Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease in children and adults. Genetic factors significantly contribute to early-onset FSGS, but the etiologies of ...most adult cases remain unknown. Genetic studies of monogenic syndromic FSGS exhibiting extra-renal manifestations have uncovered an unexpected biological role for genes in the development of both podocytes and other cellular lineages. To help define these roles, we studied two unrelated families with FSGS associated with Duane Retraction Syndrome, characterized by impaired horizontal eye movement due to cranial nerve malformation. All four affected individuals developed FSGS and Duane Retraction Syndrome in their first to second decade of life, manifested as restricted abduction together with globe retraction and narrowed palpebral fissure on attempted adduction. Hypoplasia of the abducens nerves and hearing impairment occurred in severely affected individuals. Genetic analyses revealed that affected individuals harbor a rare heterozygous substitution (p.Leu239Pro) in MAFB, a leucine zipper transcription factor. Luciferase assays with cultured monocytes indicated that the substitution significantly reduced transactivation of the F4/80 promoter, the known MAFB recognition element. Additionally, immunohistochemistry indicated reduced MAFB expression in the podocytes of patients. Structural modeling suggested that the p.Leu239Pro substitution in the DNA-binding domain possibly interferes with the stability of the adjacent zinc finger. Lastly, podocytes in neonatal mice with p.Leu239Pro displayed impaired differentiation. Thus, MAFB mutations impair development and/or maintenance of podocytes, abducens neurons and the inner ear. The interactions between MAFB and regulatory elements in these developing organs are likely highly specific based on spatiotemporal requirements.
In the present study, the positive effects of AgNPs were demonstrated for adventitious shoot formation, in vitro flowering and fruiting of
Passiflora edulis
Sims f.
edulis
—an important commercial ...crop. The results showed that shoot regeneration from lTCL (87.67%) and oTCL (100%) explants were significantly improved on the medium supplemented AgNPs. The in vitro shoots derived from TCL explants were used for shoot multiplication. The treatment with 1.0 mg/L meta-topolin (mT) and 5 mg/L AgNPs enhanced the shoot multiplication with the highest number of shoots (13.67 shoots/explant), shoot height (4.33 cm), and total chlorophyll content (33.93 nmol/cm
2
). For flowering induction, shoot tips cultured in MS medium supplemented with 7 mg/L AgNPs gave the highest of flowering rate (51.67%) and number of flowers per shoot (2.33 flowers) after 60 days of culture. In addition, shoots cultured in medium supplemented with 7 mg/L AgNPs showed significantly lower endogenous hormone of GA
3
, ABA, and melatonin levels than the control. In the treatment with 7 mg/L AgNPs, the flower bloom rate was 100% and the flower diameter was the largest (3.43 cm). The in vitro developed flowers self-fertilized and formed fruits. After 90 days of culture, the treatment supplemented with 7 mg/L AgNPs gave the highest fruiting rate (56.67%), number of fruits (1.67 fruits), and fruit diameter (1.13 cm). These findings pave the way for further research into flowering and fruiting mechanisms, as well as improving the efficient breeding process of this plant.
Key message
A first procedure has been established for in vitro flowering and fruiting of purple passion fruit via the application of nanotechnology and the thin cell layer technique. Silver nanoparticles significantly improved shoot formation, in vitro flowering and fruiting of purple passion fruit.
Mangiferin is a xanthonoid found in Mango leaves in abundance with many effects as a hypoglycemic, antioxidant, and anti-inflammatory agent, plant metabolite, and so on. However, nowadays, mango ...leaves are merely a waste product in Vietnam. To take advantage of this valuable medicinal resource, extraction conditions of mangiferin using classical and ultrasound methods were researched, and mangiferin was purified from Cat Chu mango leaves ( Mangifera indica L., Anacardiaceae) collected in Dong Thap. Ultrasound-assisted extraction method was conducted with the following conditions and mangiferin was extracted at a percentage of 6.728% with a purity of 91.11%. Purified mangiferin was evaluated using molecular absorption spectroscopy UV-Vis, scanning electron microscopy (SEM), X-ray diffraction (XRD) spectroscopy, simultaneous thermal analysis (STA: TGA/DSC), and dissolution measurement method. To optimize the solubility and permeability of mangiferin, the solid dispersion system (HPTR) was made by the combination of HPMC 6M:mangiferin at the ratio of 1:5. To investigate the acute, sub-chronic toxicity and hypolipidemia effect of HPTR as compared to purified mangiferin, we followed guidelines for preclinical and clinical trials of Traditional Medicine and Herbal Medicines by the Vietnam Ministry of Health and OECD, and used tyloxapol (Triton WR1339, 400 mg/kg, i.p.) to induce hyperlipidemia. Our results indicated that purified mangiferin and HPTR extract showed no acute toxicity and sub-chronic toxicity and has potential as an antihyperlipidemic agent. The HPTR brought about a significant decrease in total cholesterol, triglycerides and LDL-c when compared to mangiferin, however there was no significance between them.
