Obesity is a growing chronic health problem worldwide. Studies about acupuncture for obesity treatment are many. But there are some doubts about the effectiveness of acupuncture versus sham ...acupuncture in treating obesity due to its lack of medical evidence. Therefore, the aim of this study is to assess the efficacy of acupuncture for obesity treatment and provide clinic evidence. Four English databases (PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials) and four Chinese databases (China National Knowledge Infrastructure, Chinese BioMedical Database, Chinese Scientific Journal Database and Wan-Fang Data) were searched from their receptions to August 2019. Randomized controlled trials (RCTs) using the comparison between acupuncture and sham acupuncture to treat simple obesity were included. The primary outcome of body mass index (BMI) would be used to measure the effect of acupuncture on obesity. According to the trial data extraction form based on the Cochrane Handbook, two reviewers separately extracted the data. Risk of bias of the RCTs was assessed by the Cochrane Risk of Bias Tool. The study included 8 RCTs with 403 patients. When compared with sham acupuncture, acupuncture showed obviously effect in BMI reduction (MD=1.0kg/m2, 95% CI=0.6 to 1.4, P<0.001). There was also significant reduction in body weight (MD=1.85kg, 95%CI=0.82 to 2.88, p<0.001), WC (MD=0.97cm, 95%CI=0.24 to 1.71, p=0.01) and body fat mass percentage (MD=1.01, 95%CI=0.25 to 1.77, p<0.05). However, WHR (MD=0.01, 95%CI=0 to 0.03, p>0.05) was not statistically and significantly different between the acupuncture and control groups. Adverse effects were reported in 3 studies. The review suggests that acupuncture is an effective therapy for simple obesity rather than a placebo effect. This potential benefit needs to be further evaluated by longer-term and more rigorous RCTs.
Objectives
Hypothalamic dysfunction leads to glucose metabolic imbalance; however, the mechanisms still need clarification. Our current study was to explore the role of hypothalamic Hnscr in glucose ...metabolism.
Materials and Methods
Using Hnscr knockout or htNSC‐specific Hnscr overexpression mice, we evaluated the effects of Hnscr on glucose metabolism through GTTs, ITTs, serum indicator measurements, etc. Immunofluorescence staining and Western blotting were performed to test inflammation levels and insulin signalling in hypothalamus. Conditioned medium intervene were used to investigate the effects of htNSCs on neuronal cell line. We also detected the glucose metabolism of mice with htNSCs implantation.
Results
Hnscr expression decreased in the hypothalamus after high‐fat diet feed. Hnscr‐null mice displayed aggravated systematic insulin resistance, while mice with htNSC‐specific Hnscr overexpression had the opposite phenotype. Notably, Hnscr‐null mice had increased NF‐κB signal in htNSCs, along with enhanced inflammation and damaged insulin signal in neurons located in arcuate nucleus of hypothalamus. The secretions, including sEVs, of Hnscr‐deficient htNSCs mediated the detrimental effects on the CNS cell line. Locally implantation with Hnscr‐depleted htNSCs disrupted glucose homeostasis.
Conclusions
This study demonstrated that decreased Hnscr in htNSCs led to systematic glucose imbalance through activating NF‐κB signal and dampening insulin signal in hypothalamic neurons.
We discovered the lncRNA Hnscr participated in the regulation of high fat diet‐induced insulin resistance. Hnscr knockout aggravated diet‐induced insulin resistance. Mechanistically, loss of Hnscr reduced trim56 level, leading to NF‐κB activation in htNSCs. Hnscr‐deficient htNSCs also contributed to increased inflammation and insulin resistance in neurons finally damaged systematic glucose balance.
Aim： The inhaled anesthetic sevoflurane may induce cognitive impairment in both animals and humans. Previous study has shown that sevoflurane triggers ER stress and may lead to apoptosis in rat ...hippocampal neurons. In this study, we examined whether sevoflurane caused autophagy and its contributions to sevoflurane induced neuronal cell injury. Methods： H4 human neuroglioma cells were exposed to 4.1% sevoflurane for 6 h. Cell viability and apoptosis ratio were assessed using a CCK8 kit and flow cytometry, respectively. Autophagosomes in the cells were detected using GFP-LC3 plasmid transfection or transmission electronic microscopy. The expression of LC3B, p62/SQSTM, C/EBP homologous protein （CHOP） and glucose-related protein 78 （GRP78） was assessed with Western blotting. Results： Sevoflurane treatment induced apoptosis and markedly increased the LC3-11 level and GFP-LC3 puncta number, decreased p62 expression in H4 cells. Activation of autophagy by rapamycin （1 pmol/L） significantly reduced sevoflurane-induced apoptosis and increased cell viability, whereas inhibition of autophagy with 3-MA （5 mmol/L） caused the opposite effects. Furthermore, sevoflurane treatment markedly increased the expression of CHOP and GRP78, two hallmark proteins of ER stress. Inhibition of ER stress by 4-phenylbutyrate （500 pmol/L） abrogated sevoflurane-induced autophagy and apoptosis, and improved the viability. Moreover, sevoflurane-stimulated expression of CHOP and GRP78 was inhibited by rapamycin, but further enhanced by 3-MA. Conclusion： Sevoflurane treatment induces ER stress and activates autophagy, which antagonizes sevoflurane-induced apoptosis in H4 human neuroglioma cells. The results suggest that autophagy may be a potential therapeutic target in preventing sevoflurane-induced neu rotoxicity.
