Yinchen gongying decoction mitigates CCl4-induced chronic liver injury and fibrosis in mice implicated in inhibition of the FoxO1/TGF-ß1/ Smad2/3 and YAP signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis (LF) is a common reversible consequence of chronic liver damage with limited therapeutic options. Yinchen Gongying decoction (YGD) composed of two homologous plants: (Artemisia capillaris Thunb, Taraxacum monochlamydeum Hand.-Mazz.), has a traditionally application as a medicinal diet for acute icteric hepatitis. However, its impact on LF and underlying mechanisms remain unclear. AIM OF THE STUDY: This study aims to assess the impact of YGD on a carbon tetrachloride (CCl4) induced liver fibrosis and elucidate its possible mechanisms. The study seeks to establish an experimental foundation for YGD as a candidate drug for hepatic fibrosis. MATERIALS AND METHODS: LC-MS/MS identified 11 blood-entry components in YGD, and network pharmacology predicted their involvement in the FoxO signaling pathway, insulin resistance, and PI3K-AKT signaling pathway. Using a CCl4-induced LF mouse model, YGD's protective effects were evaluated in comparison to a positive control and a normal group. The underlying mechanisms were explored through the assessments of hepatic stellate cells (HSCs) activation, fibrotic signaling, and inflammation. RESULTS: YGD treatment significantly improved liver function, enhanced liver morphology, and reduced liver collagen deposition in CCl4-induced LF mice. Mechanistically, YGD inhibited HSC activation, elevated MMPs/TIMP1 ratios, suppressed the FoxO1/TGF-ß1/Smad2/3 and YAP pathways, and exhibited anti-inflammatory and antioxidant effects. Notably, YGD improved the insulin signaling pathway. CONCLUSION: YGD mitigates LF in mice by modulating fibrotic and inflammatory pathways, enhancing antioxidant responses, and specifically inhibiting FoxO1/TGF-ß1/Smad2/3 and YAP signal pathways.

Identification of peanut skin components for treating hepatocellular carcinoma via network pharmacology and in vitro experiments.

Peanut skin (PS) contains various flavonoids and phenols that have antitumor and antioxidant effects. However, no research has been conducted on PS and hepatocellular carcinoma (HCC). Therefore, this study sought to explore the potential mechanism of PS in treating HCC. PS was searched for in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SYMMAP databases. HCC targets were searched for in five major databases. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Molecular docking and molecular dynamics simulation were used for verification. Furthermore, in vitro experiments were used to verify the regulation of PS on human HCC (HepG2) cells. Ten ingredients and 95 common targets were identified for PS and HCC, respectively. The key targets of ingredients mainly relate to pathways such as hepatitis B, lipid and atherosclerosis, advanced glycation end products (AGEs)-AGE receptors (RAGEs) signaling pathway in diabetic complications, interleukin-17 (IL-17) signaling pathway, mitogen activated kinase-like protein (MAPK) signaling pathway, the PI3K-Akt signaling pathway. In addition, the molecular docking and molecular dynamics simulation analysis indicated the ingredients had strong binding ability with the targets. Moreover, in vitro experiments confirmed that luteolin can promote the apoptosis of HepG2 cells by controlling the expression of phosphorylated protein-tyrosine kinase (p-AKT). This study provides preliminary evidence that PS produces a marked effect in regulating multiple signaling pathways in HCC through multiple ingredients acting on multiple core genes, including AKT serine/threonine kinase 1 (AKT1), MYC, caspase 3 (CASP3), estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), jun proto-oncogene(JUN), and provides the basis for follow-up research to verify the mechanism of action of PS in treating HCC.

Glutamine enhances sucrose taste through a gut microbiota-gut-brain axis in Drosophila.

AIMS: Amino acids (AAs) are known to play important roles in various physiological functions. However, their effect on sweet taste perception remains largely unknown. MAIN METHODS: We used Drosophila to evaluate the effect of each AA on sucrose taste perception. Individual AA was supplemented into diets and male flies were fed on these diets for 6 days. The proboscis extension response (PER) assay was applied to assess the sucrose taste sensitivity of treated flies. We further utilized the RNA-seq and germ-free (GF) flies to reveal the underlying mechanisms of sucrose taste sensitization induced by glutamine (Gln). KEY FINDINGS: We found that supplementation of Gln into diets significantly enhances sucrose taste sensitivity. This sucrose taste sensitization is dependent on gut microbiota and requires a specific gut bacterium Acetobacter tropicalis (A. tropicalis). We further found that CNMamide (CNMa) in the gut and CNMa receptor (CNMaR) in dopaminergic neurons are required for increased sucrose taste sensitivity by Gln diet. Finally, we demonstrated that a gut microbiota-gut-brain axis is required for Gln-induced sucrose taste sensitization. SIGNIFICANCE: These findings can advance understanding of the complex interplay between host physiology, dietary factors, and gut microbiota.

Clinical and Animal Studies of Waist and Knee Scraping Therapy for Knee Osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is a degenerative condition with knee pain as the main clinical manifestation. Scraping is one of the commonly used traditional Chinese medicine treatment methods, which activates blood circulation, removes blood stasis, reduces inflammation, and so on. Although scholars have proposed that the synergistic treatment of the waist and knee for KOA is superior to simple knee treatment, there is no relevant reference literature on the application of scraping therapy. Therefore, this study aims to explore the effectiveness and potential mechanisms of waist and knee scraping therapy for treating KOA through clinical and animal studies in order to promote its clinical application. OBJECTIVE: To explore the clinical efficacy of waist and knee scraping therapy in the treatment of KOA from clinical study and increase animal study on this basis to preliminarily explore its mechanism, providing an objective basis for better treatment of KOA. METHOD: The clinical study recruited 90 KOA patients and divided them into a control group, a knee scraping group, and a waist and knee scraping group using a random number table method. All patients were evaluated for clinical efficacy, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and Traditional Chinese Medicine Syndrome Score. The KOA rat model was established using the Hulth method. The rats were randomly divided into a control group, KOA group, waist scraping group, knee scraping group, and waist and knee scraping group. During the intervention process of rats, the pain sensitivity threshold was measured, and HE staining was performed on the synovium and cartilage. The protein and mRNA expression levels of TNF-α, IL- 1ß, IL-6, PGP9.5, SP and TRPA1, TRPV4, SP, and NGF were measured by Western blot and real-time PCR. RESULTS: In the clinical study, the clinical efficacy of the 2 scraping groups was significantly higher than that of the control group. The clinical efficacy of the waist and knee scraping group on the 60th day of treatment was significantly higher than that of the knee scraping group. In terms of improving WOMAC scores, all 3 groups had significance; The function and total score of the waist and knee scraping group on the 28th day of treatment, as well as the pain, function, and total score on the 60th day, were lower than those of the knee scraping group. In terms of improving pain while standing, pain when walking on flat ground, and total score, the scraping group had significant differences. The score of heavy limbs in the waist and knee scraping group was lower than that in the knee scraping group. In an animal study, during the 4th week after modeling, there were differences in the pain sensitivity threshold between the KOA group and the waist scraping group compared to the control group, while there were differences in the pain sensitivity threshold between the knee scraping group and the waist and knee scraping group compared to the KOA group. The expression levels of various proteins and genes in the KOA group and waist scraping group increased compared to the control group; The knee scraping group and the waist and knee scraping group were lower than those in the KOA group. CONCLUSION: Scraping therapy can significantly alleviate knee joint pain and stiffness, improve joint function, and improve clinical efficacy, and the short-term and long-term effects of waist and knee scraping therapy are more significant. The scraping therapy has a definite therapeutic effect on KOA rats, which can improve the threshold of cold hyperalgesia and mechanical hyperalgesia, and the waist and knee scraping therapy is more obvious. This may be related to reducing inflammatory reactions in synovial and ganglion tissues. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR230070623.

Perspective of Calcium Imaging Technology Applied to Acupuncture Research.

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.

In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model.

Due to its intricate heterogeneity, high invasiveness, and poor prognosis, triple-negative breast cancer (TNBC) stands out as the most formidable subtype of breast cancer. At present, chemotherapy remains the prevailing treatment modality for TNBC, primarily due to its lack of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth receptor 2 (HER2). However, clinical chemotherapy for TNBC is marked by its limited efficacy and a pronounced incidence of adverse effects. Consequently, there is a pressing need for novel drugs to treat TNBC. Given the rich repository of diverse natural compounds in traditional Chinese medicine, identifying potential anti-TNBC agents is a viable strategy. This study investigated lasiokaurin (LAS), a natural diterpenoid abundantly present in Isodon plants, revealing its significant anti-TNBC activity both in vitro and in vivo. Notably, LAS treatment induced cell cycle arrest, apoptosis, and DNA damage in TNBC cells, while concurrently inhibiting cell metastasis. In addition, LAS effectively inhibited the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and signal transducer and activator of transcription 3 (STAT3), thus establishing its potential for multitarget therapy against TNBC. Furthermore, LAS demonstrated its ability to reduce tumor growth in a xenograft mouse model without exerting detrimental effects on the body weight or vital organs, confirming its safe applicability for TNBC treatment. Overall, this study shows that LAS is a potent candidate for treating TNBC.

Influence of standardized nursing intervention combined with mindfulness stress reduction training on the curative effect in patients with acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common inflammatory disease of the pancreas with high mortality rates. It is of great significance to take scientific intervention measures for patients with AP in time. AIM: To explore the effect of standardized nursing combined with mindfulness stress reduction training on the curative effect, negative emotion, and quality of life in patients with acute pancreatitis. METHODS: A total of 80 patients with acute pancreatitis admitted to The First People's Hospital of Jiangxia District Hospital from May 2021 to May 2023 were randomly divided into control group and observation group (n = 40). Patients in control group were given the standardized nursing intervention, and the observation group were given standardized nursing plus mindfulness stress reduction training intervention. The time of clinical symptom disappeared or improved, complication occurrence rate, emotional state, and quality of life score of the two groups were observed and compared. RESULTS: In comparison with the control group, the bowel sound recovery time, ventosity and abdominal pain improvement time, and venting and cacation time in observation group were shorter, and the total incidence rate of complications was reduced, showing statistically significant difference (P < 0.05). The scores of anxiety and depression in observation group were lower than those in control group (P < 0.05). Serum levels of tumour necrosis factor alpha, interleukin (IL)-6, IL-1ß and IL-8 in observation group were lower than those in control group (P < 0.05). The scores of life quality in physiology, psychology, environment and social relations in observation group were higher than those in control group, and the differences were statistically significant (P < 0.05). CONCLUSION: The application of standardized nursing intervention combined with mindfulness stress reduction training in patients with acute pancreatitis has a definite effect, which can help to ameliorate the clinical symptoms, anxiety and depression of patients, reduce the incidence rate of complications, and improve the prognosis of patients.

[Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells].

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) µg·h·mL~(-1) to(550.39±12.34) µg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) µg·h·mL~(-1) to(0.65±0.04) µg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) µg·h·mL~(-1) to(96.21±3.75) µg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.

A summary of calixarene-based fluorescent sensors developed during the past five years.

Calixarenes are "chalice like" phenol-based macrocycles that are one of the most fascinating studied scaffolds in supramolecular chemistry. Their preorganized nonpolar cavities and ion binding sites, and their well-defined conformations all lay important foundations for forming host-guest complexes. Conjugation of calixarene scaffolds with various fluorophores at either upper or lower rims has led to the development of smart fluorescent probes for inorganic molecules or ions, aliphatic or aromatic compounds, biomolecules, temperature and hypoxia, even multi-component traditional Chinese medicine (TCM). Moreover, significant advancements have been made for biological applications. This review critically summarizes the recent advances made in these areas.

Association of folic acid dosage with circulating unmetabolized folic acid in Chinese adults with H-type hypertension: a multicenter, double-blind, randomized controlled trial.

Background: There is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized clinical trial has been conducted to examine the FA-UMFA dose-response relationship. Objective: This study aimed to investigate the FA-UMFA dose-response relationship in Chinese adults with hypertension and elevated homocysteine (H-type hypertension), a population with clear clinical indication for FA treatment. Methods: The data for this study were derived from a randomized, double-blind, multicenter clinical trial of 8 FA dosages on efficacy of homocysteine (Hcy) lowering. The parent trial had three 3 stages: screening period (2-10 days), run-in period (0-2 weeks, baseline visit), and double-blind treatment period (8 weeks) with follow-up visits at the end of the 2nd, 4th, 6th, and 8th weeks of treatment. Participants were randomly assigned to 8 treatment groups corresponding to FA dosages of 0, 0.4, 0.6, 0.8, 1.2, 1.6, 2.0 mg to 2.4 mg. Results: This study included 1,567 Chinese adults aged ≥45 years with H-type hypertension. There was a positive but non-linear association between FA supplementation and UMFA levels in the dosage range of 0 mg to 2.4 mg. In the regression analysis, the coefficients for the linear and quadratic terms of FA dosage were both statistically significant (P < 0.001). Notably, the slope for UMFA was greater for FA dosages >0.8 mg (ß = 11.21, 95% CI: 8.97, 13.45) compared to FA dosages ≤0.8 mg (ß = 2.94, 95% CI: 2.59, 3.29). Furthermore, FA dosages higher than 0.8 mg did not confer additional benefits in terms of increasing 5-methyl tetrahydrofolic acid (5-MTHF, active form of folate) or reducing homocysteine (Hcy). Conclusion: In Chinese adults with H-type hypertension, this study showed a positive, non-linear, dosage-response relationship between FA supplementation ranging from 0 to 2.4 mg and circulating UMFA levels. It revealed that 0.8 mg FA is an optimal dosage in terms of balancing efficacy (increasing 5-MTHF and lowering Hcy) while minimizing undesirable elevation of UMFA. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1, identifier NCT03472508.

Lomatogonium rotatum extract alleviates diabetes mellitus induced by a high-fat, high-sugar diet and streptozotocin in rats.

BACKGROUND: Lomatogonium rotatum (LR) is traditionally used in Mongolian folk medicine as a hypoglycemic agent, but its evidence-based pharmacological effects and me-chanisms of action have not been fully elucidated. AIM: To emphasize the hypoglycemic action mechanism of LR in a type 2 diabetic rat model and examine potential biomarkers to obtain mechanistic understanding regarding serum metabolite modifications. METHODS: A high-fat, high-sugar diet and streptozotocin injection-induced type 2 diabetic rat model was established. The chemical composition of the LR was identified by high performance liquid chromatography. LR extract administrated as oral gavage at 0.5 g/kg, 2.5 g/kg, and 5 g/kg for 4 wk. Anti-diabetic effects of LR extract were evaluated based on histopathological examination as well as the measurement of blood glucose, insulin, glucagon-like peptide 1 (GLP-1), and lipid levels. Serum metabolites were analyzed using an untargeted metabolomics approach. RESULTS: According to a chemical analysis, swertiamarin, sweroside, hesperetin, coumarin, 1.7-dihydroxy-3,8-dimethoxyl xanthone, and 1-hydroxy-2,3,5 trimethoxanone are the principal active ingredients in LR. An anti-diabetic experiment revealed that the LR treatment significantly increased plasma insulin and GLP-1 levels while effectively lowering blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and oral glucose tolerance test compared to the model group. Furthermore, untargeted metabolomic analysis of serum samples detected 236 metabolites, among which 86 were differentially expressed between the model and the LR group. It was also found that LR considerably altered the levels of metabolites such as vitamin B6, mevalonate-5P, D-proline, L-lysine, and taurine, which are involved in the regulation of the vitamin B6 metabolic pathway, selenium amino acid metabolic pathway, pyrimidine metabolic pathway, and arginine and proline metabolic pathways. CONCLUSION: These findings indicated that LR may have a hypoglycemic impact and that its role may be related to changes in the serum metabolites and to facilitate the release of insulin and GLP-1, which lower blood glucose and lipid profiles.

