Association between serum magnesium and blood count: influence of type 2 diabetes and central obesity.

The relationship between serum Mg and blood cell counts in Chinese adult diabetes or central obesity was assessed by investigating 8163 subjects with China Health and Nutrition Survey (mean age 59⋅6 years, 54⋅9 % men). Participants were classified according to blood Mg (below 0⋅65 mmol/l, or 0⋅66-0⋅94 mmol/l or above 0⋅95 mmol/l), type 2 diabetes (yes/no) and central obesity (yes/no). Leucocytes, erythrocytes, platelets (PLT), Hb and glycated Hb (HbA1c) were determined using standardised methods and conditions. HbAc1, leucocytes and PLT were significantly higher among subjects with central obesity than without central obesity (P < 0⋅05). A significant increase for Hb, erythrocytes, PLT, but not leucocytes, across progressive Mg groups was observed in subjects without diabetes (P < 0⋅05). Hb, erythrocytes and HbAc1 were significantly higher among subjects with higher Mg than in subjects with lower Mg with diabetes (P < 0⋅05). Central obesity disturbed the positive association between PLT count and serum Mg. Type 2 diabetes caused metabolism disorder in serum Mg, blood sugar and blood cell count. Hb, erythrocytes and PLT, but not leucocytes, are positively correlated with serum Mg, but this association is somehow disturbed by type 2 diabetes or central obesity.

Evaluation of the haematinic, antioxidant and anti-atherosclerotic potential of Momordica charantia in cholesterol-fed experimental rats.

Background: Momordica charantia is popularly used in folk medicine in the management of hyperlipidemia and atherosclerosis. Purpose: To evaluate the anti-atherosclerotic potential of M. charantia as well as its haematinic and antioxidant potential. Methods: Seventy-two experimental rats were randomly assigned into 9 groups (I-IX) of 8 rats each. Group I (control), was given 1 ml distilled water; II received 250 mg/kg. M. charantia; III received 500 mg/kg M. charantia; IV was administered 100 mg/kg of Atorvastatin only; V was administered 30 mg/kg of cholesterol dissolved in coconut oil; VI was administered with 250 mg/kg of M. charantia plus 30 mg/kg of cholesterol. VII was treated with 500 mg/kg of M. charantia plus 30 mg/kg of cholesterol solution; VIII was administered 30 mg/kg cholesterol solution plus Atorvastatin at a dose of 100 mg/kg; IX was administered 1 ml of coconut oil only. After 60 days of administration, blood and aorta samples were obtained from the rats. The samples were subjected to biochemical, haematological and histological analysis using standard methods. Results: Glutathione peroxidase (GPx), Malondialdehyde (MDA) and Catalase (CAT) activities were significantly higher in the treated groups as compared to the control groups. There were significant increases in the monocyte counts of the groups given low dose (250 mg/kg) of the extract (LDMC), high dose (500 mg/kg) of the extract (HDMC), as well as atorvastatin. The mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) of the test groups administered were significantly higher than that of the control group. However, only the group administered with cholesterol plus HDMC showed significantly lower mean corpuscular haemoglobin concentration (MCHC) than that of the control group. Histological sections of the aorta show degeneration of the internal elastic lamina in the group fed with the diet only as well as vascular ulceration and stenosis in the aorta and heavy perivascular infiltrates of inflammatory cells. These alterations were however not visible in the groups administered with the extracts, as well as atorvastatin. Conclusion: Our findings show the possible anti-atherosclerotic potential of the extract, which could be compared to that of the standard drug (atorvastatin).

Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy.

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation.

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.

Toxicity and bioaccumulation of manganese and chromium in different organs of common carp (Cyprinus carpio) fish.