Metabolic disorders are increasingly rapidly becoming a burden on global healthcare systems. Among these, hyperlipidemia frequently leads to cardiovascular diseases such as myocardial infarction and ...cerebral stroke, posing significant life-threatening risks. The pharmacological drugs, which are often costly and may cause a range of adverse side effects detrimental to health. Allium ascalonicum L., a member of the Alliaceae family, a widely used species of the Allium genus, is commonly employed as a spice and food ingredient in Asia. Allium ascalonicum (AS) is rich in triterpenoids, phenolic acids, flavonoids, thiosulfates, and anthocyanins, whose therapeutic effects have been documented. In Chinese, Allium ascalonicum L. is known as 葱 (Cōng), which is used for various types of onions and similar plants in Chinese, including shallots. Ancient Chinese medicine documented that AS has a sweet and mildly spicy taste with a slight astringency and is warm in nature. In traditional Chinese medicine, AS is prepared as infusions, juices, and poultices to harness their health benefits, and commonly used in cooking for their nutritional and medicinal purposes. Modern medicine has discovered that this type of bulb possesses antibacterial and anti-inflammatory properties, acts as a diuretic, treats diarrhea, reduces blood sugar levels, lowers blood pressure, reduces cholesterol, and among its other roles. Currently, there is a lack of in vivo study on the cholesterol-regulating potential of AS.
For our experiments, 24 and 32 Swiss albino mice were employed to investigate the acute and sub-chronic oral toxicity according to the Guidelines for preclinical and clinical trials of Traditional Medicine and Herbal Medicines by the Vietnam Ministry of Health and OECD. To investigate the effects on hyperlipidemia, 40 mice of both sexes were divided into five groups (n = 6–8 each). Tyloxapol (Triton WR1339, 400 mg/kg, i.p.) was used to induce hyperlipidemia. Atorvastatin (60 mg/kg, p.o.) was used as the standard, and AS extract was conducted at the doses of 500 mg/kg and 1000 mg/kg. Hyperlipidemic activity was assessed using a variety of parameters.
Allium ascalonicum (AS) extract showed no acute toxicity and sub-chronic toxicity. The AS showed a significant decrease in total cholesterol, triglycerides and LDL-c but showed no changes in HDL-c.
Our results indicated that AS is safe to use for a longtime and has a potential as an antihyperlipidemic agent, possibly due to its ability to inhibit the elevation of total cholesterol, triglycerides and LDL-c. The AS is rich in phytochemicals like triterpenoids, flavonoids and saponins, which may contribute to its hypolipidemic effect.
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The large Maf transcription factors c-Maf and MafB are expressed in macrophage-lineage hematopoietic cells, but the expression patterns of MafB and c-Maf in macrophage subtypes and tissue-resident ...macrophages have not been fully analyzed. First, we analyzed MafB and c-Maf protein expression in tissue-resident macrophages. Mouse lymph nodes, spleens, lungs, and kidneys were subjected to immunohistochemistry using anti-MafB and anti-c-Maf. Both MafB and c-Maf signals were observed in lymph node macrophages. In the splenic macrophages the MafB signal was detected by anti-MafB, but the c-Maf signal was not detected. No expression of c-Maf or MafB was detected in macrophages in the lung and kidney. Flow cytometry analysis revealed a similar pattern of GFP expression in Mafb/GFP knock-in heterozygous mice. To analyze these different expression patterns in greater detail, we examined the expression of MafB and c-Maf by quantitative RT-PCR in different cytokine- or LPS-induced macrophages in vitro. MafB expression was induced by IL-10 or IL-4 with IL-13 and was reduced by LPS or GM-CSF. By contrast, c-Maf expression was induced by IL-10 and reduced by IL-4 with IL-13 or GM-CSF. These results indicate that MafB and c-Maf have different expression patterns in macrophages, suggesting differences in function.
MafB is a transcription factor that induces myelomonocytic differentiation. However, the precise role of MafB in the pathogenic function of macrophages has never been clarified. Here we demonstrate ...that MafB promotes hyperlipidemic atherosclerosis by suppressing foam-cell apoptosis. Our data show that MafB is predominantly expressed in foam cells found within atherosclerotic lesions, where MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM). In the absence of MafB, activated LXR/RXR fails to induce the expression of AIM, a protein that is normally responsible for protecting macrophages from apoptosis; thus, Mafb-deficient macrophages are prone to apoptosis. Haematopoietic reconstitution with Mafb-deficient fetal liver cells in recipient LDL receptor-deficient hyperlipidemic mice revealed accelerated foam-cell apoptosis, which subsequently led to the attenuation of the early atherogenic lesion. These findings represent the first evidence that the macrophage-affiliated MafB transcription factor participates in the acceleration of atherogenesis.
