Second messenger 2'3'-cyclic GMP-AMP (2'3'-cGAMP): the cell autonomous and non-autonomous roles in cancer progression.

Cytosolic double-stranded DNA (dsDNA) is frequently accumulated in cancer cells due to chromosomal instability or exogenous stimulation. Cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, which is activated upon binding to dsDNA to synthesize the crucial second messenger 2'3'-cyclic GMP-AMP (2'3'-cGAMP) that in turn triggers stimulator of interferon genes (STING) signaling. The canonical role of cGAS-cGAMP-STING pathway is essential for innate immunity and viral defense. Recent emerging evidence indicates that 2'3'-cGAMP plays an important role in cancer progression via cell autonomous and non-autonomous mechanisms. Beyond its role as an intracellular messenger to activate STING signaling in tumor cells, 2'3'-cGAMP also serves as an immunotransmitter produced by cancer cells to modulate the functions of non-tumor cells especially immune cells in the tumor microenvironment by activating STING signaling. In this review, we summarize the synthesis, transmission, and degradation of 2'3'-cGAMP as well as the dual functions of 2'3'-cGAMP in a STING-dependent manner. Additionally, we discuss the potential therapeutic strategies that harness the cGAMP-mediated antitumor response for cancer therapy.

Difference of carrier dynamics in a semiconductor saturable absorber mirror with and without B+ ion-implantation.

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

[Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway].

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

Imparting CO2 Electroreduction Auxiliary for Integrated Morphology Tuning and Performance Boosting in a Porphyrin-based Covalent Organic Framework.

Strategies that enable simultaneous morphology-tuning and electroreduction performance boosting are much desired for the exploration of covalent organic frameworks in efficient CO2 electroreduction. Herein, a kind of functionalizing exfoliation agent has been selected to simultaneously modify and exfoliate bulk COFs into functional nanosheets and investigate their CO2 electroreduction performance. The obtained nanosheets (Cu-Tph-COF-Dct) with large-scale (≈1.0 µm) and ultrathin (≈3.8 nm) morphology enable a superior FECH4 (≈80 %) (almost doubly enhanced than bare COF) with large current-density (-220.0 mA cm-2 ) at -0.9 V. The boosted performance can be ascribed to the immobilized functionalizing exfoliation agent (Dct groups) with integrated amino and triazine groups that strengthen CO2 absorption/activation, stabilize intermediates and enrich the CO concentration around the Cu active sites as revealed by DFT calculations. The point-to-point functionalization strategy for modularly assembling Dct-functionalized COF catalyst for CO2 electroreduction will open up the attractive possibility of developing COFs as efficient CO2 RR electrocatalysts.

The Syntheses, Structures, Fluorescence Properties and Biological Activity of two Novel Zinc(II) Complexes Controlled by the Tripodal Imidazole Ligand.

Two new zinc complexes, namely Zn(L(1))ClCH2NO(1) and {Zn(L(2))CH2NO}n▪N(CH3)3▪ClO4(2) (L(1) = 3,5-di(1H-imidazol-1-yl)pyridine L(2) = 1,3,5-tris(1-imidazolyl) benzene), have been synthesized, and characterized by IR spectra, elemental analysis, and a single crystal X-ray diffraction. Fluorescence spectroscopy indicated that two complexes presented strong DNA binding affinity constants to fish sperm DNA (FS-DNA). Gel electrophoresis assay demonstrated the ability of the complex to cleave the HL-60 DNA. Apoptotic study showed the complex exhibited significant cancer cell(KB) inhibitory rate.

The Relationship between Serum Osteocalcin Concentration and Glucose and Lipid Metabolism in Patients with Type 2 Diabetes Mellitus ­ The Role of Osteocalcin in Energy Metabolism.

