Sodium para-aminosalicylic acid attenuates combined manganese/iron-induced cortical synaptic damage in rats.

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment.

Effects of Manganese and Iron, Alone or in Combination, on Apoptosis in BV2 Cells.

The aim of study was to address the effects of manganese and iron, alone and in combination, on apoptosis of BV2 microglia cells, and to determine if combined exposure to these metals augments their individual toxicity. We used a murine microglial BV2 cell line. Cell cytotoxicity was analyzed by propidium iodide (PI) exclusion assay. Cell ROS production was analyzed by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) probe staining. Pro-inflammatory cytokine production was monitored by ELISA. Cell apoptosis was analyzed by PE Annexin V/7-AAD staining. Mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting to analyze the effect of manganese, iron alone, or their combined exposure on the activation of caspase9, P53, Bax, and Bcl2 apoptosis signaling pathways. Caspase3 activity was determined using a Colorimetric. Manganese, iron, and their combined exposure for 24 h induced the activation of BV2 microglia cells and increased ROS production and the expression of the inflammatory cytokines, IL-1ß and TNF-α. And we also found that the apoptosis rate increased, mitochondrial membrane potential decreased, apoptosis-related proteins caspase9, P53, Bax, and Bcl2 expression increased, and caspase3 activity increased. Furthermore, we found that combined manganese-iron cytotoxicity was lower than that induced by manganese exposure alone. Manganese, iron alone, or their combination exposure can induce apoptosis in glial cells. Iron can reduce the toxicity of manganese, and there is an antagonistic effect between manganese and iron.

Combined exposure to manganese and iron decreases oxidative stress-induced nerve damage by increasing Nrf2/HO-1/NQO1 expression.

BACKGROUND: Manganese (Mn) and iron (Fe) are essential trace elements for humans, yet excessive exposure to Mn or Fe can accumulate in the central nervous system (CNS) and cause neurotoxicity. The purpose of this study was to investigate the effects of Mn and Fe exposure, alone or in combination, on inducing oxidative stress-induced neurological damage in rat cortical and SH-SY5Y cells, and to determine whether combined exposure to these metals increases their individual toxicity. METHODS: SH-SY5Y cells and male Sprague-Dawley rats were used to observe the effects of oxidative stress-induced neurological damage induced by exposure to manganese and iron alone or in combination. To detect the expression of anti-oxidative stress-related proteins, Nrf2, HO-1, and NQO1, and the apoptosis-related proteins, Bcl2 and Bax, and the neurological damage-related protein, α-syn. To detect reactive oxygen species generation and apoptosis. To detect the expression of the rat cortical protein Nrf2. To detect the production of proinflammatory cytokines. RESULTS: We demonstrate that juvenile developmental exposure to Mn and Fe and their combination impairs cognitive performance in rats by inducing oxidative stress causing neurodegeneration in the cortex. Mn, Fe, and their combined exposure increased the expression of ROS, Bcl2, Bax, and α-syn, activated the inflammatory factors IL-6 and IL-12, inhibited the activities of SOD and GSH, and induced oxidative stress-induced neurodegeneration both in rats and SH-SY5Y cells. Combined Mn-Fe exposure attenuated the oxidative stress induced by Mn and Fe exposure alone by increasing the expression of antioxidant factors Nrf2, HO-1, and NQO1. CONCLUSION: In both in vivo and in vitro studies, manganese and iron alone or in combination induced oxidative stress, leading to neuronal damage. In contrast, combined exposure to manganese and iron mitigated the oxidative stress induced by exposure to manganese and iron alone by increasing the expression of antioxidant factors. Therefore, studies to elucidate the main causes of toxicity and establish the molecular mechanisms of toxicity should help to develop more effective therapeutic modalities in the future.

Contamination and health risks brought by arsenic, lead and cadmium in a water-soil-plant system nearby a non-ferrous metal mining area.

