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The aim of this work is to explore the effects of herbal medicine on secondary metabolites of microorganisms during fermentation. Clonostachys rogersoniana was found to metabolize only small amounts of polyketide glycosides rogerson B and C on fresh potatoes, but after replacing the medium to the medicinal plant Rubus delavayi Franch., the type and content of the metabolized polyketones showed significant changes. The sugars and glycosides in R. delavayi are probably responsible for the changes in secondary metabolites. Six polyketide glycosides including a new metabolite, rogerson F, and two potential antitumor compounds, TMC-151C and TMC-151D, were isolated from the extract of R. delavayi fermented by C. rogersoniana. In addition, 13 C labeling experiments were used to trace the biosynthesis process of these compounds. TMC-151C and TMC-151D showed significant cytotoxic activity against PANC-1, K562 and HCT116 cancer cells but had no obvious cytotoxic activity against BEAS-2B human normal lung epithelial cells. The yields of TMC-151C and TMC-151D reached 14.37 ± 1.52 g/kg and 1.98 ± 0.43 g/kg, respectively, after fermentation at 28 °C for 30 days. This is the first study to confirm that herbal medicine can induce microbes to metabolize active compounds. And the technology of fermenting medicinal materials can bring more economic value to medicinal plants., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The fungus Nectria sp. MHHJ-3 was isolated from Illigera rhodantha. A molecular networking-guided the secondary metabolites investigation of Nectria sp. MHHJ-3 led to the isolation of ten metabolites (1-10), including two new naphthalenone derivatives, nectrianaphthalenones A (1) and B (2), and two new steroids, nectriasteroids A (3) and B (4). Their structures were elucidated by extensive spectroscopic analysis including the HRESIMS, 1D/2D NMR and electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for 1-2 was proposed. Compounds 1 and 2 exhibited moderate acetylcholinesterase (AChE) inhibitory activities. Compounds 3 and 4 showed significant cytotoxic activity against selected tumor cells. Particularly, compound 3 exhibited the strongest activity against A549 cells with an IC 50 value of 13.73 ± 0.03 μM, which was at the same grade with that of positive control cisplatin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abnormal crosstalk between gut immune and the liver was involved in nonalcoholic steatohepatitis (NASH). Mice with methionine choline-deficient (MCD) diet-induced NASH presented an imbalance of pro-(IL-6 and IFN-γ) and anti-inflammatory cytokines (IL-10) in the intestine. We also clarified that the ratio of CD4 + T cells and found that the NASH mesenteric lymph node (MLN) presents decreased numbers of CD4 + Th17 cells but increased numbers of CD4 + CD8 + FoxP3 + regulatory T cells (Tregs). Furthermore, the intestinal immune imbalance in NASH was attributed to impaired gut chemokine receptor 9 (CCR9)/chemokine ligand 25 (CCL25) signalling, which is a crucial pathway for immune cell homing in the gut. We also demonstrated that CD4 + CCR9 + T cell homing was dependent on CCL25 and that the numbers and migration abilities of CD4 + CCR9 + T cells were reduced in NASH. Interestingly, the analysis of dendritic cell (DC) subsets showed that the numbers and retinal dehydrogenase (RALDH) activity of CD103 + CD11b + DCs were decreased and that the ability of these cells to upregulate CD4 + T cell CCR9 expression was damaged in NASH. Taken together, impaired intestinal CCR9/CCL25 signalling induced by CD103 + CD11b + DC dysfunction contributes to the gut immune imbalance observed in NASH., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Volatile organic compounds (VOCs) are extremely harmful to the human body and environment, thus it is greatly meaningful and urgent to detect VOCs. In this work, terbium-based metal-organic frameworks (Tb-MOFs) have been prepared successfully via a facile and efficient route. These well-constructed Tb-MOFs architectures exhibit characteristic green emission of Tb 3+ ion upon excitation of UV light. It is noteworthy that the Tb-MOFs can act as a convenient and efficient luminescent sensor for VOCs. Especially, the Tb-MOFs displayed high selectivity and superior sensitivity towards the sensing of styrene solution and vapor through fluorescence quenching mechanism. The Tb-MOFs can realize fast detection for styrene vapor with a response time of 30 s. The mechanism of fluorescence quenching of Tb-MOFs induced by styrene was also discussed. More importantly, we have designed a logic gate operation with the combination of the sensor for the intelligent detection of styrene. This developed type of lanthanide luminescent metal-organic frameworks (Ln-MOFs) based on the combination of fluorescence sensor and logic gate has a great application prospect in the detection of VOCs in daily life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality worldwide. Early growth response factor 1 (Egr1) plays a crucial role in cancer progression. However, its precise role in HCC has not been clear. Here, we identified the aggravating role of Egr1 in cell proliferation of HCC firstly. The expression of Egr1 was significantly increased in HCC tissues. Functionally, overexpression of Egr1 enhanced, whereas silenced Egr1 expression attenuated HCC cells proliferation in vitro. Mechanistically, up-regulated Egr1 induced cell proliferation through activating Transforming growth factor (TGF)-β1/Smad signaling pathway concomitantly with upregulation of p-Smad2 and p-Smad3. Secondly, miR-181a-5p was down-regulated in clinical HCC specimens and its expression was inversely correlated with Egr1 expression. Functionally, overexpression of miR-181a-5p inhibited, whereas decreased expression of miR-181a-5p promoted HCC cells proliferation in vitro. Furthermore, we demonstrated that miR-181a-5p overexpression directly suppressed Egr1, resulting in a down-regulated TGF-β1/Smad pathway. Besides, the silenced Egr1 expression could rescue the enhanced cell proliferation induced by miR-181a-5p inhibitor. Thus, we concluded that miR-181a-5p is a negative regulator of Egr1 that can suppress tumor proliferation in HCC through targeting Egr1/TGF-β1/Smad pathway, which may be a potential therapeutic approach of HCC., (Copyright © 2018. Published by Elsevier Ltd.)

