CS2 Group Research Articles

Efficacy and safety of esketamine combined with propofol for conscious sedation in painless colonoscopy: a prospective, randomized, double-blind controlled clinical trial

BackgroundWe explored the efficacy and safety of esketamine combined with propofol for conscious sedation in painless colonoscopy.MethodsA total of 195 patients who underwent painless colonoscopy surgery were randomly divided into three groups: the propofol deep sedation group (group DS), the sufentanil combined with propofol for conscious sedation (group CS1) and the esketamine combined with propofol for conscious sedation (group CS2). The primary outcomes of this study included the incidence of hypoxemia, hypotension, hypertension, and bradycardia and excellent and good rates of anaesthesia during colonoscopy. The secondary outcomes included perioperative changes in vital signs (MAP, HR, and SpO2), anaesthesia induction time, dischargeable time, patient and endoscopist satisfaction scores, and incidence of postoperative nausea and vomiting (PONV), drowsiness, dizziness, propofol injection pain, assisted ventilation and vasoactive medications.ResultsThe incidence of intraoperative hypoxemia in the DS group was significantly greater than that in the CS1 and CS2 groups (χ2 = 7.081, P = 0.029). The incidence of hypotension in the CS2 group was significantly lower than that in the DS and CS1 groups (χ2 = 16.278, P < 0.001). The risk of hypoxemia was 5.727 times higher in Group DS than in Group CS2 (OR 5.727; 95%CI 1.203–27.273), and the risk of hypotension was 9.864 times higher in Group DS than in Group CS2 (OR 9.864; 95%CI 2.770–35.120). The risk of hypotension in Group CS1 was 5.167 times that in Group CS2 (OR 5.167; 95%CI 1.396–19.117). The incidence of propofol injection pain, assisted ventilation, ephedrine usage and drowsiness in the DS group was significantly greater than that in the CS1 and CS2 groups (χ2 = 57.618, P < 0.001; χ2 = 9.544, P = 0.008; χ2 = 14.820, P = 0.001; χ2 = 37.257, P < 0.001). The incidence of dizziness during recovery in the CS1 group was significantly greater than that in the DS and CS2 groups (χ2 = 6.594, P = 0.037). The dischargeable time in the DS group was significantly greater than that in the CS1 and CS2 groups (F = 53.039, P < 0.001). The satisfaction scores of the endoscopist and patients in the DS group were significantly lower than those in the CS1 and CS2 groups (F = 17.390, P < 0.001; F = 19.282; P < 0.001).ConclusionsIn conclusion, esketamine combined with propofol for conscious sedation can be safely and effectively used for painless colonoscopy and has fewer complications.It is recommended for painless colonoscopy.

Integrated Molecular Docking and Experimental Analysis of Ni(II) Proline Dithiocarbamate Cytotoxicity in MCF-7 Breast Cancer Cells.

Chemotherapy is one of the most effective and widely used treatment types for breast cancer. The Ni(II) proline dithiocarbamate (Ni(II)ProDtc) complex has been synthesized as a potential anticancer agent with minimal systemic toxicity. The dithiocarbamate ligand, combined with the amino acid proline, holds promise as a radio chemotherapeutic target agent in tumors. The anticancer activity of a Ni(II) complex compound with a proline dithiocarbamate ligand was tested on the MCF-7 breast cancer cell line as part of a study on essential metal-based therapeutics. Molecular docking studies identified the active sites for the estradiol-estrogen receptor-α protein. The Ni(II)ProDtc complex was synthesized and characterized using melting point analysis, conductivity measurements, UV-Vis spectroscopy, and FT-IR spectroscopy. The cytotoxicity of the complex was evaluated in vitro using the MCF-7 breast cancer cell line. The UV-Vis spectrum at 246 nm indicated the π→π* intraligand transition of the CS2 group, while FT-IR analysis revealed peaks at 364-457 cm-1 corresponding to the bonding between Ni and Sulfur (S) and Oxygen (O) from proline. Further, the UV-Vis spectrum displayed bands at 212 and 676 nm, and FT-IR data at 387-691 cm-1, confirming the coordination of the Ni(II) atoms with sulfur, nitrogen, and oxygen in the isoleucine dithiocarbamate ligand. In vitro, cytotoxicity tests revealed that Ni(II)ProDtc induced cell death in the breast cancer cell line, showing significant morphological changes in MCF-7 cancer cells, with an IC50 value of 315.70 µg/mL. The Ni(II)ProDtc complex was successfully synthesized and demonstrates anticancer activity in MCF-7 breast cancer cells, indicating significant potential as an anticancer agent for breast cancer.

