Metal oxide nanomaterials based electrochemical and optical biosensors for biomedical applications: Recent advances and future prospectives.

The amalgamation of nanostructures with modern electrochemical and optical techniques gave rise to interesting devices, so-called biosensors. A biosensor is an analytical tool that incorporates various biomolecules with an appropriate physicochemical transducer. Over the past few years, metal oxide nanomaterials (MONMs) have significantly stimulated biosensing research due to their desired functionalities, versatile chemical stability, and low cost along with their unique optical, catalytic, electrical, and adsorption properties that provide an attractive platform for linking the biomolecules, for example, antibodies, nucleic acids, enzymes, and receptor proteins as sensing elements with the transducer for the detection of signals or signal amplifications. The signals to be measured are in direct proportionate to the concentration of the bioanalyte. Because of their simplicity, cost-effectiveness, portability, quick analysis, higher sensitivity, and selectivity against a broad range of biosamples, MONMs-based electrochemical and optical biosensing platforms are exhaustively explored as powerful early-diagnosis tools for point of care applications. Herein, we made a bibliometric analysis of past twenty years (2004-2023) on the application of MONMs as electrochemical and optical biosensing units using Web of Science database and the results of which clearly reveal the increasing number of publications since 2004. Geographical area distribution analysis of these publications shows that China tops the list followed by the United States of America and India. In this review, we first describe the electrochemical and optical properties of MONMs that are crucial for the creation of extremely stable, specific, and sensitive sensors with desirable characteristics. Then, the biomedical applications of MONMs-based bare and hybrid electrochemical and optical biosensing frameworks are highlighted in the light of recent literature. Finally, current limitations and future challenges in the field of biosensing technology are addressed.

Preparation of CH3NH3PbBr3 Perovskites Encapsulated in ZIF-8 with Improved Stability and Their Application in Fluorimetry and Information Encryption.

Metal halide perovskites (MHPs) have been promising functional materials for developing solar cells, lasers, photodetectors, and sensors due to their outstanding optical and electrical characteristics. However, they suffer from very poor stability for their high sensitivity to some environmental factors such as temperature, UV irradiation, pH, and polar solvent, which limits their extensive practical applications. Herein, a derived metal organic framework material, Pb-ZIF-8, was prepared as a precursor via a doping protocol. Then, CH3NH3PbBr3 perovskites encapsulated in ZIF-8 (CH3NH3PbBr3@ZIF-8) with green fluorescent (FL) emission were synthesized via a facile in situ protocol by using the derived metal organic frameworks material as a source of Pb element. With the protection of encapsulated ZIF-8, the perovskites material shows good FL properties under various harsh environmental conditions, which facilitates facile application in various fields. To verify the practical application potential of CH3NH3PbBr3@ZIF-8, we utilized them as FL probes to establish a highly sensitive method for detecting glutathione. Furthermore, the rapid conversion process from non-FL Pb-ZIF-8 to FL CH3NH3PbBr3@ZIF-8 was utilized to realize encryption and decryption of confidential information. This work opens an avenue to the development of perovskites-based devices with greatly improved stability in harsh external environments.

Combined pollution of heavy metals and polycyclic aromatic hydrocarbons in the soil in Shenfu Region, China: a case of three different cities.

It is a challenging issue to investigate the combined pollution of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in urban soils. The purpose of this study was to determine the concentrations of these two pollutants in soils in Shenyang, Fushun, and Fushun New District, to analyze their distribution, their interaction, and co-contamination levels. The concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry (ICP-MS), while the concentrations of 21 kinds of PAH were analyzed by gas chromatography-mass spectrometry (GC-MS). Based on the analysis of pollution concentrations and distribution patterns, the intrinsic links between heavy metals and PAHs in three different cities were assessed using a variety of multivariate analysis methods. Compared to Shenfu New District, the concentration of pollutants in Shenyang and Fushun shows a higher level. Moreover, the results of redundancy analysis (RDA) of samples may quantify the possibility of combined pollution of different heavy metal elements and PAHs. This study also affirms the important role of multivariate analysis in being used to reveal the complex interactions and spatial distribution of different pollutants.

