Defective branched-chain amino acid catabolism in dorsal root ganglia contributes to mechanical pain.

Impaired branched-chain amino acid (BCAA) catabolism has recently been implicated in the development of mechanical pain, but the underlying molecular mechanisms are unclear. Here, we report that defective BCAA catabolism in dorsal root ganglion (DRG) neurons sensitizes mice to mechanical pain by increasing lactate production and expression of the mechanotransduction channel Piezo2. In high-fat diet-fed obese mice, we observed the downregulation of PP2Cm, a key regulator of the BCAA catabolic pathway, in DRG neurons. Mice with conditional knockout of PP2Cm in DRG neurons exhibit mechanical allodynia under normal or SNI-induced neuropathic injury conditions. Furthermore, the VAS scores in the plasma of patients with peripheral neuropathic pain are positively correlated with BCAA contents. Mechanistically, defective BCAA catabolism in DRG neurons promotes lactate production through glycolysis, which increases H3K18la modification and drives Piezo2 expression. Inhibition of lactate production or Piezo2 silencing attenuates the pain phenotype of knockout mice in response to mechanical stimuli. Therefore, our study demonstrates a causal role of defective BCAA catabolism in mechanical pain by enhancing metabolite-mediated epigenetic regulation.

Green synthesis of silver nanoparticles using Phlebopus portentosus polysaccharide and their antioxidant, antidiabetic, anticancer, and antimicrobial activities.

Silver nanoparticles (AgNPs) by green synthesis from fungi polysaccharides are attracting increasing attention owing to their distinctive features and special applications in numerous fields. In this study, a cost-effective and environmentally friendly biosynthesizing AgNPs method with no toxic chemicals involved from the fruiting body polysaccharide of Phlebopus portentosus (PPP) was established and optimized by single factor experiment and response surface methodology. The optimum synthesis conditions of polysaccharide-AgNPs (PPP-AgNPs) were identified to be the reaction time of 140 min, reaction temperature of 94 °C, and the PPP: AgNO3 ratio of 1:11.5. Formation of PPP-AgNPs was indicated by visual detection of colour change from yellowish to yellowish brown. PPP-AgNPs were characterized by different methods and further evaluated for biological activities. That the Ultraviolet-visible (UV-Vis.) spectroscopy displayed a sharp absorption peak at 420 nm confirmed the formation of AgNPs. Fourier transform infrared (FTIR) analysis detected the presence of various functional groups. The lattice indices of (111), (200), (220), and (331), which indicated a faced-centered-cubic of the Ag crystal structure of PPP-AgNPs, was confirmed by X-ray diffraction (XRD) and the particles were found to be spherical through high resolution transmission electron microscopy (HRTEM). Energy dispersive X-ray spectroscopy (EDS) determined the presence of silver in PPP-AgNPs. The percentage relative composition of elements was determined as silver (Ag) 82.5 % and oxygen (O) 17.5 % for PPP-AgNPs, and did not exhibit any nitrogen peaks. The specific surface area of PPP-AgNPs was calculated to be 0.5750 m2/g with an average pore size of 24.33 nm by BET analysis. The zeta potential was -4.32 mV, which confirmed the stability and an average particle size of 64.5 nm was calculated through dynamic light scattering (DLS). PPP-AgNPs exhibited significant free radical scavenging activity against DPPH with an IC50 value of 0.1082 mg/mL. The MIC values of PPP-AgNPs for E. coli, S. aureus, C. albicans, C. glabrata, and C. parapsilosis are 0.05 mg/mL. The IC50 value of the inhibition of PPP-AgNPs against α-glucosidase was 11.1 µg/mL, while the IC50 values of PPP-AgNPs against HepG2 and MDA-MB-231 cell lines were calculated to be 14.36 ± 0.43 µg/mL and 40.05 ± 2.71 µg/mL, respectively. According to the evaluation, it can be concluded that these green-synthesized and eco-friendly PPP-AgNPs are helpful to improve therapeutics because of significant antioxidant, antimicrobial, antidiabetic, and anticancer properties to provide new possibilities for clinic applications.

Circulating metabolic signatures of heart failure in precision cardiology.

