Enhanced optical imaging and fluorescent labeling for visualizing drug molecules within living organisms.

The visualization of drugs in living systems has become key techniques in modern therapeutics. Recent advancements in optical imaging technologies and molecular design strategies have revolutionized drug visualization. At the subcellular level, super-resolution microscopy has allowed exploration of the molecular landscape within individual cells and the cellular response to drugs. Moving beyond subcellular imaging, researchers have integrated multiple modes, like optical near-infrared II imaging, to study the complex spatiotemporal interactions between drugs and their surroundings. By combining these visualization approaches, researchers gain supplementary information on physiological parameters, metabolic activity, and tissue composition, leading to a comprehensive understanding of drug behavior. This review focuses on cutting-edge technologies in drug visualization, particularly fluorescence imaging, and the main types of fluorescent molecules used. Additionally, we discuss current challenges and prospects in targeted drug research, emphasizing the importance of multidisciplinary cooperation in advancing drug visualization. With the integration of advanced imaging technology and molecular design, drug visualization has the potential to redefine our understanding of pharmacology, enabling the analysis of drug micro-dynamics in subcellular environments from new perspectives and deepening pharmacological research to the levels of the cell and organelles.

Multi-pathway on peroxymonosulfate activation by single cobalt atoms incorporated on CuO with enriched oxygen vacancies for high-efficient oxidation of tetracycline.

The development of single atom catalysts (SACs) with superior catalytic performance is a long-term goal for peroxymonosulfate (PMS) activation in advanced oxidation processes (AOPs). A novel SACs that single Co atoms anchored on CuO with enriched oxygen vacancies (Ov) is synthesized successfully by choosing a metal oxide as the carrier creatively. 100% of tetracycline (TC) can be removed by Co-CuO (Ov)/PMS system within 3 min. The corresponding reaction rate constant is 3.1068 min-1, which is much higher than that of CuO (Ov), ZIF-CoN4-C, Co-CuO (without Ov) and CoNP-CuO (Ov), respectively. Co(II) is the primary source of radical pathway (·OH and SO4·-), and its regeneration is promoted by Cu(Ⅰ). The enriched Ov is the major contribution to the nonradical pathway, which promotes the singlet oxygen (1O2) generation together with accelerates the electron transfer from TC to catalyst-PMS*. Besides, the Co-CuO (Ov) exhibits an excellent stability and anti-interference capability. This study highlights a novel strategy to promote PMS activation by incorporating the single metal atoms on a metal oxide carrier with defects to accelerate the redox of dominate metal and stabilize the metal atoms simultaneously, which may inform the design for the next generation of SACs in AOPs.

Efficient degradation of phenol by MnOOH-rGO composite with high peroxymonosulfate utilization efficiency.

A high-performance, durable, low-cost, and environmentally friendly catalyst is highly desired in advanced oxidation processes (AOPs) for water treatment. Considering the activity of Mn(Ⅲ) and the superior catalytic properties of reduced graphene oxide (rGO) in peroxymonosulfate (PMS) activation, rGO-modified MnOOH nanowires (MnOOH-rGO) were fabricated by a hydrothermal method for phenol degradation. The results showed that the composite synthesized at 120 °C with 1 wt% rGO dopant exhibited the best performance for phenol degradation. Nearly 100% of the phenol was removed by MnOOH-rGO within 30 min, which is higher than the removal rate of pure MnOOH (70%). The effects of catalyst dosages, PMS concentration, pH, temperature, and anions (Cl-, NO3-, HPO42-and HCO3-) on phenol degradation were investigated. The removal rate of chemical oxygen demand (COD) reached 26.4%, with a low molar ratio of PMS to phenol at 5:1 and a high PMS utilization efficiency (PUE) of 88.8%. The phenol removal rate remained more than 90% after five recycle with less than 0.1 mg L-1 leakage of manganese ions. Together with the results of radical quenching experiments, X-ray photoelectron spectroscopy (XPS) and electron paramagnetic resonance spectroscopy (EPR), electron transfer and 1O2 were proved to dominate the activation process. During the direct electrons transfer process, the electrons transfer from the phenol to PMS by using the Mn(Ⅲ) as the mediate with a stoichiometric ratio between PMS and phenol at 1:2, which mainly contributed to the high PUE. This work provides new insight into a high-performance Mn(Ⅲ) based catalyst on PMS activation with high PUE, good reusability, and environmentally friendly for removing organic pollutants.