TIPE1-mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway.

Recent studies have shown that tumour necrosis factor-α-induced protein 8 like-1(TIPE1) plays distinct roles in different cancers. TIPE1 inhibits tumour proliferation and metastasis in a variety of tumours but acts as an oncogene in cervical cancer. The role of TIPE1 in nasopharyngeal carcinoma (NPC) remains unknown. Interestingly, TIPE1 expression was remarkably increased in NPC tissue samples compared to adjacent normal nasopharyngeal epithelial tissue samples in our study. TIPE1 expression was positively correlated with that of the proliferation marker Ki67 and negatively correlated with patient lifespan. In vitro, TIPE1 inhibited autophagy and induced cell proliferation in TIPE1-overexpressing CNE-1 and CNE-2Z cells. In addition, knocking down TIPE1 expression promoted autophagy and decreased proliferation, whereas overexpressing TIPE1 increased the levels of pmTOR, pS6 and P62 and decreased the level of pAMPK and the LC3B. Furthermore, the decrease in autophagy was remarkably rescued in TIPE1-overexpressing CNE-1 and CNE-2Z cells treated with the AMPK activator AICAR. In addition, TIPE1 promoted tumour growth in BALB/c nude mice. Taken together, results indicate that TIPE1 promotes NPC progression by inhibiting autophagy and inducing cell proliferation via the AMPK/mTOR signalling pathway. Thus, TIPE1 could potentially be used as a valuable diagnostic and prognostic biomarker for NPC.

Circular RNA circFOXO3 promotes prostate cancer progression through sponging miR-29a-3p.

Circular RNA FOXO3 (CircFOXO3, also termed as Hsa_circ_0006404) is derived from exon 2 of forkhead box O3 (FOXO3) gene, and abnormal expression is shown in different diseases. However, whether circFOXO3 plays important roles in tumorigenesis and progression of prostate cancer (PCa) remains unclear. In this study, we found that circFOXO3 was up-regulated in both PCa tissues and serum samples. Moreover, circFOXO3 was positively correlated with the Gleason score in PCa samples. CircFOXO3 was observed to be up-regulated in Gleason score > 6 PCa samples compared with Gleason score = 6 PCa samples. Knock-down circFOXO3 could remarkably inhibit PCa cell cycle, proliferation and promote cell apoptosis in vitro. Furthermore, we demonstrated circFOXO3 could act as miR-29a-3p sponge to up-regulate SLC25A15 expression by bioinformatics analysis, dual-luciferase reporter assays and biotinylated RNA pull-down assays. SLC25A15 could reverse the tumour suppressing roles of knock-down circFOXO3 in PCa. Of note, we found that miR-29a-3p was down-regulated; however, SLC25A15 was overexpressed in PCa samples compared with normal tissues. In conclusion, circFOXO3 acts as a miR-29a-3p sponge to exhibit oncogenic activity that affects the cell cycle and cell apoptosis in PCa through transcriptional up-regulation of SLC25A15. Our analysis suggests circFOXO3 could act as promising prostate cancer biomarkers.

A novel nonsense variant in PLS3 causes X-linked osteoporosis in a Chinese family.

Osteoporosis is a complex bone metabolic disorder. Genetic factors play an important role in the development of osteoporosis. Mutations in more than 15 genes have been identified to be responsible for osteoporosis to date. Most recently, the gene PLS3 encoding plastin 3 was recognized to be involved in X-linked osteoporosis. Here, we recruited a four-generation Chinese family with X-linked osteoporosis, which had its onset in childhood and was characterized by peripheral fractures and low bone mineral density. All affected individuals shared a nonsense variant (c.244C > T) in exon 4 of PLS3 on Xq23. The variant in affected individuals segregated with the osteoporosis phenotype. By restriction analysis using Dra I, this variant was confirmed in all affected individuals but was not detected in unaffected family members or in 100 unrelated Chinese male controls. The variant was predicted to cause a premature termination of messenger RNA (mRNA) translation (p.Gln82*). The mutant mRNA degraded via the mechanism of "nonsense-mediated mRNA decay." In the present study, we identified a novel nonsense variant of PLS3 in early-onset X-linked osteoporosis and provided a novel insight into the molecular mechanism underlying the pathogenesis of osteoporosis.

Plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2.

Osteoblast differentiation is a key process in bone homeostasis. Mutations in plastin 3 have been reported to be responsible for X-linked osteoporosis. Plastin 3 and plastin 2 act synergistically to regulate osteoblast differentiation. However, the bone-related function of plastin 1, another family member of plastins, has not been assessed. In this study, we addressed the functional importance of plastin 1 in osteoblasts. We characterized the expression patterns of plastin 1 during osteoblast differentiation and revealed its important role in this process. In both HEK 293T and hFOB1.19 cells, plastin 1 was demonstrated to regulate intracellular Ca2+. Accordingly, we revealed that higher Ca2+ concentration promotes osteoblast differentiation. Finally, we found that plastin 1 may play a compensatory role in osteoporosis patients with plastin 3 deficiency. Together, our results indicate that plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2+. Our work sheds new light on the role played by plastins in bone homeostasis.

TIPE1 promotes cervical cancer progression by repression of p53 acetylation and is associated with poor cervical cancer outcome.

Previous studies have shown that TIPE1 inhibits tumor proliferation and metastasis in certain cancers; however, increased expression of TIPE1 is observed in cervical cancer cell lines and tissues, indicating it might exert a distinctive role in cervical cancer. Cell and xenograft tumorigenicity assays showed that TIPE1 facilitates cervical cancer progression in this study. Further investigation demonstrated that TIPE1 binds to p53 and impairs its activity via inhibition of its acetylation. In addition, TIPE1 promoted cell proliferation and suppressed cisplatin susceptibility in a p53-dependent manner, indicating that TIPE1 facilitates cervical cancer progression primarily through the p53 pathway. TIPE1 expression in clinical samples also demonstrated that its upregulation predicts poor prognosis in patients with cervical cancer. Taken together, the results of this study showed that TIPE1 serves as an oncogene by restricting p53 activity in the development of cervical cancer, suggesting that TIPE1 will provide a new potential target for cervical cancer therapy and can be used as a biomarker to predict patient prognosis.

Role of the Akt/mTOR signaling pathway in human papillomavirus-associated nasal and sinonasal inverted papilloma.

Nasal and sinonasal inverted papilloma (NSIP) is a benign tumor in which surface epithelial cells grow downward into the underlying supportive tissue with varying degrees of metaplasia. Human papillomavirus (HPV) has been proposed as the causal agent in the pathogenesis of this disease. Many studies have shown that HPV can activate the Akt/mechanistic target of rapamycin (mTOR) signaling pathway, but the role of this pathway in HPV-associated NSIP is largely unknown. In this study, we enrolled 40 control tissue samples and 80 NSIP tissue samples. HPV genotyping showed that 47 of the 80 examined cases of NSIP were HPV-positive (58.8%), and the most common subtype was HPV11 (20/53, 37.7%). The immunohistochemistry showed statistically significant differences in phosphorylated Akt and phosphorylated S6 ribosomal protein staining among control samples, HPV-positive NSIP and HPV-negative NSIP. The HPV11 L1-L2 plasmid increased the proliferation of normal human nasopharyngeal epithelial NP69-SV40T cells and human nasopharyngeal cancer CNE1 cells. Meanwhile, rapamycin, an mTOR inhibitor, reversed the increased cell proliferation induced by the HPV11 L1-L2 plasmid. Western blot analysis showed that Akt/mTOR/S6 were overexpressed in NP69-SV40T cells and CNE1 cells infected with the HPV11 L1-L2 plasmid. These data demonstrate that HPV promotes cell proliferation through the Akt/mTOR signaling pathway in NSIP.

