LncRNA VPS9D1-AS1 regulates miR-187-3p/fibroblast growth factor receptor-like 1 axis to promote proliferation, migration, and invasion of prostate cancer cells.

The morbidity and mortality of prostate cancer are increasing year by year, and the survival rate of prostate cancer patients after treatment is low. Therefore, investigating the molecular mechanism underlying prostate cancer is crucial for developing effective treatments. Recent studies have shown the important role of long-chain non-coding RNAs (lncRNAs) in tumorigenesis. VPS9D1-AS1 can modulate the progression of multiple cancers, but its molecular action mechanism in prostate cancer remains unknown. This study, therefore, intended to investigate the regulatory mechanism of VPS9D1-AS1 in prostate cancer. First, differentially expressed lncRNAs in prostate cancer were identified through bioinformatics approaches. The target lncRNA for the study was determined by reviewing the relevant literature and its downstream miRNA/mRNA axis was uncovered. Then, quantitative reverse transcription polymerase chain reaction was introduced to assess the expression of VPS9D1-AS1, miR-187-3p, and fibroblast growth factor receptor-like 1 (FGFRL1) at a cellular level, and Western blot was conducted to assess the protein level of FGFRL1 in cells. The results indicated that VPS9D1-AS1 and FGFRL1 were highly expressed in prostate cancer while miR-187-3p was less expressed. Besides, MTT, colony formation, wound healing, and cell invasion assays showed that silencing VPS9D1-AS1 inhibited the viability, migration ability, and invasion ability of prostate cancer cells. Dual-luciferase assay and RNA binding protein immunoprecipitation assay were performed to explore the interplay of miR-187-3p and VPS9D1-AS1 or FGFRL1. The results showed that VPS9D1-AS1 could sponge miR-187-3p, and FGFRL1 could serve as a direct target of miR-187-3p. Moreover, combined with the results of the rescue experiment, VPS9D1-AS1 was found to upregulate FGFRL1 by competitively sponging miR-187-3p to accelerate the malignant behaviors of prostate cancer cells. In conclusion, VPS9D1-AS1 could promote the phenotype progression of prostate cancer cells through targeting the miR-187-3p/FGFRL1 axis, and it has the potential to be a target for prostate cancer patients.

Dioscorea nipponica Makino: A comprehensive review of its chemical composition and pharmacology on chronic kidney disease.

Chronic kidney disease (CKD) is a widespread ailment that significantly impacts global health. It is characterized by high prevalence, poor prognosis, and substantial healthcare costs, making it a major public health concern. The current clinical treatments for CKD are not entirely satisfactory, leading to a high demand for alternative therapeutic options. Chinese herbal medicine, with its long history, diverse varieties, and proven efficacy, offers a promising avenue for exploration. One such Chinese herbal medicine, Dioscorea nipponica Makino (DNM), is frequently used to treat kidney diseases. In this review, we have compiled studies examining the mechanisms of action of DNM in the context of CKD, focusing on five primary areas: improvement of oxidative stress, inhibition of renal fibrosis, regulation of metabolism, reduction of inflammatory response, and regulation of autophagy.

Research progress on Cornus officinalis and its active compounds in the treatment of diabetic nephropathy.

Diabetic nephropathy (DN) is a kidney disorder secondary to diabetes and is one of the main diabetic microvascular complications. As the number of diabetic patients grows, DN has become the leading cause of chronic kidney disease in China. Unfortunately, no definitive cure currently exists for DN. Cornus officinalis (CO), frequently utilized in clinical settings for diabetes mellitus treatment, has proven vital in both preventing and treating DN. This article explores the pathogenesis of DN and how CO and its active compounds regulate glucose and lipid metabolism, exhibit anti-inflammatory properties, inhibit oxidative stress, regulate podocytes, and manage autophagy. The mechanism and role of and its active compounds in the treatment of DN are discussed.

YOLO-LWNet: A Lightweight Road Damage Object Detection Network for Mobile Terminal Devices.