Precision cardiology aims to implement personalized health care and precise medical decisions based on the specific characteristics of individuals. Metabolic remodeling plays a causal role in the pathogenesis of heart failure (HF). Changes in metabolic pathways such as substrate preference, high-energy phosphate metabolism and amino acid metabolism, are involved in pathological structural remodeling and functional impairment. These metabolic alterations are usually not restricted in the cardiac tissue, but also manifest in circulation. In clinical practice, blood sample is routinely used for HF screening. Metabolomics is an emerging omics technology that provides an efficient way to acquire dynamic metabolic profiles in circulation. An increasing number of metabolic biomarkers have been implicated in disease progression, making it possible to fight HF in a more effective and precise way. This review summarizes the modern analytical techniques in metabolomics as well as emerging circulating metabolites during the pathogenesis of HF, aiming to provide new insights into the prevention, diagnosis and treatment of HF in the era of precision medicine.

Obesity by High-Fat Diet Increases Pain Sensitivity by Reprogramming Branched-Chain Amino Acid Catabolism in Dorsal Root Ganglia.

Obesity is a significant health concern as a result of poor-quality diet, for example, high-fat diet (HFD). Although multiple biological and molecular changes have been identified to contribute to HFD-induced pain susceptibility, the mechanisms are not fully understood. Here, we show that mice under 8 weeks of HFD were sensitive to mechanical and thermal stimuli, which was coupled with an accumulation of branched-chain amino acids (BCAAs) in lumbar dorsal root ganglia (DRG) due to local BCAA catabolism deficiency. This HFD-induced hyperalgesic phenotype could be exacerbated by supply of excessive BCAAs or mitigated by promotion of BCAA catabolism via BT2 treatment. In addition, our results suggested that HFD-related pain hypersensitivity was associated with a pro-inflammatory status in DRG, which could be regulated by BCAA abundance. Therefore, our study demonstrates that defective BCAA catabolism in DRG facilitates HFD-induced pain hypersensitivity by triggering inflammation. These findings not only reveal metabolic underpinnings for the pathogenesis of HFD-related hyperalgesia but also offer potential targets for developing diet-based therapy of chronic pain.

Preparation, structural characterisation, and antioxidant activities of polysaccharides from eight boletes (Boletales) in tropical China.

Polysaccharides in boletes (Boletales) are economically significant to both function food and medicinal industries. The polysaccharides were extracted from the fruit bodies of eight boletes, namely, Aureoboletus longicollis, Butyriboletus hainanensis, Crocinoboletus rufoaureus, Hemioporus japonicus, Neoboletus infuscatus, Neoboletus obscureumbrinus, Tylopilus otsuensis, Xanthoconium fusciceps, which were collected from tropical China; their physicochemical properties and antioxidant activities were characterised and evaluated, respectively. The results revealed that the polysaccharides among the eight boletes were mainly composed of glucose, mannose, and galactose, with a broad molecular weight range, and contained a pyranose ring revealed by FT-IR and NMR spectral analyses. Many factors such as different species of boletes, geographic conditions, molecular weight, configuration, and monosaccharide content may affect the antioxidant power of polysaccharides, simultaneously, instead of one single factor. The antioxidant activities of the polysaccharides were measured according to in vitro assays of DPPH scavenging, superoxide anion scavenging, and ferrous ion reducing tests. The polysaccharide of C. rufoaureus has greatly superior antioxidant activity and it could serve as potential functional food or medicine.

Neoboletus infuscatus, a new tropical bolete from Hainan, southern China.

Neoboletus infuscatus (Boletaceae, Boletales) is described as a new species from Yinggeling of Hainan Tropical Rainforest National Park, southern China. It is morphologically characterized by a large basidioma with a nearly glabrous, brownish yellow, yellowish brown to pale brown pileus, pores orangish red when young, yellowish brown to brown when old, context and hymenophore staining blue when injured, a yellow stipe with red punctuations, surfaces of the pileus and the stipe usually covered with a thin layer of white pruina when young. Phylogenetic analyses of DNA sequences from part of the 28S gene, the nuclear rDNA internal transcribed spacer (ITS) region, and part of the translation elongation factor 1-α gene (TEF1) also confirm that N. infuscatus forms an independent lineage within Neoboletus. Detailed morphological description, color photos of fresh basidiomata and line-drawings of microstructures are provided.