Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits.In brain physiology,highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli.Once the brain switches its functional states,microglia are recruited to specific sites to exert their immune functions,including the release of cytokines and phagocytosis of cellular debris.The crosstalk of microglia between neurons,neural stem cells,endothelial cells,oligodendrocytes,and astrocytes contributes to their functions in synapse pruning,neurogenesis,vascularization,myelination,and blood-brain barrier permeability.In this review,we highlight the neuron-derived“find-me,”“eat-me,”and“don't eat-me”molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development.This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease,thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation

Transforming growth factor-beta（TGF-β）/bone morphogenetic protein（BMP） plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β（I/II） or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific.Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog（Hh）, Notch, Akt/m TOR, and mi RNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, mi RNAs are regulators, and b-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics.

Lactate:a prospective target for therapeutic intervention in psychiatric disease

Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs.Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte rs.Among these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years.Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant effect.In this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling molecule.In addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.

Late Holocene Isotopic and Molecular Signals in Saline Sediments of Lake Cantara South,Australia

Isotopic,biomarker,and trace elements of a 65 cm long sedimentary core from Lake Cantara south in Adelaide,Australia were measured in an effort to trace environmental change clues in the southern Hemisphere.The geochemical

Molecular Mechanisms Regulating Rapid Stress Signaling Networks in Arabidopsis

As sessile organisms plants must ronmental conditions. To survive cope with ever changing enviplants have evolved elaborate mechanisms to perceive and rapidly respond to a diverse range of abiotic and biotic stresses. Central to this response is the ability to modulate gene expression at both the transcriptional and posttranscriptional levels. This review will focus on recent progress that has been made towards understanding the rapid reprogramming of the transcriptome that occurs in response to stress as well as emerging mechanisms underpinning the reprogramming of gene expression in response to stress,

Emerging trends in early-onset gastric cancer

The incidence of early-onset gastric cancer(EOGC)is consistently increasing,and its etiology is notably complex.This increase may be attributed to distinctive factors that differ from those associated with late-onset gastric cancer(LOGC),including genetic predispositions,dietary factors,gastric microbiota dysbiosis,and screening of high-risk cases.These factors collectively contribute to the onset of cancer.EOGC significantly differs from LOGC in terms of clinicopathological and molecular characteristics.Moreover,multiple differences in prognosis and clinical management also exist.This study aimed to systematically review the latest research advancements in the epidemiological characteristics,etiological factors,clinicopathological and molecular features,prognosis,and treatment modalities of EOGC.

Advances on hormone-like activity of Panax ginseng and ginsenosides

Traditional Chinese medicine(TCM)has been paid much attentions due to the prevention and treatment of steroid hormone disorders.Ginseng,the root of Panax ginseng C.A.Meyer(Araliaceae),is one of the most valuable herbs in complementary and alternative medicines around the world.A series of dammarane triterpenoid saponins,also known as phytosteroids,were reported as the primary ingredients of Ginseng,and indicated broad spectral pharmacological actions,including anti-cancer,anti-inflammation and anti-fatigue.The skeletons of the dammarane triterpenoid aglycone are structurally similar to the steroid hormones.Both in vitro and in vivo studies showed that Ginseng and its active ingredients have beneficial hormone-like role in hormonal disorders.This review thus summarizes the structural similarities between hormones and dammarane ginsenosides and integrates the analogous effect of Ginseng and ginsenosides on prevention and treatment of hormonal disorders published in recent twenty years(1998–2018).The review may provide convenience for anticipate structure-function relationship between saponins structure and hormone-like effect.

Natural products and hepatocellular carcinoma:a review

Hepatocellular carcinoma(HCC)is the fi fth commonest cause of malignancy and the third cause of cancer mortality.There are different treatment options for HCC ranging from loco-regional therapy to surgical treatment.Different regimen of systemic chemotherapy has been tried with a poor response.Several studies aimed at discovering more molecules for the management of HCC.Those studies aimed at recognizing and targeting several signaling and molecular pathways that lead to cellular proliferation and tumor formation.In this review,we discussed the role of several agents found in natural and dietary products such as curcumin,resveratrol,fl avonoids,Rubus aleaefolius Poir total alkaloids,Livistona chinensis seed,and crocetin.We had used the names of the above-mentioned products as key words in addition to“HCC”on PubMed to fi nd studies that discussed their roles in HCC.Articles were downloaded for reviewing and discussing natural products that had adequate studies in treating HCC.