Increasing evidence supporting a causal link between obesity and endoplasmic reticulum (ER) stress in adipose tissue is being reported. Protein disulfide isomerase 4 (PDIA4) is a novel ER chaperone ...involved in the pancreatic β‐cells pathogenesis in diabetes. However, the role of PDIA4 in obesity progression remains poorly understood. To assess the relationship between PDIA4, adiponectin, and metformin, we used the palmitate‐induced inflammation in hypertrophic adipocytes and the high‐fat diet‐induced obesity mouse model. Our results revealed that palmitate‐induced hypertrophic adipocytes exhibit obesity‐associated conditions such as increased lipid accumulation, inflammation, and reduced glucose uptake. Pharmacological and genetic inhibition of PDIA4 significantly reverses these obesity‐associated conditions in adipocytes. PDIA4 mechanistically promotes obesity progression via adiponectin downregulation. Furthermore, metformin modulates PDIA4 and adiponectin expression and improves obesity‐associated conditions in both in vitro adipocytes and in vivo mouse models. Serum PDIA4 concentrations are also associated with body mass index, adiponectin, triglycerides, and inflammatory cytokines in humans. This is the first study demonstrating that PDIA4 modulates adipocytes by downregulating adiponectin. Moreover, metformin may serve as a potential therapeutic for preventing obesity via PDIA4‐targeting.
The aim of the present study was to evaluate whether probiotic administration could slow declining renal function. C57BL/6 mice (6–8 weeks of age, male) were fed a diet supplemented with adenine to ...induce chronic kidney disease (CKD). The experimental groups were additionally supplemented with 10
9
colony-forming units (CFU)/day (high-dose) and 10
7
CFU/day (low-dose) probiotics containing
Lactobacillus acidophilus
(TYCA06),
Bifidobacterium longum
subspecies
infantis
(BLI-02), and
B. bifidum
(VDD088). Renal function and histology were examined. Patients with stage 3–5 CKD and not on dialysis were recruited from July 2017 to January 2019. Two capsules of probiotics containing 2.5 × 10
9
CFU with the same composition were administered twice daily for 6 months. The decline in the estimated glomerular filtration rate (eGFR) was measured before and after the intervention. In addition, changes in the serum endotoxin and cytokine levels, gastrointestinal symptom scores, and the stool microbiota were measured. Probiotics could attenuate renal fibrosis and improve renal function in CKD mice. Thirty-eight patients completed the 6-month study. The mean baseline eGFR was 30.16 ± 16.52 ml/min/1.73 m
2
. The rate of decline in the eGFR was significantly slower, from −0.54 (−0.18, −0.91) to 0.00 (0.48, −0.36) ml/min/1.73 m
2
/month (
P
= 0.001) after 6 months of treatment. The serum levels of TNF-α, IL-6, IL-18, and endotoxin were significantly decreased after probiotic administration. Borborygmus and flatulence scores, as well as stool formation improved significantly. The abundance of
B. bifidum
and
B. breve
in the stool microbiota increased significantly. In conclusion, a combination of probiotics might attenuate renal function deterioration in CKD mice and human patients.
Increasing numbers of researchers are investigating the benefits of probiotics in enhancing exercise performance and verifying the role of the gut-muscle axis. In our previous study,
PL-02 improved ...exercise performance and muscle mass. Therefore, the purpose of this study was to investigate whether supplementation with PL-02 combined with resistance training has a synergistic effect on exercise performance and muscle mass. All the animals were assigned into four groups (
= 8/group): a sedentary control with normal distilled water group (vehicle,
= 8); PL-02 supplementation group (PL-02, 2.05 × 10
CFU,
= 8); resistance training group (RT,
= 8); PL-02 supplementation combined with resistance training group (PL-02 + RT, 2.05 × 10
CFU,
= 8). Supplementation with PL-02 for four consecutive weeks combined with resistance exercise training significantly improved the grip strength and the maximum number of crawls; increased the time of exhaustive exercise; significantly reduced the time required for a single climb; and reduced the lactate, blood ammonia, creatine kinase, and blood urea nitrogen produced after exercise (
< 0.05). In addition, it produced substantial benefits for increasing muscle mass without causing any physical damage. In summary, our findings confirmed that PL-02 or RT supplementation alone is effective in improving muscle mass and exercise performance and in reducing exercise fatigue, but the combination of the two can achieve increased benefits.
