Parkinson’s disease (PD) is a neurodegenerative disease associated with progressive impairment of motor and non-motor functions in aging people. Overwhelming evidence indicate that mitochondrial ...dysfunction is a central factor in PD pathophysiology, which impairs energy metabolism. While, several other studies have shown probiotic supplementations to improve host energy metabolism, alleviate the disease progression, prevent gut microbiota dysbiosis and alter commensal bacterial metabolites. But, whether probiotic and/or prebiotic supplementation can affect energy metabolism and cause the impediment of PD progression remains poorly characterized. Therefore, we investigated 8-weeks supplementation effects of probiotic
Lactobacillus salivarius
subsp.
salicinius
AP-32 (AP-32), residual medium (RM) obtained from the AP-32 culture medium, and combination of AP-32 and RM (A-RM) on unilateral 6-hydroxydopamine (6-OHDA)-induced PD rats. We found that AP-32, RM and A-RM supplementation induced neuroprotective effects on dopaminergic neurons along with improved motor functions in PD rats. These effects were accompanied by significant increases in mitochondrial activities in the brain and muscle, antioxidative enzymes level in serum, and altered SCFAs profile in fecal samples. Importantly, the AP-32 supplement restored muscle mass along with improved motor function in PD rats, and produced the best results among the supplements. Our results demonstrate that probiotic AP-32 and A-RM supplementations can recover energy metabolism via increasing SCFAs producing and mitochondria function. This restoring of mitochondrial function in the brain and muscles with improved energy metabolism might additionally be potentiated by ROS suppression by the elevated generation of antioxidants, and which finally leads to facilitated recovery of 6-OHDA-induced motor deficit. Taken together, this work demonstrates that probiotic AP-32 supplementation could be a potential candidate for alternate treatment strategy to avert PD progression.
We aimed to analyze CT features of persistent subsolid nodules (SSN) ≦3 cm diagnosed pathologically as adenocarcinoma spectrum to investigate whether parameters enable distinction between invasive ...pulmonary adenocarcinomas (IPAs) and pre-invasive lesions. A total of 129 patients with 141 SSNs confirmed with surgically pathologic proof were retrospectively reviewed. Of 141 SSNs, there were 57 pure ground-glass nodules (GGNs), 22 heterogeneous GGNs, and 62 part-solid nodules. SSN subclassification showed a significant linear trend with invasive degree of the adenocarcinoma spectrum (pure GGNs 7%; heterogeneous GGNs 36.4%; part-solid nodules 85.5%, P for trend <0.0001). For IPA detection in 141 SSNs, a solid part of ≧3 mm was the most specificity (sensitivity, 76.9%; specificity, 94.7%), followed by air-bronchogram sign (sensitivity, 53.8%; specificity, 89.5%), SSN subclassification (sensitivity, 81.5%; specificity, 88.2%), and a lesion size ≧12 mm (sensitivity, 84.6%; specificity, 76.3%). For IPA detection in 79 pure or heterogeneous GGNs, the heterogeneous GGN sign was the most useful finding, with most specificity (sensitivity, 66.7%; specificity, 79.1%), followed by CT attenuation (HU) of ≧-493 (sensitivity, 75%; specificity, 74.6%) and a lesion size ≧10 mm (sensitivity, 83.3%; specificity, 70.1%). In conclusion, this simple combined visual and semiquantitative analysis of CT features helps distinguish IPAs from pre-invasive lesions.
Probiotics are health beneficial bacterial populations colonizing the human gut and skin. Probiotics are believed to be involved in immune system regulation, gut microbiota stabilization, prevention ...of infectious diseases, and adjustments of host metabolic activities. Probiotics such as
Lactobacillus
and
Bifidobacterium
affect glycemic levels, blood lipids, and protein metabolism. However, the interactions between probiotics and metabolic diseases as well as the underlying mechanisms remain unclear. We used streptozotocin (STZ)-induced diabetic animal models to study the effect of Probioglu
TM
, a multi-strain probiotic supplement including
Lactobaccilus salivarius
subsp.
salicinius
AP-32,
L
.
johnsonii
MH-68,
L
.
reuteri
GL-104, and
Bifidobacterium animalis
subsp.
lactis
CP-9, on the regulation of physiochemical parameters related to type-2 diabetes. Experimental rats were randomly assigned into five groups, control group, streptozotocin (STZ)-treated rats (STZ group), STZ + 1× Probioglu
TM
group, STZ + 5× Probioglu
TM
group, and STZ + 10× Probioglu
TM
group, and physiological data were measured at weeks 0, 2, 4, 6, and 8. Our results indicate that supplementation with Probioglu
TM
significantly improved glucose tolerance, glycemic levels, insulin levels, and insulin resistance (HOMA-IR). Furthermore, we observed reduction in urea and blood lipid levels, including low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC). Probioglu
TM
administration increased the β-cell mass in STZ-induced diabetic animal models, whereas it reduced the levels of proinflammatory cytokines TNF-α, IL-6, and IL-1β. In addition, the enhancement of oxidative stress biomarkers and superoxide dismutase (SOD) activities was associated with a decrease in malondialdehyde (MDA) levels. We conclude that Probioglu
TM
attenuates STZ-induced type-2 diabetes by protecting β-cells, stabilizing glycemic levels, and reducing inflammation. Among all probiotic treating groups, the 10×Probioglu
TM
treatment revealed the best results. However, these experimental results still need to be validated by different animal models of type-2 diabetes and human clinical trials in the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obesity is a serious and costly issue to the medical welfare worldwide. Probiotics have been suggested as one of the candidates to resolve the obesity-associated problems, but how they combat obesity ...is not fully understood. Herein, we investigated the effects of Lactobacillus reuteri 263 (L. reuteri 263) on antiobesity using four groups of Sprague–Dawley rats (n=10/group), namely, C (normal diet with vehicle treatment), HE high-energy diet (HED) with vehicle treatment, 1X (HED with 2.1×109 CFU/kg/day of L. reuteri 263) and 5X (HED with 1.05×1010 CFU/kg/day of L. reuteri 263), for 8 weeks. L. reuteri 263 improved the phenomenon of obesity, serum levels of proinflammatory factors and antioxidant enzymes. More importantly, L. reuteri 263 increased oxygen consumption in white adipose tissue (WAT). The mRNA expressions of thermogenesis genes uncoupling protein-1, uncoupling protein-3, carnitine palmitoyltransferase-1 and cell death-inducing DFFA-like effector-a were up-regulated in WAT of the 5X group. Moreover, L. reuteri 263 might induce browning of WAT due to the higher mRNA levels of browning-related genes peroxisome proliferator-activated receptor-γ, PR domain containing-16, Pparγ coactivator-1α, bone morphogenetic protein-7 and fibroblast growth factor-21 in the 1X and 5X groups compared to the HE group. Finally, L. reuteri 263 altered the expressions of genes involved in glucose and lipid metabolisms in WAT, including increasing the levels of glucose transporter type 4 and carbohydrate-responsive element-binding protein and decreasing the expression of Acetyl-CoA carboxylase-1. The results suggest that L. reuteri 263 may treat obesity through energy metabolism remodeling of WAT in the high-energy-diet-induced obese rats.
and
both contain unique polyphenols called phlorotannins. Phlorotannins reportedly possess various pharmacological activities. A previous study reported that the activity of phlorotannin is strongly ...correlated with the normalization of metabolic function, and phlorotannins are extremely promising nutrients for use in the treatment of metabolic syndrome. To date, no study has explored the antihyperlipidemic effects of phlorotannins from
and
in animal models. Therefore, in the present study, we investigated the effects of phlorotannins using a rat model of high-energy diet (HED)-induced hyperlipidemia. The results showed that the rats that were fed an HED and treated with phlorotannin-rich extract from
and
had significantly lower serum fasting blood sugar (FBS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triacylglyceride (TG) and free fatty acids (FFAs) levels and hepatic TG level and had higher serum insulin, high-density lipoprotein cholesterol (HDL-C) levels and lipase activity in their fat tissues than in the case with the rats that were fed the HED alone. A histopathological analysis revealed that phlorotannin-rich extract could significantly reduce the size of adipocytes around the epididymis. In addition, the rats treated with phlorotannin-rich extract had significantly lowered interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels and increased superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities than did those in the HED group. These results suggested that the phlorotannin-rich extract stimulated lipid metabolism and may have promoted lipase activity in rats with HED-induced hyperlipidemia. Our results indicated that
and
, marine algae typically used as health foods, have strong antihyperlipidemic effects and may, therefore, be useful for preventing atherosclerosis. These algae may be incorporated into antihyperlipidemia pharmaceuticals and functional foods.
Oxidative stress plays a key role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD), which may be aggravated by concomitant PD-associated gut dysbiosis. Probiotics and ...prebiotics are therapeutically relevant to these conditions due to their antioxidant, anti-inflammatory, and gut microbiome modulation properties. However, the mechanisms by which probiotic/prebiotic supplementation affects antioxidant capacity and the gut microbiome in PD remains poorly characterized. In this study, we assessed the effects of a Lactobacillus salivarius AP-32 probiotic, a prebiotic (dried AP-32 culture medium supernatant), and a probiotic/prebiotic cocktail in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced PD. The neuroprotective effects and levels of oxidative stress were evaluated after eight weeks of daily supplementation. Fecal microbiota composition was analyzed by fecal 16S rRNA gene sequencing. The supplements were associated with direct increases in host antioxidant enzyme activities and short-chain fatty acid production, protected dopaminergic neurons, and improved motor functions. The supplements also altered the fecal microbiota composition, and some specifically enriched commensal taxa correlated positively with superoxide dismutase, glutathione peroxidase, and catalase activity, indicating supplementation also promotes antioxidant activity via an indirect pathway. Therefore, L. salivarius AP-32 supplementation enhanced the activity of host antioxidant enzymes via direct and indirect modes of action in rats with 6-OHDA-induced PD.