Heavy metal(loid)s contamination prevails in the water-soil-plant system around non-ferrous metal mining areas. The present study aimed to evaluate the heavy metal(loid)s contamination in Nandan Pb-Zn mining area (Guangxi, China). A total of 36 river water samples, 75 paired paddy soil and rice samples, and 128 paired upland soil and plant samples were collected from this area. The concentrations of arsenic (As), lead (Pb), and cadmium (Cd) in these samples were measured. Results showed that the average water quality indexes (WQIs) at the 12 sampling sites along the main river ranged from 41 to 5008, indicating the water qualities decreasing from "Excellent" to "Undrinkable". The WQIs nearby tailings or industrial park were significantly higher than those at the other sites. 34.0% and 64.5% of soil samples exceeded the risk screening values for As and Cd. The Pb and Cd concentrations in all rice samples exceeded the Chinese food safety limits by 18.7% and 82.7%, respectively. Leafy vegetables had a higher concentration of As, Pb, and Cd than other vegetables, exceeding the maximum permissible limits by 14.1%, 61.2%, and 40.0%, respectively. The biological accumulation coefficient (BAC) of Cd was the highest in rice and lettuce leaves. The hazard quotients (HQs) of As and Cd, indicating non-carcinogenic risks, were 4.15 and 1.76 in adult males, and 3.40 and 1.45 in adult females, all higher than the permitted level (1.0). The carcinogenic probabilities of As and Cd from rice and leafy vegetables consumption were all higher than 1 × 10-4. We conclude that metal(loid)s contamination of the water-soil-plant system has posed great non-carcinogenic and carcinogenic risks to the local population.

Patient-controlled intravenous administration of dexmedetomidine with nalbuphine versus sufentanil for post cesarean delivery analgesia: A retrospective observational study.

This retrospective observational study aims to investigate the patient-controlled intravenous analgesia (PCIA) of dexmedetomidine (DEX) with nalbuphine (NAL) versus sufentanil (SUF) for post-cesarean delivery management. A total of 300 women were evaluated who underwent cesarean section surgery with combined spinal-epidural anesthesia. After surgery, all patients were connected to a patient-controlled analgesia pump. The PCIA protocol was programmed with 0.11 µg/kg/h DEX in combination with 0.03 µg/kg/h SUF in Group I (n = 150) or 0.11 µg/kg/h DEX in combination with 0.03 mg/kg/h NAL in Group II (n = 150). There was no significant difference in incision pain and sedation level between the two groups within 48 h after the surgery assessed by visual analog scale (VAS) and Ramsay sedation scale, respectively. However, at 2, 6, 12, and 24 h after surgery, visceral pain at rest and at mobilization was alleviated in the Group II as compared with the Group I with lower VAS scores. Moreover, fewer adverse reactions were found in the Group II when compared with Group I, including postpartum respiratory depression, nausea/vomiting, urinary retention, and cardiovascular events. Overall, there was an increased patient satisfaction in the Group II as compared with the Group I. Based on the results of this study, it seems that adding NAL to PCIA with DEX, as compared to SUF with DEX, have an effect on reducing the intensity of visceral pain after cesarean section with less adverse reactions and higher patient satisfaction.

Protective Effects of Sodium Para-Aminosalicylic Acid on Lead and Cadmium Co-Exposure in SH-SY5Y Cells.

