Paenibacillus baimaensis sp. nov., a bacterium isolated from mountain soil in the habitat of Rhinopithecus bieti.

A novel Gram-positive strain WQ 127069T that was isolated from the soil of Baima Snow Mountain, a habitat of highly endangered Yunnan snub-nosed monkeys (Rhinopithecus bieti), was subjected to a polyphasic taxonomic study. Phylogenetic analysis based on the 16S rRNA gene sequences showed that the isolate belongs to the genus Paenibacillus, showing 98.4 and 96.08 % sequence similarity to the type strains Paenibacillus periandrae PM10T and Paenibacillus foliorum LMG 31456T, respectively. The G+C content of the genomic DNA of strain WQ127069T was 45.6 mol%. The predominant isoprenoid quinone was MK-7, and meso-diaminopimelic acid was present in peptidoglycan. The major cellular fatty acids were antiiso-C15 : 0, iso-C15 : 0 and C16 : 0. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylmonomethylethanolamine. The whole genome average nucleotide identity and digital DNA-DNA hybridization values between strain WQ 127069T and strain PM10T were 93.2 and 52.5 %, respectively. Growth occurred at 5-40 °C (optimally at 20-35 °C), pH 6-8 (optimally at pH7.0) and with 0.5-2 % (w/v) NaCl (optimally at 0.5 %). On the basis of the taxonomic evidence, a novel species, Paenibacillus baimaensis sp. nov., is proposed. The type strain is WQ 127069T (=KCTC 43480T=CCTCC AB 2022381T).

Advenella mandrilli sp. nov., a bacterium isolated from the faeces of Mandrillus sphinx.

A novel Gram-negative strain WQ 585T, isolated from the faeces of mandrills (Mandrillus sphinx) collected at Yunnan Wild Animal Park, Yunnan province, China, was subjected to a polyphasic taxonomic study. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate belongs to the genus Advenella, sharing 98.5% and 98.2% sequence similarity with the type strain Advenella alkanexedens LAM0050T and Advenella faeciporci M-07T, respectively. The predominant ubiquinone was Q-8. The major cellular fatty acids (> 10%) were C16:0, C17:0 cyclo and Summed Feature 2. The G + C content of the genomic DNA of strain WQ 585T was 49.0%. The whole genome average nucleotide identity (gANI) values of strain WQ 585T with strain A. alkanexedens LAM0050T and A. faeciporci M-07T were 86.7% and 86.7%, and the digital DNA-DNA hybridization values of strain WQ 585T with strain A. alkanexedens LAM0050T and A. faeciporci M-07T were 64.5% and 62.5%, respectively. Growth occurred at 10-45 °C (optimally at 20-30 °C), pH 6.0-9.0 (optimally at pH 7.0), and 0-5% (w/v) NaCl (optimally at 0.5-2.0%). On the basis of the taxonomic evidence, a novel species, Advenella mandrilli sp. nov., is proposed. The type strain is WQ 585T (= KCTC 82396 T = CCTCC AA 2020028 T).

Sphingobacterium bovistauri sp. nov., Isolated from the Faeces of Bos Taurus.

A novel bacterium designated WQ 366 T was isolated from the faeces of Bos taurus, foraging on the slopes of the Baima Snow Mountain in Yunnan, China. The isolate grew optimally at 30 â„ƒ and pH 7.0-8.0 without NaCl. The cells were Gram-stain-negative, aerobic, rod-shaped, non-gliding, catalase-positive, and produced yellow color colonies on Columbia Agar. A polyphasic study was applied to clarify its taxonomic position through 16S rRNA gene and genome sequence analysis, and other extensive biological typing. Phylogenetic analysis revealed that the isolate was affiliated to the genus Sphingobacterium and its 16S rRNA gene sequence was closely related to Sphingobacterium bovisgrunnientis YK2 T (97.3%), Sphingobacterium composti T5-12 T (96.4%), and Sphingobacterium cavernae 5.0403-2 T (96.4%). The calculated whole genome average nucleotide identity (ANI) and the digital DNA-DNA hybridization values between strain WQ 366 T and the three related strains were 78.3, 78.6, 73.9 and 21.2, 21.2, 21.0%, respectively. The predominant fatty acids (>10%) were iso-C15:0, iso-C17:0 3-OH, Summed Feature 3 (C16:1 ω7c and/or C16:1 ω6c), and Summed feature 9 (iso-C17:1 ω9c and 10-methyl C16:0). The main polar lipids were PE, GPL, GL, and PL. MK-7 was the major menaquinone. The genome size and the G + C content of WQ 366 T was 4.1 Mb and 34.6%, respectively. All these results indicated that strain WQ 366 T represents a novel species of the Sphingobacterium genus. Therefore, the name Sphingobacterium bovistauri sp. nov. is proposed, and the type strain is WQ 366 T (= CCTCC AA 2020029 T = KCTC 82395 T).