BACKGROUND: Recent animal studies have found that the osteocalcin secreted by osteoblasts could participate in glucose and lipid metabolism. Our study aimed to investigate the relationship between serum osteocalcin concentration and glucose and lipid metabolism in patients with type 2 diabetes mellitus. METHODS: 985 patients with type 2 diabetes were divided into the male group (n = 495) and the postmenopausal female group (n = 490). The average ages were 54.42 ± 10.535 and 64.93 ± 9.277, respectively. We collected the parameters of age, duration, fasting plasma glucose, HbA1c, fasting insulin, fasting C peptide, blood lipid, 25 (OH) VD3, parathyroid hormone (PTH), Alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), ß-C-terminal telopeptide of type I collagen (ß-CTx), osteocalcin, HOMA-IR, HOMA-ß, body mass index (BMI), and waist-to-hip ratio (WHR). The relationship of osteocalcin and these parameters were analyzed by Pearson/Spearman correlation analysis and stepwise multiple regression analysis. RESULTS: Osteocalcin was negatively correlated with HbA1c (p < 0.05) and it was also an independent relevant factor affecting HbA1c in both groups. Osteocalcin was positively correlated with HOMA-ß and it was an independent relevant factor affecting HOMA-ß in male group (p < 0.01). CONCLUSIONS: These findings indicate the association between serum osteocalcin and glucose metabolism and beta cell function. No relationship was found between osteocalcin and insulin resistance and lipid metabolism in type 2 diabetes.

Mechanisms of gastrointestinal toxicity in neuromyelitis optica spectrum disorder patients treated with mycophenolate mofetil: insights from a mouse model and human study.

Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial ß-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The ß-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF. IMPORTANCE: Neuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

[Multi-channel in vivo recording technique: microdrive array fabrication and electrode implantation in mice].

Here we describe and illustrate our methods for multi-channel in vivo recording in mice, including the fabrication of the microdrive array and the surgical procedure for implanting electrodes. The multi-channel microdrive is fabricated from printed circuit board base, screws, nuts and clamping screws. Rotation of the screw drives both the nut and the attached electrodes to move forward simultaneously. Each full turn of the screw corresponds to 280 µm in depth penetration. The recording electrodes are self-made tetrodes consisting 4 wires (13 µm in diameter). The major steps of headstage fabrication include: tetrode making, microdrive construction, headstage assembling and tetrode plating. The finished headstage is suitable for multi-channel recording in freely moving rodents with the modest weight and the adjustable number of recording electrodes. Additionally, the recording site is allowed to be manipulated after implantation at any time. In the latter part of this paper, we introduce the procedure of the implant surgery to record in bilateral hippocampus in mice. Using these headstages, we simultaneously recorded population activity in bilateral CA1 in freely behaving mice.

A Droplet Digital PCR-Based Approach for Quantitative Analysis of the Adulteration of Atlantic Salmon with Rainbow Trout.

Low-cost fish species are often used to adulterate or substitute for Atlantic salmon products, posing a serious threat to market order and public health. Hence, reliable techniques are urgently needed to detect Atlantic salmon adulteration. In this study, a precise method for identifying and quantifying adulterated Atlantic salmon with rainbow trout based on droplet digital PCR (ddPCR) testing was developed. Species-specific primers and probes were designed targeting the single-copy nuclear gene myoglobin of two salmonids. A quantitative formula for calculating the mass fraction of adulterated Atlantic salmon with rainbow trout was established based on a one-step conversion strategy, in which the DNA copy number ratios were directly transformed to meat mass fractions by introducing a fixed constant (the transfer coefficient). The dynamic range of the established ddPCR method was from 1% to 90%, with a limit of detection (LOD) of 0.2% and a limit of quantification (LOQ) of 0.8% for rainbow trout in Atlantic salmon, respectively. The quantification method demonstrated an acceptable level of repeatability and reproducibility, as the values of the relative standard deviation (RSD) for the tested meat mixtures with the known fractions were all less than 5%. Thermal and freezing treatments, as well as adding food additives within the recommended dosage limits, had no significant effect on the quantification accuracy. The method was successfully applied to detect rainbow trout adulteration in commercial raw and processed Atlantic salmon products. In comparison to real-time quantitative PCR (qPCR) testing, the established ddPCR method exhibited a higher level of stability and accuracy. Overall, the ddPCR-based quantitative method exhibited high levels of accuracy, stability, sensitivity, and practicability, suitable for applications in the routine surveillance and quality assurance of salmon products.