A comprehensive overview of PPM1B: From biological functions to diseases.

Reversible phosphorylation of proteins is an important mechanism that regulates cellular processes, which are precisely regulated by protein kinases and phosphatases. PPM1B is a metal ion-dependent serine/threonine protein phosphatase, which regulates multiple biological functions by targeting substrate dephosphorylation, such as cell cycle, energy metabolism, inflammatory responses. In this review, we summarized the occurrent understandings of PPM1B focused on its regulation of signaling pathways, related diseases, and small-molecular inhibitors, which may provide new insights for the identification of PPM1B inhibitors and the treatment of PPM1B-related diseases.

Coupling the effect of Co and Mo on peroxymonosulfate activation for the removal of organic pollutants.

Although heterogeneous cobalt-based catalysts have been widely studied and used in SO4•- based advanced oxidation processes, the efficiencies were still not high enough due to the limiting step of Co(III)/Co(II) cycle in the system. In this study, a bimetallic oxide composed of Co and Mo was designed and used for enhancing the performance of peroxymonosulfate activation on organic pollutants removal. The CoMoO4 nanorods exhibited superior catalytic activity for methylene blue (MB) degradation than Co3O4, MoO3, and their mechanical mixture, which was attributed to the synergetic effect between Co and Mo. CoMoO4 nanorods were able to efficiently degrade MB under a wide pH range of 3-11 and could maintain high efficiency in 5 cycles with less leakage of metal ions. Moreover, CoMoO4 nanorods displayed broad spectrum applicability to the different water matrix and a variety of pollutants such as phenol and Congo red. The Co(II) was proved to be the main active site of the catalyst, while Mo played an important role in promoting the Co(III)/Co(II) cycle. Surface free radicals are the main active species in the degradation process. This work provides new insights into the design of cobalt-based bimetallic catalyst and the improvement on PMS activation.

Identification of key pharmacodynamic markers of American ginseng against heart failure based on metabolomics and zebrafish model.

Background: American ginseng (Panax quinquefolium L., AG) is a traditional Chinese medicine with multiple cardiovascular protective properties. Many bioactive components have been discovered in AG over these years. However, the understanding of these key pharmacodynamic components of activity against heart failure is insufficient. Methods: A heart failure model was established using AB line wild-type zebrafish (Danio rerio) to evaluate the anti-heart failure activity of AG. Untargeted metabolomics analysis based on ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap-mass spectrometry technology (UHPLC-QE-Orbitrap-MS) was performed to screen differential components from AG samples. The potential active components were verified using the zebrafish model. Simultaneously, network pharmacology and molecular docking techniques were used to predict the possible mechanism. Finally, the key targets of six key pharmacodynamic components were verified in zebrafish using quantitative real-time-polymerase chain reaction (Q-PCR) techniques. Results: The heart failure model was successfully established in 48 h of post-fertilization (hpf) zebrafish larvae by treating with verapamil hydrochloride. The zebrafish assay showed that the anti-heart failure effects of AG varied with producing regions. The result of the herbal metabolomic analysis based on UHPLC-QE-Orbitrap-MS indicated that ginsenoside Rg3, ginsenoside Rg5, ginsenoside Rg6, malic acid, quinic acid, L-argininosuccinic acid, 3-methyl-3-butenyl-apinosyl (1→6) glucoside, pseudoginsenoside F11, and annonaine were differential components, which might be responsible for variation in efficacy. Further analysis using zebrafish models, network pharmacology, and Q-PCR techniques showed that ginsenoside Rg3, ginsenoside Rg5, ginsenoside Rg6, malic acid, quinic acid, and pseudoginsenoside F11 were the pharmacodynamic markers (P-markers) responsible for anti-heart failure. Conclusion: We have rapidly identified the P-markers against heart failure in AG using the zebrafish model and metabolomics technology. These P-markers may provide new reference standards for quality control and new drug development of AG.