Introduction: There is a plenty of evidence that supports the integral role the intestinal microbiome in the pathogenesis of ulcerative colitis (UC). Several studies have shown that different ...interventions as diet, probiotics, antibiotics or fecal microbiota transplantation can manipulate the microbiome and that can be potentially used to influence and modulate the disease activity, but the results are controversial. This study aims to clarify the role of probiotic treatment in patients with ulcerative colitis. Methods: A systematic search of 12 databases was performed to include RCTs that address probiotic treatment safety and efficacy compared to other treatment of ulcerative colitis. The methodological quality of each RCT was assessed using the Cochrane Collaborations tool. The study protocol has been registered in PROSPERO with registration number CRD42018094319. Results: Results were expressed as odds ratio(OR) with 95% confidence interval (CI). Sixteen randomized clinical trials (RCTs) that used markedly different protocols were eligible for our meta-analysis. Our outcomes were reported based on patients who took probiotics in different types and routes. In the probiotic group, the proportion of patients with Clinical remission and clinical response were higher than the placebo group, with odds ratio 2.10 (95% CI: 1.54-2.88, P<.001) and 2.12 (95% CI: 1.143.93, P<.01) respectively. On the other hand, No significant difference in terms of Endoscopic remission between the two groups with odds ratio 1.42 (95% CI: 0.85-2.40, P = 0.17). Then for our FMT and VSL#3 subgroup analysis. Achieving FMT clinical remission and clinical response in the donor FMT groups were higher than in the placebo groups; with odds ratio 2.88 (95% CI: 1.545.38, P<.001). and 1.92 (95% CI: 1.09-3.39, P = 0.024) respectively. And clinical remission in VSL#3 groups was higher than in the placebo groups; with odds ratio 2.72 (95% CI: 1.2-6.17, P<.01). Conclusion: Despite variation in the probiotics types, they appear to be effective for induction of clinical remission . Also, fecal microbiota transplant and VSL#3 are effective therapy along with other probiotic types of treatment.
The transcription factor MafB is expressed by monocytes and macrophages. Efferocytosis (apoptotic cell uptake) by macrophages is important for inhibiting the development of autoimmune diseases, and ...is greatly reduced in Mafb-deficient macrophages. Here, we show the expression of the first protein in the classical complement pathway C1q is important for mediating efferocytosis and is reduced in Mafb-deficient macrophages. The efferocytosis defect in Mafb-deficient macrophages can be rescued by adding serum from wild-type mice, but not by adding serum from C1q-deficient mice. By hemolysis assay we also show that activation of the classical complement pathway is decreased in Mafb-deficient mice. In addition, MafB overexpression induces C1q-dependent gene expression and signals that induce C1q genes are less effective in the absence of MafB. We also show that Mafb-deficiency can increase glomerular autoimmunity, including anti-nuclear antibody deposition. These results show that MafB is an important regulator of C1q.
Introduction: Crohn's disease(CD), a subtype of inflammatory bowel disease (IBD) is chronic idiopathic, relapsing nonspecific inflammatory characterized by transmural inflammation can involve any ...element of the gastrointestinal tract, Although its etiology is unclear yet, the recent studies have shown the associations between the alteration of gut microbiota and CD, furthermore, several studies suggest using probiotic, prebiotic, and synbiotic agents to manipulate the gut microbiota in the management of Crohn's disease. This study aims to bring together the evidence available on the clinical effect of probiotics in Crohn's disease patients. Methods: To identify all relevant studies, PubMed, Medline, Scopus, Web of Science, and other databases were searched. Randomized clinical trials (RCTs) compared probiotic treatment with placebo were included in this meta-analysis. Primary outcomes were clinical remission and maintenance of remission. Secondary outcomes were adverse events, relapse rate, and endoscopic recurrence rate. Results: Eight randomized clinical trials (RCTs) studies were included for meta-analysis. In the probiotic group, there was no significant difference in term of clinical remission compared to placebo, with an odds ratio of 0.89 (95% CI: 0.33-2.35, P>0.05). Also, there was no significant difference in terms of adverse events rate between the two groups with 62 out of 162 (38.2%) in the probiotic group compared with 59 out of 162 (36.4%) in placebo groups; odds ratio 1.08 (95% CI: 0.08-1.78, P>0.05). On the other hand, there was no significant difference in terms of relapse rate between two groups with 52 out of 124 (41.9%) in the probiotic group compared with 52 out of 121 (42.9%) in placebo groups; odds ratio 0.99 (95% CI: 0.58-1.69, P>0.5). Regarding endoscopic recurrence rate, there was no significant difference in two groups of patients who underwent postoperative follow-up with 76 out of 137 (55.4%) in the probiotic group compared with 88 out 147 (59.8%) in placebo groups; odds ratio 0.86 (95% CI: 0.52-1.42, P>0.05). Conclusion: Probiotic is potentially useful in Crohn's disease management. However, it appears to be effective for induction of remission, but with no significant major short-term benefits compared to placebo group. Finally, there remain many unanswered questions that require further studies before probiotic can be considered for use in the treatment of Crohn's disease.
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