Comparative Analysis of Cd Uptake and Tolerance in Two Mangrove Species (Avicennia marina and Rhizophora stylosa) with Distinct Apoplast Barriers.

Mangrove plants demonstrate an impressive ability to tolerate environmental pollutants, but excessive levels of cadmium (Cd) can impede their growth. Few studies have focused on the effects of apoplast barriers on heavy metal tolerance in mangrove plants. To investigate the uptake and tolerance of Cd in mangrove plants, two distinct mangrove species, Avicennia marina and Rhizophora stylosa, are characterized by unique apoplast barriers. The results showed that both mangrove plants exhibited the highest concentration of Cd2+ in roots, followed by stems and leaves. The Cd2+ concentrations in all organs of R. stylosa consistently exhibited lower levels than those of A. marina. In addition, R. stylosa displayed a reduced concentration of apparent PTS and a smaller percentage of bypass flow when compared to A. marina. The root anatomical characteristics indicated that Cd treatment significantly enhanced endodermal suberization in both A. marina and R. stylosa roots, and R. stylosa exhibited a higher degree of suberization. The transcriptomic analysis of R. stylosa and A. marina roots under Cd stress revealed 23 candidate genes involved in suberin biosynthesis and 8 candidate genes associated with suberin regulation. This study has confirmed that suberized apoplastic barriers play a crucial role in preventing Cd from entering mangrove roots.

Inhibition of the NF-κB signaling pathway affects gonadal differentiation and leads to male bias in Paramisgurnus dabryanus.

In recent years, sex-controlled breeding has emerged as an effective strategy to enhance the yields of economic animals with different growth characteristics, while increasing the economic benefits of aquaculture. It is known that the NF-κB pathway participates in gonadal differentiation and reproduction. Therefore, we used the large-scale loach as a research model for the present study and selected an effective inhibitor of the NF-κB signaling pathway (QNZ). This, to investigates the impacts of the NF-κB signaling pathway on gonadal differentiation during a critical period of gonad development and after maturation. Simultaneously, the sex ratio bias and the reproductive capacities of adult fish were analyzed. Our results indicated that the inhibition of the NF-κB signaling pathway influenced the expression of genes related to gonad development, regulated the gene expression related to the brain-gonad-liver axis of juvenile loaches, and finally impacted the gonadal differentiation of the large-scale loach and promoted a male-biased sex ratio. Meanwhile, high QNZ concentrations affected the reproductive abilities of adult loaches and inhibited the growth performance of offspring. Thus, our results deepened the exploration of sex control in fish and provided a certain research basis for the sustainable development of the aquaculture industry.

Xanthine dehydrogenase rewires metabolism and the survival of nutrient deprived lung adenocarcinoma cells by facilitating UPR and autophagic degradation.