BACKGROUND: Combined exposure to lead and cadmium is common in occupational environments. However, the effects of co-exposure to Pb-Cd on neurotoxicity have not been fully clarified. Sodium para-aminosalicylic acid (PAS-Na) has previously been shown to protect neurons from Pb-induced toxicity. This study aimed to investigate the beneficial effect of PAS-Na against co-exposure to Pb-Cd-induced neurodegeneration in SH-SY5Y cells. METHODS: The MTT assay was used to detect the effects of Pb and Cd alone, or in combination, on SH-SY5Y cell survival. The effects of Pb and Cd alone or in combination on oxidative stress were assessed by reactive oxygen species (ROS) level. Nrf2, the master switch for antioxidant responses, was detected by immunofluorescence. Protein expression levels of PI3K, Akt, p-Akt, Nrf2 and HO-1 were determined by Western blot analysis. RESULTS: MTT assay results established that the survival rate of SH-SY5Y cells was not significantly affected by exposure to 1 µmol/L lead, 0.25 µmol/L cadmium, and 1-fold Pb-Cd mixture (1 µmol/L Pb + 0.25 µmol/L Cd), while 10-fold Pb-Cd combined exposure (10 µmol/L Pb + 2.5 µmol/L Cd) significantly reduced the survival rate of SH-SY5Y cells. Combined Pb-Cd exposure significantly increased intracellular ROS levels, and N-Acetyl-L-cysteine (NAC) treatment in the 10 µmol/L Pb + 2.5 µmol/L Cd group significantly decreased ROS expression levels, attenuating the levels of oxidative stress. Protein expression of PI3K and p-Akt significantly decreased in the 10 µmol/L Pb + 2.5 µmol/L Cd group, while the expression of PI3K and p-Akt protein increased after PAS-Na intervention. Immunofluorescence analysis showed that levels of Nrf2 in the nucleus increased in the 10 µmol/L Pb + 2.5 µmol/L Cd group, along with Nrf2 protein levels, suggesting that Nrf2 was translocated from the cytoplasm into the nucleus upon combined Pb-Cd exposure. In addition, HO-1 protein expression level, a downstream gene product of Nrf2, was increased. In response to NAC intervention, HO-1 protein expression levels significantly decreased. PAS-Na had the same intervention effect as NAC. CONCLUSION: Combined exposure to Pb-Cd induced oxidative stress and cytotoxicity in SH-SY5Y cells. PAS-Na displayed antagonistic effects on neurodegenerative changes induced by combined Pb-Cd exposure; hence, it may afford a novel treatment modality for exposure to these metals.

Sodium Para-aminosalicylic Acid Inhibits Lead-Induced Neuroinflammation in Brain Cortex of Rats by Modulating SIRT1/HMGB1/NF-κB Pathway.

Lead (Pb) is considered to be a major environmental pollutant and occupational health hazard worldwide which may lead to neuroinflammation. However, an effective treatment for Pb-induced neuroinflammation remains elusive. The aim of this study was to investigate the mechanisms of Pb-induced neuroinflammation, and the therapeutic effect of sodium para-aminosalicylic acid (PAS-Na, a non-steroidal anti-inflammatory drug) in rat cerebral cortex. The results indicated that Pb exposure induced pathological damage in cerebral cortex, accompanied by increased levels of inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). Moreover, Pb decreased the expression of silencing information regulator 2 related enzyme 1 (SIRT1) and brain-derived neurotrophic factor (BDNF), and increased the levels of high mobile group box 1 (HMGB1) expression and p65 nuclear factor-κB (NF-κB) phosphorylation. PAS-Na treatment ameliorated Pb-induced histopathological changes in rat cerebral cortex. Moreover, PAS-Na reduced the Pb-induced increase of TNF-α and IL-1ß levels concomitant with a significant increase in SIRT1 and BDNF levels, and a decrease in HMGB1 and the phosphorylation of p65 NF-κB expression. Thus, PAS-Na may exert anti-inflammatory effects by mediating the SIRT1/HMGB1/NF-κB pathway and BDNF expression. In conclusion, in this novel study PAS-Na was shown to possess an anti-inflammatory effect on cortical neuroinflammation, establishing its efficacy as a potential treatment for Pb exposures.

Association of lead and cadmium exposure with kidney stone incidence: A study on the non-occupational population in Nandan of China.