Cisplatin-based chemotherapy is a common first-line regimen for treating non–small cell lung cancer (NSCLC). However, drug resistance is still a major problem. The purposes of this study were to ...evaluate whether sclareol can reverse cisplatin resistance and to investigate its possible mechanisms. A549 cells, the human NSCLC cells with inherent cisplatin resistance, were used to investigate synergistic effect of sclareol with cisplatin in cell proliferation and migration as well as its regulatory mechanisms in expression of excision repair cross-complementation group 1 (ERCC1), a cisplatin resistance-associated molecule. Nude mice bearing subcutaneous A549 tumors were applied to investigate synergistic activity of sclareol in anti-tumor. As comparing to the cisplatin alone group, the treatment of cisplatin combined with sclareol significantly suppressed survival rate and cell migration of A549 cells. Besides, sclareol also exhibited suppression in ERCC1 expression by inhibiting AKT-GSK3β-AP1/Snail and JNK-AP1 pathways. Furthermore, the experimental data from in vivo study also demonstrated that the combination group of cisplatin and sclareol showed the greatest anti-tumor activity, whose effect could be partially attributed to sclareol-mediated decrease in intratumoral level of ERCC1 protein. Accordingly, sclareol has potential as an adjuvant for the treatment in NSCLC patients with cisplatin resistance.
•Drug resistance is still a critical issue in clinical chemotherapy.•Platinum-based compounds, such as cisplatin, are first-line drugs for treating non-small cell lung cancer (NSCLC).•Excision repair cross-complementation group 1 (ERCC1), a DNA repair enzyme, involved in cisplatin-resistance.•Sclareol is a natural aromatic compound with the activity of suppressing ERCC1 expression.•Sclareol can be used as an adjuvant drug to enhance cytotoxic effect of cisplatin in NSCLC chemotherapy.
Oxidative stress and gut dysbiosis have been known to precede Parkinson's disease (PD). An antioxidant-rich product, mangosteen pericarp (MP), has the ability to counterbalance excessive free ...radicals and the imbalanced gut microbiota composition, suggesting the MP's capacity to delay PD progression. In this study, we explored the effects of two doses of MP extract in a unilateral 6-hydroxydopamine (6-OHDA)-induced PD rat model. We revealed that the 8-week supplementation of a low dose (LMP) and a high dose of the MP extract (HMP) improved motor function, as observed in decreased contralateral rotation, improved time spent on rod, and higher dopamine binding transporter (DAT) in the substantia nigra pars compacta (SNc). The MP extract, especially the HMP, also increased antioxidant-related gene expressions, restored muscle mitochondrial function, and remodeled fecal microbiota composition, which were followed by reduced reactive oxygen species levels in brain and inflammation in plasma. Importantly, bacterial genera
,
, and
, which were negatively correlated with antioxidant gene expressions, decreased in the HMP group. It is imperative to note that in addition to directly acting as an antioxidant to reduce excessive free radicals, MP extract might also increase antioxidant state by rebuilding gut microbiota, thereby enhanced anti-inflammatory capacity and restored mitochondrial function to attenuate motor deficit in 6-OHDA-induced PD-like condition. All in all, MP extract is a potential candidate for auxiliary therapy for PD.
Abstract only
Lung cancer is one of the most causative factors of death in cancer. Accumulating evidences implicated the possible effects of hyperlipidemia on increased risk for cancer progression. ...The purpose of this study was to investigate whether low‐density lipoprotein (LDL), a critical hyperlipidemia effector, has potential roles to modulate the cell growth and migration of lung cancer cells as well as to understand its possible regulatory mechanisms. Cell viability and migration were examined by MTT and wound healing assays, respectively. The translational and transcriptional expressions were monitored by Western blot and RT‐PCR, respectively. Experimental data showed that LDL can significantly increase cell growth and migration of A549 non‐small cell lung cancer cells by activating the ERK1/2‐MAPK pathway. Our study suggested that LDL might play as a stimulator for the progression of lung cancer in the hyperlipidemic condition. Application of lipid lowering agents may be a poteintial remedy for lung cancer therapy.
This study sought to determine the association between twinkling artifacts on color Doppler ultrasound and different types of guidewires.
Twenty-two commonly used guidewires were classified into ...three groups according to decreasing diameter (Group 1, 0.035"; Group 2, 0.018"; and Group 3, 0.014") and tested
. Severity of twinkling was visually graded into four categories (0-3, from weak to strong).
The percentages (tips/shafts) of twinkling artifacts were 100%/100% for Group 1; 0%/33.3% for Group 2; and 18.8%/31% for Group 3. The mean scores (tips/shafts) were 2.3/2.7 for Group 1; 0/0.3 for Group 2; and 0.3/0.4 for Group 3. Among them, both two guidewires with strong twinkling artifacts (score = 3) exhibited extensive rough surfaces on microscopic pictures.
The twinkling artifacts were more likely to present in guidewires with larger diameters (from 0.014" to 0.035") in our study settings. The surface roughness may be the contribution to the twinkling artifact. Internal heterogeneities, such as types of material, types of coating, tip loading, and spring coil length, do not show influence on the twinkling artifact.