Combining Metabolic Engineering and Lipid Droplet Assembly to Achieve Campesterol Overproduction in Saccharomyces cerevisiae.

Campesterol is a kind of important functional food additive. Therefore, stable and efficient campesterol biosynthesis is significant. Herein, we first knocked out the sterol 22-desaturase gene in Saccharomyces cerevisiae and expressed sterol Δ7-reductase from Pangasianodon hypophthalmus, obtaining a strain that produced 6.6 mg/L campesterol. Then, the modular expression of campesterol synthesis enzymes was performed, and a campesterol titer of 88.3 mg/L was achieved. Because campesterol is a lipid-soluble macromolecule, we promoted lipid droplet formation by exploring regulatory factors, and campesterol production was improved to 169.20 mg/L. Next, triacylglycerol lipase was used to achieve compartment campesterol synthesis. After enhancing the expression of sterol Δ7-reductase and screening cations, the campesterol titer reached 438.28 mg/L in a shake flask and 1.44 g/L in a 5 L bioreactor, which represents the highest campesterol titer reported to date. Metabolic regulation combined with lipid droplet engineering may be useful for the synthesis of other steroids as well.

Safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Impaired glucose regulation (defined as either impaired glucose tolerance or impaired fasting glucose) is an important risk factor for the development of diabetes. We aimed to evaluate the safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing diabetes in Chinese participants with impaired glucose regulation. METHODS: We did a multicentre, open-label, randomised controlled trial at 43 endocrinology departments in general hospitals across China. Eligible participants were individuals with impaired glucose regulation (ie, impaired glucose tolerance or impaired fasting glucose, or both), men or women aged 18-70 years with a BMI of 21-32 kg/m2. Eligible participants were randomly assigned (1:1) via a computer-generated randomisation to receive either standard lifestyle intervention alone or metformin (850 mg orally once per day for the first 2 weeks and titrated to 1700 mg orally per day [850 mg twice per day]) plus lifestyle intervention. Block randomisation was used with a block size of four, stratified by glucose status (impaired fasting glucose or impaired glucose tolerance), hypertension, and use of any anti-hypertensive medication. Lifestyle intervention advice was given by investigators at all participating sites. The primary endpoint was the incidence of newly diagnosed diabetes at the end of the 2-year follow-up. Analysis was done using the full analysis set and per-protocol set. This study is registered with ClinicalTrials.gov, number NCT03441750, and is completed. FINDINGS: Between April, 2017, and June, 2019, 3881 individuals were assessed for eligibility, of which 1678 (43·2%) participants were randomly assigned to either the metformin plus lifestyle intervention group (n=831) or the lifestyle intervention alone group (n=847) and received the allocated intervention at least once. During a median follow-up of 2·03 years, the incidence rate of diabetes was 17·27 (95% CI 15·19-19·56) per 100 person-years in the metformin plus lifestyle intervention group and 19·83 (17·67-22·18) per 100 person-years in the lifestyle intervention alone group. The metformin plus lifestyle intervention group showed a 17% lower risk of developing diabetes than the lifestyle intervention alone group (HR 0·83 [95% CI 0·70-0·99]; log-rank p=0·043). A higher proportion of participants in the metformin plus lifestyle intervention group reported adverse events than in the lifestyle intervention alone group, primarily due to more gastrointestinal adverse events. The percentage of participants reporting a serious adverse event was similar in both groups. INTERPRETATION: Metformin plus lifestyle intervention further reduced the risk of developing diabetes than lifestyle intervention alone in Chinese people with impaired glucose regulation, showing additional benefits of combined intervention in preventing progression to diabetes without new safety concerns. FUNDING: Merck Serono China, an affiliate of Merck KGaA, Darmstadt, Germany. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Regulation of Ethanol Assimilation for Efficient Accumulation of Squalene in Saccharomyces cerevisiae.