Ghrelin promotes hepatic lipogenesis by activation of mTOR-PPARγ signaling pathway.

Although ghrelin has been demonstrated to stimulate energy intake and storage through a central mechanism, its effect on hepatic lipid metabolism remains largely uncharacterized. Ghrelin receptor antagonism or gene deletion significantly decreased obesity-associated hepatic steatosis by suppression of de novo lipogenesis, whereas exogenous ghrelin stimulated lipogenesis, leading to hepatic lipid accumulation in mice. The effects of ghrelin were mediated by direct activation of its receptor on hepatocytes. Cultured hepatocytes responded to ghrelin with increased lipid content and expression of lipogenesis-related genes. Ghrelin increased phosphorylation of S6, the downstream target of mammalian target of rapamycin (mTOR) signaling in cultured hepatocytes, whereas ghrelin receptor antagonism reduced hepatic phosphorylation of S6 in db/db mice. Inhibition of mTOR signaling by rapamycin markedly attenuated ghrelin-induced up-regulation of lipogenesis in hepatocytes, whereas activation of hepatic mTOR signaling by deletion of TSC1 increased hepatic lipogenesis. By interacting with peroxisome proliferator-activated receptor-γ (PPARγ), mTOR mediates the ghrelin-induced up-regulation of lipogenesis in hepatocytes. The stimulatory effect of ghrelin on hepatic lipogenesis was significantly attenuated by PPARγ antagonism in cultured hepatocytes and in PPARγ gene-deficient mice. Our study indicates that ghrelin activates its receptor on hepatocytes to promote lipogenesis via a mechanism involving the mTOR-PPARγ signaling pathway.

Hyperhomocysteinemia promotes insulin resistance by inducing endoplasmic reticulum stress in adipose tissue.

Type 2 diabetes is a chronic inflammatory metabolic disease, the key point being insulin resistance. Endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of type 2 diabetes. Previously, we found that hyperhomocysteinemia (HHcy) induced insulin resistance in adipose tissue. Here, we hypothesized that HHcy induces ER stress, which in turn promotes insulin resistance. In the present study, the direct effect of Hcy on adipose ER stress was investigated by the use of primary rat adipocytes in vitro and mice with HHcy in vivo. The mechanism and the effect of G protein-coupled receptor 120 (GPR120) were also investigated. We found that phosphorylation or expression of variant ER stress markers was elevated in adipose tissue of HHcy mice. HHcy activated c-Jun N-terminal kinase (JNK), the downstream signal of ER stress in adipose tissue, and activated JNK participated in insulin resistance by inhibiting Akt activation. Furthermore, JNK activated c-Jun and p65, which in turn triggered the transcription of proinflammatory cytokines. Both in vivo and in vitro assays revealed that Hcy-promoted macrophage infiltration aggravated ER stress in adipose tissue. Chemical chaperones PBA and TUDCA could reverse Hcy-induced inflammation and restore insulin-stimulated glucose uptake and Akt activation. Activation of GPR120 reversed Hcy-induced JNK activation and prevented inflammation but not ER stress. Therefore, HHcy inhibited insulin sensitivity in adipose tissue by inducing ER stress, activating JNK to promote proinflammatory cytokine production and facilitating macrophage infiltration. These findings reveal a new mechanism of HHcy in the pathogenesis of insulin resistance.

Biomedical potency and mechanisms of marine polysaccharides and oligosaccharides: A review.

Derived from bountiful marine organisms (predominantly algae, fauna, and microorganisms), marine polysaccharides and marine oligosaccharides are intricate macromolecules that play a significant role in the growth and development of marine life. Recently, considerable attention has been paid to marine polysaccharides and marine oligosaccharides as auspicious natural products due to their promising biological attributes. Herein, we provide an overview of recent advances in the miscellaneous biological activities of marine polysaccharides and marine oligosaccharides that encompasses their anti-cancer, anti-inflammatory, antibacterial, antiviral, antioxidant, anti-diabetes mellitus, and anticoagulant properties. Furthermore, we furnish a concise summary of the underlying mechanisms governing the behavior of these biological macromolecules. We hope that this review inspires research on marine polysaccharides and marine oligosaccharides in medicinal applications while offering fresh perspectives on their broader facets.

