SP-141 targets Trs85 to inhibit rice blast fungus infection and functions as a potential broad-spectrum antifungal agent.

Rice blast is a devastating disease worldwide, threatening rice production and food security. The blast fungus Magnaporthe oryzae invades the host via the appressorium, a specialized pressure-generating structure that generates enormous turgor pressure to penetrate the host cuticle. However, owing to ongoing evolution of fungicide resistance, it is vitally important to identify new targets and fungicides. Here, we show that Trs85, a subunit of the transport protein particle III complex, is essential for appressorium-mediated infection in M. oryzae. We explain how Trs85 regulates autophagy through Ypt1 (a small guanosine triphosphatase protein) in M. oryzae. We then identify a key conserved amphipathic α helix within Trs85 that is associated with pathogenicity of M. oryzae. Through computer-aided screening, we identify a lead compound, SP-141, that affects autophagy and the Trs85-Ypt1 interaction. SP-141 demonstrates a substantial capacity to effectively inhibit infection caused by the rice blast fungus while also exhibiting wide-ranging potential as an antifungal agent with broad-spectrum activity. Taken together, our data show that Trs85 is a potential new target and that SP-141 has potential for the control of rice blast. Our findings thus provide a novel strategy that may help in the fight against rice blast.

Prognostic factors affecting the ruptured intracranial aneurysms: A 9-year multicenter study in Fujian, China.

BACKGROUND: A multicenter retrospective study was conducted to explore the factors affecting short-term prognosis and long-term outcomes of intracranial aneurysms (IA) rupture. Further, the prognosis prediction model was constructed based on survival analysis, contributing to the development of prevention strategies for aneurysmal subarachnoid hemorrhage. METHODS: Data of 1280 patients with IA rupture were gathered between 2014 and 2022 in Fujian, China. Logistic regression was implemented to study the short-term prognostic factors of IA rupture. Survival analysis of 911 patients among them was performed to explore the long-term outcome status by Cox risk assessment. Nomogram prognosis models were constructed using R software. RESULTS: The findings displayed that blood type O (OR = 1.79; P = 0.019), high systolic pressure (OR = 1.01; P < 0.001), Glasgow Coma score (GCS) 9-12 (OR = 2.73; P = 0.022), GCS < 9 (OR = 3.222; P = 0.006), diabetes (OR = 2.044; P = 0.040), and high white blood cell count (OR = 1.059, P = 0.040) were core influencing factors for poor short-term prognosis. Survival analysis revealed that age > 60 years (HR = 2.87; P = 0.001), hypertension (HR = 1.95; P = 0.001), conservative (HR = 6.89; P < 0.001) and endovascular treatment (HR = 2.20; P = 0.001), multiple ruptured IAs (HR = 2.37; P = 0.01), Fisher 3 (HR = 1.68; P = 0.09), Fisher 4 (HR = 2.75; P = 0.001), and Hunt-Hess 3 (HR = 0.55; P = 0.05) were the major risk factors for terrible long-term outcomes. CONCLUSIONS: People over 60 years with characteristics of type O blood, high systolic pressure, diabetes, high white blood cell count, and onset GCS < 12 will have more complications and a worse short-term prognosis. Those aged > 60 years with hypertension, conservative and endovascular treatment, multiple ruptured IAs, Fisher ≥ 3 and Hunt-Hess 3 have a greater risk of poor long-term prognosis.

MoCbp7, a Novel Calcineurin B Subunit-Binding Protein, Is Involved in the Calcium Signaling Pathway and Regulates Fungal Development, Virulence, and ER Homeostasis in Magnaporthe oryzae.

Calcineurin, a key regulator of the calcium signaling pathway, is involved in calcium signal transduction and calcium ion homeostasis. Magnaporthe oryzae is a devastating filamentous phytopathogenic fungus in rice, yet little is known about the function of the calcium signaling system. Here, we identified a novel calcineurin regulatory-subunit-binding protein, MoCbp7, which is highly conserved in filamentous fungi and was found to localize in the cytoplasm. Phenotypic analysis of the MoCBP7 gene deletion mutant (ΔMocbp7) showed that MoCbp7 influenced the growth, conidiation, appressorium formation, invasive growth, and virulence of M. oryzae. Some calcium-signaling-related genes, such as YVC1, VCX1, and RCN1, are expressed in a calcineurin/MoCbp7-dependent manner. Furthermore, MoCbp7 synergizes with calcineurin to regulate endoplasmic reticulum homeostasis. Our research indicated that M. oryzae may have evolved a new calcium signaling regulatory network to adapt to its environment compared to the fungal model organism Saccharomyces cerevisiae.

