A review of passive acid mine drainage treatment by PRB and LPB: From design, testing, to construction.

An extensive volume of acid mine drainage (AMD) generated throughout the mining process has been widely regarded as one of the most catastrophic environmental problems. Surface water and groundwater impacted by pollution exhibit extreme low pH values and elevated sulfate and metal/metalloid concentrations, posing a serious threat to the production efficiency of enterprises, domestic water safety, and the ecological health of the basin. Over the recent years, a plethora of techniques has been developed to address the issue of AMD, encompassing nanofiltration membranes, lime neutralization, and carrier-microencapsulation. Nonetheless, these approaches often come with substantial financial implications and exhibit restricted long-term sustainability. Among the array of choices, the permeable reactive barrier (PRB) system emerges as a noteworthy passive remediation method for AMD. Distinguished by its modest construction expenses and enduring stability, this approach proves particularly well-suited for addressing the environmental challenges posed by abandoned mines. This study undertook a comprehensive evaluation of the PRB systems utilized in the remediation of AMD. Furthermore, it introduced the concept of low permeability barrier, derived from the realm of site-contaminated groundwater management. The strategies pertaining to the selection of materials, the physicochemical aspects influencing long-term efficacy, the intricacies of design and construction, as well as the challenges and prospects inherent in barrier technology, are elaborated upon in this discourse.

Polygonum cuspidatum polysaccharide: A review of its extraction and purification, structure analysis, and biological activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum cuspidatum Sieb. et Zucc. is mainly distributed in Shanxi, Gansu, and Sichuan province of China. It is also found in Korea and Japan. Its dried roots and rhizomes are used as medicinal herbs and have been used to treat hyperglycemia and various inflammatory disorders. AIM OF THE REVIEW: This paper aims to provide an up-to-date review of the developments in the studies involving the extraction and purification, structure analysis, pharmacological effects, and potential applications of polysaccharides obtained from Polygonum cuspidatum. Additionally, the possible future research directions of this plant are discussed. MATERIALS AND METHODS: This article used "Polygonum cuspidatum polysaccharide (PCP)" and "Polygonum cuspidatum" as the keywords and gathered relevant data on Polygonum cuspidatum using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb. RESULTS: Excluding irrelevant and repetitive documents, 278 documents were finally included, of which 88 were in Chinese and 190 were in English. The CiteSpace software was used to visualize the trends and keywords in this research field. We concluded that the main extraction methods for Polygonum cuspidatum polysaccharide are water extraction and alcohol precipitation, microwave-assisted extraction, ultrasound-assisted extraction, and microjet extraction. High-performance liquid chromatography and column chromatography are also commonly used in the separation and purification of PCP. PCP has antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. This paper provides an updated and deeper understanding of PCP, serving as a theoretical foundation for the further optimization of polysaccharide structures and the development of PCP as a novel functional material for clinical application.

Research on the antipruritic active ingredients of Mikania micrantha.

Mikania micrantha is a perennial liana of the genus Mikania of the Asteraceae family. It is a commonly used medicine in South America for treating fever, malaria, dysentery, snake bites, etc. Because of its strong adaptability and ability to inhibit the growth of its associated plants, Mikania micrantha is considered an invasive species in China and is known as a plant killer. Preliminary studies have shown that Mikania micrantha has an antipruritic effect, but the antipruritic active substance is not yet clear. In this study, a 4-aminopyridine-induced itching model in mice was used to determine the antipruritic effects of petroleum ether, ethyl acetate, ethanol extraction site, and Mikania micrantha volatile oil. GC-MS was used to analyze the components of the antipruritic fractions, combined with mice itch-causing models to study the antipruritic effects of ß-caryophyllene and humulene. The safety of ß-caryophyllene was preliminarily evaluated through the acute toxicity test of mice skin. The ethyl acetate and volatile oil of Mikania micrantha have apparent antipruritic effects. Humulene and ß-caryophyllene have a quantitative-effective relationship to inhibit itching in mice. The acute toxicity test of mouse skin showed that ß-caryophyllene has no acute toxicity. This study indicated that the main antipruritic active ingredients of Mikania micrantha are ß-caryophyllene and humulene.