Squalene is a triterpene that can be obtained from fish and plant oils. It is important in cosmetics and vaccines and is a precursor for many high-value terpenes and steroids. In order to increase squalene accumulation, the mevalonate pathway was systematically enhanced. Accumulation of squalene tended to increase when ethanol was added as a carbon source during fermentation, but a high concentration of ethanol affected both the strain growth and accumulation of products. By overexpressing the key trehalose synthesis gene TPS1 and the heat shock protein gene HSP104, the content of trehalose by Saccharomyces cerevisiae (S. cerevisiae) was enhanced, and stress caused by ethanol was relieved. The OD600 value of the modified S. cerevisiae strain was increased by 80.2%, its ethanol tolerance was increased to 30 g/L, and it retained excellent activity with 50 g/L ethanol. After optimizing the fermentation conditions, the squalene titer in a 5 L bioreactor reached 27.3 g/L and the squalene content was 650 mg/g dry cell weight, the highest squalene production parameters reported to date for a microorganism.

The complexity analysis of cerebral oxygen saturation during pneumoperitoneum and Trendelenburg position: a retrospective cohort study.

BACKGROUND: The human brain is a highly complex and nonlinear system, nonlinear complexity measures such as approximate entropy (ApEn) and sample entropy (SampEn) can better reveal characteristics of brain dynamics. However, no studies report complexity of perioperative physiological signals to reveal how brain complexity associates with age, varies along with the development of surgery and postoperative neurological complications. AIM: This study examined the complexity of intraoperative regional cerebral oxygen saturation (rSO2), aiming to reveal brain dynamics during surgery. METHODS: This retrospective cohort study enrolled patients who scheduled for robot-assisted urological surgery. Intraoperative rSO2 was continuously monitored throughout the surgery. Postoperative delirium (POD) was diagnosed by the Confusion Assessment Method. ApEn and SampEn were used to characterize the complexity of rSO2. Pearson correlation coefficients were used to measure the correlation between complexity of rSO2 and age. The association between complexity of rSO2 and POD was examined using T tests. RESULTS: A total of 68 patients (mean [SD] age, 63.0 (12.0) years; 47 (69.1%) males) were include in this analysis. There was a significant reverse relationship between the complexity of rSO2 and age (The correlation coefficients range between - 0.32 and - 0.28, all p < 0.05). Patients ≥ 75 years showed significantly lower complexity of rSO2 than the other two groups. Older age remained an independent factor influencing complexity of rSO2 after adjusting for a number of covariates. Six patients (8.8%) developed POD, and POD patients had lower complexity of rSO2 compared with non-POD patients. CONCLUSIONS: The complexity of rSO2 may serve as a new candidate marker of aging and POD prediction.

Efficacy of Xuebijing Combined with Ulinastatin in the Treatment of Traumatic Sepsis and Effects on Inflammatory Factors and Immune Function in Patients.

Objective: To investigate the efficacy of xuebijing combined with ulinastatin in the treatment of traumatic sepsis and analyze the effects on inflammatory factors and immune function of patients. Methods: 182 patients with traumatic sepsis were selected from June 2017 to September 2021 in our hospital. The patients were divided into the control group and the observation group. Patients in both groups were given routine treatments such as initial resuscitation, blood transfusion, monitoring of lactic acid to guide fluid replacement, early control of infection source, selection of appropriate antibiotics, correction of acidosis, treatment of primary disease, prevention of hypothermia and stress ulcer, application of vasoactive drugs, application of glucocorticoid and nutritional support. The control group was treated with Xuebijing injection on the basis of routine treatment, and the observation group was given Xuebijing injection combined with ulinastatin treatment on the basis of routine treatment. The APACHE II score was applied to evaluate the patients before and after treatment, and the routine blood indicators, inflammatory factor indicators, immune function indicators and liver function indicators were tested. Results: After the treatment, the APACHE II score of the observation group was (10.35 ± 3.04) lower than that of the control group (15.93 ± 4.52) (P < 0.05). After treatment, the WBC and neutrophils in the observation group (15.19 ± 2.91) and (0.65 ± 0.04) were lower than those in the control group (16.42 ± 3.44) and (0.79 ± 0.05), and the PLT(162.85 ± 43.92) was higher than that in the control group (122.68 ± 36.89) (P < 0.05). After treatment, the levels of serum PCT, IL-6, TNF-α in the observation group were (11.38 ± 3.05), (10.74 ± 3.82) and (9.82 ± 2.35) lower than those in the control groups (17.34 ± 3.29), (15.28 ± 4.05) and (13.24 ± 3.06) (P < 0.05). After treatment, the levels of CD3+, CD4+, CD8+, CD4+/CD8+ in the observation group were (50.64 ± 4.98), (40.56 ± 4.82), (27.22 ± 3.29), (1.49 ± 0.24) higher than those in the control groups (46.08 ± 4.75), (34.69 ± 4.08), (25.14 ± 3.18), (1.38 ± 0.19) (P < 0.05). After treatment, the levels of TBIL and AST in the observation group were (12.35 ± 3.82), (25.66 ± 4.49) lower than those in the control group (18.43 ± 4.06), (34.58 ± 5.06) (P < 0.05). Conclusion: Xubijing combined with ulinastatin has a good effect in the treatment of patients with traumatic sepsis, which can effectively improve the condition, reduce the body's inflammatory response, and promote the recovery of patients' immune function and liver function.