The triglyceride catabolism regulated by a serine/threonine protein phosphatase, Smek1, is required for development and plant infection in Magnaporthe oryzae.

Magnaporthe oryzae is a pathogenic fungus that seriously harms rice production. Phosphatases and carbon metabolism play crucial roles in the growth and development of eukaryotes. However, it remains unclear how serine/threonine phosphatases regulate the catabolism of triglycerides, a major form of stored lipids. In this study, we identified a serine/threonine protein phosphatase regulatory subunit, Smek1, which is required for the growth, conidiation, and virulence of M. oryzae. Deletion of SMEK1 led to defects in the utilization of lipids, arabinose, glycerol, and ethanol. In glucose medium, the expression of genes involved in lipolysis, long-chain fatty acid degradation, ß-oxidation, and the glyoxylate cycle increased in the Δsmek1 mutant, which is consistent with ΔcreA in which a carbon catabolite repressor CREA was deleted. In lipid medium, the expression of genes involved in long-chain fatty acid degradation, ß-oxidation, the glyoxylate cycle, and utilization of arabinose, ethanol, or glycerol decreased in the Δsmek1 mutant, which is consistent with Δcrf1 in which a transcription activator CRF1 required for carbon metabolism was deleted. Lipase activity, however, increased in the Δsmek1 mutant in both glucose and lipid media. Moreover, Smek1 directly interacted with CreA and Crf1, and dephosphorylated CreA and Crf1 in vivo. The phosphatase Smek1 is therefore a dual-function regulator of the lipid and carbohydrate metabolism, and controls fungal development and virulence by coordinating the functions of CreA and Crf1 in carbon catabolite repression (CCR) and derepression (CCDR).

MoVast2 combined with MoVast1 regulates lipid homeostasis and autophagy in Magnaporthe oryzae.

Macroautophagy/autophagy is an evolutionarily conserved biological process among eukaryotes that degrades unwanted materials such as protein aggregates, damaged mitochondria and even viruses to maintain cell survival. Our previous studies have demonstrated that MoVast1 acts as an autophagy regulator regulating autophagy, membrane tension, and sterol homeostasis in rice blast fungus. However, the detailed regulatory relationships between autophagy and VASt domain proteins remain unsolved. Here, we identified another VASt domain-containing protein, MoVast2, and further uncovered the regulatory mechanism of MoVast2 in M. oryzae. MoVast2 interacted with MoVast1 and MoAtg8, and colocalized at the PAS and deletion of MoVAST2 results in inappropriate autophagy progress. Through TOR activity analysis, sterols and sphingolipid content detection, we found high sterol accumulation in the ΔMovast2 mutant, whereas this mutant showed low sphingolipids and low activity of both TORC1 and TORC2. In addition, MoVast2 colocalized with MoVast1. The localization of MoVast2 in the MoVAST1 deletion mutant was normal; however, deletion of MoVAST2 leads to mislocalization of MoVast1. Notably, the wide-target lipidomic analyses revealed significant changes in sterols and sphingolipids, the major PM components, in the ΔMovast2 mutant, which was involved in lipid metabolism and autophagic pathways. These findings confirmed that the functions of MoVast1 were regulated by MoVast2, revealing that MoVast2 combined with MoVast1 maintained lipid homeostasis and autophagy balance by regulating TOR activity in M. oryzae.

The crucial role of the regulatory mechanism of the Atg1/ULK1 complex in fungi.

Autophagy, an evolutionarily conserved cellular degradation pathway in eukaryotes, is hierarchically regulated by autophagy-related genes (Atgs). The Atg1/ULK1 complex is the most upstream factor involved in autophagy initiation. Here，we summarize the recent studies on the structure and molecular mechanism of the Atg1/ULK1 complex in autophagy initiation, with a special focus on upstream regulation and downstream effectors of Atg1/ULK1. The roles of pathogenicity and autophagy aspects in Atg1/ULK1 complexes of various pathogenic hosts, including plants, insects, and humans, are also discussed in this work based on recent research findings. We establish a framework to study how the Atg1/ULK1 complex integrates the signals that induce autophagy in accordance with fungus to mammalian autophagy regulation pathways. This framework lays the foundation for studying the deeper molecular mechanisms of the Atg1 complex in pathogenic fungi.

