Research and experimental verification of the molecular mechanism of berberine in improving premature ovarian failure based on network pharmacology

Based on the research methods of network pharmacology, this study analyzed the improvement effect of berberine (BBR) on premature ovarian failure (POF) and its molecular mechanism. Carry out GO and KEGG enrichment analysis by R language to obtain the potential targets and pathways of BBR in the improvement of POF. Use SD rats and ovarian granulosa cells (GCs) for experimental verification. ELISA was used to measure the content of related hormones in the serum, CCK-8 was used to measure cell viability, western blot was used to measure the content of the target protein in the ovaries and GCs, and q-RT-PCR was used to detect the expression of the target genes in the ovaries and GCs. Predicted by network pharmacology: PTEN, AKT1, FoxO1, FasL, and Bim are the targets with the highest relative correlation between BBR and POF. The results of experiments show that the treatment of low and medium doses of BBR can increase the ovarian index of rats; BBR can increase the levels of Estradiol (E2) and Anti-Mullerian hormone (AMH) in the serum of rats and reduce the levels of Follicle stimulating hormone (FSH) and Luteinizing hormone (LH). BBR can increase the cell viability of GCs; BBR can inhibit the PTEN/AKT1/FoxO1 signaling pathway and its phosphorylation level and reduce the expression of Fas/FasL and Bim mRNA. Overall, BBR can promote the ovarian to maintain normal hormone levels, protect GCs, and enhance the function of POF.</p

Unimolecular Micelles of Amphiphilic Cyclodextrin-Core Star-Like Copolymers with Covalent pH-Responsive Linkage of Anticancer Prodrugs

Multifunctional stable and stimuli-responsive drug delivery systems are important for efficient cancer treatment due to their advantages such as enhanced cancer-targeting efficiency, improved pharmacokinetics, minimized drug leaching, and reduced undesirable side effects. Here we report a robust and pH-responsive anticancer drug delivery system based on unimolecular micelles of star-like amphiphilic copolymers. The polymers (denoted as <b>CPOFs</b>) were facilely synthesized via one-step atom transfer radical polymerization of functionalizable benzoaldehyde and hydrophilic poly­[(oligo ethylene glycol) methyl ether methacrylate] as comonomers from the core of heptakis [2,3,6-tri-<i>o</i>-(2-bromo-2-methyl propionyl]-β-cyclodextrin as the initiator. Doxorubicin (DOX) as an anticancer drug was covalently linked to the benzoaldehyde groups of <b>CPOFs</b> through pH-sensitive Schiff-base bonds. The DOX-conjugated polymers, denoted as <b>CPOF–DOX</b>, formed robust unimolecular micelles with an average diameter of 18 nm in aqueous media. More importantly, these unimolecular micelles showed higher drug loading capacity and more controllable drug release characteristics, compared to our previous unimolecular micelles of β-cyclodextrin-poly­(lactic acid)-<i>b</i>-poly­[(oligo ethylene glycol) methyl ether methacrylates] that physically encapsulated DOX via hydrophobic interaction. Moreover, the <b>CPOF–DOX</b> unimolecular micelles could be internalized by human cervical cancer HeLa cells in a stepwise way and showed less cytotoxicity compared to carrier-free DOX. We foresee that <b>CPOF–DOX</b> would provide a promising robust and controllable anticancer drug delivery system for future animal study and clinical trials for cancer treatment

(a, b) The probability of failing to be matched conditioned on attractiveness <i>a</i> and degree <i>k</i> (<i>P</i>_not(<i>a</i>, <i>k</i>)) decreases exponentially with <i>a</i> and <i>k</i> in scale-free networks with <i>P</i>(<i>k</i>) ∼ <i>k</i>^−<i>γ</i>, <i>γ</i> = 3 and ⟨<i>k</i>⟩ = 5.