BACKGROUND: Environmental lead (Pb) and cadmium (Cd) pollution has been considered a risk factor in the etiology of kidney stones. However, the association between Pb and Cd exposure and kidney stone incidence has yet to be determined. OBJECTIVES: This study aimed to determine a possible the association between kidney stones with Pb and Cd exposure (alone or combined) in a non-occupational population. METHODS: Pb and Cd contaminations in soil-plant system were determined by flame atomic absorption spectrophotometry. Health risk assessment of dietary Pb or Cd intake from rice and vegetables were calculated. Kidney stones were diagnosed with urinary tract ultrasonography. Urinary cadmium (UCd) and blood lead (BPb) levels were determined by graphite-furnace atomic absorption spectrometry. Multivariate logistic regression models were constructed. RESULTS: The hazard indexes (HI) of Pb and Cd were 7.91 and 7.31. The odds ratio (OR) was 2.83 (95 %CI:1.38-5.77) in males with high BPb (BPb ≥ 100 µg/L), compared with those with low BPb (BPb＜100 µg/L). Compared to those with low BPb and low UCd (BPb＜100 µg/L and UCd＜2 µg/g creatinine), the ORs were 2.58 (95 % CI:1.17-5.70) and 3.43 (95 % CI:1.21-9.16) in females and males with high BPb and high UCd (BPb ≥100 µg/L and UCd ≥2 µg/g creatinine), respectively. The OR was 3.16 (95 % CI:1.26-7.88) in males with high BPb and low UCd (BPb ≥ 100 µg/L and UCd ＜2 µg/g creatinine), compared to those with low BPb and low UCd. CONCLUSIONS: Kidney stones incidence was increased by high Pb exposure in males, and by Pb and Cd co-exposure in males and females.

Impact of Lead Exposure on Thyroid Status and IQ Performance among School-age Children Living Nearby a Lead-Zinc Mine in China.

BACKGROUND: Lead exposure is one of the most concerning public health problems worldwide, particularly among children. Yet the impact of chronic lead exposure on the thyroid status and related intelligence quotient performance among school-age children remained elusive. OBJECTIVE: The aim of this study was to evaluate the influence of lead exposure on the thyroid hormones, amino acid neurotransmitters balances, and intelligence quotient (IQ) among school-age children living nearby a lead-zinc mining site. Other factors such as rice lead levels, mothers' smoking behavior, and diet intake were also investigated. METHODS: A total of 255 children aged 7-12 years old were recruited in this study. Blood lead level (BLL), thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH), and amino acid neurotransmitters such as glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA) were measured using graphite furnace atomic absorption spectroscopy (GFAAS), chemiluminescence immunoassay, high performance liquid chromatography (HPLC). Raven's standard progressive matrices (SPM) and the questionnaire were used to determine IQ and collect related influence factors. RESULTS: The average BLL of children was 84.8 µg/L. The occurrence of lead intoxication (defined as the BLL ≥ 100 µg/L) was 31.8%. Serum TSH levels and IQ of lead-intoxicated children were significantly lower than those without lead toxicity. The GABA level of girls with the lead intoxication was higher than those with no lead-exposed group. Correlation analyses revealed that BLL were inversely associated with the serum TSH levels (R= -0.186, p < 0.05), but positively related with IQ grades (R = 0.147, p < 0.05). Moreover, BLL and Glu were inversely correlated with IQ. In addition, this study revealed four factors that may contribute to the incidence of lead intoxication among children, including the frequency of mother smoking (OR = 3.587, p < 0.05) and drinking un-boiled stagnant tap water (OR = 3.716, p < 0.05); eating fresh fruits and vegetables (OR = 0.323, p < 0.05) and soy products regularly (OR = 0.181, p < 0.05) may protect against lead intoxication. CONCLUSION: Lead exposure affects the serum TSH, GABA levels and IQ of school-aged children. Developing good living habits, improving environment, increasing the intake of high-quality protein and fresh vegetable and fruit may improve the condition of lead intoxication.

Preventive impacts of PAS-Na on the slow growth and activated inflammatory responses in Mn-exposed rats.