Possible pharmaceutical applications can be developed from naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids.

Naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids (PIAs and PQAs) are two small groups of herbal metabolites sharing a similar pentacyclic structure with a highly oxygenated phenanthrene moiety fused with a saturated or an unsaturated N-heterocycle (indolizidine/quinolizidine moieties). Natural PIAs and PQAs only could be obtained from finite plant families (such as Asclepiadaceae, Lauraceae and Urticaceae families, etc.). Up to date, more than one hundred natural PIAs, while only nine natural PQAs had been described. PIA and PQA analogues have been applied to the development of potent anticancer agents all along because of their excellent cytotoxic activity. However, in the last two decades, other great biological properties, such as anti-inflammatory and antiviral activities were revealed successively by different pharmacological assays. Especially because of their potent antiviral activity against coronavirus (TGEV, SARS CoV and MHV) and tobacco mosaic virus, PIA and PQA analogues have attracted much pharmaceutical attention again, some of them have been used to present interesting targets for total or semi synthesis, and structure-activity relationship (SAR) study for the development of antiviral agents. In this review, natural PIA and PQA analogues obtained in the last two decades with their herbal origins, key spectroscopic characteristics for structural identification, biological activity with possible SARs and application prospects were systematically summarized. We hope this paper can stimulate further investigations on PIA and PQA analogues as an important source for potential drug discovery.

Isolation, Structural Elucidation, and Liquid Chromatography-Mass Spectrometry Analysis of Steroidal Glycosides from Polygonatum odoratum.

The rhizomes of Polygonatum odoratum represent a traditional Chinese medicine and functional food. A phytochemical investigation resulted in the isolation of eight steroidal glycosides (1-8), including two new compounds, polygonatumosides F (1) and G (2). The structures were elucidated by spectroscopic data and chemical reactions. Compound 7 showed antiproliferation activity against human hepatocellular carcinoma cell line HepG2 (IC50 of 3.2 µM). The chemical profile and contents of steroidal glycosides of P. odoratum rhizomes collected at different dates and geographical locations were also investigated, indicating that the rational harvest of P. odoratum in spring and autumn is preferable to obtain higher levels of steroidal glycosides. Compounds 1 and 7 showed the highest contents in all P. odoratum samples and have potential to serve as chemotaxonomic and chemical markers for quality control of this important plant material. 14-Hydroxylation may be a key step for the biosynthesis of compounds 1-7.

PPARγ Agonist Ameliorates the Impaired Fluidity of the Myocardial Cell Membrane and Cardiac Injury in Hypercholesterolemic Rats.

Hypercholesterolemia can increase the risk of cardiac injury, but the underlying mechanisms are not fully understood. The present study aimed to determine whether changes in the fluidity of the cardiomyocyte membrane may contribute to the increased susceptibility to myocardial ischemia/reperfusion (MI/R) injury observed in hypercholesterolemic rats. Male Wistar rats were fed a normal (n = 24) or high-cholesterol diet (n = 32) for 10 weeks. At the 6th week, the rats in the high-cholesterol diet group were treated with vehicle (n = 16, HC + V) or pioglitazone (n = 16, HC + PIO), a peroxisome proliferator-activated receptor-γ (PPARγ) agonist, and treatment lasted for the next 4 weeks. Rats in HC + V group displayed less membrane fluidity, a greater membrane cholesterol-to-phospholipid ratio (C/P), less Na+-K+-ATPase activity, and less cAMP content in their myocardial cells than rats fed a normal diet. A strong positive correlation was observed between membrane fluidity and cardiac injury, i.e., the myocardial infarct size when subjected to MI/R (30 min/24 h). Treatment with PIO restored much of the lost hypercholesterolemia-induced myocardial cell membrane fluidity, decreased membrane C/P ratio, increased Na+-K+-ATPase activity and cardiac cell cAMP content, improved cardiac function, and reduced the sizes of myocardial infarcts. Results demonstrated that hypercholesterolemia-induced decreased myocardial cell membrane fluidity may contribute to the increased susceptibility to cardiac injury, and PPARγ agonists may have therapeutic value in patients with hypercholesterolemia.