Differences of genotypes between male and female have been studied in Parkinson's disease (PD), but limited research has focused on the comparison between sexes with LRRK2 G2385 variant.
The aim of ...this study was to explore sex effects in the same genetic subtype and role of leucine-rich repeat kinase 2 (LRRK2) G2385R variants in the same sex in PD.
613 PD patients were recruited from the Movement Disorders Clinic in Ruijin Hospital. We did not include healthy controls in this study. The data collected includes demographic information, disease history, scores of motor and non-motor symptoms scales, midbrain transcranial sonography and DNA. Binary logistic regression analysis was performed to evaluate the association between clinical features and sex in LRRK2 G2385R carriers and non-carriers, as well as the association between the clinical features and LRRK2 G2385R variants in male and female sex.
Sex distribution is similar in LRRK2 G2385R carriers and non-carriers. In male sex, LRRK2 G2385R carriers showed lower risk in cognitive impairment compared with non-carriers (OR = 0.301, p = 0.003, 95%CI 0.135-0.668). In female sex, LRRK2 G2385R carriers showed lower risk in autonomic dysfunction compared with non-carrier (OR = 0.401, p = 0.040, 95%CI 0.167-0.960). In LRRK2 G2385R non-carriers, female sex showed lower risk of impairment in activity of daily living (OR = 0.610, p = 0.021, 95%CI 0.400-0.928), excessive daytime sleepiness (OR = 0.555, p = 0.007, 95%CI 0.361-0.853), substantia nigra hyperechogenicity (OR = 0.448, p = 0.019, 95%CI 0.228-0.878), autonomic dysfunction frequency (OR = 0.626, p = 0.016, 95%CI 0.428-0.917) and higher risk in mood disorders (OR = 1.691, p = 0.022, 95%CI 1.078-2.654) compared with male. In LRRK2 G2385R carriers, female sex showed a lower risk of autonomic dysfunction (OR = 0.294, p = 0.024, 95%CI 0.102-0.849) compared with male.
In contrast to male PD patients, a more benign disease course was observed in female in both LRRK2 G2385R carriers and non-carriers. However, sex differences were less notable in PD with LRRK2 G2385R variants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
New therapeutic targets and drugs are urgently needed to halt the fibrosing process in idiopathic pulmonary fibrosis (IPF). SHR‐1906 is a novel fully humanized monoclonal antibody against the ...connective tissue growth factor, which plays an essential role in the genesis of IPF. We assessed the safety, tolerability, pharmacokinetics (PKs), and immunogenicity of single dose SHR‐1906 in healthy participants. This was a randomized, double‐blind, placebo‐controlled, dose‐escalation, phase I study. Twelve healthy participants for each dose level were enrolled to receive single ascending doses of SHR‐1906 intravenously (1.5, 6, 12, 20, 30, and 45 mg/kg) or placebo and followed for 71 days. The primary end points were safety and tolerability. Treatment‐related treatment‐emergent adverse events occurred in 25 participants (46.3%) in the SHR‐1906 group and 11 (61.1%) in the placebo group. No serious adverse events occurred. Over the dose range investigated, the geometric mean clearance was 0.14–0.63 mL/h/kg, the geometric mean volume of distribution at steady‐state was 47.4–75.5 mL/kg, and the terminal elimination half‐life was 51.9–349 h. SHR‐1906 showed nonlinear PKs. The peak concentration increased in a dose‐proportional manner, whereas the area under the concentration–time curve showed a greater than dose‐proportional increase. Anti‐drug antibodies of SHR‐1906 were detected in nine of 54 participants (16.7%). A single dose of SHR‐1906 up to 45 mg/kg demonstrated a favorable tolerability profile in healthy participants. The PKs and immunogenicity of SHR‐1906 were evaluated, supporting further clinical development.
Branched-chain amino acids (BCAAs) provide nutrient signals for cell survival and growth. How BCAAs affect CD8+ T cell functions remains unexplored. Herein, we report that accumulation of BCAAs in ...CD8+ T cells due to the impairment of BCAA degradation in 2C-type serine/threonine protein phosphatase (PP2Cm)-deficient mice leads to hyper-activity of CD8+ T cells and enhanced anti-tumor immunity. CD8+ T cells from PP2Cm−/− mice upregulate glucose transporter Glut1 expression in a FoxO1-dependent manner with more glucose uptake, as well as increased glycolysis and oxidative phosphorylation. Moreover, BCAA supplementation recapitulates CD8+ T cell hyper-functions and synergizes with anti-PD-1, in line with a better prognosis in NSCLC patients containing high BCAAs when receiving anti-PD-1 therapy. Our finding thus reveals that accumulation of BCAAs promotes effector function and anti-tumor immunity of CD8+ T cells through reprogramming glucose metabolism, making BCAAs alternative supplementary components to increase the clinical efficacy of anti-PD-1 immunotherapy against tumors.
