Emerging resistance to currently used antibiotics is a global public health crisis. Because most of the biosynthetic capacity within bacterial kingdom has remained silent in previous antibiotic discovery efforts, uncharacterized gene clusters found genome–sequencing studies remain an appealing source with distinctive modes action. Here, we report naturally inspired lipopeptide called cilagicin, which chemically synthesized on basis detailed bioinformatic analysis cil cluster. Cilagicin’s...

The global spread of multidrug-resistant pathogenic fungi presents a serious threat to human health, necessitating the discovery antifungals with unique modes action1. However, conventional activity-based screening for previously undescribed antibiotics has been hampered by high-frequency rediscovery known compounds and lack new antifungal targets2. Here we report polyene antibiotic, mandimycin, using phylogeny-guided natural-product platform. Mandimycin is biosynthesized mand gene cluster,...

Infertility is a common complication in diabetic men, mainly due to the loss of germ cells by apoptotic cell death. However, effective and safe approaches prevent induction testicular apoptosis for patients have not been available. Resveratrol (RSV), group compounds called polyphenols from plants, has indicated its promising used clinically cancers cardiovascular diseases. Therefore, present study aimed determining whether RSV attenuates type 1 diabetes (T1D)-induced death mouse model. We...

Bacterial genomes contain large reservoirs of biosynthetic gene clusters (BGCs) that are predicted to encode unexplored natural products. Heterologous expression previously unstudied BGCs should facilitate the discovery additional therapeutically relevant bioactive molecules from bacterial culture collections, but large-scale manipulation remains cumbersome. Here, we describe a method parallelize identification, mobilization and heterologous BGCs. Our solution simultaneously captures numbers...

The rapid emergence of difficult-to-treat multidrug-resistant pathogens, combined with the scarcity antibiotics possessing novel mechanisms, poses a significant threat to global public health. Here, we integrated synthetic-bioinformatic natural product approach peptide optimization unveil antibiotic-producing potential Paenibacillaceae bacteria. Our culture-independent led discovery paenimycin, 11-mer depsi-lipopeptide featuring an unprecedented dual-binding mechanism. By sequestering...

In natural product discovery programs, the power of synthetic chemistry is often leveraged for total synthesis and diversification characterized metabolites. The structures that are bioinformatically predicted to arise from uncharacterized biosynthetic gene clusters (BGCs) provides a means enter this process at an early stage. recent identification non-ribosomal peptides (NRPs) containing multiple ρ-aminobenzoic acids (PABAs) led us search soil metagenomes BGCs polymerize PABA. Here, we use...

// Shuzhen Wang 1,* , Weiquan Xie Duowei 2,* Zhigang Peng Yan Zheng 2 Nan Liu 1 Wen Dai Yang Zongqiang Yong Yijun Chen State Key Laboratory of Natural Medicines and Chemical Biology, China Pharmaceutical University, Nanjing, Institute Science, * These authors contributed equally to this work Correspondence to: Chen, email: Yang, Keywords : chronic myeloid leukemia, BCR-ABL, T315I mutation, SET, protein phosphatase 2A Received February 06, 2015 Accepted March 02, Published 26, Abstract...

We identified distinct secondary-metabolite-encoding genes that are enriched (relative to adjacent bulk soil) and expressed in root ecosystems yet almost completely absent human gut aquatic environments. Several of the were distantly related encoding antimicrobials siderophores, their high sequence variability relative known sequences suggests they may encode novel metabolites have unique ecological functions.

Abstract DNA topoisomerases are attractive targets for anticancer agents. Dual topoisomerase I/II inhibitors particularly appealing due to their reduced rates of resistance. A number therapeutically relevant bacterial natural products. Mining the untapped chemical diversity encoded by soil microbiomes presents an opportunity identify additional inhibitors. Here we couple metagenome mining, bioinformatic structure prediction algorithms, and synthesis produce dual inhibitor tapcin. Tapcin is a...

