Primary care providers' knowledge, attitudes, and practices related to prediabetes in China: A cross-sectional study.

Background: The management of prediabetes has great clinical significance, and primary care providers (PCPs) play important roles in the management and prevention of diabetes in China. Nevertheless, little is known about PCPs' knowledge, attitudes, and practices (KAP) regarding prediabetes. This cross-sectional study aimed to assess the KAP regarding prediabetes among PCPs in the Central China region. Methods: This cross-sectional study was conducted using self-administered KAP questionnaires among PCPs from Central China region. Results: In total, 720 PCPs completed the survey. Most physicians (85.8%) claimed to be aware of the adverse effects of prediabetes and reported positive attitudes toward prediabetes prevention, but the PCPs' knowledge of prediabetes and management practices showed substantial gaps. The prediabetes knowledge level and practice subscale scores of the PCPs were only 54.7% and 32.6%, respectively, of the corresponding optimal scores. Female PCPs showed higher prediabetes knowledge level scores (p = 0.04) and better practice scores (p = 0.038). Knowledge and attitude scores were inversely correlated with participants' age and duration of practice (p < 0.001). The PCPs who served in township hospitals had significantly higher knowledge and attitude scores than those who served in village clinics (p < 0.001). Furthermore, knowledge and practice scores increased with increasing professional titles. Recent continuing medical education (CME) attendance had a significant positive influence on knowledge of prediabetes (p = 0.029), but more than four-fifths of the surveyed PCPs did not participate in diabetes-related CME in the past year. Conclusions: Substantial gaps were observed in PCPs' knowledge and practices regarding prediabetes in the Central China region. CME programmes were under-utilized by PCPs. Structured programmes are required to improve PCPs' prediabetes-related knowledge and practices in China.

Oxidative damage under As3+ and/or Cu2+ stress leads to apoptosis and autophagy and may be cross-talking with mitochondrial disorders in bursa of Fabricius.

Arsenic (As) exists in many forms in the whole natural environment, with As3+ the highest toxicity. Herein our study demonstrated that arsenic trioxide (As2O3) at a dose of 30 mg/kg caused serious oxidative damage to chickens' bursa of Fabricius (BF) in a time-dependent manner. Copper (Cu) is a necessary micronutrient and a key catalytic cofactor of many enzymes. We found excessive Cu (in the form of 300 mg/kg copper sulfate (CuSO4)) also induced severe oxidative stress (OxS), and its co-exposure with As3+ had a greater destructive power against oxidative system. Under electron microscope, swollen mitochondria, disappeared cristae and agglutinated chromatin were observed, accompanied by myeloid structure and autophagosome. The results showed apoptosis and autophagy occurred under the action of As3+ and Cu2+, and the situation was more serious in combined exposure group, which was further explained by terminal deoxynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine 5'-Triphosphate (dUTP) Nick-End Labeling (TUNEL). By quantitative real time polymerase chain reaction (RT-qPCR) and western blot, we found that mitochondrial dynamics were disordered under OxS, and the abnormal changes of B-cell lymphoma (Bcl)-2, p53, Bcl-2-interacting protein (Beclin)-1 and autophagy-related gene (ATG) 4B indicated the crosstalk between apoptosis and autophagy. In conclusion, apoptosis and autophagy of BF induced by As3+ and Cu2+ and mitochondrial disorder are closely related to the collapse of antioxidant system, and their connections are inseparable. Our results provide a reference for environmental risk prevention and selection of poultry feed additives and pesticides to avoid the health risks caused by As3+ and Cu2+ exposure.

The Activation of Heat-Shock Protein After Copper(II) and/or Arsenic(III)-Induced Imbalance of Homeostasis, Inflammatory Response in Chicken Rectum.

Arsenic and copper, two toxic pollutants, are powerful inducers of oxidative stress. Exposure to copper and arsenic can cause intestinal injury in cockerel. This study was carried out to investigate the effects of these two pollutants on the gastrointestinal tract of cockerels. Experimental results showed that the activity of antioxidant enzymes (catalase and glutathione peroxidase) was inhibited and the ionic balance was destroyed after exposure to copper sulfate (300 mg/kg) and/or arsenic trioxide (30 mg/kg). However, the expression of pro-inflammatory cytokines (nuclear factor kappa-B, cyclooxygenase-2, tumor necrosis factor-α, and prostaglandin E2 synthases) increased markedly. Damages to the biofilm structure and inflammatory cell infiltration were simultaneously observed during histological examination. Heat-shock proteins were also expressed in large quantities after exposure to the poisons. Collectively, exposure to arsenite and/or Cu2+ can cause rectal damage in cockerels, inducing inflammation and an imbalance in immune system responses. Sometimes, exposure to both pollutants can produce even more toxic effects. Heat-shock proteins can protect the tissue from the exotoxins but the specific mechanisms require exploration. After oral ingestion of toxins, the rectum can still be damaged, necessitating attention to the safety of poultry breeding, human food safety, and environmental protection.