<p>(a, b) The probability of failing to be matched conditioned on attractiveness <i>a</i> and degree <i>k</i> (<i>P</i>_not(<i>a</i>, <i>k</i>)) decreases exponentially with <i>a</i> and <i>k</i> in scale-free networks with <i>P</i>(<i>k</i>) ∼ <i>k</i>^−<i>γ</i>, <i>γ</i> = 3 and ⟨<i>k</i>⟩ = 5.</p

An Analysis of the Matching Hypothesis in Networks - Fig 1

<p><b>(a)</b> An example of a bipartite graph, which is composed of two disjoint sets of nodes <i>m</i> and <i>f</i>. There is no link between nodes in the same set and the connection between sets is characterized by degree distribution <i>P</i>(<i>k</i>). <b>(b)</b> The action scheme of the mate choosing process. Two nodes <i>i</i> and <i>j</i> have to undergo an intermediate stage to reach the stable long term relation. During the intermediate stage nodes <i>i</i> and <i>j</i> are also available to build relationship with other nodes. If this happens they break and their relationship is back to the initial state.</p

Novel Acid-Driven Bioinspired Self-Resettable Bilayer Hydrogel Actuator Mimicking Natural Muscles

Soft robots have great potential applications in manufacturing, disaster rescue, medical treatment, etc. Artificial muscle is one of the most important components of a soft robot. In previous years, hydrogel actuators that can be controllably deformed by the stimuli of external signals have been developed as good candidates for muscle-like materials. In this article, we successfully prepared a chemical fuel-driven self-resettable bilayer hydrogel actuator mimicking natural muscles with the aid of a new negative feedback reaction network. The actuator can temporarily deform upon the addition of H+ (chemical fuel). Subsequently, H+ accelerated the reaction between BrO3– and Fe(CN)64–, which consume H+. It resulted in the spontaneous recovery of the pH as well as the shape of the actuator. Such an actuator exhibits a great similarity with natural muscles in actuation mechanisms and automaticity in the manipulation compared to the widely reported stimuli-responsive hydrogel actuators. This illustrates that fuel-driven self-resettable hydrogel is a promising dynamic material for mimicking the functions of living creatures

The Pearson coefficient of correlation <i>ρ</i> of the attractiveness between the two coupled individuals in Erdős-Rényi networks with size 2<i>N</i> (<i>N</i> = 10,000) and varying average degree ⟨<i>k</i>⟩.

<p><i>ρ</i> increases monotonically in all three cases analyzed. However, <i>ρ</i> is largest in networks where the degree and the attractiveness are positively correlated. When they are negatively correlated, <i>ρ</i> is weakest and can even be negative.</p

An Analysis of the Matching Hypothesis in Networks - Fig 2

<p><b>(a)</b> The Pearson coefficient of correlation <i>ρ</i> of the attractiveness between the two coupled individuals in different systems. <i>ρ</i> is strongest in fully-connected systems. In sparse networks, <i>ρ</i> increases monotonically with the average degree ⟨<i>k</i>⟩ and decreases with the degree diversity. For all cases investigated, system size is 2<i>N</i> and <i>N</i> = 10,000. <b>(b)</b> The average attractiveness </p><p></p><p></p><p></p><p></p><p><mi>a</mi><mo>¯</mo></p><mi>f</mi><p></p><p></p><p></p><p></p> of individuals in the set <i>f</i> who are matched with those in a subset of <i>m</i> with attractiveness in the range [<i>a</i>_<i>m</i>−0.05, <i>a</i>_<i>m</i>+0.05) for a series of points <i>a</i>_<i>m</i>. In fully-connect systems, the less attractive individuals are bound to be coupled with ones who are also less attractive. In sparse networks, however, they are coupled with ones who are more attractive. <b>(c)</b> The attractiveness contour figure of the coupled individuals in Erdős-Rényi networks with average degree ⟨<i>k</i>⟩ = 5. A pattern emerges even when similarity is not the motivation in seeking partners. <i>a</i>_<i>m</i> and <i>a</i>_<i>f</i> are the attractiveness of nodes in sets <i>m</i> and <i>f</i>, respectively. <b>(d)</b> The attractiveness contour figure of the coupled individuals in fully-connected systems. The correlation is strongest towards the less attractive individuals (the circled part).<p></p