To solve the demand for road damage object detection under the resource-constrained conditions of mobile terminal devices, in this paper, we propose the YOLO-LWNet, an efficient lightweight road damage detection algorithm for mobile terminal devices. First, a novel lightweight module, the LWC, is designed and the attention mechanism and activation function are optimized. Then, a lightweight backbone network and an efficient feature fusion network are further proposed with the LWC as the basic building units. Finally, the backbone and feature fusion network in the YOLOv5 is replaced. In this paper, two versions of the YOLO-LWNet, small and tiny, are introduced. The YOLO-LWNet was compared with the YOLOv6 and the YOLOv5 on the RDD-2020 public dataset in various performance aspects. The experimental results show that the YOLO-LWNet outperforms state-of-the-art real-time detectors in terms of balancing detection accuracy, model scale, and computational complexity in the road damage object detection task. It can better achieve the lightweight and accuracy requirements for object detection for mobile terminal devices.

Mechanism of dioscin ameliorating renal fibrosis through NF­κB signaling pathway­mediated inflammatory response.

Dioscin (DIS) is a natural compound derived from Chinese herbal medicine. In recent years, multiple studies have reported that DIS has immunoregulation, anti­fibrosis, anti­inflammation, anti­viral and anti­tumor effects. However, the mechanism by which DIS ameliorates renal fibrosis and inflammation remains to be elucidated. The aim of the present study was to investigate the role of DIS in renal fibrosis and inflammation and to explore its underlying mechanism. It used network pharmacology to predict the targets of DIS for the treatment of renal interstitial fibrosis. The present study was performed using unilateral ureteral obstruction mice and HK­2 cells in vivo and in vitro. The mice were treated with different doses of DIS. Kidney tissues were collected for histopathology staining, western blotting, immunohistochemistry staining and reverse transcription­quantitative (RT­q) PCR. TGF­ß1 (2 ng/ml) was used to induce renal fibrosis in the cells. Then, cells were respectively treated with DIS (3.125, 6.25, 12.5 µM) and Bay11­7082 (an inhibitor of NF­κB p65 nuclear transcription, 1 µM) for another 24 h. The expressions of inflammatory factors and NF­κB pathway proteins were detected by immunofluorescence, ELISA, western blotting and RT­qPCR. DIS alleviated renal injury in the UUO mice. Mechanistically, DIS not only decreased the expressions of inflammatory factors including IL­1ß, NOD­like receptor thermal protein domain associated protein 3, monocyte chemotactic protein 1, IL­6, TNF­α and IL­18 but also reduced the level of phosphorylation of NF­κB p65 in vivo and in vitro, which was similar to the impact of Bay11­7082. DIS ameliorated renal fibrosis by inhibiting the NF­κB signaling pathway­mediated inflammatory response, which may be a therapeutic pathway for delaying chronic kidney disease.

Long-term outcomes of kidney transplantation from expanded criteria donors with Chinese novel donation policy: donation after citizens' death.

