Effects of total flavones of Abelmoschus manihot (L.) on the treatment of diabetic nephropathy via the activation of solute carriers in renal tubular epithelial cells.

As a traditional Chinese medicine, Huangkui capsule (HKC) has been used to treat patients with kidney diseases, including diabetic nephropathy (DN). We have recently demonstrated that HKC could re-regulate the activities of solute carriers (SLC)s in proximal and distal convoluted tubules of kidneys in regression of the development of DN. The main active chemical constituents of HKC are the flavones of Abelmoschus manihot (L.). The current study aims to further evaluate the efficacy of total flavones of A. manihot (TFA) in the regression of DN by analyzing SLC activities in proximal and distal convoluted tubules of kidneys. TFA (0.076 g/kg/d) or vehicle was administered in db/db mice, the animal model of type 2 diabetes and DN, daily via oral gavage for four weeks. Blood glucose levels and urinary albumin-to-creatinine ratio (UACR) were measured and used for the determination of T2D and DN. Ten SLCs, including slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 were highly expressed in proximal and distinct convoluted tubules of kidneys. Their expression at mRNA and protein levels before and after TFA treatment were analyzed with real-time RT-PCR and immunohistochemistry. Data showed that UACR in the db/db mice after TFA treatment was significantly decreased. Compared with the group of non-diabetic control, slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 in the group of DN were down-regulated but up-regulated after TFA treatment. Further analyses of whole kidney sections indicated that the numbers and structures of the nephron in db/db mice was increased and improved after TFA treatment. Thereby, the current study provides further evidence that the flavones in A. manihot have pharmacological effects on the treatment of DN by improving the biological function of SLCs in kidneys.

Differential Diagnosis of Intracranial Malignant Tumors Using MRI Based on Morphological Features and Signal Intensity Ratio of Lesions.

Objective: To investigate the clinical value of conventional MRI morphological features and signal intensity ratio in the differential diagnosis of intracranial malignant tumors (high-grade glioma (HGG), primary central nervous system Lymphoma (PCNSL) and single brain metastasis (BM). Methods: Retrospective analysis of 92 cases of HGG, 27 cases of PCNSL, and 35 cases of BM. MRI data in The General Hospital of Western Theater Command from August 2014 to December 2021, comparative analysis of morphological characteristics of tumors and lesion/normal brain parenchyma signal ratio (lesiontonormal parenchymaratio, LNR), five indexes were included T1WI signal ratio (LNRT1), T2WI signal intensity ratio (LNRT2), T2WI/T1WI signal ratio (LNRT2/T1), T1WI enhanced signal ratio (LNRT1CE) and contrast enhancement ratio (CER). The differential diagnostic performance was also assessed by subject operating characteristic (ROC) curves. Results: HGG, PCNSL, and BM were all seen more frequently in the supratentorial region, More than 50% of HGG mainly showed irregular morphology, intratumoral necrosis, cystic degeneration, peritumoral severe edema, cyclic uneven enhancement after enhancement, PCNSL significantly enhanced the main uniformity, necrosis cyst became rare, BM group showed uneven enhancement, no obvious specificity, and the differences in tumor morphology, peritumor edema, intratumor hemorrhage, necrotic cystic lesions, and enhancement patterns were statistically significant among the three (P < .05). PCNSL LNRT1 and its LNRT1CE (LNRT1: 0.558 ± 0.050, LNRT1CE: 1.637 ± 0.125) were significantly higher than those of HGG (LNRT1: 0.480 ± 0.077, LNRT1CE: 1.425 ± 0.160) and BM (LNRT1: 0.514 ± 0.120, LNRT1CE: 1.375 ± 0.122), while LNRT2 and LNRT2/T1 (LNRT2: 1.389 ± 0.086, LNRT2/T1: 2.511 ± 0.295) were significantly lower than those of HGG (LNRT2: 1.527 ± 0.191, LNRT2/T1: 3.263 ± 0.657), and BM (LNRT2: 1.504 ± 0.089, LNRT2/T1: 3.103 ± 0.830). There was no significant difference in CER among the three groups (P > .05). ROC curve analysis of LNRT1, LNRT2, LNRT1CE, and LNRT2/T1 could be used to discriminate PCNSL from HGG and BM, with LNRT1CE having the largest area under the curve of 0.873, sensitivity of 0.963 and specificity of 0.669. Conclusion: MRI lesion morphological features and signal intensity ratio are important for discriminating HGG from PCNSL and BM. As a quantitative parameter, tumor signal intensity ratio can provide an important supplement for subjective judgment, to improve the accuracy of tumor qualitative diagnosis and differential diagnosis.