Intervention effects of low-molecular-weight chondroitin sulfate from the nasal cartilage of yellow cattle on lipopolysaccharide-induced behavioral disorders: regulation of the microbiome-gut-brain axis.

Chondroitin sulfate (CS) is a sulfated linear polysaccharide with different functional activities, including antioxidant, anti-inflammatory, lipid-lowering, and immune regulation. As natural sulfated polysaccharides have high molecular weight, high apparent viscosity, low water solubility, complex structure, and high negative charge, they have difficulty binding to receptors within cells across tissue barriers, resulting in low bioavailability and unclear structure-activity relationships. In this study, an H2O2-Vc oxidative degradation system was employed to perform environmentally friendly and controllable degradation of CS extracted from the nasal cartilage of Shaanxi Yellow cattle. Two low-molecular-weight chondroitin sulfates (LMWCSs), CS-1 (14.8 kDa) and CS-2 (50.9 kDa), that exhibit strong in vitro free radical scavenging ability were obtained, and their structures were characterized. Mice intraperitoneally administered lipopolysaccharide (LPS) were used to explore the cognitive intervention effects of LMWCS. Supplementing CS-1 and CS-2 significantly downregulated the levels of the serum inflammatory factors, TNF-α and IL-1β, promoted the expression of GSH in the brain, and inhibited the production of the lipid peroxidation product, malondialdehyde (MDA), ultimately inhibiting LPS-induced cognitive impairment in mice. Surprisingly, compared to the LPS model group, the abundances of Streptococcus, Eisenbergiella, Vampirovibrio, Coprococcus, Enterococcus and Lachnoanaerobaculum were significantly increased in the intestines of mice in the CS-1 and CS-2 group, whereas those of Parabacteroides and Mycoplasma were significantly decreased. Altogether, this study provides a theoretical basis for the comprehensive utilization of agricultural and animal resources and the application of brain nutrition, anti-inflammatory, and LMWCS health products.

Incorporating pH into DFT-D+U and microflotation recovery studies on heterocyclic collector-pyrite interactions

This study adopted both computational and experimental approaches to design by modification of 2-mercaptobenzothiazole (MBT), 2-mercaptobenzoxazole (MBO) and 2-mercaptobenzimidazole (MBI) heterocyclic collectors by introducing a carbon sulphide (–CS2) group and forming 2-trithiocarbonatebenzothiazole (TTCBT), 2-trithiocarbonatebenzoxazole (TTCBO) and 2-trithiocarbonatebenzomidazole (TTCBI) derivatives collectors. The adsorption behaviour of the heterocyclic collectors (and derivatives) on pyrite and subsequent hydrophobicity at different pH conditions were characterised using molecular modelling and microflotation approaches, respectively. The computational adsorptions were performed on dry and hydrated surfaces in their neutral thiolate and thione (acidic) form on the pyrite (100) surface. It was found that under dry and neutral conditions the TTCBONa and TTCBTNa were more exothermic, while under dry and acidic conditions the TTCBIH was more exothermic followed by MBIH and MBTH. Under hydrated and neutral conditions MBONa was predicted as the most exothermic, while for hydrated and acidic conditions MBTH, TTCBTH and TTCBIH were more exothermic. It was found that under acidic conditions, the heterocyclic collectors were more exothermic than for neutral condition on the hydrated surface. The microflotation at pH = 8 showed that MBO achieved higher recoveries, while at pH = 6 MBT, TTCBT and TTCBI achieved higher recoveries that could reach 90 %. The derivatives under acidic conditions were found to have good recovery performance, which showed that the introduction of a –CS2 group on the exocyclic sulphur atom improved the affinity and therefore hydrophobicity of the mercapto-heterocyclic collectors on the pyrite surface, and thus these derivatives can enhance the flotation of pyrite minerals. In addition, the computational predictions complimented by experimental recoveries are essential to a meaningful development of modelling as a tool in mineral processing reagent design.

