Genome mining and biosynthetic pathways of marine-derived fungal bioactive natural products.

Marine fungal natural products (MFNPs) are a vital source of pharmaceuticals, primarily synthesized by relevant biosynthetic gene clusters (BGCs). However, many of these BGCs remain silent under standard laboratory culture conditions, delaying the development of novel drugs from MFNPs to some extent. This review highlights recent efforts in genome mining and biosynthetic pathways of bioactive natural products from marine fungi, focusing on methods such as bioinformatics analysis, gene knockout, and heterologous expression to identify relevant BGCs and elucidate the biosynthetic pathways and enzyme functions of MFNPs.

Diffusion-enhanced characterization of 3D chromatin structure reveals its linkage to gene regulatory networks and the interactome.

The interactome networks at the DNA, RNA, and protein levels are crucial for cellular functions, and the diverse variations of these networks are heavily involved in the establishment of different cell states. We have developed a diffusion-based method, Hi-C to geometry (CG), to obtain reliable geometric information on the chromatin from Hi-C data. CG produces a consistent and reproducible framework for the 3D genomic structure and provides a reliable and quantitative understanding of the alterations of genomic structures under different cellular conditions.

Characterization of network hierarchy reflects cell state specificity in genome organization.

Dynamic chromatin structure acts as the regulator of transcription program in crucial processes including cancer and cell development, but a unified framework for characterizing chromatin structural evolution remains to be established. Here, we performed graph inferences on Hi-C data sets and derived the chromatin contact networks. We discovered significant decreases in information transmission efficiencies in chromatin of colorectal cancer (CRC) and T-cell acute lymphoblastic leukemia (T-ALL) compared to corresponding normal controls through graph statistics.

Multi-scale gene regulation mechanism: Spatiotemporal transmission of genetic information.

Gene expression is regulated by many factors, including transcription factors, chromatin three-dimensional topology, modifications of DNA and histone proteins, and non-coding RNAs. The execution of these complex mechanisms requires an effectively coordinated regulation system. In this review, we emphasize that the multi-scale heterogeneous DNA sequence plays a fundamental and important role for gene expression activity and usage of different means of epigenetic regulation.

Expression regulation of genes is linked to their CpG density distributions around transcription start sites.

The CpG dinucleotide and its methylation behaviors play vital roles in gene regulation. Previous studies have divided genes into several categories based on the CpG intensity around transcription starting sites and found that housekeeping genes tend to possess high CpG density, whereas tissue-specific genes are generally characterized by low CpG density. In this study, we investigated how the CpG density distribution of a gene affects its transcription and regulation pattern.

[Effect of polycystin2 on differentiation and maturation of osteoblasts promoted by low-frequency pulsed electromagnetic fields].

It is known that low-frequency pulsed electromagnetic fields (PEMFs) can promote the differentiation and maturation of rat calvarial osteoblasts (ROBs) cultured . However, the mechanism that how ROBs perceive the physical signals of PEMFs and initiate osteogenic differentiation remains unknown. In this study, we investigated the relationship between the promotion of osteogenic differentiation of ROBs by 0.

Hierarchical dinucleotide distribution in genome along evolution and its effect on chromatin packing.

Dinucleotide densities and their distribution patterns vary significantly among species. Previous studies revealed that CpG is susceptible to methylation, enriched at topologically associating domain boundaries and its distribution along the genome correlates with chromatin compartmentalization. However, the multi-scale organizations of CpG in the linear genome, their role in chromatin organization, and how they change along the evolution are only partially understood.

Highly hemocompatible zwitterionic micelles stabilized by reversible cross-linkage for anti-cancer drug delivery.

Both blood stability and intelligent-responsiveness after reaching the drug-targeting site are very important features to make desirable nano-drug vehicles (NDVs). Here, a highly nonfouling cross-linked micelle based on a copolymer composed of carboxybetaine methacrylate (CBMA) as hydrophilic segment and 2-(methacryloyloxy)ethyl lipoate (MAEL) as hydrophobic and cross-linked segment is reported. Furthermore, a simple method to evaluate the hemocompatibility of NDVs through examining the activation of a blood-clotting protein (fibrinogen) was introduced.

[Tissue distribution of 1,3-diphenyl-1,3-propanedione in mice].

Objective: To investigate tissue distribution characteristics of 1,3-diphenyl-1,3-propanedione (DPPD) in mice.

Methods: Male ICR mice were dosed with DPPD 500 mg/kg via oral gavage, and the tissue samples of the heart, liver, spleen, lungs, kidneys and muscle of each mouse were collected as scheduled. At each time point, the concentrations of DPPD in the mouse tissues were measured by high performance liquid chromatography (HPLC) method.

Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice.

Aim: To investigate the hepatic protective effects of 5-methoxypsoralen (5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.

Methods: C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5, 25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen (APAP) subcutaneously at a dose of 500 mg/kg.

Protective effects of 2,4-dihydroxybenzophenone against acetaminophen-induced hepatotoxicity in mice.

Aim: To examine the effects of 2,4-dihydroxybenzophenone (BP-1), a benzophenone derivative used as an ultraviolet light absorbent, on acetaminophen (APAP)-induced hepatotoxicity in C57BL/6J mice.

Methods: Mice were administered orally with BP-1 at doses of 200, 400 and 800 mg/kg body weight respectively every morning for 4 d before a hepatotoxic dose of APAP (350 mg/kg body weight) was given subcutaneously. Twenty four hours after APAP intoxication, the serum enzyme including serum alaine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were measured and liver histopathologic changes were examined.

Dual-response nanocarrier based on graft copolymers with hydrazone bond linkages for improved drug delivery.

Core-shell micelles with biodegradability, thermo- and pH-response were successfully demonstrated by poly(2-oxepane-1,5-dione-co-epsilon-caprolactone) (P(OPD-co-CL)) grafted with hydrophilic segments of amine-terminated poly(N-isopropylacrylamide) (At-PNIPAM). To compare with the graft copolymer, P(OPD-co-CL) block PNIPAM polymer was also prepared. The micelles with core-shell structure were formed with both graft and block copolymers by self-assembly in aqueous solutions, of which PNIPAM shell is thermo-response.

Micellar carrier based on methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) block copolymers bearing ketone groups on the polyester block for doxorubicin delivery.

Block copolymers of Methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) bearing ketone groups (MPEG-b-P(CL-co-OPD)) are synthesized and evaluated for its potential to form micelles containing doxorubicin (DOX), a representative anticancer drug, by using an in vitro method based on membrane dialysis to emulate drug release in vivo. The (1)H NMR spectra of the prepared block copolymers in D(2)O solution exhibit peaks due to the P(OPD-co-CL) in decreased intensity, indicates that the polymers form micelle particles containing the hydrophilic segments in their external parts. The CMC of the copolymer decrease with an increase in the content of ketone groups in the hydrophobic chain.