The mutation spectrum of Parkinson-disease-related genes in early-onset Parkinson's disease in ethnic Chinese.

BACKGROUND AND PURPOSE: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD-related genes and determine the mutational spectrum of early-onset PD in ethnic Chinese. METHODS: In this study, whole-exome sequencing and/or gene dosage analysis were performed in 704 early-onset PD (EOPD) patients (onset age ≤45 years) and 1866 controls. Twenty-six PD-related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analysed. RESULTS: Eighty-two (11.6%, 82/704) EOPD patients carrying rare pathogenic/likely pathogenic variants in PD-related genes were identified. The mutation frequency in autosomal recessive inheritance EOPD (42.9%, 27/63) was much higher than that in autosomal dominant inheritance EOPD (0.9%, 12/110) or sporadic EOPD (8.1%, 43/531). Bi-allelic mutations in PRKN were the most frequent, accounting for 5.1% of EOPD cases. Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1, PLA2G6 and GCH1 contributed to the collective risk for EOPD. Notably, the protein-truncating variants in CHCHD2 were enriched in EOPD, especially for p.P53Afs*38, which was also found in three patients from an independent cohort of patients with late-onset PD (n = 1300). Functional experiments confirmed that truncated CHCHD2 variants cause loss of function and are linked to mitochondrial dysfunction. CONCLUSIONS: Our study reveals that the genetic spectrum of EOPD in Chinese, which may help develop genetic scanning strategies, provided more evidence supporting CHCHD2 in PD.

Research on the Molecular Interaction Mechanism between Plants and Pathogenic Fungi.

Plant diseases caused by fungi are one of the major threats to global food security and understanding the interactions between fungi and plants is of great significance for plant disease control. The interaction between pathogenic fungi and plants is a complex process. From the perspective of pathogenic fungi, pathogenic fungi are involved in the regulation of pathogenicity by surface signal recognition proteins, MAPK signaling pathways, transcription factors, and pathogenic factors in the process of infecting plants. From the perspective of plant immunity, the signal pathway of immune response, the signal transduction pathway that induces plant immunity, and the function of plant cytoskeleton are the keys to studying plant resistance. In this review, we summarize the current research progress of fungi-plant interactions from multiple aspects and discuss the prospects and challenges of phytopathogenic fungi and their host interactions.

MoOpy2 is essential for fungal development, pathogenicity, and autophagy in Magnaporthe oryzae.

The development and pathogenicity of the fungus Magnaporthe oryzae, the causal agent of destructive rice blast disease, require it to perceive external environmental signals. Opy2, an overproduction-induced pheromone-resistant protein 2, is a crucial protein for sensing external signals in Saccharomyces cerevisiae. However, the biological functions of the homologue of Opy2 in M. oryzae are unclear. In this study, we identified that MoOPY2 is involved in fungal development, pathogenicity, and autophagy in M. oryzae. Deletion of MoOPY2 resulted in pleiotropic defects in hyphal growth, conidiation, germ tube extension, appressorium formation, appressorium turgor generation, and invasive growth, therefore leading to attenuated pathogenicity. Furthermore, MoOpy2 participates in the Osm1 MAPK pathway and the Mps1 MAPK pathway by interacting with the adaptor protein Mst50. The interaction sites of Mst50 and MoOpy2 colocalized with the autophagic marker protein MoAtg8 in the preautophagosomal structure sites (PAS). Notably, the ΔMoopy2 mutant caused cumulative MoAtg8 lipidation and rapid GFP-MoAtg8 degradation in response to nitrogen starvation, showing that MoOpy2 is involved in the negative regulation of autophagy activity. Taken together, our study revealed that MoOpy2 of M. oryzae plays an essential role in the orchestration of fungal development, appressorium penetration, autophagy and pathogenesis.

Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

Associations between meteorological variation and rupture of intracranial aneurysm in Fujian, China: A 5-year multicenter study.