A pair of taxifolin-3-O-arabinofuranoside isomers from Juglans regia L.

Diaphragma juglandis Fructus has been known for its effect on tonifying kidney in traditional Uighur medicine. During our ongoing studies on the discovery of biologically active compounds from folk medicine, a pair of flavanonol glycoside isomers named (2S,3S)-taxifolin-3-O-α-d-arabinofuranoside (1) and (2S,3S)-taxifolin-3-O-α-l-arabinofuranoside (2) were isolated, among them, 1 was a new compound. It is the first report of taxifolin-3-O-arabinofuranosides in both α-d and α-l configuration forms in genus Juglans. Their structures were determined on the basis of spectroscopic analysis and chemical evidence, in combination with circular dichroism.

Nanosuspensions of poorly water-soluble drugs prepared by bottom-up technologies.

In recent years, nanosuspension has been considered effective in the delivery of water-soluble drugs. One of the main challenges to effective drug delivery is designing an appropriate nanosuspension preparation approach with low energy input and erosion contamination, such as the bottom-up method. This review focuses on bottom-up technologies for preparation of nanosuspensions. The features and advantages of drug nanosuspension, including bottom-up methods as well as the corresponding characterization techniques, solidification methods, and drug delivery dosage forms, are discussed in detail. Certain limitations of commercial nanosuspension products are also reviewed.

Up-regulation of iNOS by hypoxic postconditioning inhibits H9c2 cardiomyocyte apoptosis induced by hypoxia/re-oxygenation.

Apoptosis is a crucial mode of cell death induced by ischemia and reperfusion, and ischemic postconditioning (PostC) has been reported to inhibit cell apoptosis. Inducible nitric oxide synthase (iNOS) has been confirmed to play an important role in triggering and mediating the late cardio-protection against ischemia/hypoxia. In this study, we found that hypoxic PostC remarkably up-regulated the expression of iNOS and decreased cardiomyocyte apoptosis. Pre-treatment with 1400w (a highly selective inhibitor of iNOS) or iNOS siRNA weakened the anti-apoptotic effect of hypoxic PostC. These findings suggested that iNOS may be one of the key molecular mechanisms responsible for the inhibition of apoptosis by hypoxic PostC.

Photocatalytic oxidation of aqueous ammonia using atomic single layer graphitic-C3N4.

Direct utilization of solar energy for photocatalytic removal of ammonia from water is a topic of strong interest. However, most of the photocatalysts with effective performance are solely metal-based semiconductors. Here, we report for the first time that a new type of atomic single layer graphitic-C(3)N(4) (SL g-C(3)N(4)), a metal-free photocatalyst, has an excellent photocatalytic activity for total ammonia nitrogen (TAN) removal from water. The results demonstrated that over 80% of TAN (initial concentration 1.50 mg · L(-1)) could be removed in 6 h under Xe lamp irradiation (195 mW · cm(-2)). Furthermore, the SL g-C(3)N(4) exhibited a higher photocatalytic activity in alkaline solution than that in neutral or acidic solutions. The investigation suggested that both photogenerated holes and hydroxyl radicals were involved the TAN photocatalytic oxidation process and that the major oxidation product was NO3(-)-N. In addition, SL g-C(3)N(4) exhibited good photocatalytic stability in aqueous solution. This work highlights the appealing application of an inexpensive metal-free photocatalyst in aqueous ammonia treatment.

Biological ingredient analysis of traditional Chinese medicine preparation based on high-throughput sequencing: the story for Liuwei Dihuang Wan.