Deficiency in pulmonary surfactant proteins in mice with fatty acid binding protein 4-Cre-mediated knockout of the tuberous sclerosis complex 1 gene.

Tuberous sclerosis complex 1 (TSC1) forms a heterodimmer with tuberous sclerosis complex 2, to inhibit signalling by the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). The mTORC1 stimulates cell growth by promoting anabolic cellular processes, such as gene transcription and protein translation, in response to growth factors and nutrient signals. Originally designed to test the role of TSC1 in adipocyte function, mice in which the gene for TSC1 was specifically deleted by the fatty acid binding protein 4 (FABP4)-Cre (Fabp4-Tsc1cKO mice) died prematurely within 48 h after birth. The Fabp4-Tsc1cKO mouse revealed a much smaller phenotype relative to the wild-type littermates. Maternal administration of rapamycin, a classical mTOR inhibitor, significantly increased the survival time of Fabp4-Tsc1cKO mice for up to 23 days. Both macroscopic and microscopic haemorrhages were observed in the lungs of Fabp4-Tsc1cKO mice, while other tissues showed no significant changes. Levels of surfactant proteins A and B demonstrated a significant decrease in the Fabp4-Tsc1cKO mice, which was rescued by maternal injection of rapamycin. Co-localization of FABP4 or TSC1 with surfactant protein B was also detected in neonatal pulmonary tissues. Our study suggests that TSC1-mTORC1 may be critical for the synthesis of surfactant proteins A and B.

The Research Progress on Immortalization of Human B Cells.

Human B cell immortalization that maintains the constant growth characteristics and antibody expression of B cells in vitro is very critical for the development of antibody drugs and products for the diagnosis and bio-therapeutics of human diseases. Human B cell immortalization methods include Epstein-Barr virus (EBV) transformation, Simian virus 40 (SV40) virus infection, in vitro genetic modification, and activating CD40, etc. Immortalized human B cells produce monoclonal antibodies (mAbs) very efficiently, and the antibodies produced in this way can overcome the immune rejection caused by heterologous antibodies. It is an effective way to prepare mAbs and an important method for developing therapeutic monoclonal antibodies. Currently, the US FDA has approved more than 100 mAbs against a wide range of illnesses such as cancer, autoimmune diseases, infectious diseases, and neurological disorders. This paper reviews the research progress of human B cell immortalization, its methods, and future directions as it is a powerful tool for the development of monoclonal antibody preparation technology.