OBJECTIVE: By exploring the exposure-response relationships between meteorological factors and rupture of intracranial aneurysm (IA) to reveal the influence of meteorological variation on IA rupture under the specific climate in Fujian, China. METHOD: 7515 cases of IA rupture from several municipal medical institutions in Fujian Province as well as local meteorological data during the same period were collected from 2013 to 2017. Poisson regression and Spearman correlation analysis were applied to explore the distribution characteristics of IA rupture and how it is associated with meteorological parameters. Poisson generalized additive model was established to further analyze the exposure-response relationships between meteorological factors and IA rupture, and its hysteresis effects. RESULT: The IA rupture exhibited a negative correlation with temperature (rs = -0.323, 95% CI: -0.539 ~ -0.068) and a positive correlation with atmospheric pressure (rs = 0.397, 95% CI: 0.152-0.597) or pressure difference (rs = 0.296, 95% CI: 0.038-0.517), 21.05 â„ƒ and 1000.14 hPa were the risk thresholds for the onset ascribed to variation in temperature and atmospheric pressure, respectively. Temperature and atmospheric pressure also exerted hysteresis effects on IA rupture. Cold will increase the rupture risk in the subsequent 1-3 days, and high pressure will raise the morbidity in the next 1-2 days. Besides, drastic variations in temperature and atmospheric pressure were also associated with the higher risk of IA rupture in the next 2 days and 1 day, respectively. CONCLUSION: Temperature and atmospheric pressure have a negative and positive correlation with IA rupture in Fujian, China, respectively. Variation in temperature and atmospheric pressure exert different degrees of hysteresis effects on IA rupture.

A VASt-domain protein regulates autophagy, membrane tension, and sterol homeostasis in rice blast fungus.

Sterols are a class of lipids critical for fundamental biological processes and membrane dynamics. These molecules are synthesized in the endoplasmic reticulum (ER) and are transported bi-directionally between the ER and plasma membrane (PM). However, the trafficking mechanism of sterols and their relationship with macroautophagy/autophagy are still poorly understood in the rice blast fungus Magnaporthe oryzae. Here, we identified the VAD1 Analog of StAR-related lipid transfer (VASt) domain-containing protein MoVast1 via co-immunoprecipitation in M. oryzae. Loss of MoVAST1 resulted in conidial defects, impaired appressorium development, and reduced pathogenicity. The MoTor (target of rapamycin in M. oryzae) activity is inhibited because MoVast1 deletion leads to high levels of sterol accumulation in the PM. Site-directed mutagenesis showed that the 902 T site is essential for localization and function of MoVast1. Through filipin or Flipper-TR staining, autophagic flux detection, MoAtg8 lipidation, and drug sensitivity assays, we uncovered that MoVast1 acts as a novel autophagy inhibition factor that monitors tension in the PM by regulating the sterol content, which in turn modulates the activity of MoTor. Lipidomics and transcriptomics analyses further confirmed that MoVast1 is an important regulator of lipid metabolism and the autophagy pathway. Our results revealed and characterized a novel sterol transfer protein important for M. oryzae pathogenicity.Abbreviations: AmB: amphotericin B; ATMT: Agrobacterium tumefaciens-mediated transformation; CM: complete medium; dpi: days post-inoculation; ER: endoplasmic reticulum; Flipper-TR: fluorescent lipid tension reporter; GO: Gene ontology; hpi: hours post-inoculation; IH: invasive hyphae; KEGG: kyoto encyclopedia of genes and genomes; MoTor: target of rapamycin in Magnaporthe oryzae; PalmC: palmitoylcarnitine; PM: plasma membrane; SD-N: synthetic defined medium without amino acids and ammonium sulfate; TOR: target of rapamycin; VASt: VAD1 Analog of StAR-related lipid transfer; YFP, yellow fluorescent protein.

Renoprotective effects of brown adipose tissue activation in diabetic mice.