INTRODUCTION: The Chinese Government initiated the Donation after Citizens' Death policy in 2010. To now, it has been a major source of organs for transplant. Since it is still a young policy, corresponding clinical evidence is still urgently needed for its improvement. Compared to kidneys donated by SCD (standard criteria donor), increasing the use of ECD (expanded criteria donor) derived kidneys is a way to expand the donor pool but is also a result of the aging demography of China. This study is based on the data of kidney transplantation in our center with the Donation after Citizens' Death policy, aiming to provide a reference for the clinical use of ECD kidneys. METHOD: A retrospective study enrolled 415 kidney transplants derived from 211 donors performed between October 2011 and October 2019. A total of 311 (74.9%) organs were donated from 159 (75.4%) SCDs, and the remaining 104 (25.1%) were from 52 (24.6%) ECDs. The log-rank test was used to compare the difference in survival and postoperative complications. The Chi-square test was used to compare the occurrence of postoperative complications and postoperative renal function. The Cox regression analysis was used for risk factor screening. RESULT: Analysis showed that grafts from ECD were poorer in survival (P = 0.013), while their recipients had comparable (P = 0.16) survival. Moreover, it also was an independent risk factor for graft loss (HR 2.27, P = 0.044). There were significantly more AR occurrences in the ECD group compared with SCD group (25.0% vs. 15.8%, P = 0.004), but no significant difference was found in infection (51.9% vs. 47.6%, P = 0.497) and DGF (26.0% vs. 21.9%, P = 0.419) between them. Similarly, fewer recipients in the ECD group were free from AR within 1 year after transplantation (P = 0.040), with no statistical difference in all-cause infection prevalence in 1 year (P = 0.168). The eGFR in the ECD group was significantly worse than that in the SCD group at 3 months, 6 months, 1 year, 3 years, and the highest value posttransplant (all < 0.05), but no difference at 5 years posttransplant. Besides, results showed cardiac arrest (uncontrolled vs. controlled, HR 2.49, P = 0.049), HLA mismatch (4-6 loci vs. 0-3 loci, HR 3.61, P = 0.039), and AR occurrence (HR 2.91, P = 0.006) were demonstrated to be independent risk factors for graft loss. CONCLUSION: The ECD-derived kidney was worse than the SCD-derived kidney in terms of graft survival and AR occurrence, and trend to an inferior renal function postoperative. However, the recipient survival, DGF occurrence, and all-cause infection occurrence were similar.

MiR-200c regulates invasion, proliferation and EMT of anaplastic thyroid cancer cells by targeting parathyroid hormone like hormone.

This study aimed to explore the specific effect of miR-200c in anaplastic thyroid cancer (ATC). Hth74 and ARO cell lines were used. Proliferation, invasion, and colony formation activities of Hth74 and ARO cell lines affected by miR-200c were studied. Expression of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, Slug, and Snail) in the Hth74 and ARO cell lines were validated by western blot and qRT-PCR. In addition, the regulation of the parathyroid hormone-like hormone (PTHLH) by miR-200c was assessed. Overexpression of miR-200c inhibited the invasion, proliferation, and colony formation of the ATC cell lines, whereas its downregulation achieved the opposite results. PTHLH was found to be regulated negatively by miR-200c through a miR-200c binding site within the 3'-UTR of PTHLH. miR-200c repressed the proliferation, invasion, and EMT process of cells in ATC cell lines by targeting PTHLH post-transcriptionally, which indicates that miR-200c may be a potential target for the treatment of ATC.

Morroniside Promotes PGC-1α-Mediated Cholesterol Efflux in Sodium Palmitate or High Glucose-Induced Mouse Renal Tubular Epithelial Cells.

Lipid deposition is an etiology of renal damage caused by lipid metabolism disorder in diabetic nephropathy (DN). Thus, reducing lipid deposition is a feasible strategy for the treatment of DN. Morroniside (MOR), an iridoid glycoside isolated from the Chinese herb Cornus officinalis Sieb. et Zucc., is considered to be an effective drug in inhibiting oxidative stress, reducing inflammatory response, and countering apoptosis. To explore the protective mechanism of MOR in attenuating renal lipotoxicity in DN, we investigated the effect of MOR on an in vitro model of lipid metabolism disorder of DN established by stimulating mouse renal tubular epithelial cells (mRTECs) with sodium palmitate (PA) or high glucose (HG). Oil Red O and filipin cholesterol staining assays were used to determine intracellular lipid accumulation status. Results revealed that PA or HG stimulation inhibited the expressions of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), liver X receptors (LXR), ATP-binding cassette subfamily A member 1 (ABCA1), ABCG1, and apolipoprotein E (ApoE) in mRTECs as evidenced by western blot and quantitative real-time PCR, resulting in increased intracellular lipid deposition. Interestingly, MOR upregulated expressions of PGC-1α, LXR, ABCA1, ABCG1, and ApoE, thus reducing cholesterol accumulation in mRTECs, suggesting that MOR might promote cholesterol efflux from mRTECs via the PGC-1α/LXR pathway. Of note, silencing PGC-1α reversed the promotive effect of MOR on PA- or HG-induced cellular cholesterol accumulation. In conclusion, our results suggest that MOR has a protective effect on mRTECs under high lipid or high glucose conditions, which may be related to the promotion of intracellular cholesterol efflux mediated by PGC-1α.