Targeting the miR-122/PKM2 autophagy axis relieves arsenic stress.

Arsenic (As) is a natural hepatotoxicity inducer that is found ubiquitously in foods and environmental media. We found that arsenite exposure elicits autophagy in vivo and vitro, the specific role and regulatory mechanism of which are yet clear. MicroRNAs (miRNAs) are short noncoding RNAs that function in the posttranscriptional regulation of gene expression. Here, we report that miR-122, the most enriched constitutive miRNA in the liver, induced cell protective autophagy in arsenite-exposed hepatocytes. Arsenite exposure elevated miRNA-122 level and decreased the level of its target gene, PKM2. Under arsenic stress, overexpression of miR-122 significantly induced cell protective autophagy, characterized by lipidation of LC3-II and a corresponding consumption of p62. Conversely, autophagy inhibition by miR-122 knockdown was reversed by si-PKM2 cotransfection. We also found that miR-122 knockdown positively regulated the PI3K/Akt/mTOR pathway, and this phenomenon was reversed by cotransfecting cells with si-PKM2. Taken together, our findings show that the miR-122/PKM2 autophagy axis protects hepatocytes from arsenite stress via the PI3K/Akt/mTOR pathway; thus, miR-122 may be a potential candidate in the treatment of arseniasis.

Elemental imbalance elicited by arsenic and copper exposures leads to oxidative stress and immunotoxicity in chicken gizzard, activating the protective effects of heat shock proteins.

Arsenic (As) and copper (Cu) are ubiquitous pollutants that pose a threat to the environment. Our aim is to study the underlying mechanisms by which As and Cu act on the chicken gizzard. In order to detect ionic disorders in chicken gizzard under chronic treatment with As3+ and/or Cu2+ and whether they can induce oxidative damage as well as immune disorders, 30 mg/kg arsenic trioxide (As2O3) and/or 300 mg/kg copper sulfate (CuSO4) were added to the chicken's basal diet. After 12 weeks of exposure, trace elements were found to have significant interference, accompanied by damage to the antioxidant system. In addition, As3+ and/or Cu2+ activated the nuclear factor kappa B (NF-κB), inducing severe inflammation. At the same time, damaged structural integrity which might be caused by inflammation was discovered after hematoxylin and eosin (H&E) staining. Moreover, symbolic Th1/Th2 (Th, helper T cell) drift was also observed in treatment groups, meaning that immune function is left to be affected, and the increment in heat shock proteins may be a self-protective mechanism of gizzard. Interestingly, we found that the damage to the gizzard of chicken was aggravated in a time-dependent manner, and the combined exposure was more pathogenic than the single exposure, of which the mechanism needs further exploration. Together, this work helps move us toward a better understanding of the molecular mechanisms that mediate the interactions between Cu excess and As3+ exposures and possible health consequences in susceptible species.

Zinc alleviates arsenism in common carp: Varied change profiles of cytokines and tight junction proteins among two intestinal segments.

This study was designed to evaluate the effects of zinc on inflammation and tight junction (TJ) in different intestinal regions of common carp under sub-chronic arsenic insult. Fish were exposed to zinc (0, 1 mg/L) and arsenic trioxide (0, 2.83 mg/L) in individual or combination for a month. Inflammatory infiltration and TJ structure changes were displayed by H&E staining and transmission electron microscope. To further explore these changes, biochemical indicator (SOD), gene or protein expressions of inflammatory responses (NF-κB, IL-1ß, IL-6 and IL-8) and TJ proteins (Occludin, Claudins and ZOs) were determined. In the anterior intestine, arsenic decreased activity of SOD, mRNA levels of Occludin, Claudins and ZOs, increased mRNA levels of ILs. However, unlike the anterior intestine, arsenic has an upregulation effects of Occludin and Claudin-4 in the mid intestine. These anomalies induced by arsenic, except IL-8, were completely or partially recovered by zinc co-administration. Furthermore, transcription factor (NF-κB) nuclear translocation paralleled with its downstream genes in both intestinal regions. In conclusion, our results unambiguously suggested that under arsenic stress, zinc can partly relieve intestinal inflammation and disruption of tight junction segment-dependently.