Xanthine dehydrogenase (XDH) is the rate-limiting enzyme in purine catabolism by converting hypoxanthine to xanthine and xanthine to uric acid. The altered expression and activity of XDH are associated with the development and prognosis of multiple types of cancer, while its role in lung adenocarcinoma (LUAD) remains unknown. Herein, we demonstrated that XDH was highly expressed in LUAD and was significantly correlated with poor prognosis. Though inhibition of XDH displayed moderate effect on the viability of LUAD cells cultured in the complete medium, it significantly attenuated the survival of starved cells. Similar results were obtained in XDH-knockout cells. Nucleosides supplementation rescued the survival of starved LUAD cells upon XDH inhibition, while inhibition of purine nucleoside phosphorylase abrogated the process, indicating that nucleoside degradation is required for the XDH-mediated survival of LUAD cells. Accordingly, metabolic flux revealed that ribose derived from nucleoside fueled key carbon metabolic pathways to sustain the survival of starved LUAD cells. Mechanistically, down-regulation of XDH suppressed unfolded protein response (UPR) and autophagic flux in starved LUAD cells. Inhibition of XDH decreased the level of amino acids produced by autophagic degradation, which was accompanied with down-regulation of mTORC1 signaling. Supplementation of amino acids including glutamine or glutamate rescued the survival of starved LUAD cells upon knockout or inhibition of XDH. Finally, XDH inhibitors potentiated the anti-cancer activity of 2-deoxy-D-glucose that induced UPR and/or autophagy in vitro and in vivo. In summary, XDH plays a crucial role in the survival of starved LUAD cells and targeting XDH may improve the efficacy of drugs that induce UPR and autophagy in the therapy of LUAD.

Inhibition of Structural Transformation and Surface Lattice Oxygen Activity for Excellent Stability Li-Rich Mn-Based Layered Oxides.

Li-rich Mn-based layered oxides (LLOs) are one of the most promising cathode materials, which have exceptional anionic redox activity and a capacity that surpasses 250 mA h/g. However, the change from a layered structure to a spinel structure and unstable anionic redox are accompanied by voltage attenuation, poor rate performance, and problematic capacity. The technique of stabilizing the crystal structure and reducing the surface oxygen activity is proposed in this paper. A coating layer and highly concentrated oxygen vacancies are developed on the material's surface, according to scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. In situ EIS shows that structural transformation and oxygen release are inhibited during the first charge and discharge. Optimized 3@LRMA has an average attenuation voltage of 0.55 mV per cycle (vs 1.7 mV) and a capacity retention rate of 93.4% after 200 cycles (vs 52.8%). Postmortem analysis indicates that the successful doping of Al ions into the crystal structure effectively inhibits the structural alteration of the cycling process. The addition of oxygen vacancies reduces the surface lattice's redox activity. Additionally, surface structure deterioration is successfully halted by N- and Cl-doped carbon coating. This finding highlights the significance of lowering the surface lattice oxygen activity and preventing structural alteration, and it offers a workable solution to increase the LLO stability.

Nucleus-Targeting Nanoplatform Based on Dendritic Peptide for Precise Photothermal Therapy.

Photothermal therapy directly acting on the nucleus is a potential anti-tumor treatment with higher killing efficiency. However, in practical applications, it is often difficult to achieve precise nuclear photothermal therapy because agents are difficult to accurately anchor to the nucleus. Therefore, it is urgent to develop a nanoheater that can accurately locate the nucleus. Here, we designed an amphiphilic arginine-rich dendritic peptide (RDP) with the sequence CRRK(RRCG(Fmoc))2, and prepared a nucleus-targeting nanoplatform RDP/I by encapsulating the photothermal agent IR780 in RDP for precise photothermal therapy of the tumor nucleus. The hydrophobic group Fmoc of the dendritic peptide provides strong hydrophobic force to firmly encapsulate IR780, which improves the solubility and stability of IR780. Moreover, the arginine-rich structure facilitates cellular uptake of RDP/I and endows it with the ability to quickly anchor to the nucleus. The nucleus-targeting nanoplatform RDP/I showed efficient nuclear enrichment ability and a significant tumor inhibition effect.

Clinical and molecular characterization of 10 Chinese children with congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency.

BACKGROUND: The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of non-classical 21-hydroxylase deficiency. For this study, we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature, which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal hyperplasia. METHODS: Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed. We examined the effects of gene mutations on protease activity and constructed three-dimensional structure prediction models of proteins. RESULTS: We describe 10 patients with 11beta-hydroxylase gene mutations (n = 5, 46,XY; n = 5, 46,XX), with 10 novel mutations were reported. Female patients received treatment at an early stage, with an average age of 2.08 ± 1.66 years, whereas male patients received treatment significantly later, at an average age of 9.77 ± 3.62 years. The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C > T. All mutations lead to spatial conformational changes that affect protein stability. CONCLUSIONS: Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations. Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations. The correlation between genotype and phenotype needs further study. Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.

