[Effects of Organic Fertilizer of Kitchen Waste on Soil Microbial Activity and Function].

Changes in soil microbial activity and ecological function can be used to assess the level of soil fertility and the stability of ecosystems. To assess the fertility and safety of organic fertilizer of kitchen waste (OFK), soils containing 0% (CK), 1%, 3%, and 5% OFK were cultured, and the physical, chemical, and microbial properties of the soils were measured dynamically with routine agrochemical analysis measures and amplicon sequencing. The results showed that compared with those in CK, the contents of organic matter, available phosphorus, available potassium, NH4+-N, and NO3--N in soils with OFK increased by 23.80%-35.13%, 13.29%-29.72%, 16.91%-39.37%, 164.7%-340.2%, and 28.56%-32.71%, respectively. The activities of hydrolases related to the cycle of carbon, nitrogen, and phosphorus (α-glucosidase, leucine aminopeptidase, acid phosphatase, etc.) were also significantly higher than those of the CK treatment. OFK stimulated the growth of soil microorganisms and increased the carbon content of the microbial biomass. The amplicon sequencing analysis found that the microbial community structures of different treatments were significantly different at both the class and genus levels. In addition, it was found that the abundance of beneficial microbes in the soils with OFK increased, whereas pathogenic microbes decreased. RDA results confirmed that soil properties (including soil pH, organic matter, available nutrients, and microbial biomass) had a significant impact on microbial community structure. The results of investing bacterial community based on PICRUSt and FAPROTAX revealed that the function of the soil bacterial community was similar in the four treatments, but OFK supply significantly improved the microbial carbon utilization and metabolic ability. Moreover, by using the FUNGuild software, we found that the application of OFK increased the proportion of saprotroph-symbiotroph and symbiotroph and stimulated the growth of ectomycorrhizal fungi-undefined saprophytic fungi but inhibited plant and animal pathogenic fungi in soil. These results implied that OFK could promote the establishment of symbiotic relationships and inhibit the growth of pathogenic fungi. In summary, OFK could improve soil fertility and hydrolase activity, stimulate the growth of beneficial microorganisms, and defend against pathogens, indicating a promising use as safe and efficient organic fertilizer.

Trends in parthenolide research over the past two decades: A bibliometric analysis.

Parthenolide (PTL) is a new compound extracted from traditional Chinese medicine. In recent years, it has been proven to play an undeniable role in tumors, autoimmune diseases, and inflammatory diseases. Similarly, an increasing number of experiments have also confirmed the biological mechanism of PTL in these diseases. In order to better understand the development trend and potential hot spots of PTL in cancer and other diseases, we conducted a detailed bibliometric analysis. The purpose of presenting this bibliometric analysis was to highlight and inform researchers of the important research directions, co-occurrence relationships and research status in this field. Publications related to PTL research from 2002 to 2022 were extracted on the web of science core collection (WoSCC) platform. CiteSpace, VOSviewers and R package "bibliometrix" were applied to build relevant network diagrams. The bibliometric analysis was presented in terms of performance analysis (including publication statistics, top publishing countries, top publishing institutions, publishing journals and co-cited journals, authors and co-cited authors, co-cited references statistics, citation bursts statistics, keyword statistics and trend topic statistics) and science mapping (including citations by country, citations by institution, citations by journal, citations by author, co-citation analysis, and keyword co-occurrence). The detailed discussion of the results explained the focus and latest trends from the bibliometric analysis. Finally, the current status and shortcomings of the research field on PTLwere clearly pointed out for reference by scholars.

Cylindrin from Imperata cylindrica inhibits M2 macrophage formation and attenuates renal fibrosis by downregulating the LXR-α/PI3K/AKT pathway.