BACKGROUND: Sodium para-aminosalicylic acid (PAS-Na), an anti-tuberculosis drug, has been demonstrated its function in facilitating the Mn elimination in manganism patients and Mn-exposed models in vivo and improving the symptoms of Mn poisoning. But whether it can improve the growth retardation and inflammatory responses induced by Mn have not been reported. OBJECTIVES: This study was designed to investigate the preventive effects of PAS-Na on the development of retardation and inflammatory responses in Mn-exposed rats. METHODS: Male Sprague Dawley (SD) rats (8 weeks old, weighing 180 ± 20 g) were randomly divided into normal control group and Mn-exposed group in the 4 weeks experiment observation and normal control group, Mn-exposed group, PAS-Na preventive group and PAS-Na control group in the 8 weeks experiment observation. The Mn-exposed group received an intraperitoneal injection (i.p.) of 15 mg/kg MnCl2 and the normal control group i.p. physiological Saline in the same volume once a day for 4 or 8 weeks, 5 days per week. The PAS-Na preventive group i.p. 15 mg/kg MnCl2 along with back subcutaneous (s.c.) injection of 240 mg/kg PAS-Na once a day for 8 weeks, 5 days per week. PAS-Na control group received s.c. injection of 240 mg/kg PAS-Na along with i.p. injection of saline once daily. The body weight was determined once a week until the end of the experiment. The manganese contents in the blood were detected by graphite furnace atomic absorption spectrometry. The inflammatory factor levels (TNF-α, IL-1ß, IL-6, and PGE2) in the blood were detected by using enzyme-linked immunosorbent assay (Elisa) and each organ taking from rats were weighed and recorded. RESULTS: Mn exposure significantly suppressed the growth in rats and increased heart, liver, spleen and kidney coefficients as compared with the control group. The whole blood Mn level and serum levels of IL-1ß, IL-6, PGE2, and TNF-α in sub-chronic Mn-exposure group were markedly higher than those in the control group. However, preventive treatment with PAS-Na obviously reduced the whole blood Mn level, the spleen and liver coefficients of the Mn-exposed rats. And serum levels of IL-1ß and TNF-α were significantly reduced by 33.9% and 14.7% respectively in PAS-Na prevention group. CONCLUSIONS: PAS-Na could improve the growth retardation and alleviate inflammatory responses in Mn-exposed rats.

Pericarp and seed of litchi and longan fruits: constituent, extraction, bioactive activity, and potential utilization.

Litchi (Litchi chinensis Sonn.) and longan (Dimocarpus longan Lour.) fruits have a succulent and white aril with a brown seed and are becoming popular worldwide. The two fruits have been used in traditional Chinese medicine as popular herbs in the treatment of neural pain, swelling, and cardiovascular disease. The pericarp and seed portions as the by-products of litchi and longan fruits are estimated to be approximately 30% of the dry weight of the whole fruit and are rich in bioactive constituents. In the recent years, many biological activities, such as tyrosinase inhibitory, antioxidant, anti-inflammatory, immunomodulatory, anti-glycated, and anti-cancer activities, as well as memory-increasing effects, have been reported for the litchi and longan pericarp and seed extracts, indicating a potentially significant contribution to human health. With the increasing production of litchi and longan fruits, enhanced utilization of the two fruit by-products for their inherent bioactive constituents in relation to pharmacological effects is urgently needed. This paper reviews the current advances in the extraction, processing, identification, and biological and pharmacological activities of constituents from litchi and longan by-products. Potential utilization of litchi and longan pericarps and seeds in relation to further research is also discussed.

Effects of combined high pressure and enzymatic treatments on physicochemical and antioxidant properties of peanut proteins.

Isolated peanut protein (PPI) dispersions were pretreated by high pressure at 100, 300, and 500 MPa prior to enzymatic hydrolysis with alkaline protease (Alcalase). The degree of hydrolysis (DH) was determined by the pH-stat method, the hydrolysates profiles were analyzed by high-performance liquid chromatography (HPLC), the molecular weight distribution (MWD) was analyzed by gel filtration chromatogram (GFC), and content of SH/S-S and antioxidant activity of hydrolysates were evaluated. Results showed that HP pretreatment improved effectively the enzymatic hydrolysis of PPI, with an effective sequence of 300 > 100 > 500 MPa. However, no significant differences were observed in the peak pattern of HPLC profiles, but the peak times were earlier in HPLC profiles of the HP-treated protein. GFC analysis showed that more peptide fractions with low molecular weight appeared in the hydrolysates of the HP-treated PPI with increasing pressure. Moreover, the level of free SH of hydrolysates of the HP-treated PPI was relatively higher than non-HP-treated PPI. The hydrolysates of the HP-treated PPI exerted higher antioxidant activity (reducing power and DPPH radical scavenging) than the hydrolysates of non-HP-treated PPI. The results indicated that high pressure treatment affected the enzymatic hydrolysis of peanut protein and some protein structure properties and improved antioxidant activity of PPI hydrolysates.

Fatty acid activation in carcinogenesis and cancer development: Essential roles of long-chain acyl-CoA synthetases.

The significance of fatty acid metabolism in cancer initiation and development is increasingly accepted by scientists and the public due to the high prevalence of overweight and obese individuals. Fatty acids have different turnovers in the body: Either breakdown into acetyl-CoA to aid ATP generation through catabolic metabolism or incorporation into triacylglycerol and phospholipid through anabolic metabolism. However, these two distinct pathways require a common initial step known as fatty acid activation. Long-chain acyl-CoA synthetases (ACSLs), which are responsible for activation of the most abundant long-chain fatty acids, are commonly deregulated in cancer. This deregulation is also associated with poor survival in patients with cancer. Fatty acids physiologically regulate ACSL expression, but cancer cells could hijack certain involved regulatory mechanisms to deregulate ACSLs. Among the five family isoforms, ACSL1 and ACSL4 are able to promote ungoverned cell growth, facilitate tumor invasion and evade programmed cell death, while ACSL3 may have relatively complex functions in different types of cancer. Notably, ACSL4 is also essential for the induction of ferroptosis (another form of programmed cell death) by facilitating arachidonic acid oxidation, which makes the enzyme a desirable cancer target. The present review thus evaluates the functions of deregulated ACSLs in cancer, the possible molecular mechanisms involved and the chemotherapeutic potentials to target ACSLs. A better understanding of the pathological effects of ACSLs in cancer and the involved molecular mechanisms will aid in delineating the exact role of fatty acid metabolism in cancer and designing precise cancer prevention and treatment strategies.

Discrimination of Single Living Rat Pancreatic α, ß, δ, and Pancreatic Polypeptide (PP) Cells Using Raman Spectroscopy.

Primary pancreatic α, ß, δ, and pancreatic polypeptide (PP) cells are reliable cell models for diabetes research. However, the separation and purification of these cells in living conditions remains an obstacle for researchers. The interaction of visible light with cellular molecules can produce Raman scattering, which can be analyzed to obtain cellular intrinsic molecular fingerprints. It has been speculated that primary pancreatic α, ß, δ, and PP cells can be identified and separated from each other according to their spectral differences. To test this hypothesis, Raman spectra detection was performed on rat islet cells. Single islet cells identified by Raman scattering under living conditions were verified using immunohistochemistry. Thus, Raman data were acquired from a pure line of islet cells as a training sample and then used to establish the discriminant function. Then, using the principal component analysis-linear discriminate analysis (PCA-LDA) method, the four types of islet cells could be identified and discriminated by Raman spectroscopy. This study provides a label-free and noninvasive method for discriminating islet cell types in a randomly distributed mixed islet cell population via their physical properties rather than by using antibodies or fluorescence labeling.

Real-Time, Label-Free Detection of Local Exocytosis Outside Pancreatic ß Cells Using Laser Tweezers Raman Spectroscopy.