Evaluation of the efficacy of Abelmoschus manihot (L.) on diabetic nephropathy by analyzing biomarkers in the glomeruli and proximal and distal convoluted tubules of the kidneys.

Introduction: As a traditional Chinese medicine, Abelmoschus manihot (L.) in the form of Huangkui (HK) capsule has been used as a medication for kidney diseases, including diabetic nephropathy (DN), in China. The most significant effect of HK capsule treatment in kidney diseases is the reduction of albuminuria and proteinuria. To evaluate the efficacy of HK capsule in the regression of DN, in the current study, we analyzed the biomarkers in the glomerulus and proximal and distal convoluted tubules in the kidneys of db/db mice, the animal model for type 2 diabetes and DN. Methods: Huangkui capsules (0.84 g/kg/d) or vehicle were administered daily via oral gavage for 4 weeks in db/db mice. Urinary albumin-to-creatinine ratio and blood glucose levels were measured during the whole experimental period. Five biomarkers in the glomerulus and proximal and distal convoluted tubules in the kidneys were selected, namely, col4a3, slc5a2, slc34a1, slc12a3, and slc4a1, and their activities at mRNA and protein levels before and after HK capsule treatment were analyzed by real-time RT-PCR and immunohistochemistry. Result and discussion: After HK capsule treatment for 4 weeks, the urinary albumin-to-creatinine ratio in db/db mice was found to be significantly decreased. The activities of col4a3, slc5a2, slc34a1, slc12a3, and slc4a1 in the kidneys were upregulated in db/db mice prior to the treatment but downregulated after HK capsule treatment. Further analyses of the fields of whole kidney tissue sections demonstrated that the number of nephrons in the kidneys of db/db mice with HK capsule treatment was higher than that in the kidneys of db/db mice without HK capsule treatment. Thereby, the current study provides experimental evidence confirming the medical efficacy of A. manihot in the reduction of albuminuria and proteinuria, suggesting that A. manihot may have pharmacological efficacy in the regression of the development of type 2 diabetes-DN.

Two new benzoic acid derivatives from endophytic fungus Aspergillus versicolor.

Two new benzoic acid derivatives, named methyl(S)-3-hydroxy-4-(2- hydroxy -6-methylheptan-2-yl)benzoate (1) and 2-hydroxy-3-(6- hydroxy-6-methylhept-1-en-2-yl)benzoic acid (2), were isolated from the ethanol extract of an endophytic fungus Aspergillus versicolor derived from the medicinal plant Euphorbia royleana. The structures of compounds (1-2) were elucidated using NMR and MS methods.

Comparison of Awake and Asleep Deep Brain Stimulation for Parkinson's Disease: A Detailed Analysis Through Literature Review.

OBJECTIVES: Deep brain stimulation (DBS) for Parkinson's disease (PD) has been applied to clinic for approximately 30 years. The goal of this review is to explore the similarities and differences between "awake" and "asleep" DBS techniques. METHODS: A comprehensive literature review was carried out to identify relevant studies and review articles describing applications of "awake" or "asleep" DBS for Parkinson's disease. The surgical procedures, clinical outcomes, costs and complications of each technique were compared in detail through literature review. RESULTS: The surgical procedures of awake and asleep DBS surgeries rely upon different methods for verification of intended target acquisition. The existing research results demonstrated that the stereotactic targeting accuracy of lead placement obtained by either method is reliable. There were no significant differences in clinical outcomes, costs, or complications between the two techniques. CONCLUSION: The surgical and clinical outcomes of asleep DBS for PD are comparable to those of awake DBS.

Effect of n-3 long-chain polyunsaturated fatty acids on mild cognitive impairment: a meta-analysis of randomized clinical trials.