Deregulation of lncRNA HIST1H2AG-6 and AIM1-3 in peripheral blood mononuclear cells is associated with newly diagnosed type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is mainly affected by genetic and environmental factors; however, the correlation of long noncoding RNAs (lncRNAs) with T2DM remains largely unknown. METHODS: Microarray analysis was performed to identify the differentially expressed lncRNAs and messenger RNAs (mRNAs) in patients with T2DM and healthy controls, and the expression of two candidate lncRNAs (lnc-HIST1H2AG-6 and lnc-AIM1-3) were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman's rank correlation coefficient was used to measure the degree of association between the two candidate lncRNAs and differentially expressed mRNAs. Furthermore, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and GO (Gene Ontology) enrichment analysis were used to reveal the biological functions of the two candidate lncRNAs. Additionally, multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: The microarray analysis revealed that there were 55 lncRNAs and 36 mRNAs differentially expressed in patients with T2DM compared with healthy controls. Notably, lnc-HIST1H2AG-6 was significantly upregulated and lnc-AIM1-3 was significantly downregulated in patients with T2DM, which was validated in a large-scale qRT-PCR examination (90 controls and 100 patients with T2DM). Spearman's rank correlation coefficient revealed that both lncRNAs were correlated with 36 differentially expressed mRNAs. Furthermore, functional enrichment (KEGG and GO) analysis demonstrated that the two lncRNA-related mRNAs might be involved in multiple biological functions, including cell programmed death, negative regulation of insulin receptor signal, and starch and sucrose metabolism. Multivariate logistic regression analysis revealed that lnc-HIST1H2AG-6 and lnc-AIM1-3 were significantly correlated with T2DM (OR = 5.791 and 0.071, respectively, both P = 0.000). Furthermore, the ROC curve showed that the expression of lnc-HIST1H2AG-6 and lnc-AIM1-3 might be used to differentiate patients with T2DM from healthy controls (area under the ROC curve = 0.664 and 0.769, respectively). CONCLUSION: The profiles of lncRNA and mRNA were significantly changed in patients with T2DM. The expression levels of lnc-HIST1H2AG-6 and lnc-AIM1-3 genes were significantly correlated with some features of T2DM, which may be used to distinguish patients with T2DM from healthy controls and may serve as potential novel biomarkers for diagnosis in the future.

[Real-time cell analysis combined with pattern recognition to evaluate anaphylaxis of Zushima Injection].

This paper was aimed to establish a new method for evaluating the anaphylactoid reaction of 15 batches of Zushima Injection from different manufacturers in vitro. Basophilic leukemia cell line RBL-2 H3 cells were cultured in vitro and Compound 48/80 was selected as positive drug. Real-time cell analysis(RTCA) system was used to detect the changes of cell index(CI) value after drug intervention. The degranulation of RBL-2 H3 cells was verified with the toluidine blue staining technology by observing the changes of cell morphology and skeleton. Clustering method was used to analyze the CI values of 15 batches of Zushima Injection on RBL-2 H3 cells. The results showed Compound 48/80(20 µg·mL~(-1)) significantly changed the cell morphology and cytoskeleton, with obvious degranulation. After adding Compound 48/80, CI value decreased rapidly within 30 minutes, then decreased slowly, suggesting that RTCA system can be used for rapid and sensitive evaluation of RBL-2 H3 cell degranulation. The results of cluster analysis showed that Zushima Injection from different manufacturers had different effects on RBL-2 H3 cells. S1-S8 and Compound 48/80 groups were grouped into one cluster, which suggesting that the sample might have potential clinical anaphylaxis. S9-S15 and the normal control group were grouped into one cluster, suggesting there was no anaphylactoid reaction in the sample. In this study, a rapid in vitro anaphylaxis evaluation technique based on RTCA system and pattern recognition method was established, which can be used for rapid in vitro evaluation of anaphylaxis for traditional Chinese medicine injection.

