Network pharmacology and molecular docking to explore the mechanism of a clinical proved recipe for external use of clearing heat and removing dampness in the treatment of immune-related cutaneous adverse events.

Immune-related cutaneous adverse events (ircAEs) will undermine the patients' quality of lives, and interrupt the antitumor therapy. A clinical proved recipe for external use of clearing heat and removing dampness (Qing-Re-Li-Shi Formula, hereinafter referred to as "QRLSF") is beneficial to the treatment of ircAEs in clinical practice. Our study will elucidate the mechanism of QRLSF against ircAEs based on network pharmacology and molecular docking. The active components and corresponding targets of QRLSF were collected through traditional Chinese medicine systems pharmacology database. GeneCards, online Mendelian inheritance in man, and pharmacogenomics knowledgebase were used to screen the targets of ircAEs. The intersecting targets between drug and disease were acquired by venn analysis. Cytoscape software was employed to construct "components-targets" network. Search tool for the retrieval of interacting genes/proteins database was applied to establish the protein-protein interaction network and then its core targets were identified. Gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed to predict the mechanism. The molecular docking verification of key targets and related phytomolecules was accomplished by AutoDock Vina software. Thirty-nine intersecting targets related to QRLSF against ircAEs were recognized. The analysis of network clarified 5 core targets (STAT3, RELA, TNF, TP53, and NFKBIA) and 4 key components (quercetin, apigenin, luteolin, and ursolic acid). The activity of QRLSF against ircAEs could be attributed to the regulation of multiple biological effects via multi-pathways (PI3K-Akt pathway, cytokine-cytokine receptor interaction, JAK-STAT pathway, chemokine pathway, Th17 cell differentiation, IL-17 pathway, TNF pathway, and Toll-like receptor pathway). The binding activities were estimated as good level by molecular docking. These discoveries disclosed the multi-component, multi-target, and multi-pathway characteristics of QRLSF against ircAEs, providing a new strategy for such medical problem.

Integration of Network Pharmacology and Experimental Validation to Explore Jixueteng - Yinyanghuo Herb Pair Alleviate Cisplatin-Induced Myelosuppression.

Jixueteng, the vine of the bush Spatholobus suberectus Dunn., is widely used to treat irregular menstruation and arthralgia. Yinyanghuo, the aboveground part of the plant Epimedium brevicornum Maxim., has the function of warming the kidney to invigorate yang. This research aimed to investigate the effects and mechanisms of the Jixueteng and Yinyanghuo herbal pair (JYHP) on cisplatin-induced myelosuppression in a mice model. Firstly, ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) screened 15 effective compounds of JYHP decoction. Network pharmacology enriched 10 genes which may play a role by inhibiting the apoptosis of bone marrow (BM) cells. Then, a myelosuppression C57BL/6 mice model was induced by intraperitoneal (i.p.) injection of cis-Diaminodichloroplatinum (cisplatin, CDDP) and followed by the intragastric (i.g.) administration of JYHP decoction. The efficacy was evaluated by blood cell count, reticulocyte count, and histopathological analysis of bone marrow and spleen. Through the vivo experiments, we found the timing of JYHP administration affected the effect of drug administration, JYHP had a better therapeutical effect rather than a preventive effect. JYHP obviously recovered the hematopoietic function of bone marrow from the peripheral blood cell test and pathological staining. Flow cytometry data showed JYHP decreased the apoptosis rate of BM cells and the western blotting showed JYHP downregulated the cleaved Caspase-3/Caspase-3 ratios through RAS/MEK/ERK pathway. In conclusion, JYHP alleviated CDDP-induced myelosuppression by inhibiting the apoptosis of BM cells through RAS/MEK/ERK pathway and the optimal timing of JYHP administration was after CDDP administration.

Optical properties of ferroic Fe2O(SeO3)2 and Fe2(SeO3)3·3H2O.