Imperata cylindrica, a medicinal plant used in Traditional Chinese Medicine, has been used to treat chronic kidney disease. Extracts of I. cylindrica display anti-inflammatory, immunomodulatory, and anti-fibrotic properties. However, the active components of the extracts and their protective mechanisms have not been fully elucidated. In this study, we explored the ability of cylindrin, the main active compound extracted from I. cylindrica, to protect against renal fibrosis and to investigate the potential mechanisms involved. At high doses, cylindrin exerted protective effects against folic acid-induced kidney fibrosis in mice. Bioinformatic analysis predicted the LXR-α/PI3K/AKT pathway as a target of regulation by cylindrin. This was supported by our in vitro and in vivo results showing that cylindrin significantly downregulated the expression of LXR-α and phosphorylated PI3K/AKT in M2 macrophages and mouse renal tissues. Furthermore, high-dose cylindrin inhibited M2 polarization of IL-4-stimulated macrophages in vitro. Our results suggest that cylindrin alleviates renal fibrosis by attenuating M2 macrophage polarization through inhibition of the PI3K/AKT pathway via downregulation of LXR-α.

Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells.

BACKGROUND: With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide. METHODS: Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes. RESULTS: With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking. CONCLUSIONS: The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.

Design, synthesis and biological evaluation of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine as anti-hepatocellular carcinoma agents.

A series of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine were designed and synthesized with improved anti-hepatocellular carcinoma (HCC) activities. The optimal compound 4d showed strong activities against HepG2, Sk-Hep-1, Huh-7 and Hep3B cells with IC50 values of 0.58-1.15 µM, which were superior to positive reference cisplatin. Interestingly, 4d exhibited over 40-fold more potent activity against cisplatin-resistant HepG2/DPP cells while showing lower cytotoxicity in normal LX-2 cells. The mechanism studies revealed 4d greatly stabilized G-quadruplex DNA leading to intracellular c-MYC expression downregulation, blocked G2/M-phase cell cycle by affecting related p-cdc25c, cdc2 and cyclin B1 expressions, and induced apoptosis by a ROS-promoted PI3K/Akt-mitochondrial pathway. Furthermore, 4d possessed good pharmacokinetic properties and significantly inhibited the tumor growth in the H22 liver cancer xenograft mouse model without obvious toxicity. Altogether, the remarkably biological profiles of 4d both in vitro and in vivo would make it a promising candidate for HCC therapy.

Effects of saffron supplementation on improving sleep quality: a meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the efficacy of different dosage regimens of saffron supplementation on improving sleep quality among healthy adults, patients with insomnia or type 2 diabetes and patients under Methadone maintenance treatment (MMT). METHODS: PubMed, Embase, The Cochrane Library and other databases were searched from inception until October 2021. Randomized controlled trials (RCTs) investigating the efficacy saffron supplementation on sleep quality were included. Data were extracted independently by 2 investigators and assessed the study quality by the Cochrane risk-of-bias tool. The measurements include Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and Restorative Sleep Questionnaire (RSQ). RESULTS: The pooling of the effect sizes showed that saffron group achieve a notable treatment effect on PSQI (MD: -2.14; 95% CI: -2.86 to -1.42; P < 0.01), ISI (MD: -2.63; 95% CI: -3.70 to -2.55; P < 0.01) and RSQ (MD: 7.05; 95% CI: 1.48 to 12.62; P = 0.01) compared with placebo group. CONCLUSION: Saffron supplementation as a treatment for improving sleep quality have promising clinical application as its great improvement on all efficacy outcomes and no serious adverse advents occurred as the dose was increased. The dose of 100 mg saffron supplementation per day was proved to achieve excellent and more stable curative effect on improving sleep quality in our subgroup analysis. However, further investigation is necessary to confirm the efficacy and long-term safety of different doses of saffron for insomnia.

Loss of MIC60 Aggravates Neuronal Death by Inducing Mitochondrial Dysfunction in a Rat Model of Intracerebral Hemorrhage.

