Paracrine effects of haematopoietic cells on human mesenchymal stem cells

Stem cell function decline during ageing can involve both cell intrinsic and extrinsic mechanisms. Bone and blood formation are intertwined in bone marrow, therefore haematopoietic cells and bone cells could be extrinsic factors for each other. In this study, we assessed the paracrine effects of extrinsic factors from haematopoietic cells on human mesenchymal stem cells (MSCs). Our data showed that haematopoietic cells stimulate proliferation, osteoblast differentiation and inhibit senescence of MSCs; TNF-α, PDGF-β, Wnt1, 4, 6, 7a and 10a, sFRP-3 and sFRP-5 are dominantly expressed in haematopoietic cells; the age-related increase of TNF-α in haematopoietic cells may perform as a negative factor in the interactions of haematopoietic cells on MSCs via TNF-α receptors and then activating NF-κB signaling or Wnt/β-catenin signaling to induce senescence and reduce osteoblast differentiation in MSCs. In conclusion, our data demonstrated that there are paracrine interactions of haematopoietic cells on human MSCs; immunosenescence may be one of the extrinsic mechanisms by which skeletal stem cell function decline during human skeletal ageing

Ultrahigh energy-dissipation elastomers by precisely tailoring the relaxation of confined polymer fluids

In most cases the frequency range of a damping material is adapted to a specific application. Huang et al. design a gel filled with a polymeric fluid that bypasses this problem and offers an unusually broad window over which vibrational energy is effectively dissipated

Potential Roles of the WNT Signaling Pathway in Amyotrophic Lateral Sclerosis

The WNT signaling pathway plays an important role in the physiological and pathophysiological processes of the central nervous system and the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We reviewed the literature pertinent to WNT/β–catenin signaling in ALS from cellular studies, animal models, and human clinical trials. WNT, WNT receptors, and other components of the WNT signaling pathway are expressed in both ALS patients and transgenic mice, and are involved in the pathogenesis of ALS. Studies have shown that abnormal activation of the WNT/β–catenin signaling pathway is related to neuronal degeneration and glial cell proliferation. WNT/Ca2+ signaling is associated with the pro–inflammatory phenotype of microglia; data on the muscle skeletal receptor Tyr kinase receptor in superoxide dismutase–1–G93A mice indicate that gene therapy is necessary for successful treatment of ALS. The varying profiles of lipoprotein receptor–related protein 4 antibodies in different ethnic groups suggest that individual treatment and multifactorial personalized approaches may be necessary for effective ALS therapy. In conclusion, the WNT signaling pathway is important to the ALS disease process, making it a likely therapeutic target

Role of Alcohol Drinking in Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), increase as the population ages around the world. Environmental factors also play an important role in most cases. Alcohol consumption exists extensively and it acts as one of the environmental factors that promotes these neurodegenerative diseases. The brain is a major target for the actions of alcohol, and heavy alcohol consumption has long been associated with brain damage. Chronic alcohol intake leads to elevated glutamate-induced excitotoxicity, oxidative stress and permanent neuronal damage associated with malnutrition. The relationship and contributing mechanisms of alcohol with these three diseases are different. Epidemiological studies have reported a reduction in the prevalence of Alzheimer’s disease in individuals who drink low amounts of alcohol; low or moderate concentrations of ethanol protect against β-amyloid (Aβ) toxicity in hippocampal neurons; and excessive amounts of ethanol increase accumulation of Aβ and Tau phosphorylation. Alcohol has been suggested to be either protective of, or not associated with, PD. However, experimental animal studies indicate that chronic heavy alcohol consumption may have dopamine neurotoxic effects through the induction of Cytochrome P450 2E1 (CYP2E1) and an increase in the amount of α-Synuclein (αSYN) relevant to PD. The findings on the association between alcohol consumption and ALS are inconsistent; a recent population-based study suggests that alcohol drinking seems to not influence the risk of developing ALS. Additional research is needed to clarify the potential etiological involvement of alcohol intake in causing or resulting in major neurodegenerative diseases, which will eventually lead to potential therapeutics against these alcoholic neurodegenerative diseases

Current Status and Prospects of Targeted Therapy for Osteosarcoma

Osteosarcoma (OS) is a highly malignant tumor occurring in bone tissue with a high propensity to metastasize, and its underlying mechanisms remain largely elusive. The OS prognosis is poor, and improving the survival of OS patients remains a challenge. Current treatment methods such as surgical approaches, chemotherapeutic drugs, and immunotherapeutic drugs remain ineffective. As research progresses, targeted therapy is gradually becoming irreplaceable. In this review, several treatment modalities for osteosarcoma, such as surgery, chemotherapy, and immunotherapy, are briefly described, followed by a discussion of targeted therapy, the important targets, and new technologies for osteosarcoma treatment

The Biogenesis of miRNAs and Their Role in the Development of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects upper and lower motor neurons. As there is no effective treatment for ALS, it is particularly important to screen key gene therapy targets. The identifications of microRNAs (miRNAs) have completely changed the traditional view of gene regulation. miRNAs are small noncoding single-stranded RNA molecules involved in the regulation of post-transcriptional gene expression. Recent advances also indicate that miRNAs are biomarkers in many diseases, including neurodegenerative diseases. In this review, we summarize recent advances regarding the mechanisms underlying the role of miRNAs in ALS pathogenesis and its application to gene therapy for ALS. The potential of miRNAs to target diverse pathways opens a new avenue for ALS therapy

Methazolamide improves neurological behavior by inhibition of neuron apoptosis in subarachnoid hemorrhage mice

Subarachnoid hemorrhage (SAH) results in significant nerve dysfunction, such as hemiplegia, mood disorders, cognitive and memory impairment. Currently, no clear measures can reduce brain nerve damage. The study of brain nerve protection after SAH is of great significance. We aim to evaluate the protective effects and the possible mechanism of methazolamide in C57BL/6J SAH animal model in vivo and in blood-induced primary cortical neuron (PCNs) cellular model of SAH in vitro. We demonstrate that methazolamide accelerates the recovery of neurological damage, effectively relieves cerebral edema, and improves cognitive function in SAH mice as well as offers neuroprotection in blood- or hemoglobin-treated PCNs and partially restores normal neuronal morphology. In addition, western blot analyses show obviously decreased expression of active caspase-3 in methazolamide-treated SAH mice comparing with vehicle-treated SAH animals. Furthermore, methazolamide effectively inhibits ROS production in PCNs induced by blood exposure or hemoglobin insult. However, methazolamide has no protective effects in morality, fluctuation of cerebral blood flow, SAH grade, and cerebral vasospasm of SAH mice. Given methazolamide, a potent carbonic anhydrase inhibitor, can penetrate the blood–brain barrier and has been used in clinic in the treatment of ocular conditions, it provides potential as a novel therapy for SAH