The present research work was carried out to determine the bioaccumulation of manganese and chromium in the gills, intestine, muscles, skin and bones, as well as its acute toxicity and effects on hematological and biochemical parameters in Common carp (Cyprinus carpio). Adult carps were exposed for 96 h to manganese sulphate and chromium chloride solution, a sub lethal concentration was used in the experiment. Bioaccumulation was highest in the gills followed by intestine > muscles > skin > bones. The concentration of hematocrit (HCT) (37.3 ± 0.36), hemoglobin (HGB) (9.0 ± 0.04), Red Blood Cells (RBCs) (3.7 ± 0.025), mean corpuscular volume (MCV) (121.2 ± 0.36), mean corpuscular hemoglobin (MCH) (41.3 ± 0.3) and mean corpuscular hemoglobin concentration (MCHC) (41.06 ± 0.072) was significantly higher at 96 h (P < 0.01) after exposure to manganese and chromium, while the concentration of platelets (PLT) (16.8 ± 0.12) and white blood cells (WBCs) (62.7 ± 0.11) was lower at 96 h of exposure. Serum glutamic pyruvic transaminase (SGPT) (40.6 ± 0.4), Blood Urea (13 ± 0.1), serum triglycerides (231.21 ± 0.04), high-density lipoprotein (HDL) (39 ± 0.07), serum Alkaline PO4 (242 ± 0.2), lactate dehydrogenase (LDH) (1239 ± 13.21), and serum Uric Acid (4.81 ± 0.33) were significantly higher (P < 0.01) at 96 h of exposure. The highest concentration of serum cholesterol (339 ± 0.09), serum reatinine (0.9 ± 0.01), low density lipid (240 ± 0.2) was observed at 24 h. Serum glutamic-oxaloacetic transaminase (SGOT) (19 ± 0.13), and serum albumin were at the highest level at 72 h (3.19 ± 0.07) (P < 0.01) post exposure.

In vivo and in silico studies of Dennettia tripetala essential oil reveal the potential harmful effects of habitual consumption of the plant seed.

Dennettia tripetala G. Baker (Annonaceae), is a plant with nutritional, social economy, and medicinal values. Its rising medicinal profile makes this plant a prospect in drug discovery. However, the reported strong addictive potential among habitual consumers makes the need to establish its safety imperative. In this report, we evaluated the safety profile of the essential oil of the seed of D. tripetala (EODS) in nulliparous female Wistar rats using in vivo single and repeated dose toxicity profiling, as well as in silico toxicity profiling of its known seed oil derived phytoconstituents. Our results showed consistent significant dose-dependent alterations in relative body weights, organ-body and organ-brain weight ratios, haematological and biochemical indices, as well as liver and kidney histoarchitectures, following single and repeated oral administrations. Significant alterations in liver and kidney histoarchitectures were consistent with the observed significant increase in AST/ALT ratio, suggesting deleterious effects of EODS on the kidney and liver. However, the lack of alterations in the histoarchitectures of the hippocampus and hypothalamus suggests that the brain may not have been adversely affected. Also, the in silico analysis suggests that hepatotoxic effects of EODS may be linked to Benzylnitrile, Humulene, Linalool, (Z)-ß-Ocimene. In addition, the failure of ß-Phenylnitroethane, the most abundant phytoconstituent of EODS, to pass phases I and II in silico toxicity screening, and the presence of Caryophyllene oxide, a known toxic compound, coupled with the predicted binding of both to DNA and protein, low LD50 and high percent mortality at 250 mg/kg of repeated doses, further confirmed the potentially toxic nature of EODS. We concluded that based on our in vivo and in silico observations, there is an urgent need for public education to regulate the excessive consumption of the seeds of D. tripetala.

Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy - Observational prospective single institution analysis.

PURPOSE: Conventional osteosarcoma is an orphan disease. Current treatment approaches include combining a three drug chemotherapy schedule and surgery. The 3- and 5-year event-free survival (EFS) in localized disease is roughly 65 and 60%, respectively. The registration study of mifamurtide reported survival benefit, but some methodological controversies have been insufficient for FDA market authorization in contrast to EMA. METHODS: prospective single centre survival analysis of a mifamurtide addition to conventional therapy in 23 patients over a 5.5 year enrolment period is reported and compared to a historical control of 26 patient with localized disease. Bias arising from observational methodology was addressed using Landmark analysis and time-dependent Cox models. Blood count dynamics were analysed during the treatment. RESULTS: The adverse event profile was as expected with no dose limiting toxicities. There were no local relapses observed, one patient died in the first complete remission due to doxorubicin cardiotoxicity, one patient had pulmonary metastatic relapse. The observed 3- and 5-year EFS was 87.4% (CI 72.4-100%) and 87.4% (CI 72.4-100%), progression free survival (PFS) was 92.9% (CI 80.3-100%) and 92.9% (CI 80.3-100%), overall survival was 94.1% (CI 83.6-100) and 80.7% (CI 58.3-100), respectively. Comparison to the historical control showed statistically significant better PFS for mifamurtide patients (Landmark analysis; p = 0.044). Risk of progression was 5-times lower for the mifamurtide group (Cox model; HR 0.21, p = 0.136). Only subtle differences in lymphocyte counts were observed across treatment. CONCLUSION: the PFS benefit of mifamurtide is reported herein. The addition of mifamurtide could be considered as a best treatment option for localized osteosarcoma.

