Probiotics are considered safe and beneficial to human health. However, the safety of
AP-32 and
CP-9 in infants has not been confirmed. This study was to assess the safety of long-term oral ...administration of
AP-32 and
CP-9 in healthy infants compared with placebo. A three-arm, randomized, double-blind, placebo-controlled trial was conducted in healthy, full-term infants. Eighty-eight infants between 7 days and 2 months (60 ± 7 days) of age were selected and randomized to treatment with
AP-32,
CP-9 or placebo for 4 months. The unblinding indicated subjects were randomized to receive
CP-9 (N = 28),
AP-32 (N = 29), or placebo (N = 31). A total of 76 infants completed the 4-month treatment with fully compliance. The primary outcome was weight gain, with no significant difference in infant weight at 4 months when comparing AP-32 or CP-9 group with the placebo group, either. The head circumference and recumbent length of the CP-9 group were not significantly different from those of the placebo group. The recumbent length of the AP-32 group was slightly lower than that in the placebo group at month 4, but there was no difference between the two groups in head circumference. Overall, the growth trend of all treatments was similar without significant difference. Furthermore, there were no apparent differences between each group in digestive tolerance, the occurrence of adverse events, crying/fussing time and episodes, alpha diversity, and beta diversity. The CP-9 group showed a significant increase in the abundance of the
genus, while the AP-32 group demonstrated a significant increase in the abundance of the
genus when comparing the two probiotic groups. Our study findings indicate that the oral administration of both AP-32 and CP-9 strains has a positive impact on the maintenance of a healthy gut flora in infants. Long-term use of
AP-32 or
CP-9 is safe for infants from 7 days to 6 months of age.
Background
Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first‐line therapy. Real‐world studies comparison of efficacy and ...safety in these two regimens are limited, we therefore conduct this study to investigate these issues.
Methods
We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first‐line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance.
Results
A total of 92 patients with median age of 63.8 year‐old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow‐up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child‐Pugh class B, beyond up‐to‐seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65‐year‐old was an independent predictor associated with shorter PFS (adjust HR: 2.0850.914–4.753, p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin‐bilirubin index and Child‐Pugh score.
Conclusions
The efficacy and safety of lenvatinib are similar to A + B as a first‐line systemic therapy for unresectable HCC.
This study provides real‐world experience of lenvatinib and A + B as firstline treatment for unresectable HCC. The data showed that compared survival, response rate, and adverse events between two regimens.
Alcoholic steatohepatitis (ASH) is a complex multifactorial disease that can lead to liver fibrosis and cirrhosis if not treated promptly. Alcohol-induced oxidative stress and inflammation are the ...main factors that cause steatohepatitis and liver injury; however, probiotic bacteria in the gastrointestinal tract have been revealed to regulate immune responses and reduce oxidative stress, suggesting that functional probiotics could help to prevent ASH and liver injury. Despite numerous reports on the interactions between ASH and probiotics, the mechanisms underlying probiotic-mediated liver protection remain unknown. Therefore, the aim of the present study was to screen probiotics with high antioxidant capacity and investigate the ability of different probiotic combinations to reduce alcoholic liver disease (ALD) in a mouse model. It was identified that
(TSP05),
(TSF331) and
(TSR332) neutralized free radicals and displayed high antioxidant activity
. In addition, these three functional probiotic strains protected mice from alcohol-induced liver injury
. Mice treated with the probiotics demonstrated significantly lower alanine aminotransferase, aspartate aminotransferase and triglyceride levels, which were associated with the downregulation of the proinflammatory cytokines TNF-α and IL-6. Furthermore, probiotic treatment upregulated glutathione and glutathione peroxidase activity, which are bioindicators of oxidative stress in the liver. Collectively, the present results indicated that
strains TSP05, TSF331 and TSR332 reduced oxidative stress and inflammatory responses, thus preventing ASH development and liver injury.
