Combined angiogenic and hypertrophic gene therapy enhances skeletal muscle growth.

Skeletal muscle atrophy in response to pathophysiological stimuli or disuse includes loss of muscle mass and strength. Targeting signaling pathways regulating muscle growth can counteract muscle loss, but also unwanted side effects on muscle vascularization, oxidative metabolism, and exercise tolerance have been reported. Here, we investigated whether combined induction of angiogenesis and muscle hypertrophy can promote physiological muscle growth and improve muscle function to overcome the limitations of current hypertrophic treatments.

Soluble Activin Receptor Type IIB Improves Muscle Regeneration Following Venom-Induced Damage.

Viper bite envenoming often results in prominent skeletal muscle damage. According to our previous studies, the prolonged presence of venom toxins induced extensive muscle damage, which mimicked the outcome of chronic muscle damage often seen in human muscular dystrophies. In the case of chronic muscle damage, two critical processes occur: muscle regeneration is impaired, and fibrosis develops.

Long-term COVID-19 vaccine- and Omicron infection-induced humoral and cell-mediated immunity.

Introduction: Mutations occurring in the spike (S) protein of SARS-CoV-2 enables the virus to evade COVID-19 vaccine- and infection-induced immunity.

Methods: Here we provide a comprehensive analysis of humoral and cell-mediated immunity in 111 healthcare workers who received three or four vaccine doses and were followed up to 12 and 6 months, respectively, after the last vaccine dose. Omicron breakthrough infection occurred in 71% of the vaccinees, enabling evaluation of vaccine- and vaccine/infection-induced hybrid immunity.

Improved health by combining dietary restriction and promoting muscle growth in DNA repair-deficient progeroid mice.

Background: Ageing is a complex multifactorial process, impacting all organs and tissues, with DNA damage accumulation serving as a common underlying cause. To decelerate ageing, various strategies have been applied to model organisms and evaluated for health and lifespan benefits. Dietary restriction (DR, also known as caloric restriction) is a well-established long-term intervention recognized for its universal anti-ageing effects.

Inhibition of activin receptor 2 signalling ameliorates metabolic dysfunction-associated steatotic liver disease in western diet/L-NAME induced cardiometabolic disease.

Objective: Blockade of activin 2 receptor (ACVR2) signaling has been shown to improve insulin sensitivity and aid in weight loss. Inhibition of ACVR2 signaling restores cardiac function in multiple heart failure models. However, its potential in the treatment of obesity-related cardiometabolic disease remains unknown.

Neutralizing antibodies after the third COVID-19 vaccination in healthcare workers with or without breakthrough infection.

Background: Vaccinations against the SARS-CoV-2 are still crucial in combating the ongoing pandemic that has caused more than 700 million infections and claimed almost 7 million lives in the past four years. Omicron (B.1.

Activin A levels are raised during human tuberculosis and blockade of the activin signaling axis influences murine responses to infection.

Unlabelled: Activin A strongly influences immune responses; yet, few studies have examined its role in infectious diseases. We measured serum activin A levels in two independent tuberculosis (TB) patient cohorts and in patients with pneumonia and sarcoidosis. Serum activin A levels were increased in TB patients compared to healthy controls, including those with positive tuberculin skin tests, and paralleled severity of disease, assessed by X-ray scores.

Coronavirus spike protein-specific antibodies indicate frequent infections and reinfections in infancy and among BNT162b2-vaccinated healthcare workers.

The prevalence of seasonal human coronavirus (HCoV) infections in early childhood and adults has not been well analyzed in longitudinal serological studies. Here we analyzed the changes in HCoV (229E, HKU1, NL63, OC43, MERS, and SARS-CoV-2) spike-specific antibody levels in follow-up serum specimens of 140 children at the age of 1, 2, and 3 years, and of 113 healthcare workers vaccinated for Covid-19 with BNT162b2-vaccine. IgG antibody levels against six recombinant HCoV spike subunit 1 (S1) proteins were measured by enzyme immunoassay.

Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants.

The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric antibody-mimetic sherpabody targeted against a conserved region of the viral spike glycoprotein.

Inhibition of activin signalling reduces the growth of LβT2 gonadotroph pituitary tumours in mouse.

Pituitary tumours are benign neoplasms that derive from hormone-producing cells of the pituitary gland. While medical treatments have emerged for most subtypes, gonadotroph tumours that express follicle-stimulating hormone (FSH) and/or luteinizing hormone still lack therapeutic options apart from surgery and radiotherapy. Activin ligands are physiological regulators of production and secretion of FSH by gonadotroph cells, but their role in gonadotroph tumourigenesis remains little explored.

Steroidogenic factor 1 (NR5A1) induces multiple transcriptional changes during differentiation of human gonadal-like cells.

Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes steroidogenic factor 1 (SF1), a key regulatory factor that determines gonadal development and coordinates endocrine functions. Here, we have established a stem cell-based model of human gonadal development and applied it to evaluate the effects of NR5A1 during the transition from bipotential gonad to testicular cells. We combined directed differentiation of human induced pluripotent stem cells (46,XY) with activation of endogenous NR5A1 expression by conditionally-inducible CRISPR activation.