Preparation, characterisation and biological activity of some metal complexes derived from new dithiocarbamate of heterocyclic ligand

In this study, synthesised new ligand: potassium 2,2'-(quinoxaline-2,3-diyl)bis(1-phenylhydrazinecarbodithioate) (L). The ligand synthesised by reacting N1,N2-dip-tolyloxalamide as the starting material with CS2 and KOH to add the CS2 group and then with phenylendiammine to achieve (L).&#x0D; The ligand used in the synthesis of complexes with (CoII, NiII and CdII). The new ligand and its complexes characterised by FT-IR, UV-Vis, 1H, 13C-NMR, Mass spectroscopy, and elemental analysis, in addition to the above techniques were using magnetic moment, atomic absorption, chloride content, and melting point to describe the metal complexes.

Protective Mechanism of Cordyceps sinensis Treatment on Acute Kidney Injury-Induced Acute Lung Injury through AMPK/mTOR Signaling Pathway.

To investigate protective effect of Cordyceps sinensis (CS) through autophagy-associated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in acute kidney injury (AKI)-induced acute lung injury (ALI). Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline (NS)-treated sham group (sham group), NS-treated ischemia reperfusion injury (IRI) group (IRI group), and low- (5 g/kg·d) and high-dose (10 g/kg·d) CS-treated IRI groups (CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry (W/D) ratio of lung, levels of serum creatinine (Scr), blood urea nitrogen (BUN), inflammatory cytokines such as interleukin- β and tumor necrosis factor- α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde (MDA) and myeloperoxidase (MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 II/light chain 3 I (LC3-II/LC3-I), uncoordinated-51-like kinase 1 (ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively. The renal IRI induced pulmonary injury following AKI, resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO (P<0.01); all of these were reduced in the CS groups (P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower (P<0.05 or P<0.01), while those of LC3-II/LC3-I, ULK1, and AMPK were significantly higher in the CS2 group (P<0.05 or P<0.01). CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.

Immune depletion of the methylated phenotype of colon cancer is closely related to resistance to immune checkpoint inhibitors.

BackgroundMolecular typing based on single omics data has its limitations and requires effective integration of multiple omics data for tumor typing of colorectal cancer (CRC).MethodsTranscriptome expression, DNA methylation, somatic mutation, clinicopathological information, and copy number variation were retrieved from TCGA, UCSC Xena, cBioPortal, FireBrowse, or GEO. After pre-processing and calculating the clustering prediction index (CPI) with gap statistics, integrative clustering analysis was conducted via MOVICS. The tumor microenvironment (TME) was deconvolved using several algorithms such as GSVA, MCPcounter, ESTIMATE, and PCA. The metabolism-relevant pathways were extracted through ssGSEA. Differential analysis was based on limma and enrichment analysis was carried out by Enrichr. DNA methylation and transcriptome expression were integrated via ELMER. Finally, nearest template or hemotherapeutic sensitivity prediction was conducted using NTP or pRRophetic.ResultsThree molecular subtypes (CS1, CS2, and CS3) were recognized by integrating transcriptome, DNA methylation, and driver mutations. CRC patients in CS3 had the most favorable prognosis. A total of 90 differentially mutated genes among the three CSs were obtained, and CS3 displayed the highest tumor mutation burden (TMB), while significant instability across the entire chromosome was observed in the CS2 group. A total of 30 upregulated mRNAs served as classifiers were identified and the similar diversity in clinical outcomes of CS3 was validated in four external datasets. The heterogeneity in the TME and metabolism-related pathways were also observed in the three CSs. Furthermore, we found CS2 tended to loss methylations while CS3 tended to gain methylations. Univariate and multivariate Cox regression revealed that the subtypes were independent prognostic factors. For the drug sensitivity analysis, we found patients in CS2 were more sensitive to ABT.263, NSC.87877, BIRB.0796, and PAC.1. By Integrating with the DNA mutation and RNA expression in CS3, we identified that SOX9, a specific marker of CS3, was higher in the tumor than tumor adjacent by IHC in the in-house cohort and public cohort.ConclusionThe molecular subtypes based on integrated multi-omics uncovered new insights into the prognosis, mechanisms, and clinical therapeutic targets for CRC.