Mitochondrial damage has been reported to be a critical factor for secondary brain injury (SBI) induced by intracerebral hemorrhage (ICH). MIC60 is a key element of the mitochondrial contact site and cristae junction organizing system (MICOS), which takes a principal part in maintaining mitochondrial structure and function. The role of MIC60 and its underlying mechanisms in ICH-induced SBI are not clear, which will be investigated in this present study. To establish and emulate ICH model in vivo and in vitro, autologous blood was injected into the right basal ganglia of Sprague-Dawley (SD) rats; and primary-cultured cortical neurons were treated by oxygen hemoglobin (OxyHb). First, after ICH induction, mitochondria were damaged and exhibited mitochondrial crista-structure remodeling, and MIC60 protein levels were reduced. Furthermore, MIC60 overexpression reduced ICH-induced neuronal death both in vivo and in vitro. In addition, MIC60 upregulation reduced ICH-induced cerebral edema, neurobehavioral impairment, and cognitive dysfunction; by contrast, MIC60 knockdown had the opposite effect. Additionally, in primary-cultured neurons, MIC60 overexpression could reverse ICH-induced neuronal cell death and apoptosis, mitochondrial membrane potential collapse, and decrease of mitophagy, indicating that MIC60 overexpression can maintain the integrity of mitochondrial structures. Moreover, loss of MIC60 is after ICH-induced reduction in PINK1 levels and mislocalization of Parkin in primary-cultured neurons. Taken together, our findings suggest that MIC60 plays an important role in ICH-induced SBI and may represent a promising target for ICH therapy.

Metabonomic study of the intervention effects of Parthenolide on anti-thyroid cancer activity.

Thyroid cancer is the most common endocrine malignant tumor in the world, and its incidence is increasing. Although the mortality rate of thyroid cancer is low, its persistence/recurrence rate is high. In addition, some patients with thyroid cancer fail to respond to radiation. Therefore, it is urgent need to develop a novel treatment for thyroid cancer. Parthenolide (PTL), a traditional Chinese medicine Tanacetum parthenium extract, has shown encouraging effects in anti-tumor, anti-inflammatory and anti-malaria. However, it is unclear whether PTL has an anti-thyroid cancer effect and its possible mechanism of action. In the recent years, metabonomics has been widely used in tumors research to explore the pharmacological mechanism of drugs, but few studies used metabonomics to investigate the pharmacological effects of PTL in thyroid tumors. In order to comprehensively reveal the mechanism and effects of PTL on anti-thyroid tumors, metabonomics combined cell biological research methods were conducted. The results showed that PTL promote apoptosis of thyroid cancer cells (TPC-1) in a concentration-dependent manner. The metabolic differences between the PTL group and the control group were compared by metabonomics, and 31 potential metabolites were identified. These metabolites were mainly involved in the tricarboxylic acid cycle, amino acid metabolism, choline metabolism and lipid metabolism. These results implied that PTL may inhibit the proliferation and development of thyroid carcinoma by accelerating oxidation emergency response, inhibiting adenosine triphosphate (ATP) synthesis and metabolic imbalance. The results of this study revealed that PTL can be an effective and potential drug for the treatment of thyroid cancer.

Sonodynamic therapy in atherosclerosis by curcumin nanosuspensions: Preparation design, efficacy evaluation, and mechanisms analysis.

Previous studies have shown that curcumin (Cur) induced by ultrasound has protective effects on atherosclerosis even if low bioavailability of the Cur. The enhancement of bioavailability of the Cur further improved the curative effect of sonodynamic therapy (SDT) on atherosclerosis through nanotechnology. Nanosuspensions as a good drug delivery system had obvious advantages in increasing the solubility and improving the effectiveness of insoluble drugs. The aim of this study was to develop curcumin nanosuspensions (Cur-ns) which used polyvinylpyrrolidone (PVPK30) and sodium dodecyl sulfate (SDS) as stabilizers to improve poor water solubility and bioavailability of the Cur. And then the therapeutic effects of Cur-ns-SDT on atherosclerotic plaques and its possible mechanisms would be investigated and elucidated. Cur-ns with a small particle size has been successfully prepared and the data have confirmed that Cur-ns could be more easily engulfed into RAW264.7 cells than free Cur and accumulated more under the stimulation of the ultrasound. Reactive oxygen species (ROS) inside RAW264.7 cells after SDT led to the decrease of mitochondrial membrane potential (MMP) and the higher expression of cleaved caspase-9/3. The results of in vivo experiments showed that Cur-ns-SDT reduced the level of total cholesterol (TC) and low density lipoprotein (LDL) and promoted the transformation from M1 to M2 macrophages, relieved atherosclerosis syndrome. Therefore, Cur-ns-SDT was a potential treatment of anti-atherosclerosis by enhancing macrophages apoptosis through mitochondrial pathway and inhibiting the progression of plaques by interfering with macrophages polarization.