Fecal Microbiota Transplantation from Aged Mice Render Recipient Mice Resistant to MPTP-Induced Nigrostriatal Degeneration Via a Neurogenesis-Dependent but Inflammation-Independent Manner.

Accumulating data support a crucial role of gut microbiota in Parkinson's disease (PD). However, gut microbiota vary with age and, thus, will affect PD in an age-dependent, but unknown manner. We examined the effects of fecal microbiota transplantation (FMT) pretreatment, using fecal microbiota from young (7 weeks) or aged mice (23 months), on MPTP-induced PD model. Motor function, pathological changes, striatal neurotransmitters, neuroinflammation, gut inflammation and gut permeability were examined. Gut microbiota composition and metabolites, namely short-chain fatty acids (SCFAs), were analyzed. Neurogenesis was also evaluated by measuring the number of doublecortin-positive (DCX+) neurons and Ki67-positive (Ki67+) cells in the hippocampus. Expression of Cd133 mRNA, a cellular stemness marker, in the hippocampus was also examined. Mice who received FMT from young mice showed MPTP-induced motor dysfunction, and reduction of striatal dopamine (DA), dopaminergic neurons and striatal tyrosine hydroxylase (TH) levels. Interestingly and unexpectedly, mice that received FMT from aged mice showed recovery of motor function and rescue of dopaminergic neurons and striatal 5-hydroxytryptamine (5-HT), as well as decreased DA metabolism after MPTP challenge. Further, they showed improved metabolic profiling and a decreased amount of fecal SCFAs. High-throughput sequencing revealed that FMT remarkably reshaped the gut microbiota of recipient mice. For instance, levels of genus Akkermansia and Candidatus Saccharimonas were elevated in fecal samples of recipient mice receiving aged microbiota (AM + MPTP mice) than YM + MPTP mice. Intriguingly, both young microbiota and aged microbiota had no effect on neuroinflammation, gut inflammation or gut permeability. Notably, AM + MPTP mice showed a marked increase in DCX+ neurons, as well as Ki67+ cells and Cd133 expression in the hippocampal dentate gyrus (DG) compared to YM + MPTP mice. These results suggest that FMT from aged mice augments neurogenesis, improves motor function and restores dopaminergic neurons and neurotransmitters in PD model mice, possibly through increasing neurogenesis.

Gastric Cancer Screening Methods: A Comparative Study of the Chinese New Gastric Cancer Screening Score and Kyoto Classification of Gastritis.

Objective: To evaluate the Chinese new gastric cancer screening score (i.e., Li's score) and Kyoto Classification of Gastritis for screening gastric cancer. Methods: A total of 702 patients were scored using the two scoring methods. Gastric atrophy, intestinal metaplasia, and gastric cancer (including early gastric cancer) were compared between the two scoring methods. The area under the ROC curve, sensitivity, and specificity of the two scoring methods were evaluated. Results: Both of the two scoring methods found that gastric atrophy, intestinal metaplasia, and gastric cancer (including early gastric cancer) were all significantly higher in the medium-risk and high-risk group patients than those in the low-risk group patients. According to the Kyoto Classification of Gastritis, patients in the high-risk group had more gastric atrophy, intestinal metaplasia, and gastric cancer than those in the medium-risk group patients. Gastric atrophy, intestinal metaplasia, and gastric cancer in the low-risk and medium-risk group patients evaluated by the Li score were all significantly higher than those in patients with corresponding risk level evaluated by Kyoto Classification of Gastritis, respectively. The area under the ROC curve of the Li score was 0.702, and the sensitivity and specificity were 57.6% and 85.3%, respectively. The area under the ROC curve of the Kyoto Classification of Gastritis was 0.826, and the sensitivity and specificity were 75.4% and 83.6%, respectively. Conclusion: Both Li's score and Kyoto Classification of Gastritis showed good screening value for gastric cancer, but Kyoto Classification of Gastritis was more sensitive than the Li score.