Ferroic compounds Fe2O(SeO3)2 (FSO) and Fe2(SeO3)3·3H2O (FSOH) prepared by the hydrothermal method are characterized and their optical properties are investigated by combining with first-principles calculations. The results show that (i) FSO is antiferromagnetic below ∼110 K and becomes ferromagnetic at elevated temperatures, while FSOH is antiferromagnetic at low temperatures probably due to a change in the spin state from Fe3+ (S = 5/2) to Fe2+ (S = 2); (ii) the optical bandgap is determined to be ∼2.83 eV for FSO and ∼2.15 eV for FSOH, consistent with the theoretical calculation; and (iii) the angle-resolved polarized Raman spectroscopy results of both crystals demonstrate the strong anisotropic light absorption and birefringence effects, and the unconventional symmetricity of some Raman modes is observed, which can be interpreted from the variation of Raman scattering elements. This work can provide not only an understanding of the structure and physical properties of iron selenites, but also a strategy for exploring the anomalous Raman behaviors in anisotropic crystals, facilitating the design and engineering of novel functional devices with low-symmetry ferroic materials.

Clinical Experience of External Application of Clearing Heat and Removing Dampness in Relieving Grade 2 to 3 Rash Caused by Programed Cell Death Protein 1 (PD-1)/Programed Cell Death Ligand 1 (PD-L1) Inhibitors: A Single-Center Retrospective Study.

OBJECTIVE: In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash. METHODS: A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed. RESULTS: Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn't increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P < .0001), emotions (58.33 vs 15.48, P < .0001), functioning (46.67 vs 13.33, P < .0001) and composite (52.60 vs 14.06, P < .0001). CONCLUSION: External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs.

Pectic polysaccharides from Lilium brownii and Polygonatum odoratum exhibit significant antioxidant effects in vitro.

Two pectic polysaccharides (WLBP-A3-c and WPOP-A-c) were isolated from traditional Chinese medicines Lilium brownii and Polygonatum odoratum, respectively. Monosaccharide composition, FT-IR, NMR and enzymatic analyses indicated that both WLBP-A3-c (59 kDa) and WPOP-A-c (33 kDa) contained homogalacturonan (HG), rhamnogalacturonan I (RG-I), and rhamnogalacturonan II (RG-II) domains, with mass ratios of 76.0: 17.2:6.8 and 76.8:10.6:12.6, respectively. Two RG-I domains WLBP-A3-c-DE1 and WPOP-A-c-DE1, correspondingly obtained from WLBP-A3-c and WPOP-A-c by enzymatic hydrolysis, were composed of repeating units of [→2)-α-L-Rhap-(1 â†’ 4)-α-D-GalpA-(1→] with highly branched neutral sugar side chains at the O-4 position of Rhap, which contained arabinan, galactan, arabinogalactan I and II (AG-I and AG-II) side chains in different proportions. By comparison, WPOP-A-c exhibited higher scavenging effects against DPPH, ABTS and hydroxy radicals than WLBP-A3-c, probably because WPOP-A-c had higher contents of GalA residues and HG domains and lower molecular weight. Among three domains of WPOP-A-c, HG domain possessed the strongest activity in decreasing ROS production and promoting SOD activity, resulting in the effective protection of HepG2 cells against H2O2-induced oxidative stress. Our study provides evidence that pectins rich in HG domains from Lilium brownii and Polygonatum odoratum exhibit significant antioxidant effects, which hold potential for the application in the field of healthcare products.

Hysteroscopy In Preserving Fertility Of Women With Abnormal Pregnancy.