Network pharmacology to explore the molecular mechanisms of Prunella vulgaris for treating thyroid cancer.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy that has rapidly increased in global incidence. Prunella vulgaris (PV) has manifested therapeutic effects in patients with TC. We aimed to investigate its molecular mechanisms against TC and provide potential drug targets by using network pharmacology and molecular docking. METHODS: The ingredients of PV were retrieved from Traditional Chinese Medicine Systematic Pharmacology Database. TC-related gene sets were established using the GeneCard and OMIM databases. The establishment of the TC-PV target gene interaction network was accomplished using the STRING database. Cytoscape constructed networks for visualization. Protein-protein interaction, gene ontology and the biological pathway Kyoto encyclopedia of genes and genomes enrichment analyses were performed to discover the potential mechanism. Molecular docking technology was used to analyze the effective compounds from PV for treating TC. RESULTS: 11 active compounds and 192 target genes were screened from PV. 177 potential targets were obtained by intersecting PV and TC gene sets. Network pharmacological analysis showed that the PV active ingredients including Vulgaxanthin-I, quercetin, Morin, Stigmasterol, poriferasterol monoglucoside, Spinasterol, kaempferol, delphinidin, stigmast-7-enol, beta-sitosterol and luteolin showed better correlation with TC target genes such as JUN, AKT1, mitogen-activated protein kinase 1, IL-6 and RELA. The gene ontology and Kyoto encyclopedia of genes and genomes indicated that PV can act by regulating the host defense and response to oxidative stress immune response and several signaling pathways are closely associated with TC, such as the TNF and IL-17. Protein-protein interaction network identified 8 hub genes. The molecular docking was conducted on the most significant gene MYC. Eleven active compounds of PV can enter the active pocket of MYC, namely poriferasterol monoglucoside, stigmasterol, beta-sitosterol, vulgaxanthin-I, spinasterol, stigmast-7-enol, luteolin, delphinidin, morin, quercetin and kaempferol. Further analysis showed that oriferasterol monoglucoside, followed by tigmasterol, were the potential therapeutic compound identified in PV for the treatment of TC. CONCLUSION: The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of PV. MYC is a promising drug target to reduce oxidative stress damage and potential anti-tumor effect. Oriferasterol monoglucoside and kaempferol were 2 bioactive compounds of PV to treat TC. This provides a basis to understand the mechanism of the anti-TC activity of PV.

A review of traditional Chinese medicine Curcumae Rhizoma for treatment of glioma.

Glioma is the most common primary central nervous tumor and its malignant and high recurrence rate are seriously threatening patient's life. The prognosis of glioma patients is still poor with a variety of modern treatments. Traditional Chinese medicine (TCM) is widely used in the adjuvant treatment or alternative medicine of glioma. Curcumae Rhizoma is one of the most commonly used in traditional Chinese medicine prescriptions for its anti-tumor characteristics. There are also many studies that reveals the anti-tumor effect of its active ingredients and some of which have been made into drugs and have been used in clinical practice. This review summarizes the new research progress on Curcumae Rhizoma for the treatment of glioma in recent years.

[Intelligent co-design of material, process, and equipment for manufacturing high-quality traditional Chinese medicine preparations].

In the context of Pharma 4.0, the design tools that support the pharmaceutical Quality by Design(QbD) are iterating fast toward intelligent or smart design. The conventional development methods for traditional Chinese medicine(TCM) preparations have the limitations such as over dependence on experience, low dimensions for the designed experiment parameters, poor compatibility between the process and equipment, and high trial-and-error cost during process scale-up. Therefore, this paper innovatively proposed the intelligent co-design involving material, process, and equipment for manufacturing high-quality TCM preparations, and introduced the design philosophy, targets, tools, and applications with TCM oral solid dosage(OSD) as an example. In terms of design philosophy, the pharmaceutical design tetrahedron composed of critical material attributes, critical process parameters, critical equipment attributes, and critical quality attributes was developed. The design targets were put forward based on the product performance classification system. The design tools involve a design platform that contains several modules, such a as the iTCM material database, the processing route classification system, the system modeling and simulation, and reliability-based optimization. The roles of different modules in obtaining essential and universal design knowledge of the key common manufacturing units were introduced. At last, the applications of the co-design methodology involving material, process, and equipment in the high shear wet granulation process development and the improvement of the dissolving or dispersion capability of TCM formula granules are illustrated. The research on advanced pharmaceutical design theory and methodology will help enhance the efficiency and reliability of drug development, improve the product quality, and promote the innovation of high-end TCM products across the industry.

[Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(â ¢): classification of granule dissolving behaviors].

Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(ß-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly ß-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.

TiO2-Nanowired Delivery of Chinese Extract of Ginkgo biloba EGb-761 and Bilobalide BN-52021 Enhanced Neuroprotective Effects of Cerebrolysin Following Spinal Cord Injury at Cold Environment.

Military personnel during combat or peacekeeping operations are exposed to extreme climates of hot or cold environments for longer durations. Spinal cord injury is quite common in military personnel following central nervous system (CNS) trauma indicating a possibility of altered pathophysiological responses at different ambient temperatures. Our previous studies show that the pathophysiology of brain injury is exacerbated in animals acclimated to cold (5 °C) or hot (30 °C) environments. In these diverse ambient temperature zones, trauma exacerbated oxidative stress generation inducing greater blood-brain barrier (BBB) permeability and cell damage. Extracts of Ginkgo biloba EGb-761 and BN-52021 treatment reduces brain pathology following heat stress. This effect is further improved following TiO2 nanowired delivery in heat stress in animal models. Several studies indicate the role of EGb-761 in attenuating spinal cord induced neuronal damages and improved functional deficit. This is quite likely that these effects are further improved following nanowired delivery of EGb-761 and BN-52021 with cerebrolysin-a balanced composition of several neurotrophic factors and peptide fragments in spinal cord trauma. In this review, TiO2 nanowired delivery of EGb-761 and BN-52021 with nanowired cerebrolysin is examined in a rat model of spinal cord injury at cold environment. Our results show that spinal cord injury aggravates cord pathology in cold-acclimated rats and nanowired delivery of EGb-761 and BN-52021 with cerebrolysin significantly induced superior neuroprotection, not reported earlier.

Nanowired Delivery of Curcumin Attenuates Methamphetamine Neurotoxicity and Elevates Levels of Dopamine and Brain-Derived Neurotrophic Factor.

Curcumin is a well-known antioxidant used as traditional medicine in China and India since ages to treat variety of inflammatory ailments as a food supplement. Curcumin has antitumor properties with neuroprotective effects in Alzheimer's disease. Curcumin elevates brain-derived neurotrophic factor (BDNF) and dopamine (DA) levels in the brain indicating its role in substance abuse. Methamphetamine (METH) is one of the most abused substances in the world that induces profound neurotoxicity by inducing breakdown of the blood-brain barrier (BBB), vasogenic edema and cellular injuries. However, influence of curcumin on METH-induced neurotoxicity is still not well investigated. In this investigation, METH neurotoxicity and neuroprotective effects of curcumin nanodelivery were examined in a rat model. METH (20 mg/kg, i.p.) neurotoxicity is evident 4 h after its administration exhibiting breakdown of BBB to Evans blue albumin in the cerebral cortex, hippocampus, cerebellum, thalamus and hypothalamus associated with vasogenic brain edema as seen measured using water content in all these regions. Nissl attaining exhibited profound neuronal injuries in the regions of BBB damage. Normal curcumin (50 mg/kg, i.v.) 30 min after METH administration was able to reduce BBB breakdown and brain edema partially in some of the above brain regions. However, TiO2 nanowired delivery of curcumin (25 mg/kg, i.v.) significantly attenuated brain edema, neuronal injuries and the BBB leakage in all the brain areas. BDNF level showed a significant higher level in METH-treated rats as compared to saline-treated METH group. Significantly enhanced DA levels in METH-treated rats were also observed with nanowired delivery of curcumin. Normal curcumin was able to slightly elevate DA and BDNF levels in the selected brain regions. Taken together, our observations are the first to show that nanodelivery of curcumin induces superior neuroprotection in METH neurotoxicity probable by enhancing BDNF and DA levels in the brain, not reported earlier.

Reveal the Patterns of Prescriptions for Recurrent Respiratory Tract Infections' Treatment Based on Multiple Illustrious Senior Traditional Chinese Medicine Practitioners.