Rational construction of a triphenylphosphine-modified tetra-nuclear Cu(I) coordinated cluster for enhanced chemodynamic therapy.

A triphenylphosphine-modified tetra-nuclear Cu(I) coordinated cluster was constructed for enhanced chemodynamic therapy (CDT) by increasing the number of metal centers. Once inside human bladder cancer (T24) cells, a larger amount of copper accumulated compared with the mono-nuclear Cu(I) complex; the additional copper could generate more •OH and then induce more obvious apoptosis via a Fenton-like reaction, thus further increasing the tumor inhibition effect and ultimately improving the CDT efficiency.

CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases.

Inflammatory monocytes are key mediators of acute and chronic inflammation; yet, their functional diversity remains obscure. Single-cell transcriptome analyses of human inflammatory monocytes from COVID-19 and rheumatoid arthritis patients revealed a subset of cells positive for CD127, an IL-7 receptor subunit, and such positivity rendered otherwise inert monocytes responsive to IL-7. Active IL-7 signaling engaged epigenetically coupled, STAT5-coordinated transcriptional programs to restrain inflammatory gene expression, resulting in inverse correlation between CD127 expression and inflammatory phenotypes in a seemingly homogeneous monocyte population. In COVID-19 and rheumatoid arthritis, CD127 marked a subset of monocytes/macrophages that retained hypoinflammatory phenotypes within the highly inflammatory tissue environments. Furthermore, generation of an integrated expression atlas revealed unified features of human inflammatory monocytes across different diseases and different tissues, exemplified by those of the CD127high subset. Overall, we phenotypically and molecularly characterized CD127-imprinted functional heterogeneity of human inflammatory monocytes with direct relevance for inflammatory diseases.

Comparison of the incidence of adverse reactions between herbal decoction and Chinese patent medicine combined with western medicine in treatment of COVID-19: A protocol for systematic review and meta-analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease that has led to millions of confirmed cases and deaths worldwide. Traditional Chinese Medicine plays an irreplaceable role in the treatment and prevention of epidemics in China. Western medicine improves clinical symptoms as well as bringing many adverse reactions. The combination of Chinese and western medicine can significantly improve the clinical symptoms and efficacy of patients. Currently, there is a lack of systematic reviews on the comparison of the incidence of adverse reactions between the difference treatments. We conducted this study to evaluate the comparison of the incidence of adverse reactions between herbal decoction and Chinese patent medicine combined with western medicine in treatment of COVID-19. METHODS AND ANALYSIS: Randomized controlled trials in 9 databases from December 2019 to September 2022, will be included, without language restrictions. Two independent researchers will screen and select studies, extract data, and evaluate the study quality. The Cochrane risk-of-bias tool for randomized controlled trials will be used to assess the risk of bias in the included studies. Statistical analyses will be conducted using Review Manager. RESULTS: Our findings will compare the incidence of adverse reactions between herbal decoction and Chinese patent medicine combined with western medicine in treatment of COVID-19, which will be disseminated in a relevant conference and published in a peer-reviewed publication. ETHICS AND DISSEMINATION: This study will not include personal information. Ethical approval is not required for this study. PROSPERO REGISTRATION NUMBER: CRD42022371001.

Hypoglycemic effect of insulin-loaded hydrogel-nanogel composite on streptozotocin-induced diabetic rats.

