Copper(I)-Catalyzed Asymmetric Synthesis of P-Chiral Aminophosphinites.

Herein, a copper(I)-catalyzed reaction of diarylphosphines and O-benzoyl hydroxylamines is developed. In the cases of symmetrical diarylphosphines, a series of aminophosphinites is prepared in high yields. In the cases of unsymmetrical diarylphosphines, an array of P-chiral aminophosphinites is synthesized in high yields with high enantioselectivity by using a copper(I)-(R,RP )-Ph-FOXAP complex as a chiral catalyst. Based on several control experiments and 31 P NMR studies, a two-electron redox mechanism involving the dynamic kinetic asymmetric transformation of unsymmetrical diarylphosphines is proposed for the copper(I)-catalyzed asymmetric reaction. Finally, one representative P-chiral phosphoric amide generated through the oxidation with H2 O2 is transformed to a chiral diarylphosphinate in high yield with retained enantioselectivity, which allows further transformations towards various P-chiral tertiary phosphines.

Copper(I)-Catalyzed Asymmetric Alkylation of Unsymmetrical Secondary Phosphines.

A copper(I)-catalyzed asymmetric alkylation of HPAr1Ar2 with alkyl halides is uncovered, which provides an array of P-stereogenic phosphines in generally high yield and enantioselectivity. The electrophilic alkyl halides enjoy a broad substrate scope, including allyl bromides, propargyl bromide, benzyl bromides, and alkyl iodides. Moreover, 11 unsymmetrical diarylphosphines (HPAr1Ar2) serve as competent pronucleophiles. The present methodology is also successfully applied to catalytic asymmetric double and triple alkylation, and the corresponding products were obtained in moderate diastereo- and excellent enantioselectivities. Some 31P NMR experiments indicate that bulky HPPhMes exhibits weak competitively coordinating ability to the Cu(I)-bisphosphine complex, and thus the presence of stoichiometric HPAr1Ar2 does not affect the enantioselectivity significantly. Therefore, the high enantioselectivity in this reaction is attributed to the high performance of the unique Cu(I)-(R,RP)-TANIAPHOS complex in asymmetric induction. Finally, one monophosphine and two bisphosphines prepared by the present reaction are employed as efficient chiral ligands to afford three structurally diversified Cu(I) complexes, which demonstrates the synthetic utility of the present methodology.

Copper(I)-Catalyzed Asymmetric 1,4-Conjugate Hydrophosphination of α,ß-Unsaturated Amides.

A catalytic asymmetric conjugate hydrophosphination of α,ß-unsaturated amides is accomplished by virtue of the strong nucleophilicity of copper(I)-PPh2 species, which provides an array of chiral phosphines bearing an amide moiety in high to excellent yields with excellent enantioselectivity. Furthermore, the dynamic kinetic resolution of unsymmetrical diarylphosphines (HPAr1Ar2) is successfully carried out through the copper(I)-catalyzed conjugate addition to α,ß-unsaturated amides, which affords P-chiral phosphines with good-to-high diastereoselectivity and high enantioselectivity. 1H NMR studies show that the precoordination of HPPh2 to copper(I)-bisphosphine complex is critical for the efficient deprotonation by Barton's Base. Moreover, the relative stability of the copper(I)-(R,RP)-TANIAPHOS complex in the presence of excessive HPPh2, confirmed by 31P NMR studies, is pivotal for the high asymmetric induction, as the ligand exchange between bisphosphine and HPPh2 would significantly reduce the enantioselectivity. At last, a double catalytic asymmetric conjugate hydrophosphination furnishes the corresponding product in high yield with high diastereoselectivity and excellent enantioselectivity, which is transformed to a chiral pincer palladium complex in moderate yield. This chiral palladium complex is demonstrated as an excellent catalyst in the asymmetric conjugate hydrophosphination of chalcone.

Detection of SNPs of T2DM susceptibility genes by a ligase detection reaction-fluorescent nanosphere technique.