Background: Recurrent respiratory tract infections (RRTIs) are one of the most common diseases in children and adolescents. The causes of RRTIs are various. In addition to the factors related to infection, basic diseases such as respiratory system, immune system, and digestive system are also involved. The cost of patients' frequent medical treatment and hospitalization has been deemed to be a heavy burden to the society and family. In China, traditional Chinese medicine (TCM) is commonly used to treat RRTIs. TCM treatment has been appraised to be effective, for reducing the number of hospital stays. Illustrious senior TCM practitioners of pediatrics are recognized as a group of outstanding physicians with significantly better patient outcomes. However, different illustrious senior TCM practitioners can lead to differences in treatment strategies due to factors such as region, prescription theory, and individual differences of patients. This makes it difficult for the experience of illustrious senior TCM practitioners to be popularized. However, there have been no prescription mining studies for the treatment of RRTIs based on different and multiple illustrious senior TCM practitioners. We explored the core prescriptions and drug mechanisms through data mining based on the prescriptions of illustrious senior TCM practitioners treating RRTIs from different clinical settings. This is important to promote the effective treatment of RRTIs with TCM. The objective of this study is to reveal the strategies (core prescriptions) from the prescriptions of multiple illustrious senior TCM practitioners for the treatment of RRTIs. We hope that this core prescription can help all TCM pediatricians to improve RRTIs children's outcome. Meanwhile, it could provide a new way for researchers to study the treatment of RRTIs. Methods: In this study, we prospectively collected 400 children's prescriptions with RRTIs receiving TCM treatment from four illustrious senior TCM practitioners in different hospitals. We described and analyzed the characteristics of TCM prescriptions. The prescription regularity was analyzed by hierarchical clustering and association rules. Network pharmacology methods has been used to reveal the pathway mechanism of core prescriptions which have been mined and visualized with the help of SymMap, Genecards, KEGG, Metascape databases, and R. The execution of all methods was completed in May 2022. Results: According to RRTIs multiple clinical syndromes, five new prescriptions were obtained based on illustrious senior TCM practitioners. Among them, the prescription composed of Scutellariae radix (Huangqin), Armeniacae semen amarum (Kuxingren), Peucedani radix (Qianhu), and Pheretima (Dilong) is the core strategy for the treatment of RRTIs. Cold herbs and heat herbs in the core prescription are approximately equal. Scutellariae radix (Huangqin) was dominant, and other herbs exert synergistic effects. The core prescription covered 76 pathways and 226 herb-disease genes. It promotes the differentiation of Th1, Th2, and Th17 cells and the secretion of inflammatory factors through toll-like receptor signaling pathway in the immune system, T cell receptor signaling pathway, and PPAR signaling pathway in the endocrine system, thereby exerting immune regulation and anti-inflammation. Conclusion: In this study, we revealed the prescription regularity of TCM in the treatment of RRTIs and analyzed the mechanism of core prescriptions, which provided new ideas for the treatment of RRTIs.

Nitidine Chloride Triggers Autophagy and Apoptosis of Ovarian Cancer Cells through Akt/mTOR Signaling Pathway.

OBJECTIVE: Ovarian cancer (OC) is the eighth most common cancer with high mortality in women worldwide. Currently, compounds derived from Chinese herbal medicine have provided a new angle for OC treatment. METHODS: In this study, the cell proliferation and migration of ovarian cancer A2780/SKOV3 cells were inhibited after being treated with nitidine chloride (NC) by using MTT and Wound-Healing Assay. Flow cytometry analysis indicated NC-induced apoptosis of ovarian cancer cells, and AO and MDC staining showed that NC treatment induced the appearance of autophagosomes and autophagic lysosomes in ovarian cancer cells. RESULTS: Through the autophagy inhibition experiment of chloroquine, it was proved that NC significantly further promoted apoptosis in ovarian cancer cells. Furthermore, NC proved that it could significantly decrease the expression of autophagy-related genes such as Akt, mTOR, P85 S6K, P70 S6K, and 4E-BP1. CONCLUSION: Therefore, we suggest that NC could trigger autophagy and apoptosis of ovarian cancer cells through Akt/mTOR signaling pathway, and NC may potentially be a target for chemotherapy against ovarian cancer.

[Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine].

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Comparison of lipid structure and composition in human or cow's milk with different fat globules by homogenization.