N-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have positive effect on cognitive function with mild cognitive impairment (MCI) is still controversial. The aim for this meta-analysis was to assess the scientific evidence published in the last 10 years on the effects of n-3 LC-PUFAs intake on MCI patients to explore whether n-3 LC-PUFAs have positive effective. A comprehensive literature search was developed using the Google Scholar, EMBASE, and PubMed database. The pooled effect for all studies was calculated using random-effects model. And the terms of weighted mean difference (WMD) with 95% confidence interval (CI) was pooled and indicated the effects. Heterogeneity was assessed by I2 statistics. A total of seven randomized clinical trials involving 213 cases of intervention and 221 cases of placebo were included in this analysis. Compared with placebo, n-3 LC-PUFAs supplements effectively improved cognition in elders with MCI (WMD = 0.85, 95% CI: 0.04-1.67, Z = 2.05, P = 0.04). Slight heterogeneity was detected across studies. Our results provided further evidence that n-3 LC-PUFAs may have beneficial effect in elderly with MCI.

The use of of inulin, maltitol and lecithin as fat replacers and plasticizers in a model reduced-fat mozzarella cheese-like product.

BACKGROUND: Mono-, di- and oligosaccharides, polyhydric alcohols and lipids are three main types of plasticizers used to process food materials. In the present study, inulin, maltitol and lecithin were selected as representative oligosaccharide, polyhydric alcohol and lipid fat replacers, respectively. Their effects on the physicochemical properties of reduced-fat mozzarella cheese were evaluated. RESULTS: Lecithin reduced the hardness and increased the degree of free oil released. Inulin and lecithin decreased the hydrophobic interaction of reduced-fat cheese. Maltitol improved the elasticity of the reduced-fat cheese and increased the hydrophobic interaction within the casein matrix. Maltitol-added cheese had a lower glass transition temperature (Tg ) than the other cheeses. Maltitol significantly improved the stretchability of the reduced-fat cheese. CONCLUSION: The results obtained in the present study suggest that maltitol is an effective fat replacer in reduced-fat mozzarella cheese and might enhance the cheese's functional properties. The Tg of cheese was related to the water and fat content, fat replacer addition and cross-linking degree of casein. The relationship between Tg and the physicochemical properties of cheese will be studied in further research. © 2019 Society of Chemical Industry.

Tetramethylpyrazine attenuates periorbital allodynia and neuroinflammation in a model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a public health issue. As the major complaint in 51% of TBI patients, chronic pain is an important aspect in TBI treatment. Tetramethylpyrazine (TMP) is an important compound in Ligustrazine, an analgesic drug in traditional Chinese medicine, but its potential in relieving pain symptom in TBI has not been tested. We established a TBI mouse model with controlled cortical impact (CCI), and measured periorbital hypersensitivity with von Frey monofilaments. We examined activated microglia and astrocytes and the levels of substance P (SP) and inducible isoform of nitric oxide synthase (iNOS) with immunohistochemistry, measured mRNA and protein levels of proinflammatory cytokines with qPCR and enzyme-linked immunosorbent assay, respectively. Western blot was employed to detect molecules in NF-κB signaling pathway. RESULTS: TMP significantly attenuated periorbital hypersensitivity in TBI mice. Within 3 days after CCI, TMP attenuated activation of microglia and astrocytes, levels of SP, iNOS, and CGRP in trigeminal pathway, and levels of proinflammatory cytokines (including IL-6, TNF-α, IL-12). In isolated microglia, TMP attenuated the effects of lipopolysaccharide on the phosphorylation of cytoplasmic IKKα/ß and IKB-α, and levels of nucleic p65. CONCLUSION: TMP reversed periorbital hypersensitivity by limiting neuroinflammation at the primary stage of TBI, and could be a promising drug for pain treatment in TBI.

Repeated intra-nigrostriatal injection of phorbol myristate acetate induces microglial senescence in adult rats.