At present, how to increase insulin rapidly, availably and stably is still a conundrum in the treatment of diabetes mellitus. In vitro studies have shown that insulin can be released from hydrogel-nanogel composite according to the changes of glucose level. This study aimed to observe the glucose-lowering effects and evaluate the safety of the insulin-loaded hydrogel-nanogel composite in diabetic rats. We found that significant glycemic regulation could be observed up to 30 hours after subcutaneous injection, and the fasting blood glucose was reduced effectively. The result of an oral glucose tolerance test showed that the level of insulin expressed a stable increase from 0.5 hours to 3.5 hours, which led to a reduction of glucose with steady steps. Also, compared with Ins group, the Gel+Ins group showed slighter skin and pancreas damage, while the oxidative stress and inflammation response were similar to the normal control group. In conclusion, these results demonstrated that the glucose-lowering action of the insulin-loaded hydrogel-nanogel composite was superior to that of the regular insulin, and might thus become an insulin carrier in the future.

Effect of Baseline Characteristics on Hypoglycaemia Risk with Insulin Glargine 100 U/mL: Post Hoc Analysis of the BEYOND 7 Study.

INTRODUCTION: BEYOND 7 demonstrated that a higher starting dose (0.3 U/kg) of insulin glargine 100 U/mL (Gla-100) is as safe as the standard starting dose (0.2 U/kg) in Chinese individuals with type 2 diabetes who had uncontrolled hyperglycaemia despite receiving oral antihyperglycaemic drugs. This post hoc analysis determined the effect of baseline characteristics on hypoglycaemia risk in these individuals. METHODS: Participants from BEYOND 7 were assessed based on their age at baseline (< 60 vs. ≥ 60 years), duration of diabetes (< 10 vs. ≥ 10 years), glycated haemoglobin (HbA1c; < 9 vs. ≥ 9%) and fasting plasma glucose level (FPG; < 11 vs. ≥ 11 mmol/L). Endpoints included the proportion of participants with overall confirmed (≤ 3.9 mmol/L) and symptomatic hypoglycaemia, as well as the proportion of participants who achieved an HbA1c < 7% without hypoglycaemia, the time to first achievement of fasting blood glucose (FBG) < 7 mmol/L and the change in HbA1c from baseline between the two treatment arms in each of these subgroups. RESULTS: The proportion of participants with overall confirmed (6.1-16.7%) or symptomatic hypoglycaemia (5.7-18.4%) or the proportion who achieved HbA1c < 7.0% without hypoglycaemia (23.6-47.4%) was similar between the two treatment arms in all subgroups, with the exception of participants with a baseline duration of diabetes ≥ 10 years who experienced more symptomatic hypoglycaemia if initiating Gla-100 at a dose of 0.3 versus 0.2 U/kg. Participants aged < 60 years with an HbA1c < 9% or ≥ 9% or a duration of diabetes of 2-10 years achieved an FBG < 7.0 mmol/L in a significantly shorter time with Gla-100 starting dose of 0.3 U/kg versus 0.2 U/kg (all p < 0.001). No significant differences were seen among the subgroups in terms of change from baseline in HbA1c. CONCLUSIONS: Baseline age, duration of diabetes, HbA1c level and FPG level do not affect the risk of hypoglycaemia with a higher starting dose of Gla-100 versus its standard starting dose. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02836704.

Blood Levels of Glycated Hemoglobin, D-Dimer, and Fibrinogen in Diabetic Retinopathy.

PURPOSE: This study aimed to describe the levels of glycated hemoglobin (HbA1c), D-dimer (D-D), and fibrinogen (FIB) in different types of diabetic retinopathy (DR). METHODS: A total of 61 patients with diabetes, who were treated in our department between November 2017 and May 2019, were selected. According to their non-mydriatic fundus photography and fundus angiography results, patients were divided into three groups, ie, the non-DR (NDR) group (n=23), the non-proliferative DR (NPDR) group (n=17), and the proliferative DR (PDR) group (n=21). A control group of 20 people who had tested negative for diabetes was also included. The levels of HbA1c, D-D, and FIB were measured and compared, respectively. RESULTS: The mean values of HbA1c were 6.8% (5.2%, 7.7%), 7.4% (5.8%, 9.0%), and 8.5% (6.3%, 9.7%) in the NDR, NPDR, and PDR groups, respectively. The control group values were 4.9% (4.1%, 5.8%). These results indicated a significant statistical difference between groups. The mean values of D-D were 0.39 ± 0.21 mg/L, 1.06 ± 0.54 mg/L, and 1.39 ± 0.59 mg/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 0.36 ± 0.17 mg/L. The values of the NPDR and PDR groups were significantly higher than those of the NDR and control groups, and the value of the PDR group was significantly higher than that of the NPDR group, indicating a significant difference between the groups (P < 0.001). The mean values of FIB were 3.07 ± 0.42 g/L, 4.38 ± 0.54 g/L, and 4.46 ± 1.09 g/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 2.97 ± 0.67 g/L. The difference between the groups was statistically significant (P < 0.05). CONCLUSION: Blood levels of HbA1c, D-D, and FIB in the PDR group were significantly higher than in the NPDR group.