[The effect of fasudil via Rho/ROCK signaling pathway on the inflammation and fibrosis in human mesangial cells in high glucose medium].

OBJECTIVE: To study the effect of fasudil on inhibiting the Rho/ROCK signaling pathway under high glucose in human mesangial cells (HMCs) inflammation and fibrosis. METHODS: Synchronized HMCs were divided into following groups: (1) Normal glucose control group (NG, 5.5 mmol/L glucose); (2) High glucose group (HG, 30 mmol/L glucose); (3) Mannitol group (Man, 5.5 mmol/L glucose + 24.5 mmol/L mannitol); (4) High glucose + fasudil group (HG + F, the concentrations of fasudil were 25, 50 and 100 µmol/L, respectively). Collect the supernatant and cells at 0, 12, 24, 36, 48 and 72 h respectively, and determine the concentration changes of the RhoA, ROCK-I, connective tissue growth factor (CTGF)mRNA with real-time PCR method in the cells, then used the ELISA method to check the protein content of the fibronectin (FN), CTGF, TNFα in the supernatant. RESULTS: (1) RhoA, ROCK-I and CTGF mRNA of the HMCs cultured under the high glucose expressed significantly higher than those in the normal group, and there was certain time-dependence. Besides, there was no statistic significance by comparing Man and NG. (2)Under the high glucose situation, after the fasudil pretreatment with different concentrations and 24 h or 48 h culture with high glucose, RhoA, ROCK-I, CTGF mRNA expression was significantly decreased in HG + F, compared with HG, and there was certain concentration-dependence. (3) High glucose increased the FN, CTGF, TNFα protein secretion of HMCs in a time-dependent manner, but normal glucose and mannitol had no such effect. (4) After the fasudil pretreatment with different concentrations and culture with high glucose for 12, 24, 36, 48, 72 h, the FN, CTGF, TNFα protein secretion was significantly reduced compared with HG. CONCLUSION: Fasudil can reduce the secretion of downstream inflammatory factors and cytokines by inhibiting high glucose-activated HMCs Rho/ROCK signaling pathway, and reduce the inflammation and fibrosis of HMCs. This provides a new basis for the therapeutic target in the treatment of diabetic nephropathy.

Effects of anti-diabetic drugs on sarcopenia: Best treatment options for elderly patients with type 2 diabetes mellitus and sarcopenia.

Human life expectancy increases as society becomes more developed. This increased life expectancy poses challenges associated with the rapid aging of the population. Sarcopenia, an age-related disease, has become a worldwide health issue. Patients with sarcopenia experience decreases in muscle mass and function, becoming frail and eventually bedridden. Type 2 diabetes mellitus (T2DM) is also a major health issue; the incidence of T2DM increases with aging. T2DM is associated with reduced muscle strength and poor muscle quality and may contribute to acceleration of the aging process, augmenting age-related sarcopenia. Recent studies indicate that elderly patients with diabetes are at an increased risk for sarcopenia. Therefore, these older diabetic patients with sarcopenia need specific anti-diabetic therapies targeting not only glycemic control but also sarcopenia, with the goal of preventing sarcopenia in pre-sarcopenic patients. Presently, various types of hypoglycemic drugs are available, but which hypoglycemic drugs are better suited for geriatric T2DM patients with sarcopenia remains undetermined. In this review, we discuss the association between diabetes and sarcopenia in geriatric patients, and how anti-diabetic drugs may influence sarcopenia outcomes. This review will guide clinical workers in the selection of drugs best suited for this patient population.