OBJECTIVE: To establish a high throughput, low cost, and simple nanotechnology-based method for the detection of single nucleotide polymorphism (SNP) loci in type 2 diabetes mellitus (T2DM). METHODS: Multiplex ligase detection reaction (LDR) amplification was performed using fluorescently labeled magnetic nanosphere-bound upstream LDR probes and downstream probes labeled with a unique fluorescent group for each SNP locus. The amplified LDR products were separated by magnetic nanospheres and then scanned by fluorescence spectroscopy. Four SNP loci associated with T2DM were detected, including the rs13866634 locus in SLC30A8, rs10811661in CDKN2A/2B, rs1111875 in the HHEX gene, and rs7903146 in the TCF7L2 gene. The SNP genotype was also determined by DNA sequencing as a control. RESULTS: The SNP genotypes of the four gene loci determined by the nanosphere-based multiplex LDR method were consistent with the DNA sequencing results. The accuracy rate was 100%. CONCLUSION: A method based on multiplex PCR and LDR was established for simultaneous detection of four SNP loci of T2DM susceptibility genes.

Genetic Investigation of Complement Pathway Genes in Type 2 Diabetic Retinopathy: An Inflammatory Perspective.

Diabetic retinopathy (DR) has complex multifactorial pathogenesis. This study aimed to investigate the association of complement pathway genes with susceptibility to DR. Eight haplotype-tagging SNPs of SERPING1 and C5 were genotyped in 570 subjects with type 2 diabetes: 295 DR patients (138 nonproliferative DR [NPDR] and 157 proliferative DR [PDR]) and 275 diabetic controls. Among the six C5 SNPs, a marginal association was first detected between rs17611 and total DR patients (P = 0.009, OR = 0.53 for recessive model). In stratification analysis, a significant decrease in the frequencies of G allele and GG homozygosity for rs17611 was observed in PDR patients compared with diabetic controls (Pcorr = 0.032, OR = 0.65 and Pcorr = 0.016, OR = 0.37, resp.); it was linked with a disease progression. A haplotype AA defined by the major alleles of rs17611 and rs1548782 was significantly predisposed to PDR with increased risk of 1.54 (Pcorr = 0.023). Regarding other variants in C5 and SERPING1, none of the tagging SNPs had a significant association with DR and its subgroups (all P > 0.05). Our study revealed an association between DR and C5 polymorphisms with clinical significance, whereas SERPING1 is not a major genetic component of DR. Our data suggest a link of complement pathway with DR pathogenesis.

Protective effects of testosterone propionate on reproductive toxicity caused by Endosulfan in male mice.

To investigate the protective effect of testosterone propionate (TP) on reproductive toxicity caused by endosulfan in male mice, three group experiments were designed: the control group received 0 and 0, the endosulfan group received 0.8 and 0, and the endosulfan + TP group received 0.8 mg/kg/d endosulfan and 10 mg/kg/d TP, respectively. The results showed that TP significantly prevented the declines of concentration and motility rates in sperm, reduced the rate of sperm abnormalities in epididymis; and antagonized the decreases in spermatogenous cell and sperm numbers in testes induced by endosulfan. TP also decreased the numbers of cavities formed, prevented the decreases of plasma testosterone and androgen receptor (AR) mRNA in testicular tissue, alleviated the increase of LH induced by endosulfan. It is likely that TP relieve the reproductive toxicity by reversing the endosulfan-induced decreases in testosterone secretion and AR expression that resulted from the alteration of Leydig cell function.

In vitro mechanistic study of endosulfan-induced spermatogenic cell apoptosis in the mouse.