Peroxisome proliferator-activated receptor gamma (PPARγ) participates in the process of insulin resistance (IR), a crucial pathophysiology in non-alcoholic fatty liver disease (NAFLD). Meanwhile, suppressor of cytokine signaling3 (SOCS3) also regulates IR in NAFLD. Both PPARγ and SOCS3 play a role in NAFLD through regulating IR, while it is unclear whether these two proteins interact to regulate hepatic steatosis. PPARγ, SOCS3 and its associated JAK2/STAT3 pathway were analyzed using Kuppfer cells (KCs) treatment with LPS and BRL-3A cells treatment with palmitic acid, KC-conditioned medium (KCCM), PPARγ agonist rosiglitazone (ROZ) or JAK2 inhibitor AG490 to demonstrate the role of PPARγ and SOCS3 in hepatocytes steatosis. As LPS concentration increasing, phagocytosis activity of KCs decreased; but releasing of TNF-α and IL-6 increased. After treatment with KCCM, mRNA level of SOCS3, JAK2 and STAT3 as well as protein expression of SOCS3, p-JAK2 and p-STAT3 in steatosis BRL-3A cells increased significantly, which were inhibited by AG490 or ROZ treatment. Taken together, these results indicated that KCCM attributed to KCs dysfunction facilitated hepatocyte steatosis through promoting expressing SOCS3; but PPARγ agonist ROZ alleviated steatosis through reducing SOCS3 expression by inhibiting JAK2/STAT3 in hepatocytes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neurological complications have rarely been described after blood transfusion. Posterior reversible encephalopathy syndrome (PRES) is a recently recognized entity affecting predominantly the posterior cerebral hemispheres. We report two distinctive cases with history of chronic anemia that developed headache, blurred vision and seizure after blood transfusion. Magnetic resonance imaging indicated vasogenic edema consistent with PRES., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Oxytocin (OXT), a nonapeptide hormone of posterior pituitary, reaches the central nervous system from systemic blood circulation with a difficulty because of the blood-brain barrier (BBB). The interest has been expressed in the use of the nasal route for delivery of OXT to the brain directly, exploiting the olfactory pathway. Our previous study has demonstrated that OXT in the central nervous system rather than the blood circulation plays an important role in rat pain modulation. The communication tried to investigate the interaction between the OXT and pain modulation in Chinese patients with headache to understand the OXT effect on human pain modulation. The results showed that (1) intranasal OXT could relieve the human headache in a dose-dependent manner; (2) OXT concentration in both plasma and cerebrospinal fluid (CSF) increased significantly in headache patients in relation with the pain level; and (3) there was a positive relationship between plasma and CSF OXT concentration in headache patients. The data suggested that intranasal OXT, which was delivered to the central nervous system through olfactory region, could treat human headache and OXT might be a potential drug of headache relief by intranasal administration., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Cardiac triacylglycerol (TAG) stores buffer the intracellular availability of long chain fatty acid (LCFA) that act as nuclear receptor ligands, substrate for lipotoxic derivatives, and high energy-yield fuel. The kinetic characteristics of TAG turnover and homeostatic mechanisms linking uptake and storage dynamics in hearts have until now remained elusive. This work examines TAG pool dynamics in the intact beating heart, under normal conditions and in response to acute gene expression-induced changes in CD36. Dynamic mode (13)C NMR elucidated multiple kinetic processes in (13)C-palmitate incorporation into TAG: an initial, saturable exponential component and a slower linear rate. Although previous work indicates the linear component to reflect TAG turnover, we hypothesized the saturable exponential to reflect transport of LCFA across the sarcolemma. Thus, we overexpressed the LCFA transporter CD36 through cardiac-specific adenoviral infection in vivo. Within 72 h, CD36 expression was increased 40% in intact hearts, accelerating the exponential phase relative to PBS-infused hearts. TAG turnover also increased with elevations in adipose triglyceride lipase (ATGL) and a modest increase in diacylglycerol acyltransferase 1 (DGAT1), without a significant expansion of the intracellular lipid pools. The results demonstrate a dynamic system of reciprocal gene regulation that couples saturable LCFA uptake across the sarcolemma to TAG synthesis/lipolysis rates.