Hepatoprotective effects of zinc (II) via cytochrome P-450/reactive oxygen species and canonical apoptosis pathways after arsenite waterborne exposure in common carp.

Chronic arsenicosis has threatened the survival of aquatic animals with molecular mechanisms yet clear. In the present study, liver damage was evident by fluctuated activities of transaminases and declined ATPases in common carp under arsenic (As) exposure for 30 days. Mechanically, As significantly decreased cytochrome P-1A (CYP1A) activity and increased reactive oxygen species (ROS) content, which corroborated mitochondrial dysfunction in the hepatocytes. This hypothesis was further suggested by Caspase-3-executed apoptosis by death receptor pathway (Fas, TNF-α and Caspase-8) and mitochondrial pathway (Bax, Bcl-2 and Caspase-9). The above results indicated that As-elicited oxidative damage lead to apoptotic hepatic injury in carp. On the contrary, zinc (Zn) exerted an ROS scavenger and an antidote to As in the present model evidenced by alleviated liver injury and restored liver function index. Moreover, Zn and As co-administration displayed partially recovered CYPs enzyme system and quenched apoptotic positive cells compared As treated alone. These outcomes could be applied to develop counter practices based on Zn preparations to decrease the biotoxicity of As.

Arsenic trioxide or/and copper sulfate co-exposure induce glandular stomach of chicken injury via destruction of the mitochondrial dynamics and activation of apoptosis as well as autophagy.

Arsenic and copper are naturally occurring element. Contamination from natural processes and anthropogenic activities can be discovered all over the world and their unique interactions with the environment lead to widespread toxicity. When the content was excessive, the organism would be hurt seriously. The glandular stomach is an important organ of the poultry gastrointestinal tract. This study was aimed to investigate the toxicity of arsenic trioxide or/and copper sulfate (As or/and Cu) on chicken glandular stomach. Seventy-two 1-day-old Hy-Line chickens were randomly divided into control (C) group, arsenic trioxide (As) group, copper sulfate (Cu) group and arsenic trioxide and copper sulfate (AsCu) group, and exposed to 30 mg/kg arsenic trioxide or/and 300 mg/kg copper sulphates for 12 weeks. The indicators of mitochondrial dynamics, apoptosis and autophagy were tested in the glandular stomach. The results showed that exposure to As or/and Cu caused mitochondrial dynamic imbalance. Additionally, the levels of pro-apoptosis and autophagy indicators were increased and the levels of anti-apoptosis indicators were decreased in the treatment groups. Beyond that, in the treatment groups, we could clearly see karyopyknosis and chromatin condensation were associated with increased apoptosis rate, as well as the disappearance of the nuclear membrane, the swelling of mitochondria and the accumulation of autophagosomes were involved in the death of cells. It was worth noting that the glandular stomach lesions were time-dependent, and the combination of As and Cu were worse than the As and Cu alone. Collectively, our results suggest that As or/and Cu aggravate mitochondrial dysfunction, apoptosis and autophagy in a time-dependent manner, and the combined toxicity of As and Cu was higher.

The cardiotoxicity of the common carp (Cyprinus carpio) exposed to environmentally relevant concentrations of arsenic and subsequently relieved by zinc supplementation.

Waterborne exposure to arsenic trioxide (As2O3) is inevitable due to its widespread industrial and agricultural applications. Oxidative stress and cascaded programmed cell death is now hypothesized to be the dominant mechanisms of arseniasis evidenced in vivo and in vitro. This study aimed to explore the interaction of divalent zinc ion (Zn2+), an efficient reactive oxygen species (ROS) scavenger with arsenite in the heart of common carp, and extensively investigated the exact signaling molecules involved. Significant induction of cardiotoxicity including oxidative stress, apoptosis and autophagy was evident in heart tissues following arsenite exposure (P < 0.05). The dissipation of antioxidant enzymes (SOD and CAT) was induced by ROS burst, leading to oxidative damage and lipid peroxidation (MDA). Arsenite induced classic apoptotic hallmarks, characterized by chromatin degradation and subsequent formation of clumps adjacent, and elevated expression of Bax/Bcl-2 and Caspase family, and also increased autophagic flux evidenced by accelerated formation (LC3) and degradation (p62) of autophagosomes. PI3K/Akt/mTOR pathway was phosphorylated inhibited, while MAPK signaling (p38, ERK and JNK) displayed elevated phosphorylation levels in arsenite-exposed heart tissues. In contrast, above phenomena were effectively inhibited by Zn2+, which supplement attenuated arsenite-induced myocardial toxicity through inhibition of apoptosis and autophagy via PI3K/Akt/mTOR pathway, as well as suppressing intracellular ROS cluster via activating antioxidative system via MAPK pathway. Our results provided experimental explanation and evidences for cardiotoxicity of arsenite. Furthermore, our findings hint that the application of zinc preparations may provide a candidate for the prevention and treatment for arsenic poisoning.