Serum level of free thyroxine is an independent risk factor for non-alcoholic fatty liver disease in euthyroid people.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem concern in recent decades. The specific mechanism of NAFLD is still not clear. Previous studies had shown the correlation between NAFLD and thyroid dysfunction. The correlation between thyroid hormones within the euthyroid range and NAFLD has not yet been clarified. This study sought to investigate the association between NAFLD and thyroid hormones in euthyroid patients. METHODS: A retrospective cross-sectional study was conducted at Beijing Tiantan Hospital from January 1, 2019, to October 1, 2021. Eighty-one NAFLD patients with normal thyroid function and 34 healthy individuals were enrolled. Participants' demographic information, biochemical parameters, and thyroid hormone levels were collected. The severity of NAFLD was assessed by abdominal computed tomography (CT). The association between NAFLD and thyroid hormones was analyzed. RESULTS: Patients in the NAFLD group were older and more likely to be female than those in the healthy control group (P<0.05). Compared to the healthy control group, the serum levels of fasting plasma glucose (FPG), alanine transaminase (ALT), plasma aspartate transaminase (AST), triglyceride, gamma-glutamyl transferase (γ-GT), and uric acid (UA) were higher, but the levels of high-density lipoprotein cholesterol (HDL-C), and free thyroxine (FT4) were lower in the NAFLD group (P<0.05). NAFLD is more severe in females than males (P<0.05). ALT, AST, low-density lipoprotein cholesterol (LDL-C), γ-GT, tetraiodothyronine, and free triiodothyronine (FT3) levels increased significantly as the severity of NAFLD increased (P<0.05). The results of the Spearman correlation analysis indicated that the severity of NAFLD was positively correlated with ALT (r=0.376, P=0.001), AST (r=0.275, P=0.015), and LDL (r=0.313, P=0.007). The multiple logistic regression analysis showed that age [odds ratio (OR) =1.071; 95% confidence interval (CI): 1.010-1.136, P=0.021], ALT (OR =1.091; 95% CI: 1.034-1.150, P=0.001), HDL-C (OR =0.085; 95% CI: 0.010-0.690, P=0.021), and FT4 (OR =0.738; 95% CI: 0.545-1.001, P=0.046) were independently related to the risk of NAFLD in patients with normal thyroid function. CONCLUSIONS: FT4 within the normal range was lower in the NAFLD group compared to the healthy control group. The serum level of FT4 is an independent risk factor of NAFLD in euthyroid people.

MEX3A promotes nasopharyngeal carcinoma progression via the miR-3163/SCIN axis by regulating NF-κB signaling pathway.

Mex-3 RNA Binding Family Member A (MEX3A) is an RNA-binding protein that plays complex and diverse roles in the development of various malignancies. However, its role and mechanism in nasopharyngeal carcinoma (NPC) remain undefined and were therefore evaluated in this study. By analyzing Gene Expression Omnibus data and using tissue microarrays, we found that MEX3A is significantly upregulated in NPC and negatively associated with prognosis. Notably, MEX3A depletion led to decreased cell proliferation, invasion, and migration, but increased apoptosis in NPC cells in vitro, while inhibiting tumor growth in vivo. Using whole-transcript expression arrays and bioinformatic analysis, we identified scinderin (SCIN) and miR-3163 as potential downstream targets of MEX3A in NPC. The regulatory mechanisms of MEX3A, SCIN and miR-3163 were further investigated using rescue experiments. Importantly, SCIN depletion and miR-3163 inhibition reversed and rescued the oncogenic effects of MEX3A, respectively. Moreover, NF-κB signaling inhibition reversed the oncogenic effects of both SCIN and MEX3A. In summary, our results demonstrate that MEX3A may promote NPC development and progression via the miR-3163/SCIN axis by regulating NF-κB signaling, thus providing a potential target for NPC treatment.

MBTPS2 exacerbates albuminuria in streptozotocin-induced type I diabetic nephropathy by promoting endoplasmic reticulum stress-mediated renal damage.

BACKGROUND: The membrane-bound transcription factor protease site 2 (MBTPS2) is an intramembranous metalloprotease involved in the regulation of ER stress response, however, whether it is associated with DN is unknown. RESULTS: We report that MBTPS2 expression is upregulated in the renal cortex of diabetic mice induced by streptozotocin (STZ), a murine model of insulinopenic type 1 DN. Functionally, in vivo, MBTPS2 overexpression exacerbates and its knockdown attenuates albuminuria, which indicate a detrimental role of MBTPS2 played in albuminuria development in DN mice. We further show that MBTPS2 promotes ER stress and renal damage in DN mice, and that reducing ER stress via a chemical chaperone 4-phenylbutyric acid (4-PBA) markedly rescues MBTPS2-exacerbated renal damage and albuminuria severity. CONCLUSIONS: Collectively, our study associates the function of MBTPS2 in DN albuminuria with ER stress regulation, thus underscoring the notorious role of maladaptive ER response in influencing DN albuminuria.

Role of endoplasmic reticulum stress in hepatic glucose and lipid metabolism and therapeutic strategies for metabolic liver disease.