Homogenization is used in human milk to add supplements for premature infants and in cow's milk to make it more uniform and stable for commercial purposes. However, it may destroy the milk fat globule (MFG) structure and composition, affecting its functional characteristics. This study aims to compare human and cow's milk with particle size ranges of 4-6 µm (large-sized), 1-2 µm (medium-sized), and 0.3-0.5 µm (small-sized) before and after homogenization at different pressure levels. CLSM and SDS-PAGE were used to perform the structural characterization. The lipid compositions were analyzed using GC and LC-MS. The results showed that homogenization obviously changed the MFG structure and its lipid composition. After homogenization, more caseins and whey proteins were adsorbed on both the human and cow's milk fat globule interface, while the proteins observed in human milk were dispersed. This could be attributed to the different types and contents of proteins initially. The influence of homogenization on milk phospholipids was higher than triacylglycerols and fatty acids, which was highly correlated with their initial distributions in MFGs. These results provide new information about the interfacial composition of human and cow's milk fat globules upon homogenization and establish the scientific basis for homogenization application in human and cow's milk to help explore their potential functions.

Tanshinone IIA and hepatocellular carcinoma: A potential therapeutic drug.

Because of its high prevalence and poor long-term clinical treatment effect, liver disease is regarded as a major public health problem around the world. Among them, viral hepatitis, fatty liver, cirrhosis, non-alcoholic fatty liver disease (NAFLD), and autoimmune liver disease are common causes and inducements of liver injury, and play an important role in the occurrence and development of hepatocellular carcinoma (HCC). Tanshinone IIA (TsIIA) is a fat soluble polyphenol of Salvia miltiorrhiza that is extracted from Salvia miltiorrhiza. Because of its strong biological activity (anti-inflammatory, antioxidant), it is widely used in Asia to treat cardiovascular and liver diseases. In addition, TsIIA has shown significant anti-HCC activity in previous studies. It not only has significant anti proliferation and pro apoptotic properties. It can also play an anti-cancer role by mediating a variety of signal pathways, including phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-B (NF-κB). This review not only reviews the existing evidence and molecular mechanism of TsIIA's anti-HCC effect but also reviews the liver-protective effect of TsIIA and its impact on liver fibrosis, NAFLD, and other risk factors for liver cancer. In addition, we also conducted network pharmacological analysis on TsIIA and HCC to further screen and explore the possible targets of TsIIA against hepatocellular carcinoma. It is expected to provide a theoretical basis for the development of anti-HCC-related drugs based on TsIIA.

The San-Qi-Xue-Shang-Ning formula protects against ulcerative colitis by restoring the homeostasis of gut immunity and microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a major cause of morbidity and mortality due to repetitive remissions and relapses, and many severe complications, including colitis-associated cancer (CAC). The San-Qi-Xue-Shang-Ning (SQ) formula has been utilized in clinical practice to treat gut diseases, but its pharmacological evidence is limited and awaits elucidation. AIM OF THE STUDY: Here, we elucidated the molecular mechanisms of the SQ formula. MATERIALS AND METHODS: Its therapeutic value in combating UC and CAC was predicted from network pharmacology and weighted gene co-expression network analysis (WGCNA). Experimental colitis models were established by feeding dextran sodium sulfate (DSS) to C57BL/6N mice for 7 days, and they were subjected to the SQ formula for 14 days. High-throughput technologies and biochemical investigations were executed to corroborate the anti-colitis effect. RESULTS: Network pharmacology and WGCNA demonstrated that the targets of the SQ formula were associated with interleukin-17 (IL-17), tumor necrosis factor (TNF), IL-1b and peroxisome proliferators-activated receptor (PPAR) signaling pathways, and correlated with the survival in patients with colorectal cancer. In mice with colitis, the SQ treatment hindered colitis progression in a dose-dependent manner, as evidenced by the rescued colon length and weight loss, improved colonic epithelial integrity, and abolished crypt loss. In addition to the suppressed serum IL-17, TNFα, and IL-1b levels, the SQ-treated colitis mice exhibited decreased colonic protein abundance of hypoxia-inducible factor-1α (HIF-1 α), PPARα, and Caspase3 (Casp3) with an increased PPARγ expression. Concurrently, the high dose of SQ promoted the alternative activation of peritoneal macrophages by increasing Arg1 and inhibiting iNOS2, thereby facilitating the migration of NCM460 cells and controlling TNF-induced reactive oxygen species production and apoptosis in intestinal organoids. In colitis-accompanied dysbiosis, the SQ formula reversed the decreased microbiota diversity indexes and restored the microbiome profile in the murine colitis models. CONCLUSION: The SQ formula is a potent anti-colitis drug that facilitates inflammation resolution and restores gut microbiota homeostasis.