The examination of insulin (Ins) exocytosis at the single-cell level by conventional methods, such as electrophysiological approaches, total internal reflection imaging, and two-photon imaging technology, often requires an invasive microelectrode puncture or label. In this study, high concentrations of glucose and potassium chloride were used to stimulate ß cell Ins exocytosis, while low concentrations of glucose and calcium channel blockers served as the blank and negative control, respectively. Laser tweezers Raman spectroscopy (LTRS) was used to capture the possible Raman scattering signal from a local zone outside of the cell edge. The results show that the frequencies of the strong signals from the local zones outside the cellular edge in the stimulated groups are greater than those of the control. The Raman spectra from the cellular edge, Ins and cell membrane were compared. Thus, local Ins exocytosis activity outside pancreatic ß cells might be observed indirectly using LTRS, a non-invasive optical method.

The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis.

Although there have been many studies identifying clinical and pathologic factors that may predict central lymph node metastases (CLNM) in papillary thyroid microcarcinoma (PTMC) patients without clinically cervical lymph node metastasis (cN0), the results were inconsistent. And whether prophylactic central lymph node dissection (pCLND) should be performed in cN0 PTMC remains controversial. The EMBASE, PubMed, MEDLINE and the Cochrane Library were searched until Oct 2015 to identify relevant studies. Primary outcomes were clinical and pathologic factors for CLNM. Secondary outcomes included CLNM rate, surgical complications of hypocalcaemia and recurrent laryngeal nerve(RLN) injury and neck recurrences. Statistical analysis was performed using Stata 12.0. Fourteen eligible studies enrolling 4573 patients were included in this meta-analysis. The overall incidence of CLNM was 33 % (95 % CI 29-37). An elevated risk of CLNM was significantly associated with male gender (OR 2.33, 95 % CI 1.71-3.17), age <45 years (OR 1.27, 95 % CI 1.08-1.48), tumor size >5 mm (OR 2.16, 95 % CI 1.87-2.50), multifocality (OR 1.73, 95 % CI 1.45-2.05), extrathyroidal extension (OR 1.99, 95 % CI 1.66-2.37) and lymphovascular invasion (OR 3.87, 95 % CI 1.64-9.10), but not with thyroid bilaterality (OR 1.41, 95 % CI 0.89-2.22) and chronic lymphocytic thyroiditis (OR 0.98, 95 % CI 0.66-1.47). The pooled frequency of permanent hypocalcaemia, permanent RLN injury and neck recurrences was 1.1, 0.5 and 2.8 %, respectively. cN0 PTMC patients have a considerable CLNM rate and have a low pooled incident of surgical complications and neck recurrences with pCLND. Six unfavorable clinical and pathologic factors, which were significantly associated with CLNM, were identified. These findings may help guide the application of pCLND or subsequent treatment in cN0 PTMC.

Cadmium Exposure is Associated with the Prevalence of Dyslipidemia.