Destruction of redox and mitochondrial dynamics co-contributes to programmed cell death in chicken kidney under arsenite or/and copper (II) exposure.

BACKGROUND: Sub-chronic arsenic (arsenite) exposure-induced oxidative toxicity leads to adverse effects in various organ systems, especially the kidney. Copper sulphate (Cu2+), known for its extensive uses in agriculture, has also been reported to have pro-oxidation properties. Both of these two potential toxic elements can bio-accumulate through food chain, thus endangering human health. However, their interaction study in the kidney is scanty. AIM: To investigate the synergism effects of Cu2+ in arseniasis-elicited oxidative stress and cascaded renal injury in chickens. RESULTS: Arsenite intoxication decreased renal antioxidant system along with ATPases. Arsenite exposure also significantly elicited disequilibrium of mitochondrial homeostasis, accompanying by elevated apoptotic and autophagic cell death. The disturbed morphological and ultrastructural changes further corroborated arsenite nephrotoxicity. These anomalies aligned with the findings in Cu2+ groups, which co-administrated with arsenic further deteriorated these pathological changes. This synergism was achieved partially via the inactivation of phosphoinositide-3-kinase/protein kinase b/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway through the activation of P53. CONCLUSIONS: Copper excess and arsenic exposure can function independently or cooperatively to affect oxidative stress, mitochondrial dynamics and programmed cell death. These results highlighted the need to take precautions against copper and arsenic co-exposure when considering their impact in susceptible animals/populations.

The disturbance of autophagy and apoptosis in the gizzard caused by copper and/or arsenic are related to mitochondrial kinetics.

As toxic elements when excessive, arsenic (As) and copper (Cu) are two naturally occurring elements that may be ingested by the organism at the same time. However, the precise damaged mechanism and the pathways that are activated by As and/or Cu is rarely researched in gizzard, a unique organ of birds. In this study, ultrastructural observations, TdT-mediated dUTP Nick-End Labeling, real-time quantitative PCR and Western blotting were performed to evaluate the toxic effects of chronic exposure to Cu2+ and/or arsenite on chicken gizzard. The results revealed that increased apoptosis and autophagy levels induced by Cu2+ and arsenite appeared to be independent of oxidative stress, which didn't have significant changes in different treatment groups at the same time point. Nevertheless, the redox balance gradually deviated with the extension of time. And increased mitochondrial division and decreased fusion were also caused by Cu2+ and arsenite. In conclusion, apoptosis and autophagy in gizzard induced by Cu2+ and/or arsenite, at least, strongly linked with the disruption of mitochondrial homeostasis. Our study showed that the combination of Cu2+ and arsenite produces stronger toxicity. The results of this study can serve as a reference for agicultural feeding and environmental protection, that is, to avoid the combined exposure of Cu2+ and arsenite to prevent greater economic losses and health risks.

Discrepant effects of copper (II) stress on different types of skeletal muscles in chicken: Elements and amino acids.

Different distributions of 28 elements and 17 amino acids in pectoralis, wing biceps brachii and leg gastrocnemius of chicken upon CuSO4 (300 mg/kg) exposure for 90 days were investigated. Accompanied by copper accumulation, pathological injuries were observed in those three kinds of skeletal muscles using histological and ultrastructural methods. Based on data obtained, we analyzed leg gastrocnemius displayed the most increases (P < 0.000) in all three kinds of elements detected, including macroelements (131%), essential microelements (129%) and toxic microelements (179%) than the other two skeletal muscles. Furthermore, decreased total amino acids (P = 0.006), a susceptibility of lipid peroxidation/oxidative stress and a disequilibrium of nutrition and taste were analyzed in the leg gastrocnemius, indicating an unsuitability for human consumption. Intriguingly, these anomalies were scarce in pectoralis and wing biceps brachii. Combined with multivariate analysis we may conclude that leg gastrocnemius are more vulnerable to copper stress than pectoralis and wing biceps brachii in chicken.