To investigate the mechanisms of endosulfan-induced reproductive toxicity, the spermatogenic cell lines (GC-1 spg) of mice were treated with 0, 6, 12, and 24 µg/ml endosulfan for 24 h in vitro The results showed that endosulfan induced apoptosis as well as oxidative stress and mitochondrial dysfunction. Reactive oxygen species and damage of mitochondrial structure were considered as major factors to GC-1 spg cells apoptosis. We further examined the expression of apoptosis-related proteins in mitochondria pathway by Western blot and immunohistochemistry analysis as well as activities. The results showed that endosulfan significantly improved the expressions of cytochrome c and B-cell lymphoma 2 (Bcl-2)-associated X protein and increased the activities of caspases 9 and 3 as well as the downregulation of the expression of Bcl-2 in GC-1 spg cells. The results suggested that exposure to endosulfan might induce the apoptosis of spermatogenic cells via mitochondria-dependent pathway mediated by oxidative stress resulting in the damage of mitochondrial structure and mitochondrial dysfunction.

Variance of Serum Lipid Levels in Stroke Subtypes.

BACKGROUND: An increasing number of epidemiological studies have identified a close relationship between dyslipidemia and atherosclerotic stroke. Indeed, lipid metabolism is significantly different among the different ischemic stroke subtypes. There are few studies available regarding risk factors for specific subtypes of ischemic stroke, and in particular, there is little evidence about the role of dyslipidemia. The aim of this study is to determine the relationship between acute ischemic stroke subtype and serum lipid level. METHODS: The levels of serum lipid including TC, TG, LDL-C, HDL-C, apoA, apoB, apoE, and LP (a) were tested in 362 ischemic stroke patients and 181 healthy controls. Lipid levels were analyzed in stroke subtypes according to the TOAST classification. RESULTS: Levels of TC, TG, LDL-C, apoA, apoB, apoE, and LP (a) were significantly higher and HDL-C levels were significantly lower in the patient group relative to control. The TC/HDL-C ratio, TG/HDL-C ratio, and LDL-C/HDL-C ratio were remarkably higher in the patient group. The levels of TC, TG, LDL-C, apoA, apoB, apoE, and LP(a) were markedly higher and HDL-C was markedly lower in the large-artery atherosclerosis stroke subtype relative to the cardioembolism subtype. Compared with the small-vessel occlusion group, the level of LP(a), TC, and TC/HDL-C were strikingly higher in the cardioembolism group. The TC/HDL-C ratio was different among subgroups, with the large-artery atherosclerosis group exhibiting the highest value. For TC, TG, LDL-C, apoA, apoB, apoE, LP(a), TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C levels a statistically significant difference was found between the large-artery atherosclerosis group and the small-vessel occlusion group. CONCLUSIONS: We found that LDL-C and TC levels may be independent predictors for the occurrence of large-artery atherosclerotic stroke.

Endoplasmic reticulum stress is involved in the connection between inflammation and autophagy in type 2 diabetes.

Type 2 diabetes is a chronic inflammatory disease. A number of studies have clearly demonstrated that cytokines such as interleukin 1ß (IL1ß) contribute to pancreatic inflammation, leading to impaired glucose homeostasis and diabetic disease. There are findings which suggest that islet ß-cells can secrete cytokines and cause inflammatory responses. In this process, thioredoxin-interacting protein (TXNIP) is induced by endoplasmic reticulum (ER) stress, which further demonstrates a potential role for ER stress in innate immunity via activation of the NOD-like receptor (NLRP) 3/caspase1 inflammasome and in diabetes pathogenesis via the release of cytokines. Recent developments have also revealed a crucial role for the autophagy pathway during ER stress and inflammation. Autophagy is an intracellular catabolic system that not only plays a crucial role in maintaining the normal islet architecture and intracellular insulin content but also represents a form of programmed cell death. In this review, we focus on the roles of autophagy, inflammation, and ER stress in type 2 diabetes but, above all, on the connections among these factors.

A role for curcumin in preventing liver fibrosis in animals: a systematic review and meta-analysis.