Novel Acid-Driven Bioinspired Self-Resettable Bilayer Hydrogel Actuator Mimicking Natural Muscles

Soft robots have great potential applications in manufacturing, disaster rescue, medical treatment, etc. Artificial muscle is one of the most important components of a soft robot. In previous years, hydrogel actuators that can be controllably deformed by the stimuli of external signals have been developed as good candidates for muscle-like materials. In this article, we successfully prepared a chemical fuel-driven self-resettable bilayer hydrogel actuator mimicking natural muscles with the aid of a new negative feedback reaction network. The actuator can temporarily deform upon the addition of H+ (chemical fuel). Subsequently, H+ accelerated the reaction between BrO3– and Fe(CN)64–, which consume H+. It resulted in the spontaneous recovery of the pH as well as the shape of the actuator. Such an actuator exhibits a great similarity with natural muscles in actuation mechanisms and automaticity in the manipulation compared to the widely reported stimuli-responsive hydrogel actuators. This illustrates that fuel-driven self-resettable hydrogel is a promising dynamic material for mimicking the functions of living creatures

Elongation of a Trigonal-Prismatic Copper Cluster by Diphosphine Ligands with Longer Spacers

A pair of alkynyl–diphosphine-coprotected copper(I) clusters, namely, [Cu6(4-MeO-PhCC)5(dppe)3](ClO4) [Cu6; dppe = 1,2-bis(diphenylphosphino)ethane] and [Cu11(H)(4-MeO-PhCC)8(dpppe)3](ClO4)2 [Cu11; dpppe = 1,5-bis(diphenylphosphino)pentane], featuring trigonal-prismatic frameworks have been synthesized by a reduction method. Their molecular structures are determined by X-ray crystallography and characterized by multiple techniques. The length of the spacer of the diphosphine ligand can directly affect the aspect ratio of the clusters. Cu6 with dppe as ligands has a trigonal-prismatic core. The longer alkyl spacer of dpppe helps to elongate the trigonal-prismatic framework to form Cu11, with its trigonal-prismatic framework encapsulating a Cu5H unit. Electrospray ionization mass spectrometry, 2H NMR, and liberations of hydrogen further verify the presence of a hydride in the cluster. Density functional theory calculations help to locate the position of the hydride and understand the electronic structures of the clusters. Cu11 is the first alkynyl–phosphine-coprotected copper hydride cluster. These two clusters show distinct luminescence properties. The compact Cu6 is phosphorescent upon radiation, while the longer Cu11 with more flexibility is nonluminous. This work enriches the family of copper hydrides and demonstrates the ligand effects in the extension of the length and structural complexity of clusters

Liquid Density of 2‑Methoxyethyl Acetate, 2‑Ethylhexyl Acetate, and Diethyl Succinate at Temperatures from 283.15 K to 363.15 K and Pressures up to 100 MPa

The density data for 2-ethylhexyl acetate, 2-methoxyethyl acetate, and diethyl succinate were reported. The density measurements were conducted with a high-pressure vibrating-tube densimeter over 9 isotherms at (283.15 to 363.15) K and 16 isobars at (0.1 to 100) MPa. The uncertainty of each obtained datum was estimated, and the expanded uncertainties of density measurements with a confidence level of 0.95 (<i>k</i> = 2) of density measurement for 2-ethylhexyl acetate, 2-methoxyethyl acetate, and diethyl succinate are 0.1 %. The experimental densities were correlated with the Tait-type equation, and the absolute average percentage deviations were 0.010 %, 0.009 %, and 0.011 % for 2-ethylhexyl acetate, 2-methoxyethyl acetate, and diethyl succinate, respectively. In addition, the isothermal compressibility and the isobaric thermal expansivity were derived from the Tait-type equation