The plasma exosomal miR-1180-3p serves as a novel potential diagnostic marker for cutaneous melanoma.

BACKGROUND: Exosomes are a promising tool in disease detection because they are noninvasive, cost-effective, sensitive and stable in body fluids. MicroRNAs (miRNAs) are the main exosomal component and participate in tumor development. However, the exosomal miRNA profile among Asian melanoma patients remains unclear. METHODS: Exosomal miRNAs from the plasma of melanoma patients (n = 20) and healthy individuals (n = 20) were isolated and subjected to small RNA sequencing. Real-time PCR was performed to identify the differential miRNAs and to determine the diagnostic efficiency. Proliferation, scratch and Transwell assays were performed to detect the biological behavior of melanoma cells. RESULTS: Exosomal miRNA profiling revealed decreased miR-1180-3p expression as a potential diagnostic marker of melanoma. The validation group of melanoma patients (n = 28) and controls (n = 28) confirmed the diagnostic efficiency of miR-1180-3p. The level of miR-1180-3p in melanoma cells was lower than that in melanocytes. Accordingly, the level of miR-1180-3p was negatively associated with the proliferation, migration and invasion of melanoma cells. Functional analysis and target gene prediction found that ST3GAL4 was a potential target and highly expressed in melanoma tissues and was negatively regulated by miR-1180-3p. Knockdown of ST3GAL4 hindered the malignant phenotype of melanoma cells. CONCLUSIONS: This study indicates that reduced exosomal miR-1180-3p in melanoma patient plasma is a promising diagnostic marker and provides novel insight into melanoma development.

Sphingobacterium rhinopitheci sp. Nov., isolated from the faeces of Rhinopithecus bieti in China.

A novel bacterium, WQ 047T, was isolated from the faeces of Rhinopithecus bieti, a highly endangered primate endemic to China. The cells were aerobic, oval/rod-shaped, Gram-stain-negative, non-motile, catalase positive, and produced yellow pigmented colonies on Columbia Agar. The taxonomic position of WQ 047T was clarified by applying a polyphasic study based on 16S rRNA gene sequence phylogenetic analysis, extensive biological typing, and whole genome sequencing. Phylogenetic analysis indicated that stain WQ 047T belonged to the genus Sphingobacterium and its 16S rRNA gene sequence exhibited 96.47% pairwise similarity with that of the closest relatives Sphingobacterium nematocida M-SX103T. The calculated whole genome average nucleotide identity (ANI) value between strain WQ 047T and strain M-SX103 was 72.3%. The digital DNA-DNA hybridization value of strain WQ 047T and M-SX103T was 15.73%, which was obtained by calculating the genome-to-genome distance. The major fatty acids were C15:0 iso, C17:0 iso 3-OH, Summed Feature 3 (C16:1 ω7c/C16:1 ω6c) and Summed feature 9 (iso-C17:1ω9c and/or 10-methyl C16:0). The predominant polar lipids were PE, PL and APL. MK-7 was the predominant menaquinone. The G + C content of WQ 047T was 34.89 mol% according to genome analysis. All these characteristics were consistent with those of the genus of Sphingobacterium. Therefore, based on these results, we propose a novel species for which the name Sphingobacterium rhinopitheci sp. Nov. is proposed, with the type strain WQ 047T (= CCTCC AA 2020026T = KCTC82393T).

Faecalibacter rhinopitheci sp. nov., a bacterium isolated from the faeces of Rhinopithecus bieti.

A novel Gram-stain-negative strain, WQ 117T, isolated from the faeces of Rhinopithecus bieti collected at Yunnan Snub-nosed Monkey National Park, Yunnan province, PR China, was subjected to a polyphasic taxonomic study. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate represented a member of the genus Faecalibacter, sharing 97.64 % sequence similarity with the type strain Faecalibacter macacae YIM 102668T. The G+C content of the genomic DNA of WQ117T was 30.5 mol%. The predominant isoprenoid quinone was MK-6. The major cellular fatty acids was iso-C15 : 0. The whole genome average nucleotide identity (gANI) values and the digital DNA-DNA hybridization values between WQ 117T and YIM 102668T were 79.66 % and 22.20 %, respectively. Growth occurred at 0-50 °C (optimally at 28-35 °C), pH 7.0-9.0 (optimally at pH 8.0) and with 0-2 % (w/v) NaCl (optimally without NaCl). On the basis of the taxonomic evidence, a novel species, Faecalibacter rhinopitheci sp. nov., is proposed. The type strain is WQ 117T (=KCTC 82394T=CCTCC AA 2020027T).

Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring.

Maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to ANG II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks before mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis and paraventricular nucleus revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared with age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.

Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring.

Accumulating evidence indicates that maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that alter angiotensin II (ANG II) and TNF-α actions and sensitize the ANG II-elicited hypertensive response in adult offspring. All offspring were cross fostered by dams on the same or opposite diet to yield the following four groups: offspring from normal-fat control diet-fed dams suckled by control diet-fed dams (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group). RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAS components, NADPH oxidase, and proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring also showed decreased cardiac baroreflex sensitivity and increased pressor responses to intracerebroventricular microinjection of either ANG II or TNF-α. Furthermore, chronic systemic infusion of ANG II resulted in enhanced upregulation of mRNA expression of RAS components, NADPH oxidase, and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented hypertensive response in the OHC, OCH, and OHH groups compared with the OCC group. The results suggest that maternal HFD blunts cardiac baroreflex function and enhances pressor responses to ANG II or proinflammatory cytokines through upregulation of the brain RAS, oxidative stress, and inflammation. NEW & NOTEWORTHY The results of our study indicate that a maternal high-fat diet during either pregnancy or lactation is sufficient for perinatal programming of sensitization for hypertension, which is associated with hyperreactivity of central cardiovascular nuclei that, in all likelihood, involves elevated expression of the renin-angiotensin system, NADPH oxidase, and proinflammatory cytokines. The present study demonstrates, for the first time, the central mechanism underlying maternal high-fat diet sensitization of the hypertensive response in adult offspring.

Circ_0003575 knockdown alleviates ox-LDL-induced human aortic endothelial cell dysfunction in atherosclerosis by miR-637/TRAF6 axis.

BACKGROUND: Circular RNAs (circRNAs) are involved in the progression of atherosclerosis (AS). The present study aimed to determine the functions and mechanism of circ_0003575 in AS. METHODS: Oxidized low-density lipoprotein (ox-LDL) was used to induce human aortic endothelial cells (HAECs) to establish an AS cell model. Cell Counting Kit-8 (CCK-8) assay and 5'-ethynyl-2'-deoxyuridine (EdU) assay were conducted to assess cell proliferation. Flow cytometry analysis was utilized to quantify cell apoptosis. Tube formation assay was performed to analyze angiogenesis ability. Enzyme linked immunosorbent assay (ELISA) was used to examine the concentrations of inflammatory factors. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were manipulated for the expression of circ_0003575, microRNA-637 (miR-637) and TNF receptor associated factor 6 (TRAF6). Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were adopted to estimate the downstream targets of circ_0003575. RESULTS: Ox-LDL treatment repressed the proliferation and angiogenesis and promoted the apoptosis and inflammation in HAECs. Circ_0003575 knockdown ameliorated ox-LDL-induced injury of HAECs. Circ_0003575 interacted with mi-R-637, which directly targeted TRAF6. Inhibition of miR-637 reversed the impacts of circ_0003575 knockdown on HAEC injury. Moreover, miR-637 overexpression promoted cell proliferation and angiogenesis and inhibited cell apoptosis and inflammation by targeting TRAF6 in ox-LDL-treated HAECs. Further, circ_0003575 silencing inhibited the activation of NF-κB pathway. CONCLUSION: Circ_0003575 knockdown alleviated ox-LDL-induced HAEC damage by regulating miR-637/TRAF6 and NF-κB pathways.

Prognostic factors in young patients with ST-segment elevation myocardial infarction.

OBJECTIVE: The prognostic factors of young patients aged ≤40 years with ST-segment elevation myocardial infarction (STEMI) remain unclear. This study explored risk factors that may affect the 1-year prognosis of young STEMI patients by analyzing patient data of baseline, clinical regimen, and secondary prevention. METHODS: Baseline and clinical data were collected from 420 STEMI patients aged ≤40 years. One year of follow-up was performed to record and compare the differences in data between patients with and without adverse events. Binary logistic regression analysis with controls for confounding factors was used to evaluate prognosis-related independent factors. RESULTS: The overall incidence of cardiovascular adverse events was 15.95%. Comparison of the subgroups revealed that regardless of adjustment for confounding factors, prognoses of the patients were affected by the following factors: BMI, marital status, serum apolipoprotein(a) (ApoA) levels, number of diseased vessels, treatment regimen, compliance of secondary prevention, improvement of lifestyle, and adjusted comorbidities ( P  < 0.05). Independent analysis of adverse events revealed that BMI, number of diseased vessels, and compliance of secondary prevention were independent factors of recurrent acute myocardial infarction in patients. Serum ApoA level, treatment regimen, and compliance of secondary prevention were independent influence factors of heart failure in patients. Marital status and serum ApoA level were independent factors of malignant arrhythmias in patients. BMI, compliance of secondary prevention, and improvement of lifestyle were independent factors of cardiac death in patients. CONCLUSION: This study determined the influential factors for the prognosis of STEMI patients aged ≤40 years as follows: BMI, marital status, comorbidities, number of diseased vessels, regimen, compliance of secondary prevention, and improvement of lifestyle. The risk of cardiovascular adverse events may be reduced by modulating the influential factors.