Objective: Hysteroscopy has a positive role in the treatment of abnormal pregnancy, with less damage to the patient, good surgical effect, rapid postoperative recovery, and positive clinical value. This work aimed to explore the role and value of hysteroscopy in preserving the fertility of women with abnormal pregnancies. Methods: 60 patients with abnormal pregnancies in Maanshan Maternal and Child Health Care Hospital were enrolled from December 1, 2021 to December 31, 2022. They were grouped Based on treatment methods: controls (30 cases) and observation groups (30 cases). The average age of the control group was 30.66 ± 5.32 years, with a BMI of 23.36 ± 2.15 kg/m2, and an educational duration of 12.24 ± 3.61 years. The observation group had an average age of 30.18 ± 5.71 years, a BMI of 23.23 ± 2.53 kg/m2, and an educational duration of 12.33 ± 3.28 years. Controls adopted the traditional method (laparoscopic surgery), and an observation group was given with hysteroscopic localization and removal of pregnancy products. The surgical conditions, postoperative recovery, cure rate, complications, preoperative and postoperative blood human chorionic gonadotropin (HCG) level and 36-Item Short Form Health Survey (SF-36) score were compared between the two groups. Results: The observation group had a significantly shorter surgical time of 10.22 minutes, a postoperative hemostasis time of 7.32 days, a menstrual recovery time of 25.73 days, and a time for blood HCG turning negative of 10.76 days compared to the control group (P < .05). The observation group also experienced significantly less intraoperative bleeding, with 6.22 ml compared to 11.69 ml in the control group (P < .05). The cure rate of controls was 83.33%, and that of the observation group was 100.00%. The cure rate of the observation group was obviously higher as against controls. The incidence of complications in the observation group was 6.67%, and that in controls was 26.67%. The incidence of complications in the observation group was clearly lower as against controls. Through operation, the serum HCG levels of two groups were clearly decreased, the SF-36 scores were clearly increased, and the changes in the observation group were more obvious (P < .05). Conclusion: Compared to traditional surgery, hysteroscopy examination demonstrates multiple advantages in the management of abnormal pregnancies, primarily attributed to its minimally invasive nature, high precision, minimal tissue trauma, and quick recovery. This contributes to providing a safer and more effective treatment, increasing patient satisfaction, and reducing healthcare costs, with a positive impact on patient care and clinical practice. However, this work had a relatively small sample size, a single source of patients, and a short duration, which necessitates future validation through the expansion of the sample size and multicenter research. A more comprehensive assessment of long-term postoperative effects is required to confirm the long-term advantages of this treatment method.

Treatment of uterine scar cystoid diverticulum by hysteroscopy combined with laparoscopy.

OBJECTIVE: To report a patient with prolonged intermenstrual bleeding and a cystic mass at a cesarean scar treated with laparoscopic folding sutures and hysteroscopic canalization. DESIGN: A 4.0 cm-cystic mass formed at the uterine scar caused continuous menstrual blood outflow in the diverticulum and was treated with hysteroscopy combined with laparoscopy. SETTING: University hospital. PATIENTS: A 38-year-old woman of childbearing age who had undergone two cesarean sections and two abortions reported vaginal bleeding for 10 years, which began shortly after the second cesarean section. Curettage was performed, but no abnormality was found. The patient unsuccessfully tried to manage her symptoms with traditional Chinese medicine and hormone drugs. The muscular layer of the lower end of the anterior wall of the uterus was weak, and there were cystic masses on the right side. INTERVENTION: The bladder was stripped from the lower uterine segment under laparoscopy, and the surrounding tissue of the mass at the uterine scar was separated. The position of the cesarean scar defect was identified by hysteroscopy combined with laparoscopy, and the relationship between the uterine mass and surrounding tissues was analyzed. An electric cutting ring resection on both sides of the obstruction was performed to eliminate the valve effect. The active intima of the scar diverticulum was destroyed by electrocoagulation, followed by laparoscopic treatment of the uterine scar diverticulum mass. An intraoperative tumor incision revealed visible bloody fluid mixed with intimal material. The uterine scar diverticulum defect was repaired using 1-0 absorbable barbed continuous full-thickness mattress fold sutures. Finally, the bilateral round ligament length was adjusted so that the uterus tilted forward. MAIN OUTCOME MEASURES: Recovery of menstruation and anatomy of the uterine isthmus. RESULTS: The operation was successful, and the postoperative recovery was fast. There was no interphase bleeding at the 1-month follow-up, and the uterine scar diverticulum was repaired, with the thickness of the uterine scar muscle layer increasing to 0.91 cm. CONCLUSION: The simple, straightforward procedure to resolve the abnormal cystic, solid mass formed because of the continuous deposition of blood in the uterine scar diverticulum involved laparoscopic folding and docking sutures combined with hysteroscopic canal opening.