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•CD8+ T cells from PP2Cm−/− mice exhibit high BCAA content and enhanced functionality•BCAA accumulation in CD8+ T cells promotes Glut1 expression and glucose uptake•BCAA supplementation magnifies CD8+ T cell effector with altered glucose metabolism•BCAAs synergize with anti-PD-1 regimen in anti-tumor immunity
Yao et al. report that BCAA accumulation in CD8+ T cells upregulates Glut1 expression and increases glucose uptake, leading to reprogramming CD8+ T cell metabolic features prone to anti-tumor immunity. BCAAs might become alternative supplementary components to increase the clinical efficacy of immune checkpoint inhibitors.
The heterogeneous oxidation of isoprene (C
5
H
8
) by metal-oxide particles, such as the typical mineral aerosols TiO
2
, plays an important role in the isoprene atmospheric chemistry. However, the ...underlying mechanism of C
5
H
8
oxidation remains elusive owing to the complexities of aerosol surfaces and reaction channels. Herein, we report the gas-phase reactions of Ti
x
O
y
+
(
x
= 1-7,
y
= 1-14) cations with isoprene by using mass spectrometry and density functional theory (DFT) calculations. Five types of reaction channels were observed: association, hydrogen atom transfer (HAT), C-C bond cleavage, combined oxygen atom transfer (OAT) and HAT and combined OAT and C-C bond cleavage. It is noteworthy that formaldehyde is known as the major oxidation product of isoprene/hydroxyl radicals in the atmosphere. In addition, CO has not been observed in the reactions of isoprene with gas-phase ions. Therefore, the reaction mechanisms of CH
2
O and CO generation observed in Ti
2
O
5
+
/C
5
H
8
and Ti
4
O
8
+
/C
5
H
8
systems were further investigated by DFT calculations, and the calculated results are in agreement with the experimental observations. In these two reactions, both Ti and O atoms can be the adsorption sites for C
5
H
8
. The reaction channels and mechanistic information gained in these gas-phase model reactions may offer fundamental insights relevant to the corresponding oxidation processes over titanium oxide aerosols in the atmosphere.
The reactions of isoprene with titanium oxide cluster cations were investigated. Five reaction types were classified, and several neutral oxygenated products, including CO, CH
2
O (formaldehyde), C
3
H
4
O, C
5
H
6
O, C
5
H
7
O and so on, were generated.
MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, and survival and may be useful for acute myeloid leukemia (AML) diagnosis and prognosis. In this study, we defined a ...novel miRNA, hsa-miR-12462, through small RNA sequencing of the bone marrow (BM) cells from 128 AML patients. Overexpression of hsa-miR-12462 in AML cells (U937 and HL-60) significantly decreased their growth rate when compared with those of the wild-type and MOCK controls. In a xenograft mouse model, tumor weight and size in the mice bearing the U937 cells with hsa-miR-12462 overexpression were significantly reduced when compared with those bearing the mock cells. The AML cells overexpressing hsa-miR-12462 had increased sensitivity to cytarabine chemotherapy. Combining the data from the MiRDB, an online microRNA database ( http://mirdb.org ), with the RNA-sequencing results, SLC9A1 was predicted to be one of the targets of hsa-miR-12462. hsa-miR-12462 was further confirmed to bind exclusively to the 3'UTR of SLC9A1 in U937 cells, leading to downregulation of SLC9A1. In summary, a higher level of hsa-miR-12462 in AML cells is associated with increased sensitivity to cytarabine chemotherapy via downregulation of SLC9A1.
This study investigated the effects of different bulking agents (i.e., sawdust, wheat straw, rice straw, and corncob) on bacterial structure and functions for organic degradation during food waste ...in-situ rapid biological reduction (IRBR) inoculated with microbial agent. Results showed that the highest organic degradation (409.5 g/kg total solid) and volatile solids removal efficiency (41.0%) were achieved when wheat straw was used, largely because the degradation of readily degradable substrates and cellulose was promoted by this bulking agent. Compared with other three bulking agents, the utilization of wheat straw was conducive to construct a more suitable environmental condition (moisture content of 18.0–28.2%, pH of 4.91–5.87) for organic degradation during IRBR process, by virtue of its excellent structural and physiochemical properties. Microbial community analysis suggested that the high-moisture environment in rice straw treatment promoted the growth of
Staphylococcus
and inhibited the activity of the inoculum. By contrast, lowest bacterial richness was observed in corncob treatment due to the faster water loss. Compared with these two bulking agents, sawdust and wheat straw treatment led to a more stable bacterial community structure, and the inoculated
Bacillus
gradually became the dominant genus (36.6–57.8%) in wheat straw treatment. Predicted metagenomics analysis showed that wheat straw treatment exhibited the highest carbohydrate metabolism activity which improved the pyruvate, amino sugar and nucleotide sugar metabolism, and thereby promoted the organic degradation and humic substrate production. These results indicated that wheat straw was a more desirable bulking agent, and revealed the potential microbial organics degradation mechanism in IRBR process.
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