Gouty arthritis is the one of the most painful arthritis and is caused by an inflammatory reaction. This study investigated whether astaxanthin (AXT), which has documented anti‐inflammatory and ...antioxidant properties, exhibits protective effects against monosodium urate (MSU) crystal‐induced inflammation. Cell viability of J774A.1 murine macrophages was assessed by AXT dose‐dependent incubation by MTT assays, and expression levels of iNOS and COX‐2 proteins as well as secretion of IL‐1β were also analyzed under MSU crystals stimulation with or without AXT treatment. The production of inflammatory mediators was found to significantly decrease with AXT treatment, and the formation of the inflammasome complex was also attenuated when cells were co‐stimulated with MSU crystals and AXT. Furthermore, we found that expression of the MAPK pathway was downregulated in J774A.1 cells. AXT also inhibited the induction of COX‐2 and IL‐6 in human chondrocytes and synovial fibroblasts by western blots. Finally, an MSU crystal intra‐articular injection rat model for gouty arthritis was utilized in which treatment groups received 5‐daily intraperitoneal injections of AXT prior to MSU crystal stimulation, or once intra‐articular injections of AXT following MSU crystal stimulation for 6 hours. Results of synovitis score analysis revealed that inflammation was significantly attenuated in the group which received intraperitoneal AXT injection prior to MSU crystal stimulation compared to the group which received MSU only. These results indicate that AXT attenuates the effects of MSU crystal‐induced inflammation by suppressing the production of pro‐inflammatory cytokines and inflammatory mediators. Our findings that the anti‐inflammatory activities of AXT may be beneficial in the treatment of MSU crystal‐induced arthritis.
Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan ...National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks.
According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015.
A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330-0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476-0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001).
This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Atherosclerosis is characterized by the buildup of plaque inside arteries. Our recent studies demonstrated that polyphenolic natural products can reduce oxidative stress, inflammation, angiogenesis, ...hyperlipidemia, and hyperglycemia. A previous study also showed that mulberry water extract (MWE) can inhibit atherosclerosis and contains considerable amounts of polyphenols. Therefore, in the present study, we investigated whether mulberry polyphenol extract (MPE) containing high levels of polyphenolic compounds could affect vascular smooth muscle cell (VSMC; A7r5 cell) motility. We found that MPE inhibited expression of FAK, Src, PI3K, Akt, c-Raf, and suppressed FAK/Src/PI3K interaction. Further investigations showed that MPE reduced expression of small GTPases (RhoA, Cdc42, and Rac1) to affect F-actin cytoskeleton rearrangement, down-regulated expression of MMP2 and vascular endothelial growth factor (VEGF) mRNA through NFκB signaling, and thereby inhibited A7r5 cell migration. Taken together, these findings highlight MPE inhibited migration in VSMC through FAK/Src/PI3K signaling pathway.
One-third of patients with end-stage chronic kidney disease (CKD) experience diabetic nephropathy (DN), which worsens the progression of renal dysfunction. However, preventive measures for DN are ...lacking.
TYCA06,
subsp.
BLI-02, and
VDD088 probiotic strains have been demonstrated to delay CKD progression. This study evaluated their biological functions to stabilize blood-glucose fluctuations and delay the deterioration of renal function. The db/db mice were used to establish a DN animal model. This was supplemented with 5.125 × 10
CFU/kg/day (high dose) or 1.025 × 10
CFU/kg/day (low dose) mixed with probiotics containing TYCA06, BLI-02, and VDD088 for 8 weeks. Blood urea nitrogen (BUN), serum creatinine, blood glucose, and urine protein were analyzed. Possible mechanisms underlying the alleviation of DN symptoms by probiotic strains were evaluated through in vitro tests. Animal experiments revealed that BUN, serum creatinine, and blood glucose upon probiotic administration were significantly lower than in the control group. The rate of change of urine protein decreased significantly, and blood pressure, glucose tolerance, and renal fibrosis were improved. In vitro testing indicated that TYCA06 and BLI-02 significantly increased acetic acid concentration. TYCA06, BLI-02, and VDD088 were associated with better antioxidation, anti-inflammation, and glucose consumption activities relative to the control. A combination of the probiotics TYCA06, BLI-02, and VDD088 attenuated renal function deterioration and improved blood-glucose fluctuation in a diabetes-induced CKD mouse model.
subsp.