The perioperative application of continuous cerebral autoregulation monitoring for cerebral protection in elderly patients.

BACKGROUND: The majority of surgical patients aged 65 years and over are accompanied with underlying conditions, making them susceptible to perioperative cerebral complications. Here, we investigated the clinical value of continuous cerebral autoregulation (CA) monitoring in protecting against cerebral dysfunction in elderly patients undergoing surgery. METHODS: This study enrolled 40 elderly patients (aged ≥65 years) and 40 middle-aged patients (aged 45 to 64 years) selected to undergo robotic-assisted laparoscopic radical prostatectomy. Cerebral oxygenation was assessed by regional cerebral oxygen saturation (rScO2) using near-infrared spectroscopy (NIRS). CA function was estimated using the cerebral oximetry index (COX), which is the rolling correlation between rScO2 and the mean arterial pressure (MAP). With the patient in the Trendelenburg position, the rScO2, MAP, calculated COX, HR, end-tidal CO2, and sevoflurane concentrations were continuously recorded. Standardized anesthesia was administered to all patients (sevoflurane, propofol, remifentanil, and rocuronium). Postoperative delirium (POD) was screened for daily using the Confusion Assessment Method (CAM). The primary outcome was the difference in periods of CA dysfunction between the elderly and middle-aged groups. Secondary outcomes included the incidence of POD and the optimal MAP range in the 2 groups. RESULTS: Taking positive COX values (cutoff ≥0.3) to reflect periods of CA dysfunction, we found that the cumulative duration of CA dysfunction in the Trendelenburg position was longer in elderly patients than in middle-aged patients [ratio of cumulative time of CA dysfunction: middle-aged group, 32.8% (26.3%, 43.1%) vs. elderly group, 42.2% (33.1%, 51.2%)] (P<0.01), which showed that CA function was less efficient in elderly patients. Three patients (7.5%) in the elderly group and 1 patient (2.5%) in the middle-aged group screened positive for POD on at least 1 day during their hospital stay. Additionally, using the COX-based method, we estimated the optimal MAP targets in the middle-aged and elderly groups to be (67.8±8.9, 116.4±10.5) and (71.2±12.5, 111.3±8.9) mmHg, respectively. CONCLUSIONS: The brains of patients ≥65 years are more vulnerable to systemic insult compared with those of middle-aged patients. POD may be associated with CA dysfunction. NIRS-derived COX can be used to identify the optimal MAP range.

CD127 imprints functional heterogeneity to diversify monocyte responses in human inflammatory diseases.

Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.

Corrigendum to "Dexmedetomidine Postconditioning Alleviates Hypoxia/Reoxygenation Injury in Senescent Myocardial Cells by Regulating lncRNA H19 and m6A Modification".

[This corrects the article DOI: 10.1155/2020/9250512.].

The changing features of serum adropin, copeptin, neprilysin and chitotriosidase which are associated with vascular endothelial function in type 2 diabetic retinopathy patients.