ZIP9 mediates the effects of DHT on learning, memory and hippocampal synaptic plasticity of male Tfm and APP/PS1 mice.

Androgens are closely associated with functions of hippocampal learning, memory, and synaptic plasticity. The zinc transporter ZIP9 (SLC39A9) regulates androgen effects as a binding site distinct from the androgen receptor (AR). However, it is still unclear whether androgens regulate their functions in hippocampus of mice through ZIP9. Compared with wild-type (WT) male mice, we found that AR-deficient male testicular feminization mutation (Tfm) mice with low androgen levels had learning and memory impairment, decreased expression of hippocampal synaptic proteins PSD95, drebrin, SYP, and dendritic spine density. Dihydrotestosterone (DHT) supplementation significantly improved these conditions in Tfm male mice, although the beneficial effects disappeared after hippocampal ZIP9 knockdown. To explore the underlying mechanism, we first detected the phosphorylation of ERK1/2 and eIF4E in the hippocampus and found that it was lower in Tfm male mice than in WT male mice, it upregulated with DHT supplementation, and it downregulated after hippocampal ZIP9 knockdown. Next, we found that the expression of PSD95, p-ERK1/2, and p-eIF4E increased in DHT-treated mouse hippocampal neuron HT22 cells, and ZIP9 knockdown or overexpression inhibited or further enhanced these effects. Using the ERK1/2 specific inhibitor SCH772984 and eIF4E specific inhibitor eFT508, we found that DHT activated ERK1/2 through ZIP9, resulting in eIF4E phosphorylation, thus promoting PSD95 protein expression in HT22 cells. Finally, we found that ZIP9 mediated the effects of DHT on the expression of synaptic proteins PSD95, drebrin, SYP, and dendritic spine density in the hippocampus of APP/PS1 mice through the ERK1/2-eIF4E pathway and affected learning and memory. This study demonstrated that androgen affected learning and memory in mice through ZIP9, providing new experimental evidence for improvement in learning and memory in Alzheimer's disease with androgen supplementation.

Renal herb formula protects against hyperuricemic nephropathy by inhibiting apoptosis and inflammation.

BACKGROUND: Hyperuricemic nephropathy may be induced by the elevation and accumulation of uric acid in kidney after hyperuricemia, which leads to kidney residential cells apoptosis and inflammation. Renal herb formula (RHF) is a self-designed formula based on traditional Chinese medicine theory and clinical practice in kidney disease treatment. In the literature available currently, there is not yet research article reporting the reno-protective effect of RHF against hyperuricemic nephropathy. PURPOSE: This study was performed to analyze the bioactive compound profiles of RHF, evaluate its protective effects against hyperuricemic nephropathy, and investigate the mechanisms of actions regarding apoptosis and inflammation. METHODS: Ultra-performance liquid chromatography with a diode-array detector was applied to establish fingerprint and chemical composition of RHF. Potassium oxonate was used to induce hyperuricemic nephropathy in mice, and uric acid was used to stimulate apoptosis and inflammatory response in HK-2 cells, while the mice and cells were treated with RHF to explore its reno-protective effects and mechanisms. RESULTS: It was found that chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A-C may be the characteristic components of RHF. RHF treatment could improve kidney functions in mice with hyperuricemic nephropathies, such as decreasing urine protein, uric acid, and creatinine and serum uric acid, creatinine, and urea nitrogen. Histopathological observations showed that RHF treatment ameliorated kidney glomerular hypotrophy, tubular damage, and inflammatory infiltration. Mechanism studies revealed that RHF inhibited kidney residential cell apoptosis and inflammatory response by targeting the p53-associated intrinsic apoptosis pathway and NF-κB-mediated inflammatory pathway. CONCLUSION: Taken together, it could be concluded that RHF exerted reno-protective effects against hyperuricemic nephropathy through reducing apoptosis and inflammation. RHF and the bioactive compounds chlorogenic acid analogs as promising candidates may be developed into novel and effective drugs for hyperuricemic nephropathy treatment and management.