Age-related changes in haematological parameters and biochemical markers of healing in the stomach of rats with acetic acid induced injury.

This study examined the changes in haematological and biochemical variables in response to gastric mucosa injury in male Wistar rats divided into four groups according to their ages (3, 6, 12, and 18 months). 0.2 ml of acetic acid was injected intraluminal into the stomach glandular portion of each rat for 45 seconds under anaesthesia. Collection of blood and stomach samples occurred on days 3, 7, 14 and 21 post-induction of gastric ulcer. The results obtained from this study showed 100 % area of gastric mucosa healed in 3-month old rats, 91.72 %, 68.52 % and 62.81 % area of mucosa treated in 6, 12 and 18-month old rats respectively on day 21 post-induction of gastric ulcer. Increased circulation of blood cells in younger rats occurred, neutrophil-lymphocyte ratio (NLR) was decreased in younger rats (3 and 6 months) significantly (p < 0.05) when compared to older rats (12 and 18 months). Lipid peroxidation and glutathione (GSH) levels were elevated in older rats (12 and 18 months) significantly (p < 0.05) when compared to younger rats (3 and 6 months). In comparison, superoxide dismutase (SOD) and catalase levels were decreased in older rats (12 and 18 months) significantly (p < 0.05) when compared to younger rats (3 and 6 months). Histological evaluation showed evidence of early healing with re-epithelialisation and angiogenesis in younger rats, but older rats showed delayed healing. The study showed that the slower rate of healing of gastric ulcer with advancing age in rats might be due to reducing circulating blood cells and anti-inflammatory activities during healing via a lipid peroxidation-dependent mechanism.

Sub-chronic dermal exposure to aircraft engine oils impacts the reproductive organ weights and alters hematological profiles of Sprague Dawley rats.

There is little data available for the toxicity of used aircraft engine oils relative to their unused (new) versions. This study was conducted to determine if grade 3 (G3) and 4 (G4) aircraft engine oils in their new states (G3-N and G4-N) and their used versions (G3-U and G4-U) have the potential to induce toxicity via dermal application. Male and female Sprague Dawley rats were dermally exposed to water (control), new and used versions of G3 and G4 oils to determine the oil sub-chronic toxicity potentials. A volume of 300 µL of undiluted oil was applied to the pad of the Hill Top Chamber System©. Then the chamber was attached to a fur-free test site located at the back of the rat for 6 h/day for 5 consecutive days/week for 21 days (15 total exposures). Recovery rats also received similar treatments and were kept for 14 days post-exposure to screen for reversibility, persistence, or delayed occurrence of toxic effects. Both G3 and G4 oils had a significant impact on the weight of male and female reproductive organs: testes weights for recovery rats exposed to G3-N significantly decreased (12%) relative to controls; G3-N and G3-U decreased uterus weights by 23% and 29%, respectively; G4-N decreased uterus weights by 32% but were resolved at the end of the recovery period; G4-N increased the weight of the adrenals and spleen for females by 34% and 27%, respectively, during the recovery period. G3 and G4 induced more changes in female blood indices than in those for males. Of all versions of oils, G4-N induced the most changes in profiles of female blood. G4-N significantly decreased the white blood cells, lymphocytes, neutrophils, eosinophils and increased the mean platelet volumes. Interestingly, males were not affected by exposure to G4-N oil. While G3-N decreased the white blood cells and lymphocytes for females it slightly increased those for males. In summary, G3 and G4 oils impacted the weights for male and reproductive organs. This study highlights the health risks that aircraft maintenance workers may be exposed to if precautions are not taken to minimize exposure to these oils.

Data on the application of early coagulation support protocol in the management of major trauma patients.

This article provides additional data on the application of early coagulation support protocol in the management of major trauma patients. Data come from a retrospective analysis reported in the article "Early coagulation support protocol: a valid approach in real-life management of major trauma patients. Results from two Italian centres" [1]. Data contain information about the relationship between differences in resource use and mortality outcomes, and patient demographic and clinical features at presentation. Furthermore, a comparison between resource consumption, the probability of multiple transfusions and the mortality outcomes among propensity-score matched patients is reported.