Objective: This meta-analysis aimed to determine the efficacy of curcumin in preventing liver fibrosis in animal models. Methods: A systematic search was conducted on studies published from establishment to November 2023 in PubMed, Web of Science, Embase, Cochrane Library, and other databases. The methodological quality was assessed using Sycle's RoB tool. An analysis of sensitivity and subgroups were performed when high heterogeneity was observed. A funnel plot was used to assess publication bias. Results: This meta-analysis included 24 studies involving 440 animals with methodological quality scores ranging from 4 to 6. The results demonstrated that curcumin treatment significantly improved Aspartate aminotransferase (AST) [standard mean difference (SMD) = -3.90, 95% confidence interval (CI) (-4.96, -2.83), p < 0.01, I2 = 85.9%], Alanine aminotransferase (ALT)[SMD = - 4.40, 95% CI (-5.40, -3.40), p < 0.01, I2 = 81.2%]. Sensitivity analysis of AST and ALT confirmed the stability and reliability of the results obtained. However, the funnel plot exhibited asymmetry. Subgroup analysis based on species and animal models revealed statistically significant differences among subgroups. Furthermore, curcumin therapy improved fibrosis degree, oxidative stress level, inflammation level, and liver synthesis function in animal models of liver fibrosis. Conclusion: Curcumin intervention not only mitigates liver fibrosis but also enhances liver function, while concurrently modulating inflammatory responses and antioxidant capacity in animal models. This result provided a strong basis for further large-scale animal studies as well as clinical trials in humans in the future. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024502671.

Establishment of a mandible defect model in rabbits infected with multiple bacteria and bioinformatics analysis.

Objective: A model of chronic infectious mandibular defect (IMD) caused by mixed infection with Staphylococcus aureus and Pseudomonas aeruginosa was established to explore the occurrence and development of IMD and identify key genes by transcriptome sequencing and bioinformatics analysis. Methods: S. aureus and P. aeruginosa were diluted to 3 × 108 CFU/mL, and 6 × 3 × 3 mm defects lateral to the Mandibular Symphysis were induced in 28 New Zealand rabbits. Sodium Morrhuate (0.5%) and 50 µL bacterial solution were injected in turn. The modeling was completed after the bone wax closed; the effects were evaluated through postoperative observations, imaging and histological analyses. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein‒protein interaction (PPI) network analyses were performed to investigate the function of the differentially expressed genes (DEGs). Results: All rabbits showed characteristics of infection. The bacterial cultures were positive, and polymerase chain reaction (PCR) was used to identify S. aureus and P. aeruginosa. Cone beam CT and histological analyses showed inflammatory cell infiltration, pus formation in the medullary cavity, increased osteoclast activity in the defect area, and blurring at the edge of the bone defect. Bioinformatics analysis showed 1,804 DEGs, 743 were upregulated and 1,061 were downregulated. GO and KEGG analyses showed that the DEGs were enriched in immunity and osteogenesis inhibition, and the core genes identified by the PPI network were enriched in the Hedgehog pathway, which plays a role in inflammation and tissue repair; the MEF2 transcription factor family was predicted by IRegulon. Conclusion: By direct injection of bacterial solution into the rabbit mandible defect area, the rabbit chronic IMD model was successfully established. Based on the bioinformatics analysis, we speculate that the Hedgehog pathway and the MEF2 transcription factor family may be potential intervention targets for repairing IMD.

Sarpogrelate inhibits the expression of ICAM-1 and monocyte-endothelial adhesion induced by high glucose in human endothelial cells.