Differences and biocontrol potential of haustorial endophytic fungi from Taxillus Chinensis on different host plants.

BACKGROUND: To explore the community composition and diversity of the endophytic fungi in Taxillus chinensis, samples of the parasites growing on seven different hosts, Morus alba, Prunus salicina, Phellodendron chinense, Bauhinia purpurea, Dalbergia odorifera, Diospyros kaki and Dimocarpus longan, were isolated. The strains were identified by their morphological characteristics and their internal transcribed spacer (ITS) sequences. RESULTS: 150 different endophytic fungi were isolated from the haustorial roots of the seven hosts with a total isolation rate of 61.24%. These endophytic fungi were found to belong to 1 phylum, 2 classes, 7 orders, 9 families, 11 genera and 8 species. Among of them, Pestalotiopsis, Neopestalotiopsis and Diaporthe were the dominant genera, accounting for 26.67, 17.33 and 31.33% of the total number of strains, respectively. Diversity and similarity analyses showed that the endophytic fungi isolated from D. longan (H'=1.60) had the highest diversity index. The highest richness indexes were found in M. alba and D. odorifera (both 2.23). The evenness index of D. longan was the highest (0.82). The similarity coefficient of D. odorifera was the most similar to D. longan and M. alba (33.33%), while the similarity coefficient of P. chinense was the lowest (7.69%) with M. alba and D. odorifera. Nine strains showed antimicrobial activities. Among them, Pestalotiopsis sp., N. parvum and H. investiens showed significant antifungal activity against three fungal phytopathogens of medicinal plants. At the same time, the crude extracts from the metabolites of the three endophytic fungi had strong inhibitory effects on the three pathogens. Pestalotiopsis sp., N. parvum and H. investiens had the strongest inhibitory effects of S. cucurbitacearum, with inhibitory rates of 100%, 100% and 81.51%, respectively. In addition, N. parvum had a strong inhibitory effect on D. glomerata and C. cassicola, with inhibitory rates of 82.35% and 72.80%, respectively. CONCLUSIONS: These results indicate that the species composition and diversity of endophytic fungi in the branches of T. chinensis were varied in the different hosts and showed good antimicrobial potential in the control of plant pathogens.

Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy.

Narcolepsy with cataplexy is a sleep disorder caused by deficiency in the hypothalamic neuropeptide hypocretin/orexin (HCRT), unanimously believed to result from autoimmune destruction of hypocretin-producing neurons. HCRT deficiency can also occur in secondary forms of narcolepsy and be only temporary, suggesting it can occur without irreversible neuronal loss. The recent discovery that narcolepsy patients also show loss of hypothalamic (corticotropin-releasing hormone) CRH-producing neurons suggests that other mechanisms than cell-specific autoimmune attack, are involved. Here, we identify the HCRT cell-colocalized neuropeptide QRFP as the best marker of HCRT neurons. We show that if HCRT neurons are ablated in mice, in addition to Hcrt, Qrfp transcript is also lost in the lateral hypothalamus, while in mice where only the Hcrt gene is inactivated Qrfp is unchanged. Similarly, postmortem hypothalamic tissues of narcolepsy patients show preserved QRFP expression, suggesting the neurons are present but fail to actively produce HCRT. We show that the promoter of the HCRT gene of patients exhibits hypermethylation at a methylation-sensitive and evolutionary-conserved PAX5:ETS1 transcription factor-binding site, suggesting the gene is subject to transcriptional silencing. We show also that in addition to HCRT, CRH and Dynorphin (PDYN) gene promoters, exhibit hypermethylation in the hypothalamus of patients. Altogether, we propose that HCRT, PDYN, and CRH are epigenetically silenced by a hypothalamic assault (inflammation) in narcolepsy patients, without concurrent cell death. Since methylation is reversible, our findings open the prospect of reversing or curing narcolepsy.

[Effects of propiconazole on physiological and biochemical properties of Panax notoginseng and dietary risk assessment].