Vascular endothelial growth factor (VEGF) was investigated in the present study to see whether it could provide a therapeutic opportunity for the treatment of Alzheimer's disease (AD). PDGF-hAPP(V717I) transgenic mice were treated with VEGF or PBS by intraperitoneal injection for three consecutive days. The results showed that VEGF ameliorated the memory impairment of mice, accompanied by CD34(+) cells increasing in peripheral blood, vWF(+) vessels increasing in hippocampus, and CD34(+)/VEGFR2(+), vWF(+)/VEGFR2(+) and BrdU(+)/vWF(+) cells expressing in hippocampus. Furthermore, the level of choline acetyltransferase (ChAT) was considerably enhanced and Aβ deposition was decreased in the brains of mice upon VEGF treatment. These observations suggest that VEGF should be pursued as a novel therapeutic agent for treatment of AD., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the expression of Livin in bladder cancer, investigate its clinical and prognostic implications, and explore the effect of gene Livin transfection on the proliferation and apoptosis in bladder cancer cells., Methods: The expression of Livinalpha and beta was detected in 48 bladder cancer samples (G(1) in 23 cases, G(2) in 17 cases, and G(3) in 8 cases. Of the 48 cases, 17 developed relapse) and 15 non-tumor bladder tissues by Western blot and reverse transcription PCR (RT-PCR). Livinalpha-pcDNA3.1(+) was constructed and transfected into T24, BIU-87 and EJ bladder cancer cells. The clone activity of the transfected cells was detected by colony formation analysis. MTT was used to determine the cell proliferation assay. Flow cytometry and acridine orange staining were used to examine apoptosis. Caspase 3 activity assay was also measured., Results: Expression of Livinalpha, but not beta, was detected in 19 of the 48 bladder cancer samples; G(1) was 39.13%, G(2) and G(3) were 41.18% and 37.50%, respectively, which showed no significant (P > 0.05), but not in 15 non-tumor bladder tissues. The positive rate of Livinalpha was significant higher in relapse tumors (58.82%) than in primary tumors (29.03%) (P < 0.05). By the end of 2 years follow-up, the relapse rate in Livin positive patients was 68.42%, and 37.93% in Livin negative group. The difference between the two groups was significant (P < 0.05). Additionally, overexpression of Livinalpha clearly stimulated cell proliferation and inhibited chemical induced apoptosis in bladder cancer cells., Conclusions: Livin may serve as a promising marker to identify the relapse risk in bladder cancer, and targeting Livin could offer a therapeutic benefit in apoptosis-inducing treatment.

Background: Atrial fibrillation (AF) with poorly controlled ventricular response is known to be detrimental to ventricular function, conversely, heart failure (HF) increases susceptibility to AF., Objective: This study sought to examine the electropathological effects of 3 months of atrial fibrillation (AF) in dogs with and without concomitant ventricular dysfunction., Methods: Three groups of dogs were studied: dogs with chronic AF induced by rapid pacing and concomitant ventricular dysfunction induced by rapid ventricular response with intact atrioventricular node (AVN), dogs with ablated AVN and AF while the ventricle was paced at 80 beats/min, and normal sham dogs. After 3 months of AF, the first 2 groups underwent direct current cardioversion (DCCV) to normal sinus rhythm and were monitored for 3 months, followed by retesting of AF susceptibility. Tissue fibrosis was assessed at various sites by trichrome staining and quantitative immunohistochemistry., Results: AF was induced within 12 +/- 4 days and 30 +/- 13 days, respectively, in the intact and ablated AVN groups (P <.01). After 3 months of AF, left ventricular ejection fraction was 30.4% +/- 10.1% and 55% +/- 5% in the intact and ablated AVN groups (P <.01), respectively. After 3 months of normal sinus rhythm, AF was reinduced after 4 +/- 2 and 7.2 +/- 2 days, respectively (P = NS). There were no regional differences and an abundance of fibrosis within atria. Atrial fibrosis was significantly increased in intact AVN versus ablated AVN and sham groups, and also was greater in AVN-ablated versus sham dogs. Ventricular fibrosis was increased in intact AVN versus ablated AVN and sham groups and was not significantly different in ablated AVN and sham groups., Conclusion: AF without ventricular dysfunction results in atrial fibrosis and increased susceptibility to AF, suggesting that AF alone causes atrial fibrosis. AF with rapid ventricular response further increases atrial and ventricular fibrosis. Conversion to normal sinus rhythm should be done as early as possible to avoid atrial and ventricular fibrosis and increased susceptibility to AF.