BACKGROUND: Brown adipose tissue (BAT) has been regarded as a potential target organ to combat obesity and related metabolic disorders. However, the effect of BAT activation on the development of diabetic kidney disease (DKD) remains unclear. METHODS: Diabetic mice were induced by streptozotocin (STZ) combined with a high-fat diet. To activate BAT, mice were administered 1 mg/kg per day, i.p., CL316,243, a ß3 -adrenergic receptor agonist, for 4 weeks. Blood glucose, serum lipids, adipokines, 24-hour urinary albumin, 8-hydroxydeoxyguanosine (8-OHdG), and circulating microRNA (miRNA) levels were analyzed, in addition to renal pathology. Histological changes (fibrosis, inflammation) were evaluated in the kidneys, as was the expression of oxidative stress-related genes. Renal signaling pathways (fibroblast growth factor [Fgf]21/ß-klotho/FGF receptor 1c and AMP-activated protein kinase[AMPK]/sirtuin 1 [Sirt1]/peroxisome proliferator-activated receptor-γ coactivator-1α [Pgc1α]) were also evaluated. RESULTS: Compared with untreated STZ-diabetic mice, CL316,243 treatment reduced blood glucose, albeit not significantly (20.58 ± 3.55 vs 23.60 ± 3.90 mM), and significantly decreased triglycerides and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Simultaneously, BAT activation significantly decreased 24-hour urinary albumin (34.21 ± 6.28 vs 70.46 ± 15.81 µg/24 h; P < 0.05) and 8-OHdG, improved renal fibrosis, inflammation, and oxidative stress, and ameliorated renal morphological abnormalities. In addition to enhancing BAT activity, CL316,243 significantly increased serum adiponectin concentrations and renal Fgf21 sensitivity, and reactivated the renal AMPK/Sirt1/Pgc1α signaling pathway. Furthermore, CL316,243 treatment increased levels of some circulating miRNAs and downregulated expression of their target genes in the kidney. CONCLUSIONS: Activating BAT could improve kidney injury in diabetic mice via metabolic improvements and renal AMPK activation by beneficial adipokines and miRNAs.

[Exendin-4 alleviates diabetic cardiomyopathy in mice by regulating Sirt1/PGC1α].

OBJECTIVE: To investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks, respectively. The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC. The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice. RESULTS: Compared with the normal control mice, the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels (P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFß1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFß1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice. CONCLUSIONS: Exendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.

[Research progress of traditional Chinese medicine intervention vascular cognitive impairment].

Vascular cognitive impairment (VCI) is a kind of syndrome from mild cognitive impairment to dementia, which is caused by different vascular factors. It can be prevented and delayed the progress of VCI and even reversed cognitive impairment before it progresses to vascular dementia by early diagnosis and intervention. Many experimental and clinical studies have confirmed that traditional Chinese medicine (TCM) monomer, effective fraction, compound preparation,etc can improve vascular cognitive function. Our paper summarizes the research progress in the concept, pathogenesis, cellular and molecular mechanisms, and TCM treatment of VCI.

[Clinical analysis of 939 patients with adrenal lesions detected by abdominal computed tomography].

OBJECTIVE: To investigate the prevalence, etiology and clinical characteristics of adrenal lesions detected by abdominal computed tomography (CT). METHODS: This retrospective study was conducted in patients with adrenal lesions detected by abdominal CT examinations in Nanfang Hospital between July, 2014 and June, 2015. The clinical data of the patients were collected for analysis of the demographics, comorbidities, imaging characteristics, biochemical profiles, clinical diagnosis and intervention. RESULTS: A total of 939 patients with adrenal lesions were identified from 19 004 patients undergoing abdominal CT scan over the defined period. The mean age of the patients was 53.2 years and 560 of the patients were male. Among the total cases with adrenal lesions, the percentages of cases with adrenal masses tended to increase progressively with age. Endocrine studies were done in 270 of the total patients, which identified non-functioning masses in 38.9%, primary aldosteronism in 16.3%, Cushing's syndrome in 4.1%, subclinical Cushing's syndrome in 7.0%, and pheochromocytomas in 7.0% of the cases. Adrenal incidentalomas was detected in 191 patients, with a detection rate of 1.0% among the overall patients undergoing abdominal CT scans. Imaging study detected adenomas (70.3%), cortical carcinomas (2.4%), and metastases (0.5%). Of 191 patients with adrenal incidentalomas, only 76 (39.8%) underwent endocrine evaluation, including 34 with nonfunctioning adrenal masses, 17 with pheochromocytoma, 7 with primary aldosteronism, and 5 with subclinical Cushing's syndrome. CONCLUSION: s The overall detection rates of adrenal lesions and adrenal incidentalomas by abdominal CT were 4.9% and 1.0%, respectively, in our cohort of patients undergoing the examination over the defined period. Although most of the lesions were benign and nonfunctioning, malignant and functional lesions were also detected. As many as 60% of the patients with adrenal incidentalomas did not have hormonal testing. Clinicians need to have greater awareness of adrenal incidentalomas and standard protocol for its management should be established.

Kidney Function and Cognitive Impairment in People Aged 80 Years and Over with Untreated Hypertension: A Cross-Sectional Survey.