Hyperglycemia is the major cause of diabetic angiopathy. Sarpogrelate hydrochloride is an antiplatelet drug, and expected to be useful in the treatment of chronic arterial occlusive diseases. The aim of our study was to evaluate the possible effects of sarpogrelate hydrochloride on adhesion molecule expression and its underlying mechanism in the prevention and treatment of cardiovascular disorders. Intercellular adhesion molecule-1 (ICAM-1) expression and superoxide dismutase (SOD) activity were determined after endothelial cells were exposed to high glucose in the absence and presence of sarpogrelate hydrochloride. Coincubation of endothelial cells with high glucose for 24 h resulted in a significant increase of monocyte-endothelial cell adhesion and the expression of ICAM-1 (P < 0.01). These effects were abolished by sarpogrelate hydrochloride and sarpogrelate hydrochloride significantly increased SOD activities (40 ± 8 vs. 47 ± 7, n = 8, P < 0.01). The low dose sarpogrelate group (0.1 µM) had significantly higher monocyte-endothelial cell adhesion and the expression of ICAM-1 than medium dose sarpogrelate group (1.0 µM) and high dose sarpogrelate group (10.0 µM) (P < 0.05 for comparison among three groups and P < 0.01 for difference between low and high dose sarpogrelate groups). These findings suggested that sarpogrelate hydrochloride was able to protect vascular endothelium from dysfunction induced by high glucose.

Association of CFH and CFB gene polymorphisms with retinopathy in type 2 diabetic patients.

OBJECTIVES: The complement system is a key component of innate immunity and has been implicated in the pathogenesis of diabetic retinopathy (DR). This study aimed at investigating whether polymorphisms of two genes in the complement pathway, complement factor H (CFH) and complement factor B (CFB), are associated with DR. METHODS: 552 well-defined subjects with type 2 diabetes, consisting of 277 DR patients and 275 diabetic controls, were recruited. Four Tag-SNPs rs1048709, rs537160, rs4151657, and rs2072633 in CFB and rs800292 (I62V) in CFH were examined using TaqMan Genotyping Assays. RESULTS: There were significant increases in the frequencies of A allele and AA genotype for rs1048709 in DR patients compared with diabetic controls (P(corr) = 0.035, OR = 1.42; P(corr) = 0.02, OR = 2.27, resp.): meanwhile, significant decreases in the frequencies of A allele and AA genotype for rs800292 were observed in DR patients compared with diabetic controls (P(corr) = 0.04, OR = 0.72; P(corr) = 0.015, OR = 0.51, resp.). Joint effect of these two loci was also identified. Moreover, rs800292/AA genotype was found to be related with delayed progression to DR. CONCLUSIONS: CFH-rs800292 and CFB-rs1048709 are associated with the presence of DR, which strengthens the concept that complement system plays an important role in the pathogenesis of DR.

Involvement of endoplasmic reticulum stress in apoptosis of testicular cells induced by low-dose radiation.

The study examined the role of endoplasmic reticulum stress (ERS) and signaling pathways of inositol-requiring enzyme-1 (IRE1), RNA-activated protein kinase-like ER kinase (PERK) and activating transcription factor-6 (ATF6) in apoptosis of mouse testicular cells treated with low-dose radiation (LDR). In the dose-dependent experiment, the mice were treated with whole-body X-ray irradiation at different doses (25, 50, 75, 100 or 200 mGy) and sacrificed 12 h later. In the time-dependent experiment, the mice were exposed to 75 mGy X-ray irradiation and killed at different time points (3, 6, 12, 18 or 24 h). Testicular cells were harvested for experiments. H(2)O(2) and NO concentrations, and Ca(2+)-ATPase activity were detected by biochemical assays, the calcium ion concentration ([Ca(2+)]i) by flow cytometry using fluo-3 probe, and GRP78 mRNA and protein expressions by quantitative real-time RT-PCR (qRT-PCR) and Western blotting, respectively. The mRNA expressions of S-XBP1, JNK, caspase-12 and CHOP were measured by qRT-PCR, and the protein expressions of IRE1α, S-XBP1, p-PERK, p-eIF2α, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP by Western blotting. The results showed that the concentrations of H2O2 and NO, the mRNA expressions of GRP78, S-XBP1, JNK, caspase-12 and CHOP, and the protein expressions of GRP78, S-XBP1, IRE1α, p-PERK, p-eIF2α, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP were significantly increased in a time- and dose-dependent manner after LDR. But the [Ca(2+)]i and Ca(2+)-ATPase activities were significantly decreased in a time- and dose-dependent manner. It was concluded that the ERS, regulated by IRE1, PERK and ATF6 pathways, is involved in the apoptosis of testicular cells in LDR mice, which is associated with ERS-apoptotic signaling molecules of JNK, caspase-12 and CHOP.