Anti-inflammatory effects of the root, stem and leaf extracts of Chloranthus serratus on adjuvant-induced arthritis in rats.

Context: Chloranthus serratus [(Thunb.) Roem. et Schult, (Chloranthaceae)] is a folk medicine used for the treatment of rheumatoid arthritis.Objective: The aim of this study was to investigate anti-arthritic effects of the ethanol extracts of the roots (ER), stems (ES) and leaves (EL) of C. serratus on adjuvant arthritis rats and related mechanisms.Materials and methods: The rats were immunized by intradermal injection of complete Freund's adjuvant (CFA, 0.18 mL) into the right hind feet, and received intragastric administrations of the ER, ES and EL (2.07, 1.61 and 0.58 g/kg/d, respectively) for 14 days. The anti-arthritic activity was assessed by swelling rates, serum indicators, antioxidant capacity, histopathological and immunohistochemical analyses.Results: The LD50 of the ER, ES and EL was higher than 10.35, 8.05 and 2.90 g/kg/p.o., respectively. Extract treatments decreased swelling rates, tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), interleukin 1 beta (IL-1ß), migration inhibitory factor 1 (MIF-1), immunoglobulin G (IgG) and immunoglobulin M (IgM) levels and positive expression of VEGF in the arthritic rats (p < 0.01 or p < 0.05). The ER significantly decreased NO (3.91 ± 0.61 µmol/L), IL-6 (75.67 ± 16.83 pg/mL) and malondialdehyde (MDA) (2.28 ± 0.32 nmol/mL) contents and clearly increased IFN-γ (2082 ± 220.93 pg/mL) and superoxide dismutase (SOD) (601.98 ± 38.40 U/mL) levels. The ES and EL did not reverse the changes in some indicators. All the extracts alleviated inflammatory cell infiltration and synovial cell proliferation. Among them, the ER was the most pronounced.Discussion and conclusions: ER exerts the most promising effects, as shown by inhibiting the releases of inflammatory cytokines and enhancing antioxidant capacity, which provides a scientific basis for further research on C. serratus and its clinical applications.

MiR-7-5pand miR-451 as diagnostic biomarkers for papillary thyroid carcinoma in formalin-fixed paraffin-embedded tissues.

MiR-7-5p and miR-451 are important members of the small RNA family, which have been shown to be significantly downregulated in various human tumors and play a key role in the occurrence and development of tumors. However, little is known about their role in endocrine malignancies. This study aimed to investigate the diagnostic value of miR-7-5p and miR-451 levels in formalin-fixed paraffin-embedded tissues of papillary thyroid carcinoma (PTC) patients, as well as the relationship between clinicopathological characteristics and the two miRNAs. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression levels of miR-7-5p and miR-451 in 101 PTC tissues and in 40 nodular goiter tissues (controls). MiR-7-5p and miR-451 levels were significantly downregulated in PTC patients compared with controls (P < 0.001). MiR-7-5p expression was further downregulated in tumors with larger diameter and advanced tumor stages (all P < 0.05). Moreover, the two miRNAs showed great capability of discriminating PTC patients from controls with 89.5% (miR-7-5p) and 76.8% (miR-451) diagnostic accuracy. Furthermore, according to univariable/multivariate logistic regression, miR-7-5p was significantly associated with PTC (P < 0.001). In conclusion, MiR-7-5p and miR-451 may be used as potential diagnostic biomarkers for identification and validation of PTC patients. Moreover, miR-7-5p appears to be associated with the aggressiveness of PTC.

Exogenous Nitric Oxide and Phosphorus Stress Affect the Mycorrhization, Plant Growth, and Associated Microbes of Carya illinoinensis Seedlings Colonized by Tuber indicum.