Cis‑diammine‑dichloro‑platinum II‑based adjuvant chemotherapy provides an alternative therapy to improve the survival of patients with lung tumors, especially those non‑small cell cancer (NSCLC). However, drug resistance is a large clinical problem and its underlying mechanism remains unclear. In present study, NSCLC A549 cells were treated low concentration cisplatin in order observe determine development chemoresistance, via growth curves, colony forming assays apoptosis assays. Then...

Natural products are a major source of new antibiotics. Here we utilize biosynthetic instructions contained within metagenome-derived congener gene clusters (BGCs) to guide the synthesis improved antibiotic analogues. Albicidin and cystobactamid first members class broad-spectrum ρ-aminobenzoic acid (PABA)-based Our search for PABA-specific adenylation domain sequences in soil metagenomes revealed that BGCs this family common nature. Twelve were bio-informatically predicted encode six...

Cationic nonribosomal lipopeptides (CNRLPs) from Paenibacillus spp. have been a rewarding source of Gram-negative-active antibiotics. Here we systematically screened sequenced bacterial genomes for CNRLP biosynthetic gene clusters (BGCs) that predicted might encode additional Total chemical synthesis the bioinformatically products seven such BGCs led to our identification new laterocidine, tridecaptin, and paenibacterin-like antibiotics with potent activity against both...

Abstract Total knee arthroplasty (TKA) is the most common and cost-effective treatment for older adults with long-standing osteoarthritis. During TKA, muscle cells suffer from prolonged oxygen deficiency, which leads to altered cell metabolism that reduces energy demand maintains homeostasis before blood flow restored. This study focused on role of lncRNA muscleblind-like 1 antisense RNA (MBNL1-AS1) in protecting sevoflurane-pretreated mice against ischemia-reperfusion (I/R) injury after as...

Abstract Background Rheumatoid arthritis (RA), a chronic autoimmune disease, affects around 1% population worldwide, with the life quality of patients severely reduced. In this study, it is intended to explore role long non‐coding RNA X‐inactive specific transcript (lncRNA XIST) in RA and underlying mechanisms associated let‐7c‐5p signal transducer activator transcription 3 (STAT3). Methods LncRNA XIST, let‐7c‐5p, STAT3 expressions were determined normal cartilage tissues, their relationship...

A novel thiol fluorophore was synthesized to be selectively attached the non-reducing end of low molecular weight heparin (LMWH) via a Michael addition. Double labeling LMWH demonstrated feasible approach for determination heparinase II activity by FRET.

Cilagicin is a Gram-positive active antibiotic that has dual polyprenyl phosphate binding mechanism impedes resistance development. Here we bioinformatically screened predicted non-ribosomal polypeptide synthetase encoded structures to search for antibiotics might similarly avoid Synthesis and bioactivity screening of the identified led three are against multidrug-resistant pathogens, two which, paenilagicin virgilagicin, did not lead even after prolonged exposure.

Oxidative stress-induced mitochondrial function and cell apoptosis to osteoblasts, plays a critical role in the pathophysiology of osteoporosis. However, mechanisms underlying such process remain not yet clear. We aims this study investigate possible SMAD (the mothers against decapentaplegic homolog 4 (SMAD4) oxidative apoptosis, homo sapiens osteoblast hFOB1.19 cells. Results demonstrated that treatment with more than 100 μM H2O2 significantly downregulated cellular viability, whereas...

Abstract Glycosaminoglycans (GAG) lyases are useful biocatalysts for the preparation of oligosaccharides, but their substrate spectra limited to same family. Thus, degradation activity across families GAG is advantageous and desirable various applications. In this study, residue Lys130 at entrance monomeric heparinase III from Pedobacter heparinus ATCC 13125 was replaced by cysteine, resulting mutant K130C showed novel catalytic in degrading hyaluronic acid without affecting its native...

The present study aimed to investigate the diagnostic and prognostic values of contrast‑enhanced ultrasound (CEUS) combined with diffusion‑weighted magnetic resonance imaging (DW‑MRI) in different subtypes breast cancer (BC). CEUS DW‑MRI were conducted 232 patients BC prior surgical treatment. Patients categorized as having luminal A subtype, B triple‑negative subtype or human epidermal growth factor receptor 2 (Her‑2)‑positive according their expression estrogen (ER), progesterone (PR)...