Copper(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of 1,3-enynes and azomethine ylides.

Herein, we report a copper(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides and 1,3-enynes, which provides a series of chiral poly-substituted pyrrolidines in high regio-, diastereo-, and enantioselectivities. Both 4-aryl-1,3-enynes and 4-silyl-1,3-enynes serve as suitable dipolarophiles while 4-alkyl-1,3-enynes are inert. Moreover, the method is successfully applied in the construction of both tetrasubstituted stereogenic carbon centers and chiral spiro pyrrolidines. The DFT calculations are also conducted, which imply a concerted mechanism rather than a stepwise mechanism. Finally, various transformations started from the pyrrolidine bearing a triethylsilylethynyl group and centered on the alkyne group are achieved, which compensates for the inertness of 4-alkyl-1,3-enynes in the present reaction.

Changes in serum tumor markers in type 2 diabetes mellitus with microalbuminuria.

Objectives: The objective of this study was to investigate changes in serum tumor markers in type 2 diabetes mellitus (T2DM) with microalbuminuria and analyze the relationship between tumor markers and microalbuminuria. Methods: A total of 956 T2DM patients aged 40-70 years hospitalized in the Department of Endocrinology, Xinhua Hospital, China, affiliated with Shanghai Jiaotong University School of Medicine, were enrolled from January 2018 to December 2020. The sample comprised 313 T2DM patients with microalbuminuria and 643 T2DM patients with normal urinary microalbumin levels. After assessing the changes in serum tumor markers in T2DM with microalbuminuria, we analyzed the risk of microalbuminuria by the serum tumor marker category using multiple logistic regression analysis. Results: Serum CEA, CA199, CA125, CA153, CA211, SCC, CA242, and CA50 levels were significantly higher in T2DM patients with microalbuminuria than in those without microalbuminuria, while serum AFP levels were lower in the microalbuminuria group (P < 0.05). Following adjustment of confounders, serum CEA, CA211, and SCC were independently associated with microalbuminuria in T2DM. An ROC curve was used to estimate the cutoff point of tumor markers for microalbuminuria. Taking the values under the cutoff points as a reference, values for CEA, CA211, and SCC above the cutoff points indicated a significantly high risk of microalbuminuria. The OR of increased CEA for microalbuminuria was 2.006 (95%CI 1.456-2.765), the OR of increased CA211 for microalbuminuria was 1.505 (95%CI 1.092-2.074), and the OR of increased SCC for microalbuminuria was 1.958 (95%CI 1.407-2.724). Conclusion: Several serum tumor markers were related to microalbuminuria in T2DM. Serum tumor markers such as CEA, SCC, and CA211 may indicate early diabetic nephropathy, particularly when elevated in combination.

Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection: a randomized controlled trial.

BACKGROUND: Saline nasal irrigation is an effective therapy for relieving common cold symptoms. This study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation (PSNI) on children with mild and asymptomatic infection with Omicron. METHODS: This randomized controlled trial was conducted in Shanghai, China, and 403 children with mild and asymptomatic infection with Omicron were included. These children were allocated into the PSNI group and the control group. The primary outcome was the duration of viral shedding (DVS), and the secondary outcome was the change in clinical symptoms. RESULTS: The median age of all participants was 5.59 (6.26) years old. The DVS was significantly shorter in the PSNI group [2.40 (1.13)] than in the control group [3.09 (2.14)] (P = 0.014). The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group [hazard ratio (HR), 1.27; 95% confidence interval (CI), 1.04-1.55; P = 0.017]. Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI group. The proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group, but there was no evidence showing that PSNI contributes to the benefit compared with the control group. CONCLUSION: PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

Recent advances in understanding the biochemical and molecular mechanism of diabetic cardiomyopathy.