BACKGROUND: Cadmium is a widespread environmental and occupational pollutant that accumulates in human body with a biological half-life exceeding 10 years. Cadmium exposure has been demonstrated to increase rates of cardiovascular diseases. Whether occupational cadmium exposure is associated with the increase in the prevalence of dyslipidemia and hence contributes to the risk of cardiovascular diseases is still equivocal. To test the hypothesis that exposure to cadmium is related to the prevalence of dyslipidemia, we examined the associations between blood cadmium concentration and the prevalence of dyslipidemia in workers occupationally exposed to cadmium in China. METHODS: A cross-sectional survey on demographic data, blood cadmium level and lipid profile in cadmium exposed workers from seven cadmium smelting factories in central and southwestern China was conducted. We measured blood cadmium concentration and lipid components of 1489 cadmium exposed workers. The prevalence of dyslipidemia was compared across blood cadmium quartiles. Associations between the blood cadmium concentrations and the prevalence of dyslipidemia were assessed using confounder adjusted linear and logistic regressions. RESULTS: The blood cadmium concentration was 3.61±0.84µg/L ( mean ±SD). The prevalence of dyslipidemia in this occupational population was 66.3%. Mean blood cadmium concentration of workers with dyslipedemia was significantly higher than that of workers without dyslipidemia (p <0.01). The prevalence of dyslipidemia increased dose-dependently with elevations in blood cadmium concentrations (p for trend <0.001). Elevated levels of blood cadmium were associated with BMI, education attainment, income, smoking status and duration of exposure (all p <0.01). Furthermore, the profile of blood lipid was obviously changed in this occupational population. The prevalence of high TC, high TG, Low HDL-C and high LDL-C rose with increases in blood cadmium levels dose-dependently (p for trend <0.001). The odds ratios (95% confidence interval) for dyslipidemia across the increasing blood cadmium quartiles were 1.21(1.16-1.55), 1.56(1.11-1.87), 1.79(1.26-2.25) respectively (referencing to 1.00; p for trend <0.001), after multivariate adjustment for BMI, education attainment, income, lifestyle factors and duration of exposure, the association between blood cadmium concentrations and the prevalence of dyslipidemia remained unchanged (all p for trend <0.001). CONCLUSION: Elevated blood cadmium concentration is associated with prevalence of dyslipidemia. Cadmium exposure could alter lipid metabolism in humans. It is imperative to control cadmium exposure of occupational population in cadmium related industries and reduce adverse health effects.

The significance of combining radiotherapy with chemotherapy for early stage extranodal natural killer/T-cell lymphoma, nasal type: a systematic review and meta-analysis.

Abstract Radiotherapy is regarded as a primary treatment for early stage extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL). However, whether combined modality treatment (CMT) comprising radiotherapy and chemotherapy is necessary remains controversial. A systematic review and meta-analysis of studies was performed to evaluate the significance of combining radiotherapy with chemotherapy for early stage ENKTL. Comparison of CMT and radiotherapy alone (RT) showed no significant difference by the measurement of complete response (CR) (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.73-1.58; p = 0.73), 5-year overall survival rate (OS) (HR 0.73; 95% CI 0.45-1.19; p = 0.21) and progression-free survival rate (PFS) (HR 0.76; 95% CI 0.50-1.17; p = 0.21). Additional chemotherapy did not decrease systemic failure (OR 1.52; 95% CI 0.97-2.40; p = 0.07), as well as locoregional failure (OR 0.94; 95% CI 0.52-1.73; p = 0.85). The results may support the assertion that the combination of radiotherapy with chemotherapy cannot improve treatment outcomes, but rather it increases adverse effects and financial costs. However, these results should be interpreted with caution.

Banana ethylene response factors are involved in fruit ripening through their interactions with ethylene biosynthesis genes.

The involvement of ethylene response factor (ERF) transcription factor (TF) in the transcriptional regulation of ethylene biosynthesis genes during fruit ripening remains largely unclear. In this study, 15 ERF genes, designated as MaERF1-MaERF15, were isolated and characterized from banana fruit. These MaERFs were classified into seven of the 12 known ERF families. Subcellular localization showed that MaERF proteins of five different subfamilies preferentially localized to the nucleus. The 15 MaERF genes displayed differential expression patterns and levels in peel and pulp of banana fruit, in association with four different ripening treatments caused by natural, ethylene-induced, 1-methylcyclopropene (1-MCP)-delayed, and combined 1-MCP and ethylene treatments. MaERF9 was upregulated while MaERF11 was downregulated in peel and pulp of banana fruit during ripening or after treatment with ethylene. Furthermore, yeast-one hybrid (Y1H) and transient expression assays showed that the potential repressor MaERF11 bound to MaACS1 and MaACO1 promoters to suppress their activities and that MaERF9 activated MaACO1 promoter activity. Interestingly, protein-protein interaction analysis revealed that MaERF9 and -11 physically interacted with MaACO1. Taken together, these results suggest that MaERFs are involved in banana fruit ripening via transcriptional regulation of or interaction with ethylene biosynthesis genes.