2-hydroxy-3-methylanthraquinone from Hedyotis diffusa Willd induces apoptosis in human leukemic U937 cells through modulation of MAPK pathways.

The herb of Hedyotis diffusa Willd (H. diffusa Willd), an annual herb distributed in northeastern Asia, has been known as a traditional oriental medicine for the treatment of cancer. Recently, Chinese researchers have discovered that two anthraquinones isolated from a water extract of H. diffusa Willd showed apoptosis-inducing effects against cancer cells. However, the cellular and molecular mechanisms responsible for this phenomenon are poorly understood. The current study determines the role of mitogen-activated protein kinases (MAPK) in human leukemic U937 cells apoptosis induced by 2-hydroxy-3-methylanthraquinone from H. diffusa. Our results showed that 2-hydroxy-3-methylanthraquinone decreased phosphorylation-ERK1/2 (p-ERK1/2), and increased p-p38MAPK, but did not affect expressions of p-JNK1/2 in U937 cells. Moreover, treatment of U937 cells with 2-hydroxy-3-methylanthraquinone resulted in activation of caspase-3. Furthermore, PD98059 (ERK1/2 inhibitor) significantly enhanced 2-hydroxy-3-methylanthraquinone-induced apoptosis in U937 cells, whereas caspase-3 inhibitor or SB203580 (p-p38MAPK inhibitor), decreased apoptosis in U937 cells. Taken together, our study for the first time suggests that 2-hydroxy-3-methylanthraquinone is able to enhance apoptosis of U937 cells, at least in part, through activation of p-p38MAPK and downregulation of p-ERK1/2. Moreover, the triggering of caspase-3 activation mediated apoptotic induction.

Active lipids of Ganoderma lucidum spores-induced apoptosis in human leukemia THP-1 cells via MAPK and PI3K pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Lingzhi) is traditionally drug, which has been traditionally effective used in the treatment of chronic hepatopathy, hypertension, hyperglycemia and cancer. MATERIALS AND METHODS: THP-1 and HL-60 apoptosis induced by active lipids of Ganoderma lucidum spores was quantified by flow cytometry using FITC-conjugated annexin V and PI; MAPK and Akt were measured by Western blot, and caspase-3, -8 and -9 activities were also detected by spectrophotometric assay. RESULTS: Our results showed that active lipids of Ganoderma lucidum spores decreased phosphorylation-ERK1/2 (P-ERK1/2), P-Akt and increased P-JNK1/2, but did not affect expressions of P-p38 MAPK in THP-1 cells. Moreover, treatment of THP-1 cells with active lipids of Ganoderma lucidum spores resulted in activation of caspase-3, -8 and -9. Furthermore, LY294002 (Akt inhibitor) or PD98059 (ERK1/2 inhibitor) significantly enhanced active lipids of Ganoderma lucidum spores-induced apoptosis in THP-1 cells, whereas caspase inhibitors or SP600125 (JNK inhibitor), decreased apoptosis in THP-1 cells. CONCLUSION: Taken together, our study for the first time suggests that active lipids of Ganoderma lucidum spores is able to enhance apoptosis in THP-1 cells, at least in part, through inhibition of ERK1/2, Akt and activation of JNK1/2 signaling pathways. Moreover, it also triggers caspase-3, -8 and -9 activation mediated apoptotic induction.