Cardiovascular complications account for significant morbidity and mortality in the diabetic population. Diabetic cardiomyopathy (DCM), a prominent cardiovascular complication, has been recognized as a microvascular disease that may lead to heart failure. During the past few decades, research progress has been made in investigating the pathophysiology of the disease; however, the exact molecular mechanism has not been elucidated, making therapeutic a difficult task. In this review article, we have discussed a number of diabetes-induced metabolites such as glucose, advanced glycation end products, protein kinase C, free fatty acid and oxidative stress and other related factors that are implicated in the pathophysiology of the DCM. An understanding of the biochemical and molecular changes especially early in the DCM may lead to new and effective therapies toward prevention and amelioration of DCM, which is important for the millions of individuals who already have or are likely to develop the disease before a cure becomes available.

Role of the Na(+)/Ca(2+) exchanger on the development of diabetes mellitus and its chronic complications.

Diabetes mellitus (DM) is a serious metabolic disorder with micro- and macrovascular complications that results in significant morbidity and mortality. It is well established that cytosolic Ca(2+) play an important role in controlling insulin secretion in pancreatic ß-cells. The Na(+)/Ca(2+) exchanger (NCX), an ion transport protein, is expressed in the plasma membrane of virtually all animal cells. NCX is a reversible carrier that can mediate the transport of Ca(2+) across the plasma membrane in both directions. Therefore, great efforts have been made to identify NCX associated with DM. NCX is expressed in several tissues, and acts in the protection against intracellular calcium overload; in the regulation of insulin secretion by beta cells, and in improving vascular endothelium-dependent relaxation. All these mechanisms are associated with DM pathogenesis and its chronic complications. Therefore, NCX is a candidate protein for the development of these disorders. Only a few studies investigated NCX in relation to chronic complications of diabetes, with inconclusive results.

Mitochondrial energy metabolism dysfunction involved in reproductive toxicity of mice caused by endosulfan and protective effects of vitamin E.

The experiment was designed to study the mechanism of reproductive toxicity caused by endosulfan in mice and protective effects of vitamin E. The experiment was composed of three groups: the control group did not receive any endosulfan and vitamin E; the endosulfan exposed group received 0.8 mg/kg/d endosulfan and 0mg/kg/d vitamin E; and the endosulfan+vitamin E group received 0.8 mg/kg/d endosulfan and 100mg/kg/d vitamin E. The results showed that vitamin E significantly reversed the decline of the concentration and motility rate of sperm, and inhibited the increase of sperm abnormality rate caused by endosulfan. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and lactate dehydrogenase-C4 (LDH-C4) and the level of adenosine triphosphate (ATP) in the endosulfan+vitamin E group were higher while the malondialdehyde (MDA) content was significantly lower than those of the endosulfan exposed group. The results from pathology and electron microscope observed showed vitamin E decreased the cavities formation by desquamating of spermatogenic cells, stopped the ruptures and disappearances of mitochondrial cristaes in spermatogenic cells, and prevented the breakages and partial dissolvings of sperm tails induced by endosulfan. It is likely that endosulfan could directly damage sperm structures by oxidative stress, leading to a decrease in sperm quantity and quality. It also could indirectly cause a decline in reproductive function by damaging the structure of mitochondria, resulting in energy metabolism dysfunction, which could be one of the mechanisms behind the reproductive toxicity induced by endosulfan. It was inferred that vitamin E helps maintain the structural integrities of sperm architecture and prevent mitochondrial dysfunction through inhibiting oxidative stress, and thereby prevent the reproductive dysfunctions caused by endosulfan.