Although Traditional Chinese Medicine (TCM) preparations have long history with successful applications, the scientific and systematic quality assessment of TCM preparations mainly focuses on chemical constituents and is far from comprehensive. There are currently only few primitive studies on assessment of biological ingredients in TCM preparations. Here, we have proposed a method, M-TCM, for biological assessment of the quality of TCM preparations based on high-throughput sequencing and metagenomic analysis. We have tested this method on Liuwei Dihuang Wan (LDW), a TCM whose ingredients have been well-defined. Our results have shown that firstly, this method could determine the biological ingredients of LDW preparations. Secondly, the quality and stability of LDW varies significantly among different manufacturers. Thirdly, the overall quality of LDW samples is significantly affected by their biological contaminations. This novel strategy has the potential to achieve comprehensive ingredient profiling of TCM preparations.

DNA extraction protocol for biological ingredient analysis of Liuwei Dihuang Wan.

Traditional Chinese medicine (TCM) preparations are widely used for healthcare and clinical practice. So far, the methods commonly used for quality evaluation of TCM preparations mainly focused on chemical ingredients. The biological ingredient analysis of TCM preparations is also important because TCM preparations usually contain both plant and animal ingredients, which often include some mis-identified herbal materials, adulterants or even some biological contaminants. For biological ingredient analysis, the efficiency of DNA extraction is an important factor which might affect the accuracy and reliability of identification. The component complexity in TCM preparations is high, and DNA might be destroyed or degraded in different degrees after a series of processing procedures. Therefore, it is necessary to establish an effective protocol for DNA extraction from TCM preparations. In this study, we chose a classical TCM preparation, Liuwei Dihuang Wan (LDW), as an example to develop a TCM-specific DNA extraction method. An optimized cetyl trimethyl ammonium bromide (CTAB) method (TCM-CTAB) and three commonly-used extraction kits were tested for extraction of DNA from LDW samples. Experimental results indicated that DNA with the highest purity and concentration was obtained by using TCM-CTAB. To further evaluate the different extraction methods, amplification of the second internal transcribed spacer (ITS2) and the chloroplast genome trnL intron was carried out. The results have shown that PCR amplification was successful only with template of DNA extracted by using TCM-CTAB. Moreover, we performed high-throughput 454 sequencing using DNA extracted by TCM-CTAB. Data analysis showed that 3-4 out of 6 prescribed species were detected from LDW samples, while up to 5 contaminating species were detected, suggesting TCM-CTAB method could facilitate follow-up DNA-based examination of TCM preparations.

Up-regulation of hypoxia-inducible factor-1α enhanced the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats.

Hyperlipidemia is an independent risk factor in the development of ischemic heart disease, which can increase myocardial susceptibility to ischemia/reperfusion (I/R) injury. Ischemic postconditioning (PostC) has now been demonstrated as a novel strategy to harness nature's protection against myocardial I/R injury in normal conditions. However, the effect of PostC on hyperlipidemic animals remains elusive. It has been shown in our previous study that PostC reduces the myocardial I/R injury, and hypoxia-inducible factor-1α (HIF-1α) may play an important role in the cardioprotective mechanisms of PostC on normal rats. Here, we tested the hypothesis that the cardioprotection of PostC on hyperlipidemic rats is associated with the up-regulated HIF-1α expression. Male Wistar rats were fed with a high-fat diet for 8 weeks, and then randomly divided into five groups: sham, I/R, dimethyloxalylglycine (DMOG) + I/R, PostC, and DMOG + PostC group. The detrimental indices induced by I/R injury included infarct size, plasma creatine kinase (CK) activity and caspase-3 activity. The results showed that PostC could reduce the infarct size, when compared with the I/R group, which was consistent with the significant lower levels of plasma CK activity and caspase-3 activity, and that it increased the expression of HIF-1α in hyperlipidemic rats. When DMOG was given before PostC to up-regulate HIF-1α protein level, the degree of I/R injury was attenuated. In conclusion, these data suggested that the up-regulation of HIF-1α may be one of the cardioprotective mechanisms of PostC against I/R injury in hyperlipidemic rats.

Isolation and structural elucidation of novel cholestane glycosides and spirostane saponins from Polygonatum odoratum.