Molecular classification reveals the diverse genetic and prognostic features of gastric cancer: A multi-omics consensus ensemble clustering

BackgroundGlobally, gastric cancer (GC) is the fifth most common tumor. It is necessary to identify novel molecular subtypes to guide patient selection for specific target therapeutic benefits. MethodsMulti-omics data, including transcriptomics RNA-sequencing (mRNA, LncRNA, miRNA), DNA methylation, and gene mutations in the TCGA-STAD cohort were used for the clustering. Ten classical clustering algorithms were executed to recognize patients with different molecular features using the “MOVICS” package in R. The activated signaling pathways were evaluated using the single-sample gene set enrichment analysis. The differential distribution of gene mutations, copy number alterations, and tumor mutation burden was compared, and potential responses to immunotherapy and chemotherapy were also assessed. ResultsTwo molecular subtypes (CS1 and CS2) were recognized by ten clustering algorithms with consensus ensembles. Patients in the CS1 group had a shorter average overall survival time (28.5 vs. 68.9 months, P = 0.016), and progression-free survival (19.0 vs. 63.9 months, P = 0.008) as compared to those in the CS2 group. Extracellular associated biological process activation was higher in the CS1 group, while the CS2 group displayed the enhanced activation of cell cycle-associated pathways. Significantly higher total mutation numbers and neoantigens were observed in the CS2 group, along with specific mutations in TTN, MUC16, and ARID1A. Higher infiltration of immunocytes was also observed in the CS2 group, reflective of the potential immunotherapeutic benefits. Moreover, the CS2 group could also respond to 5-fluorouracil, cisplatin, and paclitaxel. The similar diversity in clinical outcomes between CS1 and CS2 groups was successfully validated in the external cohorts, GSE62254, GSE26253, GSE15459, and GSE84437. ConclusionThe findings provided novel insights into the GC subtypes through integrative analysis of five -omics data by ten clustering algorithms. These could provide potential clinical therapeutic targets based on the specific molecular features.

Cigarette smoke exposure causes systemic and autonomic cardiocirculatory changes in rats depending on the daily exposure dose

AimsTo evaluate the systemic changes and autonomic cardiocirculatory control of awaken rats chronically exposed to the cigarette smoke (CS) of 1 or 2 cigarettes/day. Main methodsRats were exposed to clean air (control) or cigarette smoke of 1 (CS1) or 2 (CS2) cigarettes/animal/day for 30 days. Then, arterial pressure (AP) and heart rate (HR) were recorded in conscious rats to assess spontaneous baroreflex sensitivity and HR and AP variabilities. Evoked baroreflex and cardiac autonomic tone were evaluated by vasoactive drugs and autonomic blockers, respectively. In another group, ventilatory and cardiovascular parameters were recorded under hypoxia and hypercapnia stimulus. At the end of protocols, heart, lung, kidneys and liver were collected for histological analysis. Key findingsRats exposed to CS showed morphological changes, being more evident in the CS2 group. Also, less weight gain and cardiac hypertrophy were prominent in CS2 rats. Basal AP and HR, spontaneous baroreflex sensitivity and cardiovascular variabilities were similar among groups. CS exposure progressively blunted the bradycardia response to phenylephrine (−2.2 ± 0.1 vs. −1.7 ± 0.2 vs. −1.5 ± 0.2) while the tachycardia response to sodium nitroprusside was slightly increased compared to control. Vagal tone was not affected by CS, but CS2 rats exhibited higher sympathetic tone (−25 ± 4 vs. −28 ± 4 vs. −56 ± 9) and lower intrinsic HR (411 ± 4 vs. 420 ± 8 vs. 390 ± 6). Exposure to CS of 2 cigarettes also exacerbated the reflex cardiovascular and ventilatory responses to hypoxia and hypercapnia. SignificanceCS exposure for 30 days promoted systemic changes and autonomic cardiocirculatory dysfunction in rats depending on the daily exposure dose.