Molecular mechanism of phosphorous signaling inducing anthocyanin accumulation in Arabidopsis.

Anthocyanins, flavonoid compounds derived from secondary metabolic pathways, play important roles in various biological processes. Phosphorus (P) is an essential macroelement for plant growth and development, and P-starvation usually results in anthocyanin accumulation. However, the molecular mechanism of P deficiency promotes anthocyanin biosynthesis has not been well characterized. Here, we provided evidence that the P signaling core protein PHOSPHATE STARVATION RESPONSE1 (PHR1) is physically associate with transcription factors (TFs) involved in anthocyanidin biosynthesis, including PRODUCTION OF ANTHOCYANIN PIGMENTS1 (PAP1/MYB75), MYB DOMAIN PROTEIN 113 (MYB113) and TRANSPARENT TESTA 8 (TT8). PHR1 and its homologies positively regulated anthocyanin accumulation in Arabidopsis seedlings under P-deficient conditions. Disruption of PHR1 simultaneously rendered seedlings hyposensitive to limiting P, whereas the overexpression of PHR1 enhanced P- deficiency-induced anthocyanin accumulation. Genetic analysis demonstrated that 35S:PHR1-2HA-5 seedlings partially recovers the P deficiency insensitive phenotype of myb-RNAi and tt8 mutants. In summary, our study indicated that protein complexes formed by PHR1 and MBW complex directly mediate the process of P-deficiency-induced anthocyanin accumulation, providing a new mechanistic understanding of how P-deficient signaling depends on the endogenous anthocyanin synthesis pathway to promote anthocyanin accumulation in Arabidopsis.

The Wu-Shi-Cha formula protects against ulcerative colitis by orchestrating immunity and microbiota homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) has become a healthy burden worldwide due to its insidious onset and repetitive relapse, with a rather complex etiology, including inappropriate immune response, dysbiosis, genetic susceptibility, and unhealthy diets. The Wu-Shi-Cha (WSC) formula is a widely utilized drug to protect against gastrointestinal disorders. AIM OF THE STUDY: The study aspired to dissect the pertinent mechanisms of the WSC to treat UC. MATERIALS AND METHODS: Network pharmacology and weighted gene co-expression network analysis (WGCNA) were performed to predict the targets of WSC in the context of UC and colorectal cancer. Dextran sodium sulfate (DSS) was used to construct murine models of experimental colitis, and the WSC was given to colitis mice for 14 days. Feces and colon samples were subjected to 16S rRNA gene sequencing combined with liquid chromatography-mass spectrometry (LC-MS) and biochemical experiments, respectively. RESULTS: Network pharmacology analysis predicted that the WSC formula could orchestrate inflammation, infection, and tumorigenesis, and WGCNA based on The Cancer Genome Atlas (TCGA) database showed a potent anti-neoplastic effect of the WSC therapy for colorectal cancer. The WSC therapy rescued bursts of pro-inflammatory cytokines and colonic epithelial collapse in DSS-induced colitis mice. Moreover, the high dose of WSC treatment facilitated the alternative activation of peritoneal macrophages (Mφs) and these Mφs were conducive to the survival of intestinal stem cells (ISCs), and the disturbed homeostasis of gut microbiota was re-established after WSC treatment, as evidenced by the decreased colonization of pathological taxa in the fecal samples. CONCLUSION: The WSC formula suppresses inflammation and re-establishes the homeostasis of gut microbiota, thereby ameliorating colitis progression.

New insight into scale inhibition during tea brewing: Ca2+/Mg2+ complexing and alkalinity consumption.

Scale not only affects the taste and color of water, but also increases the risks of osteoporosis and cardiovascular diseases associated with drinking it. As a popular beverage, tea is rich many substances that have considerable potential for scale inhibition, including protein, tea polyphenols and organic acids. In this study, the effect of tea brewing on scale formation was explored. It was found that the proteins, catechins and organic acids in tea leaves could be released when the green tea was brewed in water with sufficient hardness and alkalinity. The tea-released protein was able to provide carboxyl groups to chelate with calcium ions (Ca2+), preventing the Ca2+ from reacting with the carbonate ions (CO32-). The B rings of catechins were another important structure in the complexation of Ca2+ and magnesium ions (Mg2+). The carboxyl and hydroxyl groups on the organic acids was able to form five-membered chelating rings with Ca2+ and Mg2+, resulting in a significant decrease in Ca2+ from 100.0 to 60.0 mg/L. Additionally, the hydrogen ions (H+) provided by the organic acids consumed and decreased the alkalinity of the water from 250.0 to 131.4 mg/L, leading to a remarkable reduction in pH from 8.93 to 7.73. It further prevented the bicarbonate (HCO3-) from producing CO32- when the water was heated. The reaction of the tea constituents with the hardness and alkalinity inhibited the formation of scale, leading to a significant decrease in turbidity from 10.6 to 1.4 NTU. Overall, this study provides information to help build towards an understanding of the scale inhibition properties of tea and the prospects of tea for anti-scaling in industrial applications.