To study the residue and dietary risk of propiconazole in Panax notoginseng and the effects on physiological and bioche-mical properties of P. notoginseng, we conducted foliar spraying of propiconazole on P. notoginseng in pot experiments. The physiolo-gical and biochemical properties studied included leaf damage, osmoregulatory substance content, antioxidant enzyme system, non-enzymatic system, and saponin content in the main root. The results showed that at the same application concentration, the residual amount of propiconazole in each part of P. notoginseng increased with the increase in the times of application and decreased with the extension of harvest interval. After one-time application of propiconazole according to the recommended dose(132 g·hm~(-2)) for P. ginseng, the half-life was 11.37-13.67 days. After 1-2 times of application in P. notoginseng, propiconazole had a low risk of dietary intake and safety threat to the population. The propiconazole treatment at the recommended concentration and above significantly increased the malondialdehyde(MDA) content, relative conductivity, and osmoregulatory substances and caused the accumulation of reactive oxygen species in P. notoginseng leaves. The propiconazole treatment at half(66 g·hm~(-2)) of the recommended dose for P. ginseng significantly increased the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) in P. notoginseng leaves. The propiconazole treatment at 132 g·hm~(-2) above inhibited the activities of glutathione reductase(GR) and glutathione S-transferase(GST), thereby reducing glutathione(GSH) content. Proconazole treatment changed the proportion of 5 main saponins in the main root of P. notoginseng. The treatment with 66 g·hm~(-2) propiconazole promoted the accumulation of saponins, while that with 132 g·hm~(-2) and above propiconazole significantly inhibited the accumulation of saponins. In summary, using propiconazole at 132 g·hm~(-2) to prevent and treat P. notoginseng diseases will cause stress on P. notoginseng, while propiconazole treatment at 66 g·hm~(-2) will not cause stress on P. notoginseng but promote the accumulation of saponins. The effect of propiconazole on P. notoginseng diseases remains to be studied.

miR-363-3p/PTEN is involved in the regulation of lipid metabolism by genistein in HepG2 cells via ERß.

BACKGROUND: Genistein (GEN) is one of the most well-known phytoestrogens identified in various legumes. Although increasing evidence shows GEN has a potential use in phytotherapy to regulate lipid metabolism, its therapeutic mechanisms have not yet been completely elucidated, especially epigenetic alterations of miRNAs to alleviate lipid accumulation in the liver remains unknown. PURPOSE: To clarify how GEN modulates the miRNA profile in HepG2 cells and investigate molecular mechanisms of the modulated miRNA on regulating hepatic lipid metabolism. METHODS: The miRNA microarray was performed to compare the miRNAs expression patterns, followed by determining principal miRNA and its target gene associated with hepatic lipid metabolism modulated by GEN. miR-363-3p mimics (mi) and phosphatase and tensin homolog (PTEN)-siRNA were transfected into HepG2 cells and GEN was further treated with the cells for 24 h RESULTS: GEN induced downregulation of miR-363-3p and upregulation of PTEN, which was a target mRNA of miR-363-3p. The miR-363-3p mi led to an upregulation of sterol-regulatory element-binding protein-1c (SREBP-1c) and its downstream lipid synthesis-related factors in HepG2 cells. In addition, the inhibition of PTEN led to an increase of lipogenesis, which was associated with the AKT/mTOR signal regulation. However, GEN treatment could abrogate the lipogenic effects of miR-363-3p mi or PTEN siRNA. The modulation was associated with estrogen receptor ß (ERß). CONCLUSION: We discerned a new mechanism that GEN regulated hepatic lipid metabolism by inhibiting miR-363-3p, which could be mediated via ERß and by targeting PTEN in HepG2 cells. Additionally, GEN reduced hepatic lipid accumulation by regulating PTEN-AKT/mTOR signal. It implicated a protective role of GEN by elucidating its epigenetic modification of the miRNA modulated by ERß on improving hepatic lipid metabolism and provided novel evidence of the mechanism on targeting miR-363-3p/PTEN in treating hepatic lipid disorders.