Linking coping styles and enzymatic activity of energy metabolism in the wedge sole (Dicologlossa cuneata)

Knowledge of individual behavioural variations (coping styles) can be a very useful tool for aquaculture, since it could allow to adapt the culture conditions to the different behavioural traits and, thus, to reduce the stress in the fish getting in this way a better production. The objective of this work was the identification of coping styles and their possible association with energy metabolism enzyme activities in the wedge sole (Dicologlossa cuneata). After submitting the fish to different tests (Feeding Recovery, Novel Object, Aggression and Restraining), the results showed a high individual variation, especially in the adaptation to a new environment (CV = 90.92 %), latency to escape (CV = 114.14 %) and plasma cortisol levels (CV = 105.56 %), thus showing the existence of coping styles in this species. Two different personalities were defined: the CS1 group (reactive individuals) and the CS2 group (proactive individuals). The CS1, unlike the CS2, presented a shorter latency to escape, higher number of escape attempts, a longer duration of escape attempts, and higher plasma cortisol levels after an acute stress. In addition, significant differences were detected for Glycogen phosphorylase (GPase) that acts in glycogenolysis, presenting the group CS1 the highest values (0.80 ± 0.17 vs. 0.48 ± 0.02 U mg prot−1). In conclusion, this study demonstrates for the first time the existence of coping style in D. cuneata, proving effective the tests applied for this identification. Two different groups were observed with specific behavioural and physiological responses that fit the proactive and reactive patterns. Furthermore, these groups showed differences in the energy metabolism of carbohydrates in basal state.

Outcomes of direct stenting in patients with ST-elevated myocardial infarction.

We compared direct stenting (DS) with conventional stenting (CS) - i.e., stenting after predilation - during primary percutaneous coronary intervention (P-PCI) in terms of procedural results and long-term mortality in patients with ST-elevated myocardial infarction (STEMI). We retrospectively analyzed 2306 patients (mean age 59years, 22% female) who underwent P‑PCI within 12 h of symptom onset. Patients were then followed up prospectively for clinical events. Patients were divided into aDS group (n= 597) and aCS group (n= 1709). The CS group was further divided into aCS-1 group (baseline thrombolysis in myocardial infarction [TIMI] flow grade≥ 1) and aCS-2 group (baseline TIMI flow grade 0). Main outcome measures were postprocedural myocardial reperfusion and all-cause mortality in long-term follow-up. Patients in the DS group had ahigher percentage of final TIMI-3 flow, myocardial blush grade3 and complete ST-segment resolution, better left ventricular ejection fraction, and alower incidence of distal embolization compared with CS patients. In-hospital (1.5 vs. 4.6%, respectively, p= 0.001) and long-term all-cause mortality (8.8 vs. 17.0%, respectively, p< 0.001) were significantly lower in the DS group than in the CS group. Kaplan-Meier survival analysis showed similar survival rates in the DS and CS-1 groups (log-rank p= 0.40), but significantly worse survival in the CS-2 group than in the other groups (log-rank p< 0.001). After adjusting for risk factors, DS was not found to be apredictor of long-term mortality. DS in P‑PCI was associated with better postprocedural angiographic results and long-term survival. However, the DS group had similar in-hospital and long-term mortality to matched patients in the CS group.