In the artificial cultivation of truffles, ectomycorrhizal colonization level, host plant quality, and the associated microbes in the rhizosphere soil are vitally important. To explore the effects of nitric oxide (NO) and phosphorus (P) stress on the early symbiosis of truffles and host plants, different concentrations of exogenous NO donor sodium nitroprusside (SNP) and P were applied to Carya illinoinensis seedlings inoculated with the Chinese black truffle (Tuber indicum). The growth of T. indicum-mycorrhized seedlings and their mycorrhizal colonization rate were investigated. Additionally, the denitrifying bacterial community harboring NO reductase (norB) genes and the fungal community in the rhizosphere of the host were analyzed by high-throughput sequencing. The results showed that the colonization rate of T. indicum was significantly influenced by SNP treatments and P stress, with the highest level being obtained when the SNP was 100 µmol/L under low P stress (5 µmol/L). Treatment with 100 µmol/L SNP alone also increased the colonization rate of T. indicum and had positive effects on the plant height, stem circumference, biomass, root-shoot ratio and root POD activity of the seedlings at different times after inoculation. Under low P stress, the 100 µmol/L SNP increased the richness of the norB-type denitrifying bacterial community. Interestingly, the diversity and richness of norB-type denitrifying bacteria were significantly positively correlated with the colonization rate of T. indicum. SNP treatments under low P stress altered the abundance of some dominant taxa such as Alphaproteobacteria, Gammaproteobacteria, Pseudomonas, Ensifer, and Sulfitobacter. Evaluation of the fungal community in the rhizosphere revealed that 100 µmol/L SNP treatment alone had no noticeable effect on their richness and diversity, but it did shape the abundance of some fungi. Buellia, Podospora, Phaeoisaria, Ascotaiwania, and Lophiostoma were more abundant following exogenous NO application, while the abundance of Acremonium, Monographella, and Penicillium were decreased. Network analysis indicated that T. indicum was positively and negatively correlated with some fungal genera when treated with 100 µmol/L SNP. Overall, these results revealed how exogenous NO and P stress influence the symbiosis of truffles and host plants, and indicate that application of SNP treatments has the potential for ectomycorrhizal synthesis and truffle cultivation.

Circular RNA Expression Profiling and the Potential Role of hsa_circ_0089172 in Hashimoto's Thyroiditis via Sponging miR125a-3p.

Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs), but the role of circRNAs in Hashimoto's thyroiditis (HT) has not been defined. In this study, peripheral blood samples from five patients with HT and five healthy volunteers were investigated by Illumina HiSeq Sequencer. A total of 627 differentially expressed circRNAs including 370 upregulated and 257 downregulated ones were identified in HT patients. Four upregulated circRNAs indicated the same rising tendency toward sequencing results. The expression of hsa_circ_0089172 was upregulated and correlated positively with the serum level of the thyroid peroxidase antibody. Two perfectly matched binding sites of miR-125a-3p were found in hsa_circ_0089172 sequences with bioinformatics tools. The expression of miR-125a-3p was decreased in the HT patients and correlated inversely with an elevated level of hsa_circ_0089172. Moreover, knockdown of hsa_circ_0089172 resulted in an increase of the expression of miR-125a-3p in vitro. Receiver operating characteristic (ROC) curve analysis suggested that hsa_circ_0089172 had significant value in HT diagnosis. Taken together, these results demonstrate that hsa_circ_0089172 as a potential diagnostic biomarker of HT and may play a crucial role in the pathogenesis of HT via sponging miR-125a-3p.

miR-21 facilitates the diagnostic value of miR-138 for papillary thyroid cancer in formalin-fixed paraffin-embedded tissues.