Thermographic evaluation of acupoints in lower limb region of individuals with osteoarthritis: A cross-sectional case-control study protocol.

PURPOSE: Acupuncture has been widely used in the treatment of knee osteoarthritis (KOA), but the selection of acupoints is indeterminate and lacks biological basis. The skin temperature of acupoints can reflect the state of local tissue and may be a potential factor for guiding acupoint selection. This study aims to compare the skin temperature of acupoints between KOA patients and the healthy population. STUDY DESIGN AND METHODS: This is a protocol for a cross-sectional case-control study with 170 KOA patients and 170 age- and gender-matched healthy individuals. Diagnosed patients aged 45 to 70 will be recruited in the KOA group. Participants in the healthy group will be matched with the KOA group based on mean age and gender distribution. Skin temperature of 11 acupoints (ST35, EX-LE5, GB33, GB34, EX-LE2, ST34, ST36, GB39, BL40, SP9, SP10) will be extracted from infrared thermography (IRT) images of the lower limbs. Other measurements will include demographic data (gender, age, ethnicity, education, height, weight, BMI) and disease-related data (numerical rating scale, pain sites, duration of pain, pain descriptors, pain activities). DISCUSSION: The results of this study will provide biological evidence for acupoint selection. This study is a precondition for follow-up studies, in which the value of optimized acupoint selection will be verified. TRIAL REGISTRATION: ChiCTR2200058867.

Natural flavonoids derived from herbal medicines are potential anti-atherogenic agents by inhibiting oxidative stress in endothelial cells.

As the common pathological basis of various cardiovascular diseases, the morbidity and mortality of atherosclerosis (AS) have increased in recent years. Unfortunately, there are still many problems in the treatment of AS, and the prevention and treatment of the disease is not ideal. Up to now, the occurrence and development of AS can roughly include endothelial cell dysfunction, vascular smooth muscle cell proliferation, inflammation, foam cell production, and neoangiogenesis. Among them, endothelial dysfunction, as an early event of AS, plays a particularly important role in promoting the development of AS. In addition, oxidative stress occurs throughout the causes of endothelial dysfunction. Some previous studies have shown that flavonoids derived from herbal medicines are typical secondary metabolites. Due to its structural presence of multiple active hydroxyl groups, it is able to exert antioxidant activity in diseases. Therefore, in this review, we will search PubMed, Web of Science, Elesvier, Wliey, Springer for relevant literature, focusing on flavonoids extracted from herbal medicines, and summarizing how they can prevent endothelial dysfunction by inhibiting oxidative stress. Meanwhile, in our study, we found that flavonoid represented by quercetin and naringenin showed superior protective effects both in vivo and in vitro, suggesting the potential of flavonoid compounds in the treatment of AS.

Effects of S-Adenosylmethionine on Cognition in Animals and Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is increasing evidence that supplementation of S-adenosylmethionine (SAM) can improve cognitive function in animals and humans, although the outcomes are not always inconsistent. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the correlation between SAM supplementation and improved cognitive function. METHODS: We searched studies in the PubMed, Cochrane Library, Embase, Web of Science, and Clinical Trials databases from January 1, 2002 to January 1, 2022. Risk of bias was assessed using the Cochrane risk of bias 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation risk of bias (animal studies) tools; and evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. STATA software was employed to perform meta-analysis, and the random-effects models was used to evaluate the standardized mean difference with 95% confidence intervals. RESULTS: Out of the 2,375 studies screened, 30 studies met the inclusion criteria. Meta-analyses of animal (p = 0.213) and human (p = 0.047) studies showed that there were no significant differences between the SAM supplementation and control groups. The results of the subgroup analyses showed that the animals aged ≤8 weeks (p = 0.027) and the intervention duration >8 weeks (p = 0.009) were significantly different compared to the controls. Additionally, the Morris water maze test (p = 0.005) used to assess the cognitive level of the animals revealed that SAM could enhance spatial learning and memory in animals. CONCLUSION: SAM supplementation showed no significant improvement in cognition. Therefore, further studies are needed to assess the effectiveness of SAM supplementation.