Validation of the Anticolitis Efficacy of the Jian-Wei-Yu-Yang Formula.

Background: Inflammatory bowel disease (IBD) is a major cause of morbidity and mortality due to its repetitive remission and relapse. The Jian-Wei-Yu-Yang (JW) formula has a historical application in the clinic to combat gastrointestinal disorders. The investigation aimed to explore the molecular and cellular mechanisms of JW. Methods: 2% dextran sodium sulfate (DSS) was diluted in drinking water and given to mice for 5 days to establish murine models of experimental colitis, and different doses of JW solution were administered for 14 days. Network pharmacology analysis and weighted gene co-expression network analysis (WGCNA) were utilized to predict the therapeutic role of JW against experimental colitis and colitis-associated colorectal cancer (CAC). 16S rRNA sequencing and untargeted metabolomics were conducted using murine feces. Western blotting, immunocytochemistry, and wound healing experiments were performed to confirm the molecular mechanisms. Results: (1) Liquid chromatography with mass spectrometry was utilized to confirm the validity of the JW formula. The high dose of JW treatment markedly attenuated DSS-induced experimental colitis progression, and the targets were enriched in inflammation, infection, and tumorigenesis. (2) The JW targets were related to the survival probability in patients with colorectal cancer, underlying a potential therapeutic value in CRC intervention. (3) Moreover, the JW therapy successfully rescued the decreased richness and diversity of microbiota, suppressed the potentially pathogenic phenotype of the gut microorganisms, and increased cytochrome P450 activity in murine colitis models. (4) Our in vitro experiments confirmed that the JW treatment suppressed caspase3-dependent pyroptosis, hypoxia-inducible factor 1α (HIF1α), and interleukin-1b (IL-1b) in the colon; facilitated the alternative activation of macrophages (Mφs); and inhibited tumor necrosis factor-α (TNFα)-induced reactive oxygen species (ROS) level in intestinal organoids (IOs). Conclusion: The JW capsule attenuated the progression of murine colitis by a prompt resolution of inflammation and bloody stool and by re-establishing a microbiome profile that favors re-epithelization and prevents carcinogenesis.

Poly-l-lysine derivative-coated black phosphorus as a nanoplatform for photothermal chemotherapy to enhance anti-tumor efficiency.

Severe systemic toxicity and side effects are major obstacles to the success of chemotherapy for tumors. Regardless of the choice of chemotherapy drugs, the safety of drug delivery materials is crucial, and therefore, there have been various efforts to improve the therapeutic effect and the biological safety of drug delivery systems (DDSs). In this study, a dual stimulus-response DDS (PLL-SS@DOX-BP) was constructed based on the biomaterials of black phosphorus (BP) nanosheets and poly-l-lysine (PLL) to enhance the treatment of doxorubicin hydrochloride (DOX) for breast cancer. The PLL derivative was nano-coated on the surface of drug-loaded BP nanosheets, and it prevented premature leakage of the drug and maintained the stability of the DDS. The introduced disulfide bonds and photothermal agent BP enabled the redox and near-infrared responsive drug release of the DDS, and the coated PLL derivative on the nanocarrier decreased premature leakage of the drug before the DDS reached the tumor tissues. The in vitro and in vivo experiments showed that the combination of biomaterial (PLL) and photothermal material (BP nanosheets) exhibited excellent biological safety and remarkable drug delivery capacity. Moreover, the pharmacodynamic studies indicated that PLL-SS@DOX-BP is a powerful vehicle for photothermal therapy in combination with chemotherapy. Compared with chemotherapy alone, the developed DDS displayed enhanced anti-tumor efficiency with decreased systemic toxicity, and thus, it has the potential to be a promising anti-tumor treatment strategy.