Much attention has been paid to cholestane-type steroidal glycosides because of their importance from the perspectives of both chemical diversity and significant biological activities. A phytochemical investigation of the rhizomes of Polygonatum odoratum (Liliaceae) resulted in the isolation of three novel cholestane-type steroidal glycosides (1-3) with unique Δ(14,16)-unsaturated D-ring structures as well as two novel spirostane-type steroidal saponins (4 and 5) and three known steroidal glycosides (6-8). Their structures were determined by various spectroscopic methods and chemical reactions. Steroidal saponin 7 showed significant antifungal activity against Candida albicans JCM1542 (MIC 3.1 µg/mL) and Aspergillus fumigatus JCM1738 (MIC 6.3 µg/mL).

A new minor homoisoflavonoid from Caesalpinia sappan.

Homoisoflavonoid is a special type of flavonoid with the perspectives of both chemical diversity and significant biological activities. During our ongoing studies on the discovery of novel homoisoflavonoids from traditional Chinese medicines, a new minor 3,4-di-O-substituted homoisoflavonoid, 3',4-di-O-methylepisappanol (1), was isolated from Caesalpinia sappan, and its structure was determined to be (3R,4R)-3,7-dihydroxy-3-(3'-methoxy-4'-hydroxybenzyl)-4-methoxychroman by various spectroscopic analyses. Meanwhile, a known xanthone derivate, 2-methoxy-3-hydroxyxanthone (2) was also isolated, which is the first example from the genus Caesalpinia.

[A new triterpenoid from Pittosporum glabratum Lindl].

The roots of Pittosporum glabratum Lindl. (Pittosporaceae) have been used as a folk medicine for the treatment of rheumatic arthritis, insomnia and hypertension. Only a few chemical or biological studies on P. glabratum have been reported. As part of our ongoing phytochemical research on this plant, four compounds were isolated. Their structures were identified as 3beta, 6beta, 19alpha, 21alpha, 24-pentahydroxy-12-en-28-oleanolic acid (1), 3-O-beta-D-glucuronopyranosyl-28-O-beta-D-glucopyranosyl siaresinolic acid (2), 3, 4, 5-trimethoxyphenyl-1-O-beta-D-(5-O-syringoyl)-apiofuranosyl-(1 --> 6)-beta-D-glucopyranoside (3) and 3, 4, 5-trimethoxyphenol-1-O-beta-D-apiofuranosyl-(1 --> 6)-beta-D-glucopyranoside (4) on the basis of physical evidence and spectroscopic analysis. Among them, compound 1 is a new triterpenoid, and compounds 2-4 are isolated from the genus Pittosporum for the first time.

[The up-regulation of hypoxia inducible factor-1α by hypoxic postconditioning reduces hypoxia/reoxygenation-induced injury in heart-derived H9c2 cells].

The aim of the present study was to explore the effects of hypoxic postconditioning (PostC) on heart-derived H9c2 cells injury induced by hypoxia/reoxygenation (H/R) and the expression of hypoxia inducible factor-1α (HIF-1α), and to analyze the relationship between them. Cultured H9c2 cardiac muscle cells were subjected to 3-hour hypoxia and 2-hour reoxygenation to simulate ischemia and reperfusion, or underwent 3 cycles of 5-min reoxygenation and 5-min hypoxia preceding the long reoxygenation to simulate ischemic postconditioning. Cell viability, lactate dehydrogenase (LDH) activity, and caspase-3 activity were detected respectively to investigate the cell injury induced by H/R. The level of HIF-1α mRNA was measured by real-time PCR. Western blot was used to determine HIF-1α protein level. The results showed that postconditioning significantly increased H9c2 cell viability, reduced the activity of LDH and caspase-3. Simultaneously, postconditioning up-regulated the HIF-1α protein level. Moreover, after DMOG, an inhibitor of proline hydroxylase (PHD) which targeted to HIF-1α degradation, was used to stabilize HIF-1α protein level, the reduction of H9c2 cells injury was comparable to that by postconditioning. There was a significant linear positive relationship between HIF-1α protein level and cell viability (r = 0.743, P < 0.01). After HIF-1α gene was silenced by siRNA, the cardio-protective effects of postconditioning was significantly weakened. These data suggest that up-regulation of HIF-1α plays an important role in the cardio-protection of postconditioning.