BACKGROUND: miR-138 was thought to be anti-tumor miRNA for its ability of suppressing tumor growth. The objective of this study was to evaluate the potential predictive value of miR-138 and its combination with miR-21 in formalin-fixed paraffin-embedded (FFPE) tissues of papillary thyroid cancers (PTCs). METHODS: miR-138/miR-21 expression was tested in 101 PTC and 51 benign thyroid nodule (control) patients using quantitative real-time PCR. Clinical and pathological characteristics of enrolled subjects were obtained from medical records. RESULTS: miR-138 was significantly down-regulated in PTC compared with controls (median 0.0122 vs. 0.0943), and miR-138 exhibited capability of discriminating PTC from controls, with a diagnostic accuracy of 71.1% (sensitivity 84.3%, specificity 49.5%). A combination of miR-138 and miR-21 increased the diagnostic accuracy to 79.1% (sensitivity 73.3%, specificity 76.5%). Multivariate logistic regression confirmed the association between miR-138/miR-21 expression and PTC diagnosis. Moreover, miR-138 expression was further down-regulated in PTC with capsule invasion compared with PTC tissues without capsule invasion (median 0.0043 vs. 0.0373, P=0.003). CONCLUSIONS: MiR-138 expression was not only associated with onset of PTC, but also the aggressiveness of PTC. A combination of miR-138 and miR-21 enhanced the diagnostic value of individual biomarkers.

The Uneven Distribution of Mating Type Genes in Natural and Cultivated Truffle Orchards Contributes to the Fructification of Tuber indicum.

The aim of this study was to investigate the pattern of distribution of mating type (MAT) genes of Tuber indicum in ectomycorhizosphere soils from natural T. indicum-producing areas and cultivated truffle orchards and ascocarp samples from different regions. Quantitative real-time PCR and multiplex PCR were used to weight the copy numbers of MAT1-1-1 and MAT1-2-1 in natural truffle soils and cultivated orchard soils. The effect of limestone on the pattern of truffle MAT genes and the correlation between soil properties and the proportion of MAT genes were also assessed. These results indicated that an uneven and nonrandom distribution of MAT genes was common in truffle-producing areas, cultivated truffle orchards, and ascocarps gleba. The competition between the two mating type genes and the expansion of unbalanced distribution was found to be closely related to truffle fructification. Limestone treatments failed to alter the proportion of the two mating type genes in the soil. The content of available phosphorus in soil was significantly correlated with the value of MAT1-1-1/MAT1-2-1 in cultivated and natural ectomycorhizosphere soils. The application of real-time quantitative PCR can provide reference for monitoring the dynamic changes of mating type genes in soil. This study investigates the distributional pattern of T. indicum MAT genes in the ectomycorhizosphere soil and ascocarp gleba from different regions, which may provide a foundation for the cultivation of T. indicum.

The protective effect of asiatic acid on podocytes in the kidney of diabetic rats.

The essential ingredient of Centella asiatic is asiatic acid (AA). There are a lot of biological activities in AA, such as anti-oxidant, anti-diabetic. However, so far, there have been no reports on the underlying protective mechanism of AA on podocytes. In this research, we observed the morphological changes of podocytes in diabetic rats by optics microscope and transmission electron microscopy and the protective effect of AA. Additionally, we investigated the expressions of nephrin, desmin and p-JNK, JNK in podocytes of diabetic rats and the influence of AA on podocytes and JNK signaling pathway. The results showed that AA could reduce renal function and urinary albumin. It could attenuate abnormal pathological findings of podocytes in kidney tissue of diabetic rats. Besides, treatment with AA could significantly improve the expression of nephrin and decrease expression of desmin. The ratio of p-JNK protein to JNK protein in podocytes was reduced considerably by AA. With the treatment dose of AA increased, the renal protective effect of AA was gradually improved. These results indicate that asiatic acid has a significant protective effect on diabetic nephropathy. Potential mechanisms include inhibiting the production of oxidants effectively, protection of podocytes, and suppression of the JNK signaling pathway activation. Therefore, there is an excellent prospect of using AA to treat diabetic nephropathy.

The association of ACE gene polymorphism with diabetic kidney disease and renoprotective efficacy of valsartan.