AIMS: Adropin (AD), copeptin (CP), neprilysin (NEP) and chitotriosidase (CHIT1) have been associated with the regulation of vascular endothelial function. In this work, we analyzed the plasma concentrations of cytokines (AD, CP, NEP and CHIT1) in type 2 diabetic patients with or without retinopathy (DR) to predict the risk of DR for diabetic patients. METHOD: A total of 392 patients diagnosed as type 2 diabetes mellitus (T2DM) and 120 healthy volunteers as a control group were enrolled in this study. T2DM patients were divided into three groups: diabetes without retinopathy (NDR, n = 174) group, non-proliferative diabetic retinopathy (NPDR, n = 118) group and proliferative diabetic retinopathy (PDR, n = 100) group. The serum AD, CP, NEP and CHIT1 levels of subjects were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: We reported a significant decrease in AD and a significant increase in CP, NEP and CHIT1 in NDR as well as DR patients when compared with controls (p < 0.05), the lower level of AD and significantly higher levels of CP, NEP and CHIT1 were seen in DR patients compared to NDR group (p < 0.05), at the same time, we observed the lowest level of AD and the highest levels of CP, NEP and CHIT1 in the PDR group. Logistic regression analysis showed that AD was a protective factor for DR, conversely, CP, NEP and CHIT1 were the independent risk factors (p < 0.05). Moreover, receiver operating characteristic curve analyses indicated that CP had greater diagnosis capacity with an AUC (the areas under the ROC curve) of 0.901 than AD, NEP, CHIT1 for DR patients. CONCLUSION: The decreased AD level and the elevated CP, NEP and CHIT1 levels involved in vascular endothelial function may be evidence facilitating the presence of DR. Thereby they can be explored to use as promising non-invasive biomarkers for prediction of DR severity, distinguishing DR from diabetic patients.

Sonic Hedgehog Signaling Contributes to Chronic Post-Thoracotomy Pain via Activating BDNF/TrkB Pathway in Rats.

PURPOSE: Some patients undergoing thoracotomy may suffer from chronic post-thoracotomy pain (CPTP). Treatment of CPTP has been a clinical challenge and the underlying mechanisms of CPTP remain elusive. Recently, sonic hedgehog (Shh) signaling has been shown to be associated with various pain states but its role in the pathogenesis of CPTP is still unclear. METHODS: CPTP was induced in rats by thoracotomy. Rats were divided into CPTP group and non-CPTP group based on the mechanical withdrawal threshold (MWT). Rats were administered with Shh signaling inhibitor cyclopamine and activator smoothened agonist (SAG), and then evaluated by MWT and cold allodynia testing. The expressions of Shh signaling (Shh ligand, patched and smoothened receptor, Gli transcription factors), brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase receptor B (Trk-B), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in rat T4-5 spinal cord dorsal horn (SDH) were detected by Western blotting and immunohistochemistry. RESULTS: The expression of Shh signaling significantly increased and the BDNF/TrkB pathway was activated in T4-5 SDH of CPTP rats. Cyclopamine attenuated hyperalgesia and down-regulated the expressions of Gil1, BDNF, p-TrkB, p-PI3K and p-Akt in CPTP rats. SAG induced hyperalgesia in non-CPTP rats and elevated the expressions of Gil1, BDNF, p-TrkB, p-PI3K and p-Akt. CONCLUSION: Shh signaling may contribute to CPTP via activating BDNF/TrkB signaling pathway, and inhibition of Shh signaling may effectively alleviate CPTP.

Synthesis, structural characterization and antitumor activity of six rare earth metal complexes with 8-hydroxyquinoline derivatives.

The rare earth metal Gd(III), Yb(III), Lu(III), Eu(III), Tb(III) and Ho(III) complexes 1-6 with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (H-L) as ligands were synthesized. The in vitro cytotoxicity assay indicated that the cytotoxicity of 1 was equivalent to cisplatin and higher than that of H-L and other complexes towards T24 tumor cells. The mechanism study indicated that 1 caused significant up-regulation of the proteins p27, p21 and p53 in T24 cells and cell cycle arrest in G2 phase. In addition, 1 induced effective T24 cells apoptosis via mitochondrial dysfunction pathway, which was indicated by changes in mitochondrial membrane potential (Δψ), reactive oxygen species (ROS), intracellular Ca2+ and the mitochondria-related proteins (including cytochrome C (Cyt C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated x (Bax) and apoptotic protease activating factor-1 (Apaf-1)). Moreover, 1 could activate caspase-3/8/9 in T24 cells. Therefore, complex 1 is a promising and potent anticancer drug candidate.