Depletion of G9A attenuates imiquimod-induced psoriatic dermatitis via targeting EDAR-NF-κB signaling in keratinocyte.

Psoriasis is a common and recurrent inflammatory skin disease characterized by inflammatory cells infiltration of the dermis and excessive proliferation, reduced apoptosis, and abnormal keratosis of the epidermis. In this study, we found that G9A, an important methyltransferase that mainly mediates the mono-methylation (me1) and di-methylation (me2) of histone 3 lysine 9 (H3K9), is highly expressed in lesions of patients with psoriasis and imiquimod (IMQ)-induced psoriasis-like mouse model. Previous studies have shown that G9A is involved in the pathogenesis of various tumors by regulating apoptosis, proliferation, differentiation, and invasion. However, the role of G9A in skin inflammatory diseases such as psoriasis remains unclear. Our data so far suggest that topical administration of G9A inhibitor BIX01294 as well as keratinocyte-specific deletion of G9A greatly alleviated IMQ-induced psoriatic alterations in mice for the first time. Mechanistically, the loss function of G9A causes the downregulation of Ectodysplasin A receptor (EDAR), consequently inhibiting the activation of NF-κB pathway, resulting in impaired proliferation and increased apoptosis of keratinocytes, therefore ameliorating the psoriatic dermatitis induced by IMQ. In total, we show that inhibition of G9A improves psoriatic-like dermatitis mainly by regulating cell proliferation and apoptosis rather than inflammatory processes, and that this molecule may be considered as a potential therapeutic target for keratinocyte hyperproliferative diseases such as psoriasis.

Discovery of WD-890: A novel allosteric TYK2 inhibitor for the treatment of multiple autoimmune diseases.

Tyrosine kinase 2 (TYK2) as a member of Janus kinase (JAK) family, mainly mediates the signaling of type I interferons (IFN), interleukin-12 (IL-12) and interleukin-23 (IL-23), which has become an attractive target for treatment of immune and inflammatory diseases. However, the development of selective TYK2 inhibitors is challenging due to the high homology of the catalytic kinase domain among the JAK family members. Here, we report a novel and potent allosteric inhibitor, WD-890, which binds to the pseudokinase domain of TYK2 with high selectivity and inhibits its function. We accomplished a series of preclinical studies to demonstrate the therapeutic efficacy of WD-890 in four animal models: systemic lupus erythematosus (SLE), psoriasis, psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). The pharmacokinetic and toxicology results further indicate that WD-890 has favorable absorption, distribution, metabolism, and excretion (ADME) properties and tolerable toxicity. In conclusion, our study shows that WD-890 could be a promising oral TYK2 inhibitor for future treatment of autoimmune diseases.

Association of Serum Vitamin D With Psoriasis and Effect Modification by Central Obesity.

Background: Psoriasis is a chronic recurrent inflammatory disease involving many common mechanisms associated with obesity, such as systemic inflammation and vitamin D deficiency. This study aimed to examine the association of the serum concentration of 25-hydroxyvitamin D with psoriasis and the effect modification by obesity among the affected patients. Methods: A mixed cross-section study was conducted. We consecutively included untreated psoriasis patients from the outpatients who visited the Department of Dermatology of Xiangya Hospital and recruited 205 gender-matched healthy controls from the Hunan Civil Servant Cohort. In both groups, we measured the serum 25-hydroxyvitamin D level, body mass index (BMI), waist-hip-ratio (WHR) and other psoriasis-related clinical indicators. Results: A total of 203 psoriasis outpatients and 205 gender-matched cohort participants with complete data of serum vitamin D concentration were included in the analysis. The serum vitamin D levels of the two groups were close to each other, while the mean WHR of the psoriasis outpatients was significantly higher. Compared with the controls, the risk of psoriasis increased significantly when the vitamin D level decreased from 20 to 10 nmol/L. A significant interaction between the serum vitamin D level and the obesity category (BMI × WHR) was identified. After stratification by WHR, vitamin D was not associated with psoriasis in subjects with normal WHR. In contrast, the association between vitamin D deficiency and psoriasis retained and the effect size augmented in patients with central obesity. Conclusions: WHR may modify the association between serum vitamin D and psoriasis. Treatment advocating Vitamin D supplements may tailor to psoriasis patients with metabolic disorders.

Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat.

Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD.