Effects of co-supplementation of chromium and magnesium on metabolic profiles, inflammation, and oxidative stress in impaired glucose tolerance.

PURPOSE: To evaluate the effects of chromium (Cr) and magnesium (Mg) ions on metabolic profiles, inflammation, and oxidative stress with impaired glucose tolerance (IGT) and insulin resistance (IR). METHODS: 120 individuals with IGT and IR were randomly divided into four groups treated with (1) chromium, (2) magnesium, (3) chromium and magnesium or (4) placebo. Metabolic and inflammatory indicators were measured at baseline and after 3 months intervention. RESULTS: Comparison among groups showed that fasting plasma glucose (FPG), 2 h post glucose (2hPPG), fasting insulin (FINS) and homeostatic model assessment for insulin resistance (HOMA-IR) in Cr + Mg group were significantly decreased compared with the other three groups (p < .05), and high density lipoprotein (HDL-c) levels were higher. 8-iso prostaglandin F2 alpha (8-iso-PGF2a) decreased in Cr, Mg, and Cr + Mg groups compared with placebo (p < .05), and 8-iso-PGF2a decreased in Cr + Mg groups compared with Cr group and Mg groups (p > .05). Intra-group comparison showed that the levels of FPG, 2hPPG and FINS in Cr + Mg group were significantly decreased after intervention (p < .05), and FINS in Mg group was significantly decreased (p < .01). The levels of HDL-c and triacylglycerol (TG) in Cr + Mg group were significantly improved (p < .05). The level of HDL-c in Mg group was significantly improved compared with baseline (p < .05). Compared with baseline, high-sensitivity C-reactive protein (hsCRP) levels in Cr + Mg group and Mg group were significantly decreased (p < .05). CONCLUSIONS: The co-supplementation of Cr and Mg improves glycemic and lipid levels and reduces the inflammatory response and oxidative stress profiles of individuals with impaired glucose tolerance and insulin resistance.

Gradual Traction Reduction With the Ilizarov Method for Tile C1.2 Old Pelvic Fracture: A Case Report.

CASE: A 20-year-old man with a Tile C1.2 pelvic fracture was treated with skeletal traction. After 3 months, the patient was unable to stand and walk, and the right lower limb was shortened by 7 cm. Radiographs showed that the sacroiliac joint dislocation was not reduced. Gradual traction reduction with the Ilizarov method was used to correct sacroiliac joint dislocation, and open internal fixation was performed. Postoperatively, the old pelvic fracture was successfully reduced without sacral plexus injury. CONCLUSION: Gradual traction reduction with the Ilizarov method can reduce the risk of sacral plexus injury and achieve satisfactory reduction of Tile C1.2 old pelvic fractures.

Risk of having pulmonary tuberculosis in type 2 diabetes: A hospital-based matched case-control study.

BACKGROUND AND OBJECTIVES: Diabetes mellitus (DM) leads to nearly 3-fold higher risk of pulmonary tuberculosis (TB), indicating an increasing challenge to public health in low-to-middle income countries. Till now, the risk factor is still uncertain. We carried out this study with the main purpose to identify the risk factors of having TB in DM patients. METHODS AND STUDY DESIGN: A hospital-based matched case-control study was conducted in Qingdao, China from March, 2016 to January, 2018. Cases were DM patients with concurrent TB (DM-TB). Each case was matched with two controls, patients with DM only of similar age, sex and DM course. Cox regression of conditional logistic analysis was used to define the risk factors for having TB in DM, and then sensitivity analysis was carried out. RESULTS: We identified 315 patients, including 105 cases and 210 controls. Smokers had a higher risk of having TB with a multivariable adjusted odds ratio (aOR) of 12.45 than non-smokers. Poor glycemic control (aOR=2.66), frequency of DM re-examination <1 time/year (aOR=3.39), as well as TB contact history was also independently related with higher risk, while BMI ≥24 (aOR=0.42), education level ≥ college (aOR=0.11) showed a negative association. CONCLUSIONS: Poor glycemic control, smoking, low frequency of reexamination was associated with higher risk of having TB in DM, while overweight and obesity, high education levels showed a negative association. These findings provide clues to target DM populations prone to TB, which may be of help to halt the epidemic of TB in high burden countries.

Joint replenishment of zinc and folic acid enhances the anti-depressive effect of paroxetine via increasing serum calcium and copper and decreasing serum arsenic.

Insufficient zinc and folic acid levels are associated with depression and poor response to antidepressants. This study aimed to investigate the influences of combined zinc and folic acid replenishment on the anti-depressive effect of paroxetine. Male rats were randomly divided into five groups: control (C), model (M), paroxetine (MP), zinc + folic acid (MZnF), and zinc + folic acid + paroxetine (MZnFP) groups. Rats were exposed to mild unpredictable stress for 3 weeks as a depression model. The combinations of drug and supplements were applied via daily gavage for 4 weeks. The open field test was conducted to observe behavioral changes. A chemiluminescence method was used to detect folacin, and inductively coupled plasma mass spectrometry was used to detect serum elements. Supplementation of zinc and folic acid significantly improved behavior responses to paroxetine, including movement speed, total distance, and central zone frequency. In addition, higher calcium and copper levels and a lower arsenic level were found in the serum of the MZnFP group. Thus, supplementation of zinc and folacin can enhance the anti-depressive effect of paroxetine, and the mechanism is potentially related to the improved levels of calcium and copper and a reduced level of arsenic.

Lactobacillus casei improves depression-like behavior in chronic unpredictable mild stress-induced rats by the BDNF-TrkB signal pathway and the intestinal microbiota.

Lactobacillus casei (L. casei), a kind of probiotics, is known as a "healthy triple benefit bacterium" along with Lactobacillus acidophilus and Bifidobacterium. L. casei is associated with the alteration of the intestinal flora population, and the gut microbiota-brain axis has been demonstrated to play an important role in many central nervous system diseases. The aim of this study was to evaluate the effectiveness of L. casei intervention in ameliorating mental disorders and potential mechanisms using a rat model with depression-like behaviour induced by chronic unpredictable mild stress (CUMS). L. casei intervention improved the CUMS-induced depression-like behaviors of rats, including a reduced body growth rate, decreased sucrose preference, increased immobility time, and lowered moving distance and velocity. In addition, L. casei intervention amended the gut microbiota structure changes induced by CUMS in rats. Furthermore, L. casei intervention reversed the CUMS-induced protein expression changes of monoamines dopamine, noradrenaline and 5-hydroxytryptamine, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase receptor B (TrkB), and N-methyl-d-aspartic acid receptor 1, as well as CUMS-induced activations of ERK1/2 and p38 MAPK signal pathways. These findings suggested that L. casei could significantly protect against depression in rats, which was possibly associated with the alterations in the gut microbiota composition and mediation of BDNF-TrkB signaling.

The emerging role of the piRNA/piwi complex in cancer.

Piwi interacting RNAs (piRNAs) constitute novel small non-coding RNA molecules of approximately 24-31 nucleotides in length that often bind to members of the piwi protein family to play regulatory roles. Recently, emerging evidence suggests that in addition to the mammalian germline, piRNAs are also expressed in a tissue-specific manner in a variety of human tissues and modulate key signaling pathways at the transcriptional or post-transcriptional level. In addition, a growing number of studies have shown that piRNA and PIWI proteins, which are abnormally expressed in various cancers, may serve as novel biomarkers and therapeutic targets for tumor diagnostics and treatment. However, the functions of piRNAs in cancer and their underlying mechanisms remain incompletely understood. In this review, we discuss current findings regarding piRNA biogenetic processes, functions, and emerging roles in cancer, providing new insights regarding the potential applications of piRNAs and piwi proteins in cancer diagnosis and clinical treatment.

Chimeric antigen receptor (CAR)-modified NK cells against cancer: Opportunities and challenges.

NK cells may have great potential in tumor immunotherapy because they can kill tumor cells directly and quickly. Chimeric antigen receptor is a fusion protein composed of extracellular antigen recognition domain, transmembrane domain and intracellular signal domain. Rapid development of CAR-modified T cells has made tremendous achievements in the treatment of malignancies, especially hematological malignancies. However, there are many deficiencies in clinical application of CAR-T cell therapy. Car-modified NK cells have attracted much attention because they may avoid these shortcomings. At present, preclinical and clinical studies have shown that CAR-NK cell therapy may play significant anti-tumor role and it is safer than CAR-T cell therapy. Nevertheless, CAR-NK cell therapy still faces some challenges, such as the expansion and activation of primary NK cells in vitro, the difficulty to store and ship NK cell products and the low transduction efficiency. Thus further research is still needed to optimize CAR-NK cell therapy. Building better CAR-NK cells is important to improve the treatment efficacy and combination therapy offers a novel direction of NK-cell based immunotherapy.

Improvement of symptoms in a rat model of depression through combined zinc and folic acid administration via up-regulation of the Trk B and NMDA.

The aim of this study was to observe the influence of combined zinc and folic acid administration on depression and to explore its mechanism of action. Male Sprague Dawley rats were randomly divided into five groups: control, model, paroxetine (P), zinc + folic acid (ZnY), and zinc + folic acid + paroxetine (ZnYP) groups. Rat models of depression were established by chronic mild unpredictable stress for three weeks. These rats were then treated with different interventions for four weeks and the sucrose preference test was then performed to observe changes in rats' behavior. An HPLC-electrochemical method was used to detect the levels of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the frontal cortex. qRT-PCR was employed to detect the mRNA levels of tyrosine kinase receptor B (Trk B) and N-methyl-D-aspartate acid (NMDA) in the frontal cortex; Western blotting was used to detect the protein levels of brain derived neurotrophic factor (BDNF) in the frontal cortex. The results showed that compared with the model group, sucrose consumption, 5-HT, NE and DA levels were significantly increased in the ZnY group (P < 0.05). Also the mRNA levels of Trk B and NMDA were significantly increased in the ZnY group compared with the model group (P < 0.001). No significant up-regulation of BDNF was observed in the ZnY group. We conclude that combined administration of zinc and folic acid can improve the symptoms of depression-model rats, and its mechanism is related to increased levels of 5-HT, DA and NE in the brain, and to the up-regulation of Trk B and NMDA.

Severe hypovitaminosis D in active tuberculosis patients and its predictors.

BACKGROUND & AIMS: Tuberculosis (TB) patients have a significant vitamin D deficiency (VDD) endemic, which may be closely related to the onset and progress of the disease. The comorbidity of diabetes (DM) and TB has posed an increasing challenge in recent years. However, the influence of DM on TB and the possible mechanism are still uncertain. We carried out this study to identify the nutritional status of vitamin D (VD) in TB patients in a northern city in China (latitude 36° N) and investigate the possible predictors of severe vitamin D deficiency (SVDD). METHODS: A cross-sectional study including 461 active TB patients (192 with and 269 without DM) were randomly selected from Qingdao Chest Hospital from June 2015 to August 2016. We measured serum 25 hydroxyvitamin D [25(OH)D], and investigated the association between sociodemographic, dietary intake, DM, body mass index (BMI), severity of initial TB signs and symptoms (TB score) and VD status. Multivariate logistic regression analysis was used to define the possible predictors of SVDD. RESULTS: The median serum 25(OH)D concentration was 8.50 ng/mL. Of the 461 TB patients included, 383 (83.1%) had VDD [25(OH)D < 20 ng/mL], and 217 (47.1%) had SVDD [25(OH)D < 8 ng/mL]. The variables associated with serum 25(OH)D concentrations were DM, outdoor activity level, TB score and BMI (p < 0.05). Patients with severe TB score had nearly 5 fold higher risk of having SVDD compared with those in mild subgroup [OR (95% CI) = 4.919 (2.644-9.150), p < 0.001]. Low outdoor activity level also increased the odds of SVDD, while DM and high fish consumption showed protect effects. CONCLUSIONS: Severe hypovitaminosis D is prevalent in active TB patients, and the main predictors of SVDD were severe TB score, low outdoor activity, inadequate fish consumption. Lowered serum 25(OH)D may be associated with increased risk of TB in DM.

Combined chromium and magnesium decreases insulin resistance more effectively than either alone.