Pentraxin-3 and adropin as inflammatory markers of early renal damage in type 2 diabetes patients.

PURPOSE: Renal inflammatory response is involved in the development and progression of diabetic kidney disease (DKD). We sought to evaluate pentraxin-3 (PTX3) and adropin variability as inflammatory markers among type 2 diabetes mellitus (T2DM) patients with different urinary albumin, and to examine if these factors assist in the early diagnosis of diabetic kidney disease. METHODS: We enrolled 447 T2DM patients and 100 healthy non-diabetic control subjects in this study. The patients with T2DM were divided into three groups based on their urinary albumin/creatinine ratio (UACR): the normoalbuminuric group (DM group, UACR < 30 mg/g); the microalbuminuric group (DKD1 group, 30 ≤ UACR ≤ 300 mg/g); the macroalbuminuric group (DKD2 group, UACR > 300 mg/g). The levels of PTX3 and adropin were determined by enzyme-linked immunosorbent assay (ELISA). Spearman correlation and multiple linear regression analysis were performed to determine the correlations among these inflammatory markers and other clinical parameters. Receiver operating characteristic (ROC) curves analysis was used to assess the diagnostic potential of PTX3 and adropin for DKD. RESULTS: Compared to non-diabetes, serum levels of PTX3 were distinctly elevated, whereas the adropin were significantly declined in diabetic patients (p < 0.05). Significantly higher levels of PTX3 and lower levels of adropin were seen in the macroalbuminuric patients compared with the microalbuminuric patients (p < 0.05). Multiple stepwise linear regression analysis showed that the control of hemoglobin A1c (HbA1c) and UACR were independent factors associated with PTX3 and adropin. In addition, ROC curves analysis showed PTX3 and adropin could be used to evaluate the early detect of DKD, further adropin might be a better marker than PTX3 in compliance with their veracity. CONCLUSION: As inflammatory markers, the diverse changes of pentraxin-3 and adropin showed that they may forecast the renal damage in diabetic patients in varying degrees and link with the pathogenesis of diabetic kidney disease.

Left maxillary sinus tumour-induced hypophosphataemic osteomalacia and combined with thyroid papillary carcinoma: a case report and literature review.

Tumour-induced osteomalacia (TIO) is a rare disease characterised by hypophosphataemia and clinical symptoms of osteomalacia. Herein we report the case of a 29-year-old man who was admitted to hospital with progressive bone pain and was diagnosed with TIO caused by maxillary sinus tumours. In the preoperative evaluation, it was found that the patient had thyroid malignant tumours at the same time. Two operations were performed separately on the left maxillary sinus tumour and thyroid tumour after complete examination. After tumour resections, the symptoms of bone pain were relieved and the level of blood phosphorus was restored, long-term replacement therapy was needed for thyroid. When a patient is diagnosed with TIO, it is necessary to screen for the presence of other malignant tumours and explore the treatment options in order to benefit patients preferably.

Altered features of neurotransmitters: NPY, α-MSH, and AgRP in type 2 diabetic patients with hypertension.

OBJECTIVE: To investigate the features of neuropeptide Y (NPY), α-melanocyte stimulating hormone (α-MSH), and agouti-related protein (AgRP) in type 2 diabetes mellitus (T2DM) patients with hypertension. METHODS: Patients with T2DM (n = 384) and healthy volunteers (n = 80) were enrolled into this study. Serum NPY, α-MSH, and AgRP levels were detected using ELISA. RESULTS: Significantly higher NPY and lower α-MSH and AgRP levels were observed in patients with diabetes compared with those without diabetes, and the mean NPY levels increased, while α-MSH and AgRP levels decreased, with the development of hypertension compared with diabetic patients without hypertension. α-MSH and AgRP levels decreased with an increase in blood pressure in hypertension compared with the non-hypertension patients. Multiple stepwise linear regression analysis showed that NPY, α-MSH, and AgRP levels were closely associated with blood pressure and glucose control. Receiver operating characteristic (ROC) curve analyses indicated that α-MSH may be a better marker compared with NPY and AgRP for regulating glucose and blood pressure and to distinguish between T2DM patients with and without hypertension. CONCLUSION: NPY, α-MSH, and AgRP might play different roles and be closely related to the occurrence and development of diabetes and hypertension.