Phorbol myristate acetate (PMA), as a potent tumor promoter, may induce microglial senescence. The present study investigated the effect of PMA infection on microglial senescence. From 58 male Sprague­Dawley rats, 10 were randomly selected and divided into a PMA injection group, containing five rats (0.5 µg/µl PMA) and a control group, containing five rats (commensurable 0.9% saline). Immunofluorescent staining of Iba­1 and enzyme­linked immunosorbent assay analyses of the expression levels of tumor necrosis factor (TNF)­α and interleukin (IL)­1 ß were performed in these two groups. The remaining 48 rats were randomly divided into the following three groups, each containing 16 rats: Repeated injection control group (commensurable normal saline, once a week for 4 weeks), single PMA injection group (0.5 µg/µl PMA, once in the first week) and repeated injection PMA group (0.5 µg/µl PMA, once a week for 4 weeks). The expression levels of p21, detected using double immunofluorescence staining with Iba­1, and ß­galactosidase, via double immunohistochemical staining of Iba­1, were examined in these three groups. The results indicated that a single injection of PMA did not change the microglial morphology and had no significant effects on the expression levels of TNF­α and IL­1ß, compared with the control group (P>0.05). Following four repeated injections of PMA, the microglia in the substantia nigra presented with features of senescence, characterized by increased expression levels of ß-galactosidase (P<0.001) and p21 (P<0.001), compared with the repeated injection control group. In conclusion, repeated intra-nigrostriatal treatment with PMA induced microglial senescence with increased expression levels of ß-galactosidase and p21 in the substantia nigra of the rats.

[Analysis of 14 elements for Jinhua bergamot by X-ray fluorescence spectrometry and elemental analyser].

The content of the elements C, H, O and N in Jinhua bergamot was analysed by using Vario III elemental analyser, the bergamot sample was scanned by using X-ray fluorescence spectrometer with PW2400 wavelength dispersion, and the content of the elements Mg, Al, P, S, Cl, K, Ca, Mn, Fe and Sr was analysed by using IQ+ analytical method. It turned out that the result is more ideal if the content of the elements C, H, O and N is processed as fix phase, and the analytical result is more ideal if, to prevent the sample skin from coming off, the sample is wrapped with mylar film with the film coefficient adjusted.

Amelioration of experimental autoimmune encephalomyelitis by ß-elemene treatment is associated with Th17 and Treg cell balance.

Experimental autoimmune encephalomyelitis (EAE), an animal mode of multiple sclerosis (MS), was previously considered that is mediated by Th1 cells. However, a number of recent studies provided strong evidence that T helper cells that produce interleukin (IL)-17 (Th17) and anti-inflammatory CD4+ Foxp3+ regulatory T cells (Tregs) play a dominant role in the pathogenesis of EAE. ß-elemene is a natural antitumor plant drug with the role of multiple target, and it has been found to pass through the blood-brain barrier easily. It also has been strongly implicated as an immune modulatory agent, but the precise mechanisms of its action are largely unknown. In the present study, we mainly investigated the efficacy and mechanism of ß-elemene against EAE in vivo and vitro. The treatment of C57 mice with ß-elemene significantly delayed the onset of EAE, markedly suppressed MOG-specific T cell proliferation in a dose-dependent manner, dramatically reduced the IL-17, IL-6, IL-23, and RORγt production and induced the Foxp3 expression in both the periphery and the inflamed spinal cord. These findings indicated that ß-elemene amelioration EAE was, to a large extent, due to inhibit differentiation and development of Th17 cells depends on down-regulating expression of IL-6, IL-23, RORγt signaling, and promoting expansion in Treg cells. Suggesting it is useful in the control of MS and other Th17 cell-mediated inflammatory diseases.

Downregulation of IL-17 and IFN-gamma in the optic nerve by beta-elemene in experimental autoimmune encephalomyelitis.

BACKGROUND: beta-elemene is a natural antitumor plant drug. Beneficial effects of beta-elemene therapy have been demonstrated in some kinds of tumor clinically. Especially, it has been found to pass through the blood brain barrier easily. Other reports have indicated that immune disorder that appeared in some tumors usually can be seen in demyelinating diseases including multiple sclerosis and experimental autoimmune encephalomyelitis. However, no information regarding the effects of beta-elemene therapy on the T helper cell subsets, Th1 or Th17 cells in experimental autoimmune encephalomyelitis has been found. METHODS AND FINDINGS: We first determined morphologically that beta-elemene therapy markedly suppressed the inflammation in experimental autoimmune encephalomyelitis optic nerve. We then determined the effect in vivo of beta-elemene on Treg cells and Th17 and Th1 cells. We found that beta-elemene treatment modulated immune balance in both the periphery and the inflamed optic nerve by promoting less downregulation in Treg cells, inhibiting Th17 and Th1 polarization. CONCLUSIONS: Taken together, our finding reveals an important new locus where beta-elemene induces substantial protection in experimental autoimmune encephalomyelitis optic nerve through signaling to several critical subsets of immune cells that reside in the peripheral and central nervous system.