The endoplasmic reticulum is the most abundant membrane organelle in eukaryotic cells. It is an important site of membrane and secretory protein folding and glycolipid synthesis and transport, and it is responsible for regulating intracellular calcium homeostasis. When the load of protein synthesis and folding exceeds the processing capacity of the endoplasmic reticulum, the excessive accumulation of misfolded proteins leads to endoplasmic reticulum stress and activates the cellular unfolded protein response. Hepatocytes contain an abundance of smooth and rough endoplasmic reticulum, which can sense changes in various nutritional metabolic and external stimuli and mediate the regulation of glucose and lipid metabolism by activating the unfolded protein response signaling pathways. Endoplasmic reticulum stress plays a very important role in metabolic regulation and in the occurrence and development of liver diseases. This review summarizes the recent research progress on the unfolded protein response and hepatic glucose and lipid metabolism and discusses the mechanism linking endoplasmic reticulum stress with glucose and lipid metabolism disorders and related metabolic liver diseases to improve the understanding of the molecular pathological basis of major chronic diseases such as obesity, type II diabetes and nonalcoholic fatty liver disease.

mTOR and the differentiation of mesenchymal stem cells.

The mammalian target of rapamycin (mTOR), an evolutionarily conserved serine-threonine protein kinase, belongs to the phosphoinositide 3-kinase (PI3K)-related kinase family, which contains a lipid kinase-like domain within their C-terminal region. Recent studies have revealed that mTOR as a critical intracellular molecule can sense the extracellular energy status and regulate the cell growth and proliferation in a variety of cells and tissues. This review summarizes our current understanding about the effects of mTOR on cell differentiation and tissue development, with an emphasis on the lineage determination of mesenchymal stem cells. mTOR can promote adipogenesis in white adipocytes, brown adipocytes, and muscle satellite cells, while rapamycin inhibits the adipogenic function of mTOR. mTOR signaling may function to affect osteoblast proliferation and differentiation, however, rapamycin has been reported to either inhibit or promote osteogenesis. Although the precise mechanism remains unclear, mTOR is indispensable for myogenesis. Depending on the cell type, rapamycin has been reported to inhibit, promote, or have no effect on myogenesis.

Effects of Des-acyl Ghrelin on Insulin Sensitivity and Macrophage Polarization in Adipose Tissue.

BACKGROUND AND OBJECTIVES: Obesity is the accumulation of adipose tissue caused by excess energy in the body, accompanied by long-term chronic low-grade inflammation of adipose tissue. More than 50% of interstitial cells in adipose tissue are macrophages, which produce cytokines closely related to insulin resistance. Macrophage biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2 (anti-inflammatory). This study aimed to investigate the effect of gastric hormone des-acyl ghrelin (DAG) on the polarization phenotype of macrophages and elucidate the role of macrophages in adipose tissue inflammation and insulin sensitivity and its molecular mechanism. METHODS: Mice were subcutaneously administrated with DAG in osmotic minipumps. The mice were fed a normal diet or a high-fat diet (HFD). Different macrophage markers were detected by real-time revere transcription polymerase chain reaction. RESULTS: Exogenous administration of DAG significantly inhibited the increase of adipocyte volume caused by HFD and reduced the number of rosette-like structures in adipose tissue. HFD in the control group significantly increased M1 macrophage markers, tumor necrosis factor α (TNFα), and inducible NO synthase (iNOS). However, these increases were reduced or even reversed after DAG administration in vitro. The M2 markers, macrophage galactose type C-type Lectin-1 (MGL1), arginase 1 (Arg1), and macrophage mannose receptor 1 (MRC1) were decreased by HFD, and the downward trend was inhibited or reversed after DAG administration. Although Arg1 was elevated after HFD, the fold increase after DAG administration in vitro was much greater than that in the control group. CONCLUSION: DAG inhibits adipose tissue inflammation caused by HFD, reduces infiltration of macrophages in adipose tissue, and promotes polarization of macrophages to M2, thus alleviating obesity and improving insulin sensitivity.