A novel synthesis of 4-toluene 9H-carbazole-9-carbodithioate, electropolymerization and impedance study

A novel synthesis of 4-toluene 9H-carbazole-9-carbodithioate (TCzC) was chemically synthesized and character- ized by Fourier Transform Infrared (FTIR), proton nuclear magnetic resonance ( 1 H-NMR), and carbon nuclear magnetic resonance ( 13 C-NMR) spectroscopies. Specific (Csp) and double layer capacitances (Cdl) of the electro-coated poly(car- bazole) and poly(TCzC) films were obtained on glassy carbon electrode (GCE) by impedimetric method with DC potential from -0.1 to +1.0 V by increasing potential of 0.2 V. The polymers were characterized by Cyclic voltammetry (CV), Fourier transform infrared reflectance-attenuated total reflection spectroscopy (FTIR-ATR), Atomic force microscopy (AFM), and Electrochemical impedance spectroscopy (EIS). The use of additional variable (DC potential) helped to disam- biguate the equivalent circuit model of R(C(R(Q(RW))))(CR). Simulation results were compared with experimental data. In this study, substituted group effects of CS2 and tosyl on carbazole polymer were investigated by EIS technique. CS2 group together with tosyl group in the structure of carbazole decreased the specific capacitance value (Csp = 0.43 mF·cm -2 ) com- pared to PCz (Csp = 1.44 mF·cm -2 ). Electropolymerization formation was seriously affected by substituted groups of CS2 and tosyl on conjugation system because of the electron donor and acceptor ability.

Facile synthesis of functionalizated carbon nanospheres for determination of Cu2+

In this research, quantities of carbon nanospheres (CNSs) were prepared with a convenient and low cost method at atmospheric pressure and functionalized with the xanthate group in a simple way. The materials were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), Fourier transform infrared spectra (FT-IR), and X-ray photoelectron spectroscopy (XPS). In addition, the carbon nanospheres (CNSs) xanthate was applied to fabricate a modified carbon paste electrode (CPE) for the selective and sensitive determination of Cu(2+). Also, the xanthate with a -CS2 group was applied as a chelating agent to enrich Cu(2+) in the determination of Cu(2+) ions. In square wave stripping voltammetry (SWSV), the carbon nanospheres xanthate-modified CPE displayed linear response to Cu(2+) in the concentration range of 8.0 × 10(-8) M to 2.2 × 10(-6) M with a detection limit (S/N = 3) of 3.55 × 10(-8) M. The modified electrode exhibited excellent analytical performance in terms of high repeatability. Finally, it was applied to detect Cu(2+) in the wastewater samples with high accuracy and good recovery, indicating its promising application in the routine analysis of metal ions.

Experimental renal preservation by normothermic resuscitation perfusion with autologous blood

Normothermic perfusion (NP) has the potential to improve metabolic support and maintain the viability of ischaemically damaged organs. This study investigated the effects of NP compared with current methods of organ preservation in a model of controlled non-heart-beating donor (NHBD) kidneys. Porcine kidneys (n = 6 in each group) were subjected to 10 min warm ischaemia and then preserved as follows: 2 h cold storage (CS) in ice (CS2 group), 18 h CS (CS18 group), 18 h cold machine perfusion (CP group) or 16 h CS + 2 h NP (NP group). Renal haemodynamics and function were measured during 3 h reperfusion with autologous blood using an isolated organ perfusion system. Increasing CS from 2 to 18 h reduced renal blood flow (mean(s.d.) area under the curve (AUC) 444(57) versus 325(70) ml per 100 g; P = 0.004), but this was restored by NP (563(119) ml per 100 g; P = 0.035 versus CS18). Renal function was also better in CS2, CP and NP groups than in the CS18 group (mean(s.d.) serum creatinine fall 92(6), 79(9) and 64(17) versus 44(13) per cent respectively; P = 0.001). The AUC for serum creatinine was significantly lower with CS for 2 h than for 18 h (mean(s.d.) 1102(2600) versus 2156(401) micromol/l.h; P = 0.001), although values in CP and NP groups were not significantly different from those in the CS2 group (1354(300) and 1756(280) micromol/l.h respectively). Two hours of NP increased the adenosine 3'-triphosphate : adenosine 3'-diphosphate ratio to a significantly higher level than the preperfusion values in all other groups (P = 0.046). NP with oxygenated blood was able to restore depleted ATP levels and reverse some of the deleterious effects of CS.