28-day inhalation toxicity of 3-methoxybutyl chloroformate in rats.

The 28-day repeated inhalation study was applied for hazard assessment of 3-methoxybutyl chloroformate (3-MBCF) in Sprague Dawley rats. Groups of five rats per sex were exposed 6 h/day, 5 days per week for 4 weeks to test substance concentration (ranging from 3 to 12 ppm) using a whole-body exposure system. At the terminal sacrifice, following blood collection and gross pathological examination, organ weights were determined and fixed organs were examined. The micronucleus test was performed using bone marrow cells. Exposure of 3-MBCF induced mortality at concentrations above 6 ppm. Decreases in body weight and food intake, hematologic alterations, organ weight changes, and gross and microscopic findings were seen even at the lowest concentrations of 3 ppm. Histopathology revealed principal test substance exposure correlated with lesions in the respiratory tract in both male and female rats above 3 ppm. Groups of male rats exposed above 6 ppm show microscopic lesions in spleens, livers, testes and epididymides; however, the micronucleated polychromatic erythrocytes frequency in bone marrow cells was not changed. Based on histopathology of the respiratory tract and other organs, the no observed adverse effect level (NOAEL) of 3-MBCF in the present study was less than 3 ppm.

Haematological evaluation of sodium fluoride toxicity in oryctolagus cunniculus.

Blood is promptly affected by environmental pollutants and toxicants that can cause many metabolic disorders. The high level of fluoride acts as a potential pollutant, insecticide and rodenticide with very high toxicity, associated with the hematological damage. This study aimed to determine the toxicity of Sodium Fluoride on hematological parameters in Oryctolagus cunniculus. Twenty rabbits were acclimatized and divided in to control group and three experimental groups.Experimental group-I, II and III were treated with 10, 30 and 50 mg/kg body weight doses of Sodium Fluoride orally. Various blood parameters such as TEC, Hb, HCT, MCV, MCH, MCHC, TLC and PLT count were investigated. Result findings showed that values of blood indices in experimental groups were significantly lower than the control group. Oneway ANOVA was applied for statistical analysis. The outcomes of the current studies indicated the reduction in RBC counts (anemia), leukocyte count (leukocytopenia), monocytosis, eosinopenia, neutrophilia and thrombocytosis on fluoride intoxication. Hematological disruptions like microcytic hypochromic anemia and decreased leukocyte count may be linked to the inflammatory effects of Sodium Fluoride on lymphatic organs.

Hepatitis E Virus Superinfection and Clinical Progression in Hepatitis B Patients.

Hepatitis E virus (HEV) infection may cause acute hepatitis and lead to hepatic failure in developing and developed countries. We studied HEV seroprevalences in patients with hepatitis B virus (HBV) infection to understand the consequences of HEV superinfection in a Vietnamese population. This cross-sectional study was conducted from 2012 to 2013 and included 1318 Vietnamese patients with HBV-related liver diseases and 340 healthy controls. The case group included patients with acute (n = 26) and chronic hepatitis B (n = 744), liver cirrhosis (n = 160), hepatocellular carcinoma (n = 166) and patients with both liver cirrhosis and hepatocellular carcinoma (n = 222). Anti-HEV IgG and IgM antibodies were assessed in patients and controls by ELISA. HEV-RNA was identified by PCR assays and sequencing. Seroprevalences of anti-HEV IgG among hepatitis B patients and controls were 45% and 31%, respectively (adjusted P = 0.034). Anti-HEV IgM seroprevalences were 11.6% and 4.7% in patients and controls, respectively (adjusted P = 0.005). Seroprevalences were higher among the elder individuals. When stratifying for patient groups, those with liver cirrhosis had the highest anti-HEV IgG (52%) and anti-HEV IgM (19%) seroprevalences. Hepatitis B patients with current HEV infection had abnormal liver function tests compared to patients with past or without HEV infection. One HEV isolate was retrieved from a patient with both liver cirrhosis and hepatocellular carcinoma and identified as HEV genotype 3. This study indicates high prevalences of HEV infection in Vietnamese HBV patients and among healthy individuals and shows that HEV superinfection may influence the outcome and progression of HBV-related liver disease.