BACKGROUND/AIMS: Both kidney dysfunction and cognitive impairment are common problems in hypertensive patients. However, few studies have explored the association between these conditions in hypertensive patients aged 80 or over. The current study was undertaken to determine the impact of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) on cognitive impairment among an 80-year-old population with untreated hypertension in China. METHODS: A total of 395 hypertensive patients aged 80 or over were assessed for the presence of cognitive impairment according to the 30-item Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a score below 24 on MMSE. eGFR was evaluated using the Chinese Modification of Diet in Renal Disease equation. CKD was defined according to categorical approach, which is based on "YES" (eGFR below 60 ml/min) or "NO" (eGFR above 60 ml/min). RESULTS: The mean (SD) age was 83.0 ± 2.6 years for the sample, of whom 69.8% were female. There were 59 (14.9%) and 280 (71.1%) prevalent cases of CKD and cognitive impairment, respectively. CKD patients were older, had higher scores on Activity of Daily Living (ADL), and lower score on MMSE. After controlling for potential confounding, multiple logistic regressions demonstrated that both CKD and eGFR were associated with cognitive impairment in hypertensive patients aged 80 or over. CONCLUSION: Our study found that both CKD and eGFR were associated with cognitive impairment among hypertensive patients aged 80 or over in China. Therefore, targeted screening for cognitive impairment should be considered in these patients with CKD.

[Expressions of inflammatory and fibrogenic factors in perinephric and subcutaneous adipose tissues of patients with adrenocorticotropic hormone-independent Cushing's syndrome].

OBJECTIVE: To investigate the expressions of inflammation- and fibrosis-related genes in perinephric and subcutaneous adipose tissues in patients with adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome. METHODS: The perinephric and subcutaneous adipose tissues adipose tissues were obtained from 8 patients with ACTH-independent Cushing's syndrome undergoing laparoscopic retroperitoneal adrenalectomy. Real-time PCR was used to detect the mRNA expression levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metallopeptidase 2 (MMP-2), TIMP metallopeptidase inhibitor 1 (TIMP-1), early growth response 1 (EGR1), CCAAT/enhancer binding protein ß(CEBPß), uncoupling protein 1(UCP-1), PPARγ coactivator 1 alpha (PGC1α) and cell death-inducing DFFA-like effector a (CIDEA). RESULTS: The mRNA level of CIDEA was significantly higher in the perinephric adipose tissue (peri-N) than in the subcutaneous adipose tissue (subQ) (P<0.05). The expressions of CEBPß, UCP-1, and PGC1α mRNA in the peri-N were similar with those in the subQ. The expressions of IL-6, TIMP1 and EGR1 mRNA in the subQ were significantly higher than those in the peri-N (P<0.05). No significant difference in TNF-α and MMP-2 mRNA levels was found between peri-N and subQ. CONCLUSION: The expression levels of the inflammation- and fibrosis-related genes are higher in the subQ than in the peri-N of patients with ACTH-independent Cushing's syndrome, suggesting that chronic exposure to endogenous hypercortisolism may cause adipose tissue dysfunction.

Pulmonary hypertension in polymyositis.

Pulmonary hypertension (PH) is relatively common in connective tissue diseases. However, few studies have focused on the pulmonary hypertension (PH) associated with polymyositis (PM). Our aim is to investigate the prevalence of PH and determine the associated factors for PH in patients with PM. Multicenter study of 61 patients with PM underwent evaluation including general information, physical examination, laboratory indictors, thoracic high-resolution CT (HRCT) imaging, and transthoracic echocardiography (TTE). TTE was performed to estimate the pulmonary arterial pressure. PH was defined as resting systolic pulmonary artery pressure (sPAP) ≥40 mmHg. PH was identified in ten patients (16.39 %) who had few cardiopulmonary symptoms. PM patients with PH had higher prevalence of interstitial lung disease (ILD) and pericardial effusion (PE) compared with patients without PH (18 vs. 11.5 %, p = 0.005; 11.5 vs. 9.8 %, p = 0.004; respectively). After controlling for age, gender, and potential factors, ILD and PE were independently associated with PH in patients with PM in multivariate analysis (OR = 8.193, 95 % CI 1.241-54.084, p = 0.029; OR = 8.265, 95 % CI 1.298-52.084, p = 0.025; respectively). Depending on TTE, the possible prevalence of PH was 16.39 % in patients with PM. Both ILD and PE may contribute to the development of PH in PM.

Combined effects of curcumin and triptolide on an ovarian cancer cell line.

BACKGROUND: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro. METHODS: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting. RESULTS: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect. CONCLUSIONS: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.