The +838 C/G MT2A polymorphism, metals, and the inflammatory/immune response in carotid artery stenosis in elderly people.

Carotid artery stenosis (CS) is a well-established risk factor for stroke. Increased proinflammatory chemokines, enhanced metallothionein (MT), and altered metal homeostasis may play roles in atherosclerosis progression and plaque destabilization. MT may sequester zinc during chronic inflammation, provoke zinc deficiency, and modulate NK cell cytotoxicity. A recent investigation of older patients with diabetes and atherosclerosis showed an association between the -209 A/G MT2A polymorphism, CS, and zinc status. In this study, we evaluated the relationship between two MT2A polymorphisms (-209 and + 838 locus), metal status, and inflammatory/immune response in older patients with CS only (the CS1 group) or with CS and previous cerebrovascular episodes (transient ischemic attack or stroke) (the CS2 group). A total of 506 individuals (188 CS1, 100 CS2, and 218 healthy controls) were studied. Atherosclerotic patients (CS1 and CS2) showed increased levels of MT, MCP-1, and RANTES, reduced NK cell cytotoxicity, and altered trace element concentrations (zinc, copper, magnesium, iron). The +838 C/G MT2A polymorphism was differently distributed in CS1 and CS2 patients, who displayed the GG genotype (C-) with significantly higher frequency than elderly controls. C- carriers showed increased MCP-1 and decreased NK cell cytotoxicity, CD56+ cells, and intracellular zinc availability along with decreased zinc, copper, and magnesium content in erythrocytes and increased iron in plasma. C- carriers also showed a major incidence of soft carotid plaques. In conclusion, the +838 C/G MT2A polymorphism seems to influence inflammatory markers, zinc availability, NK cell cytotoxicity, and trace element status, all of which may promote CS development.

The +838 C/G MT2A Polymorphism, Metals, and the Inflammatory/Immune Response in Carotid Artery Stenosis in Elderly People

Carotid artery stenosis (CS) is a well-established risk factor for stroke. Increased proinflammatory chemokines, enhanced metallothionein (MT), and altered metal homeostasis may play roles in atherosclerosis progression and plaque destabilization. MT may sequester zinc during chronic inflammation, provoke zinc deficiency, and modulate NK cell cytotoxicity. A recent investigation of older patients with diabetes and atherosclerosis showed an association between the -209 A/G MT2A polymorphism, CS, and zinc status. In this study, we evaluated the relationship between two MT2A polymorphisms (-209 and + 838 locus), metal status, and inflammatory/immune response in older patients with CS only (the CS1 group) or with CS and previous cerebrovascular episodes (transient ischemic attack or stroke) (the CS2 group). A total of 506 individuals (188 CS1, 100 CS2, and 218 healthy controls) were studied. Atherosclerotic patients (CS1 and CS2) showed increased levels of MT, MCP-1, and RANTES, reduced NK cell cytotoxicity, and altered trace element concentrations (zinc, copper, magnesium, iron). The +838 C/G MT2A polymorphism was differently distributed in CS1 and CS2 patients, who displayed the GG genotype (C-) with significantly higher frequency than elderly controls. C- carriers showed increased MCP-1 and decreased NK cell cytotoxicity, CD56+ cells, and intracellular zinc availability along with decreased zinc, copper, and magnesium content in erythrocytes and increased iron in plasma. C- carriers also showed a major incidence of soft carotid plaques. In conclusion, the +838 C/G MT2A polymorphism seems to influence inflammatory markers, zinc availability, NK cell cytotoxicity, and trace element status, all of which may promote CS development.