Directly immersible silicon photonic probes: Application to rapid SARS-CoV-2 serological testing.

Silicon photonic probes based on broad-band Mach-Zehnder interferometry are explored for the first time as directly immersible immunosensors alleviating the need for microfluidics and pumps. Each probe includes two U-shaped waveguides allowing light in- and out-coupling from the same chip side through a bifurcated fiber and a mechanical coupler. At the opposite chip side, two Mach-Zehnder interferometers (MZI) are located enabling real-time monitoring of binding reactions by immersion of this chip side into a sample.

Coordinated activation of TGF-β and BMP pathways promotes autophagy and limits liver injury after acetaminophen intoxication.

Ligands of the transforming growth factor-β (TGF-β) superfamily, including TGF-βs, activins, and bone morphogenetic proteins (BMPs), have been implicated in hepatic development, homeostasis, and pathophysiology. We explored the mechanisms by which hepatocytes decode and integrate injury-induced signaling from TGF-βs and activins (TGF-β/Activin) and BMPs. We mapped the spatiotemporal patterns of pathway activation during liver injury induced by acetaminophen (APAP) in dual reporter mice carrying a fluorescent reporter of TGF-β/Activin signaling and a fluorescent reporter of BMP signaling.

Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants.

Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.

Treatment with Soluble Activin Type IIB Receptor Ameliorates Ovariectomy-Induced Bone Loss and Fat Gain in Mice.

Introduction: In postmenopausal osteoporosis, hormonal changes lead to increased bone turnover and metabolic alterations including increased fat mass and insulin resistance. Activin type IIB receptors bind several growth factors of the TGF-β superfamily and have been demonstrated to increase muscle and bone mass. We hypothesized that ActRIIB-Fc treatment could improve bone and muscle mass, inhibit fat accumulation, and restore metabolic alterations in an ovariectomy (OVX) model of postmenopausal osteoporosis.

Adapting the Scar-in-a-Jar to Skin Fibrosis and Screening Traditional and Contemporary Anti-Fibrotic Therapies.

Skin fibrosis still constitutes an unmet clinical need. Although pharmacological strategies are at the forefront of scientific and technological research and innovation, their clinical translation is hindered by the poor predictive capacity of the currently available fibrosis models. Indeed, customarily utilised scarring models are conducted in a low extracellular matrix milieu, which constitutes an oxymoron for the in-hand pathophysiology.

p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition.

Skeletal muscle, the most abundant tissue in the body, plays vital roles in locomotion and metabolism. Understanding the cellular processes that govern regulation of muscle mass and function represents an essential step in the development of therapeutic strategies for muscular disorders. Myostatin, a member of the TGF-β family, has been identified as a negative regulator of muscle development.

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants.

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.

Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women.

Objectives: Maternal serum inhibin-A, pregnancy associated plasma protein-A (PAPP-A) and PAPP-A2 together with placental growth factor (PlGF), maternal risk factors and uterine artery pulsatility index (UtA PI) were analysed to study their ability to predict pre-eclampsia (PE).

Study Design: Serial serum samples for the nested case-control study were collected prospectively at 12-14, 18-20 and 26-28 weeks of gestation from 11 women who later developed early-onset PE (EO PE, diagnosis < 34 + 0 weeks of gestation), 34 women who developed late-onset PE (LO PE, diagnosis ≥ 34 + 0 weeks) and 89 controls.

Main Outcome Measures: Gestational age -adjusted multiples of the median (MoM) values were calculated for biomarker concentrations.

Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs.

Skeletal muscle wasting is commonly associated with chronic kidney disease (CKD), resulting in increased morbidity and mortality. However, the link between kidney and muscle function remains poorly understood. Here, we took a complementary interorgan approach to investigate skeletal muscle wasting in CKD.

Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue.

The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis.

The Activin/Follistatin Axis Is Severely Deregulated in COVID-19 and Independently Associated With In-Hospital Mortality.

Background: Activins are members of the transforming growth factor-β superfamily implicated in the pathogenesis of several immunoinflammatory disorders. Based on our previous studies demonstrating that overexpression of activin-A in murine lung causes pathology sharing key features of coronavirus disease 2019 (COVID-19), we hypothesized that activins and their natural inhibitor follistatin might be particularly relevant to COVID-19 pathophysiology.

Methods: Activin-A, activin-B, and follistatin were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in 3 independent centers, and compared with demographic, clinical, and laboratory parameters.

Muscle follistatin gene delivery increases muscle protein synthesis independent of periodical physical inactivity and fasting.

Blocking of myostatin and activins effectively counteracts muscle atrophy. However, the potential interaction with physical inactivity and fasting in the regulation of muscle protein synthesis is poorly understood. We used blockade of myostatin and activins by recombinant adeno-associated virus (rAAV)-mediated follistatin (FS288) overexpression in mouse tibialis anterior muscle.