INTRODUCTION: To investigate the associations between the insertion/deletion (I/D) polymorphisms in the angiotensin converting enzyme (ACE) gene and susceptibility to diabetic kidney disease (DKD); and the efficacy of valsartan in reducing the urine protein in Type 2 diabetes mellitus (T2DM) patients. MATERIALS AND METHODS: We enrolled 128 T2DM patients in this study, including 54 cases with DKD (DKD+) and 74 controls (DKD-). The ACE polymorphism was assayed by polymerase chain reaction (PCR), and the genotype distribution and allele frequency were analyzed. The DKD+ group was subdivided into the DD, ID and II subgroups, based on their genotypes. In addition, patients with DKD received valsartan treatment for 12 weeks. We determined changes in the urinary albumin to creatinine ratio (ACR) and serum creatinine (SCr). RESULTS: The frequencies of the genotypes DD and ID were higher in the DKD+ than in the DKD- group. The frequency of allele D was higher, and of allele I was lower, in the DKD+ than in DKD- group (p < 0.05). Following valsartan treatment, albuminuria was significantly decreased in subgroups DD and ID (p < 0.05). CONCLUSIONS: In T2DM patients, the ACE I/D polymorphism was associated with onset of DKD. Furthermore, the ACE I/D polymorphism influenced the renoprotective response to valsartan: Patients with the DD genotype benefitted the most from this treatment.

The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients.

Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobinA1c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1DM patients (duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion.

OBJECTIVE: To determine the safety and effects on insulin secretion of umbilical cord (UC) mesenchymal stromal cells (MSCs) plus autologous bone marrow mononuclear cell (aBM-MNC) stem cell transplantation (SCT) without immunotherapy in established type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Between January 2009 and December 2010, 42 patients with T1D were randomized (n = 21/group) to either SCT (1.1 × 10(6)/kg UC-MSC, 106.8 × 10(6)/kg aBM-MNC through supraselective pancreatic artery cannulation) or standard care (control). Patients were followed for 1 year at 3-month intervals. The primary end point was C-peptide area under the curve (AUC(C-Pep)) during an oral glucose tolerance test at 1 year. Additional end points were safety and tolerability of the procedure, metabolic control, and quality of life. RESULTS: The treatment was well tolerated. At 1 year, metabolic measures improved in treated patients: AUCC-Pep increased 105.7% (6.6 ± 6.1 to 13.6 ± 8.1 pmol/mL/180 min, P = 0.00012) in 20 of 21 responders, whereas it decreased 7.7% in control subjects (8.4 ± 6.8 to 7.7 ± 4.5 pmol/mL/180 min, P = 0.013 vs. SCT); insulin area under the curve increased 49.3% (1,477.8 ± 1,012.8 to 2,205.5 ± 1,194.0 mmol/mL/180 min, P = 0.01), whereas it decreased 5.7% in control subjects (1,517.7 ± 630.2 to 1,431.7 ± 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA1c decreased 12.6% (8.6 ± 0.81% [70.0 ± 7.1 mmol/mol] to 7.5 ± 1.0% [58.0 ± 8.6 mmol/mol], P < 0.01) in the treated group, whereas it increased 1.2% in the control group (8.7 ± 0.9% [72.0 ± 7.5 mmol/mol] to 8.8 ± 0.9% [73 ± 7.5 mmol/mol], P < 0.01 vs. SCT). Fasting glycemia decreased 24.4% (200.0 ± 51.1 to 151.2 ± 22.1 mg/dL, P < 0.002) and 4.3% in control subjects (192.4 ± 35.3 to 184.2 ± 34.3 mg/dL, P < 0.042). Daily insulin requirements decreased 29.2% in only the treated group (0.9 ± 0.2 to 0.6 ± 0.2 IU/day/kg, P = 0.001), with no change found in control subjects (0.9 ± 0.2 to 0.9 ± 0.2 IU/day/kg, P < 0.01 vs. SCT). CONCLUSIONS: Transplantation of UC-MSC and aBM-MNC was safe and associated with moderate improvement of metabolic measures in patients with established T1D.