Cyclosporin A Has a Protective Effect with Induced Upregulation of Hsp70 and nNOS on Severe Spinal Cord Ischemic Injury in Rabbits

The purpose of this study is to ascertain the neuroprotective effect of cyclosporin A on the 25-min surgical ischemia model in the spinal cords of rabbits with neuropathological correlation and histoimmunochemical analyses measuring HSP70 and neuronal NOS (nNOS). New Zealand white rabbits were randomly divided into four groups (each n = 8): the C2, C7, Cs2, and Cs7 groups. The C2 and C7 groups underwent a 25-min surgical aortic cross-clamp without intervention and were sacrificed respectively on day 2 and on day 7 postoperatively. The Cs2 and Cs7 groups received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed respectively on day 2 and day 7 postoperatively. Neurologic functions were evaluated on postoperative days 2 and 7 using the Tarlov scoring system. Then the rabbits were sacrificed for histopathologic observation. HSP 70 and nNOS stains with TUNEL assay were done for the C2 and Cs2 groups. All rabbits survived the experimental procedure. Tarlov's score for the Cs7 group (2.75 ± 0.89) was significantly higher than that of the C7 group (1.25 ± 1.39) (p <. 05). Tarlov's score of the Cs7 group was also statistically higher on day 7 than on day 2 (p <. 05). Strong correlation between the neurological and histological scorings was found. The TUNEL assay showed that the mean number of positive cells in the C2 group was 17.5 ± 22.6 and in the Cs2 group was 12.5 ± 11.1, but there was no statistically significant difference between the groups. There was more expression of HSP70 and nNOS in the cyclosporin groups than in the ischemia groups. In conclusion, this study demonstrates that cyclosporin A reduces neurological injury in the rabbit model of 25-min spinal cord ischemia. The neuroprotective effect of cyclosporin A against ischemia seems to be related to overexpressions of nNOS and HSP70.

Synthesis and spectroscopic characterization of new organotin(IV) complexes with bis(3,5-dimethylpyrazol-1-yl)dithioacetate

New organotin(IV) derivatives containing the anionic ligand bis(3,5-dimethylpyrazolyl)dithioacetate [L2CS2]− have been synthesized by reaction of SnR n X4− n (R = Me, Ph, n Bu or Cy; n = 1–3) acceptors and Li[L2CS2]. Mononuclear complexes of the type [L2CS2]R n SnCl4− n −1} have been obtained and fully characterized by elemental analyses and FT-IR in the solid state, and by NMR (1H and 119Sn) spectroscopy, conductivity measurements and electrospray ionization mass spectrometry (ESI-MS) in solution. ESI-MS spectra of methanol solutions of diorganotin derivatives, recorded with fragmentor potentials of 0, 50, 100 and 150 V, show the occurrence at 150 V of peaks attributable to the loss of the CS2 group from the ligands and the formation of stable tetraorganodistannoxane species.

Synthesis and characterisation of cyanodithioimidocarbonate [C2N2S2]2- complexes.

[PPh4]2[M(C2N2S2)2](M = Pt, Pd) and [Pt(C2N2S2)(PR3)2](PR3= PMe2Ph, PPh3) and [Pt(C2N2S2)(PP)](PP = dppe, dppm, dppf) were all obtained by the reaction of the appropriate metal halide containing complex with potassium cyanodithioimidocarbonate. The dimeric cyanodithioimidocarbonate complexes [[Pt(C2N2S2)(PR3)]2](PR3 = PMe2Ph), [M[(C2N2S2)(eta5-C5Me5)]2](M = Rh, Ir)and [[Ru(C2N2S2)(eta6-p-MeC6H4iPr)]2] have been synthesised from the appropriate transition metal dimer starting material. The cyanodithioimidocarbonate ligand is S,S and bidentate in the monomeric complexes with the terminal CN group being approximately coplanar with the CS2 group and trigonal at nitrogen thus reducing the planar symmetry of the ligand. In the dimeric compound one of the sulfur atoms bridges two metal atoms with the core exhibiting a cubane-like geometry.

CS2 and EV Group reveal bumping technology relationship

CS2 and EV Group reveal bumping technology relationship