Obesity is a worldwide health problem. Calorie-restricted diets constitute a common intervention for treating obesity. However, an improper calorie-restricted diet can lead to malnutrition, fatigue, ...poor concretion, muscle loss, and reduced exercise performance. Probiotics have been introduced as an alternative treatment for obesity. In the present study, we tested the weight loss and exercise performance enhancement effectiveness of probiotic strains of different origins, including four isolated from an Olympic weightlifting gold medalist (
subsp.
OLP-01,
PL-02,
subsp.
SA-03, and
subsp.
LY-66). A high-fat diet (HFD) was used to induce obesity in 16 groups of mice (
= 8/group). The mice were administered probiotic supplements at a dosage of 4.1 × 10
CFU/kg/day for 10 weeks. All probiotic supplementation groups showed a significant reduction in body weight and fat mass compared with the HFD group. TYCA06, CS-773, BLI-02, PL-02, bv-77, and OLP-01 were the most effective in facilitating weight loss and fat reduction, which may be due to fatty-acid absorbing activity. PL-02, LY-66, TYCA06, CS-773, and OLP-01 elevated the animals' grip strength and exhaustive running duration. PL-02, LY-66, and OLP-01 increased tissue glycogen (liver and muscle) levels and muscle capillary density and reduced blood lactate production levels after exercise. In conclusion, OLP-01, PL-02, LY-66, TYCA06, and CS-773 were highly effective in enhancing weight loss and exercise performance. This study should be repeated on humans in the future to further confirm the findings.
The oral cavity plays a crucial role in food digestion and immune protection. Thus, maintaining oral health is necessary. Postbiotic and heat-killed probiotic cells have shown increased antibacterial ...potential with stable viability compared with live strains. However, clinical evidence regarding their effect on oral health is insufficient. Therefore, in this study, we tested postbiotic lozenges of
subsp.
AP-32,
ET-66, and
LPL28 and heat-killed probiotic lozenges of
subsp.
AP-32 and
ET-66 for their effect on oral health. In total, 75 healthy individuals were blindly and randomly divided into placebo, postbiotic lozenge, and heat-killed probiotic lozenge groups and were administered the respective lozenge type for 4 weeks. Postbiotic and heat-killed probiotic lozenge groups demonstrated antibacterial activities with a considerable increase in
in their oral cavity. Furthermore, their salivary immunoglobulin A,
, and
increased. Subjective questionnaires completed by the participants indicated that participants in both the experimental groups developed better oral health and intestinal conditions than those in the placebo group. Overall, our study revealed that a food additive in the form of an oral postbiotic or heat-killed probiotic lozenge may effectively enhance oral immunity, inhibit the growth of oral pathogens, and increase the numbers of beneficial oral microbiota.
Unhealthy lifestyle has been associated with obesity and type 2 diabetes. Whereas its association with vascular complications in patients with long-duration of type 2 diabetes is still uncertain.
A ...total of 1188 patients with long-duration of type 2 diabetes from the Taiwan Diabetes Registry (TDR) data were analyzed. We stratified the severity of unhealthy lifestyle via scoring three factors (sleep duration <7 or >9 h, sit duration ≥ 8h, and meal numbers ≥ with night snack) and analyzed their associations with the development of vascular complications using logistic regression analysis. Besides, we also included 3285 patients with newly diagnosed type 2 diabetes as the comparison.
Increased numbers of factors that stand for unhealthy lifestyle were significantly associated with the development of cardiovascular disease, peripheral arterial occlusion disease (PAOD) and nephropathy in patients with long-duration of type 2 diabetes. After adjusting multiple covariables, having ≥ 2 factors of unhealthy lifestyle remained significant associations with cardiovascular disease and PAOD, with an odds ratio (OR) of 2.09 (95% confidence interval CI 1.18-3.69) and 2.68 (95% CI 1.21-5.90), respectively. Among individual factor for unhealthy lifestyle behaviors, we revealed that eating ≥ 4 meals per day with night snack increased the risk of cardiovascular disease and nephropathy after multivariable adjustment (OR of 2.60, 95% CI 1.28-5.30; OR of 2.54, 95% CI 1.52-4.26, respectively). Whereas sit duration for ≥ 8 h per day increased the risk of PAOD (OR of 4.32, 95% CI 2.38-7.84).
Unhealthy lifestyle is associated with increased prevalence of macro- and micro-vascular comorbidities in Taiwanese patients with long-duration type 2 diabetes.