BACKGROUND AND OBJECTIVES: Peroral supplementation with trivalent-chromium (Cr) or magnesium (Mg) has been shown to improve insulin resistance (IR). The objective of this study was to determine whether combined peroral supplementation with Cr and Mg improves IR more effectively than Cr or Mg alone. METHODS AND STUDY DESIGN: Subjects (n=120, age range 45-59 years old) and diagnosed with IR were randomly divided into four groups and monitored for a period of 3 months: group 1 (the placebo control group), group 2 (160 µg/d Cr), group 3 (200 mg/d Mg), and group 4 (160 µg/d Cr plus 200 mg/d Mg). Fasting blood glucose (FBG), fasting insulin (FIns), erythrocyte Cr and Mg content, and glucose-transporter-4 (GLUT4) and glycogen-synthase-kinase-3ß (GSK3ß) mRNA levels in activated T-lymphocytes were measured, and insulin resistant index (IRI) was calculated. RESULTS: Significant decreases between the baseline and study conclusion values of FBG (0.37 mmol/L, p<0.01), FIns (2.91 µIU/mL, p<0.01) and IRI (0.60, p<0.01) were observed in group 4, but not groups 1-3. Similarly, compared with baseline, significant changes in GLUT4 (2.9-fold increase, p<0.05) and GSK3ß (2.2-fold decrease, p<0.05) mRNA levels in activated T-lymphocyte were observed at the study's conclusion in group 4, but not in groups 1-3. CONCLUSIONS: Our results indicate that combining peroral supplementation with Cr and Mg improves IR more effectively than Cr or Mg alone, and this may be attributable to increased induction and repression, respectively, of GLUT4 and GSK3ß expression.

Supplementation with magnesium and vitamin E were more effective than magnesium alone to decrease plasma lipids and blood viscosity in diabetic rats.

Although magnesium and vitamin E (VE) have differing effects on diabetes, both are beneficial. We hypothesized that preventive supplementation of magnesium combined with VE could improve the metabolism of lipids and blood viscosity more effectively than the use of magnesium or VE alone. Our objective was to detect the effects of preventive supplementation of magnesium combined with VE on lipid peroxidation, lipid metabolic parameters, and blood viscosity in diabetic rats. Six dietary groups, all fed with high-energy diets, were formed and studied for 8 weeks: control group (C); VE group (E); middle-dose magnesium group (MM); high-dose magnesium group (HM); VE plus middle-dose magnesium group (EMM); and VE plus high-dose magnesium group (EHM). Compared with C group, malondialdehyde was inhibited in the E, EMM, and EHM groups (all P < .05); total cholesterol decreased in all 5 treated groups, and significant differences were found in groups E (P = .004), MM (P = .017), EMM (P = .016), and EHM (P = .020). Compared with the C group, high-density lipoprotein levels were elevated in the HM (P = .027) and EHM (P = .021) groups, and low-density lipoprotein levels were lower in the E (P = .010), EMM (P = .025), and EHM (P = .015) groups. Differences between middle and high shear rates of blood viscosity were significant in all treated groups compared with the C group (all P

Inhibitory effect of polypeptide from Chlamys farreri on UVA-induced apoptosis in human keratinocytes.

Polypeptide from Chlamys farreri (PCF, Mr = 879) is a novel marine active product isolated from gonochoric Chinese scallop Chlamys farreri which has been served as sea food for several thousand years. As an octapeptide, PCF consists of 8 amino acids, namely, Pro, Asn, Ser, Thr, Arg, Hyl, Cys, and Gly. PCF had been identified as a marine chemopreventive drug that protected hairless mice's epidermis against UV-induced damage in our previous study. However, the molecular mechanisms that underlie the effect of PCF on ultraviolet A-induced apoptosis in ketatinocytes are not well understood yet. In the present study, PCF was investigated as a potential inhibitory agent for UVA-induced apoptosis in a human keratinocyte cell line, HaCaT. The effects of PCF on UVA-induced generation of ROS and MDA, DNA damage, apoptosis rate were examined. We also investigated whether PCF could inhibit UVA-induced decreasing of mitochondrial membrane potential and the changing of morphology of the cells. We found that, compared with UVA only group, PCF attenuated UVA-induced generation of ROS and MDA, increased the mitochondrial membrane potential, and decreased the apoptosis rate. These results indicate that PCF may protect HaCaT keratinocytes against UVA-induced apoptosis.