BLI-02,
ET-66,
LPL28, and
TYCA06, isolated from healthy breast milk, miso, and the healthy human gut, were assessed for safety in this study. BLI-02, LPL28, TYCA06, and ET-66 exhibited no ...antibiotic resistance and mutagenic activity in the Ames test at the highest dosage (5000 μg/plate). No genotoxicity was observed in micronucleus and chromosomal aberration assays in rodent spermatogonia at the maximum dosage of 10 g/kg body weight (BW). No acute and sub-chronic toxicity occurred in mice and rats at the maximum tested dosage of 10 g/kg BW and 1.5 g/kg BW, respectively. The lyophilized powder of these strains survived a low pH and high bile salt environment, adhering strongly to Caco-2 cells. Unique antimicrobial activities were noted in these strains, with BLI-02 demonstrating the best growth inhibition against
, LPL28 exhibiting the best growth inhibition against
, and ET-66 showing the best growth inhibition against
. Based on the present study, the lyophilized powder of these four strains appears to be a safe probiotic supplement at tested dosages. It should be applicable for clinical or healthcare applications.
The fermented broth of lactic acid bacteria (LFB)was the side product while lactic acid bacteria produced; however, it was abundant of antimicrobial activity. That might be a good candidate for feed ...additive in aquaculture. In this study, the fermented broth of Lactobacillus paracasei GL-156, the most antibacterial activity, was further evaluated the safety, growth performance gut microbiota. Common carp consumed the feed in dose of 1000 ppm LFB, the survival was no significant different with control group, but the growth performance was significant increased. In the intestine microbiota analysis, the treatment fish shown the decrease of vibrio, but no different of total bacterial count. These results demonstrate the LFB from GL-156 in enhancing the growth performance, inhibiting the growth of pathogenic bacteria, and promoting the growth of probiotic organisms. Compare with live probiotics currently used in aquaculture, using LFB will achieved beneficial effects equally, while providing superior tolerance to manufacturing processes, and in the lower cost.
Traumatic brain injury (TBI) is a prevalent head injury worldwide which increases the risk of neurodegenerative diseases. Increased reactive oxygen species (ROS) and inflammatory chemokines after TBI ...induces secondary effects which damage neurons. Targeting NADPH oxidase or increasing redox systems are ways to reduce ROS and damage. Earlier studies show that C–C motif chemokine ligand 5 (CCL5) has neurotrophic functions such as promoting neurite outgrowth as well as reducing apoptosis. Although CCL5 levels in blood are associated with severity in TBI patients, the function of CCL5 after brain injury is unclear. In the current study, we induced mild brain injury in C57BL/6 (wildtype, WT) mice and CCL5 knockout (CCL5-KO) mice using a weight-drop model. Cognitive and memory functions in mice were analyzed by Novel-object-recognition and Barnes Maze tests. The memory performance of both WT and KO mice were impaired after mild injury. Cognition and memory function in WT mice quickly recovered after 7 days but recovery took more than 14 days in CCL5-KO mice. FJC, NeuN and Hypoxyprobe staining revealed large numbers of neurons damaged by oxidative stress in CCL5-KO mice after mTBI. NADPH oxidase activity show increased ROS generation together with reduced glutathione peroxidase-1 (GPX1) and glutathione (GSH) activity in CCL5-KO mice; this was opposite to that seen in WT mice. CCL5 increased GPX1 expression and reduced intracellular ROS levels which subsequently increased cell survival both in primary neuron cultures and in an overexpression model using SHSY5Y cell. Memory impairment in CCL5-KO mice induced by TBI could be rescued by i.p. injection of the GSH precursor – N-acetylcysteine (NAC) or intranasal delivery of recombinant CCL5 into mice after injury. We conclude that CCL5 is an important molecule for GPX1 antioxidant activation during post-injury day 1–3, and protects hippocampal neurons from ROS as well as improves memory function after trauma.
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