment options have been limited to supportive care for many years. During the last decades, the elucidation of the molecular mechanisms underlying several RA paved the way for developing new treatments. Innovative treatments other than supportive care and allogeneic bone marrow transplantation are currently in clinical trials for β-thalassemias, sickle

Experimental Drugs for Chemotherapy- and Cancer-Related Anemia.

Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Stan

Differentiation of Human Parthenogenetic Embryonic Stem Cells into Functional Hepatocyte-like Cells.

Stem cell and tissue engineering-based therapies for acute liver failure (ALF) have been limited by the lack of an optimal cell source. We aimed to determine the suitability of human parthenogenetic embryonic stem cells (hPESCs) for the development of strategies to treat ALF. We studied the ability of human parthenogenetic embryonic stem cells (hPESCs) with high whole-genome SNP homozygosity, which were obtained by natural activation during in vitro fertilization (IVF), to differentiate into functional hepatocyte-like cells in vitro by monolayer plane orientation. hPESCs were induced on a sing