Non-virus genetic treatment for Parkinson’s disease (PD) via plasmid glial cell-line derived neurotrophic factor (pGDNF) has shown potential for repairing damaged dopaminergic neurons. However, ...development of this gene therapy is largely hampered by the insufficient transfection efficiency as a result of the cell membrane, lysosome, and cytoskeleton meshwork.
In this study, we propose the use of polyethylenimine (PEI)-superparamagnetic iron oxide-plasmid DNA (pDNA)-loaded microbubbles (PSp-MBs) in conjunction with focused ultrasound (FUS) and two-step magnetic navigation to provide cavitation, proton sponge effect and magnetic effects to increase the efficiency of gene delivery.
The gene transfection rate in the proposed system was 2.2-fold higher than that of the commercial agent (TransIT®-LT1). The transfection rate could be boosted ∼11%, ∼10%, and 6% by cavitation-magnetic hybrid enhanced cell membrane permeabilization, proton sponge effect, and magnetic-assisted cytoskeleton-reorganization, respectively. In vivo data suggested that effective gene delivery with this system results in a 3.2-fold increase in recovery of dopaminergic neurons and a 3.9-fold improvement in the motor behavior when compared to untreated genetic PD mice.
We proposed that this novel FUS-magnetic hybrid gene delivery platform could be integrated with a variety of therapeutic genes for treating neurodegenerative diseases in the future.
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•The outcome of gene therapy for Parkinson’s disease is limited by cell membrane, lysosome, and cytoskeleton meshwork.•This study proposed an ultrasound-magnetic hybrid platform to overcome obstacles in current non-virus gene delivery.•Improving gene delivery efficiency could repair dopaminergic neurons and motor function in MitoPark Parkinson’s disease animal.
Unresectable esophageal cancer harbors high mortality despite chemoradiotherapy. Better patient selection for more personalized management may result in better treatment outcomes. We presume the ...ratio of maximum standardized uptake value (SUV) of metastatic lymph nodes to primary tumor (NTR) in 2-deoxy-2-18Ffluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT) may provide prognostic information and further stratification of these patients.
The patients with non-metastatic and unresectable esophageal squamous cell carcinoma (SCC) receiving FDG PET/CT staging and treated by chemoradiotherapy were retrospectively reviewed. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off value for NTR. Kaplan-Meier method and Cox regression model were used for survival analyses and multivariable analyses, respectively.
From 2010 to 2016, 96 eligible patients were analyzed. The median follow-up time was 10.2 months (range 1.6 to 83.6 months). Using ROC analysis, the best NTR cut-off value was 0.46 for prediction of distant metastasis. The median distant metastasis-free survival (DMFS) was significantly lower in the high-NTR group (9.5 vs. 22.2 months, p = 0.002) and median overall survival (OS) (9.5 vs. 11.6 months, p = 0.013) was also significantly worse. Multivariable analysis revealed that NTR was an independent prognostic factor for DMFS (hazard ratio HR 1.81, p = 0.023) and OS (HR 1.77, p = 0.014).
High pretreatment NTR predicts worse treatment outcomes and could be an easy-to-use and helpful prognostic factor to provide more personalized treatment for patients with non-metastatic and unresectable esophageal SCC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Our previous study demonstrated the therapeutic potential of gallic acid (GA) for controlling tumor metastasis through its inhibitory effect on the motility of AGS cells. A noteworthy finding in our ...previous experiment was increased RhoB expression in GA-treated cells. The aim of this study was to evaluate the role of RhoB expression on the inhibitory effects of GA on AGS cells. By applying the transfection of RhoB siRNA into AGS cells and an animal model, we tested the effect of GA on inhibition of tumor growth and RhoB expression. The results confirmed that RhoB-siRNA transfection induced GA to inhibit AGS cells’ invasive growth involving blocking the AKT/small GTPase signals pathway and inhibition of NF-κB activity. Finally, we evaluated the effect of GA on AGS cell metastasis by colonization of tumor cells in nude mice. It showed GA inhibited tumor cells growth via the expression of RhoB. These data support the inhibitory effect of GA which was shown to inhibit gastric cancer cell metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-κB activity. Thus, GA might be a potential agent in treating gastric cancer.
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► GA could downregulate AKT signal via increased expression of RhoB. ► GA inhibits metastasis in vitro in gastric carcinoma. ► GA inhibits tumor growth in nude mice model.
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