Efficacy and safety of Tongmai Jiangtang capsule combined with conventional therapy in the treatment of diabetic peripheral neuropathy: a systematic review and meta-analysis.

Background: Recently, more and more Chinese patent drugs have been proved to be effective in the treatment of diabetic peripheral neuropathy (DPN). Tongmai Jiangtang capsule (TJC) is one of the representative ones. The present meta-analysis integrated data from several independent studies to determine the efficacy and safety of TJCs combined with routine hypoglycemic therapy for DPN patients, and to evaluate the quality of evidence. Methods: SinoMed, Cochrane Library, PubMed, EMBASE, Web of Science, CNKI, Wanfang, VIP databases and registers were searched for randomized controlled trials (RCTs) involving TJC treatment of DPN up to February 18, 2023. Two researchers independently used the Cochrane risk bias tool and comprehensive reporting criteria for Chinese medicine trials to evaluate the methodological quality and reporting quality of the qualified studies. RevMan5.4 was used for Meta-analysis and evidence evaluation, with scores determined for recommendations, evaluation, development and GRADE. The Cochrane Collaboration ROB tool was used to evaluate the quality of the literature. The results of Meta-analysis were represented by forest plots. Results: A total of 8 studies were included involving a total sample size of 656 cases. TJCs combined with conventional treatment (CT) could significantly accelerate myoelectricity graphic nerve conduction velocity, including that median nerve motor conduction velocity was faster than those of CT alone [mean difference (MD) = 5.20, 95% confidence interval (CI): 4.31-6.10, P < 0.00001], peroneal nerve motor conduction velocity was faster than those of CT alone (MD = 2.66, 95% CI: 1.63-3.68; P < 0.00001), median nerve sensory conduction velocity was faster than those of CT alone (MD = 3.06, 95% CI: 2.32-3.81, P < 0.00001), and peroneal nerve sensory conduction velocity was faster than those of CT alone (MD = 4.23, 95% CI: 3.30-5.16, P < 0.00001). The total efficiency of the TJCs + CT group was higher than that of the CT group (RR = 1.41, 95% CI: 1.28-1.56, P < 0.00001). The HbA1c after treatment in the TJCs + CT group was lower than that in the CT group (P < 0.05). No adverse drug reactions (ADRs) were reported in the combined TJCs or CT groups. Conclusions: TJCs combined with CT reduced the severity of DPN symptoms and no treatment-associated ADRs were reported. However, these results should be considered with caution because there was marked heterogeneity in the research data. Therefore, more stringent RCTs should be designed to validate the efficacy of TJCs in DPN patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=264522, identifier: CRD42021264522.

Protective effects of resolvin D1 in Pseudomonas aeruginosa keratitis.

PURPOSE: Here, we explored the protective effects of resolvin D1 (RvD1) in Pseudomonas aeruginosa (PA) keratitis. METHODS: C57BL/6 (B6) mice were used as an animal model of PA keratitis. Plate counting and clinical scores were used to assess the severity of the infection and the therapeutic effects of RvD1 in the model. Myeloperoxidase assay was used to detect neutrophil infiltration and activity. Quantitative PCR (qPCR) was used to examine the expression of proflammatory and anti-inflammatory mediators. Immunofluorescence staining and qPCR were performed to identify macrophage polarization. RESULTS: RvD1 treatment alleviated PA keratitis severity by decreasing corneal bacterial load and inhibiting neutrophil infiltration in the mouse model. Furthermore, RvD1 treatment decreased mRNA levels of TNF-α, IFN-γ, IL-1ß, CXCL1, and S100A8/9 while increasing those of IL-1RA, IL-10, and TGF-ß1. RvD1 treatment also reduced the aggregation of M1 macrophages and increased that of M2 macrophages. RvD1 provided an auxiliary effect in gatifloxacin-treated mice with PA keratitis. CONCLUSION: Based on these findings, RvD1 may improve the prognosis of PA keratitis by inhibiting neutrophil recruitment and activity, dampening the inflammatory response, and promoting M2 macrophage polarization. Thus, RvD1 may be a potential complementary therapy for PA keratitis.

Exploration of the anti-liver injury active components of Shaoyao Gancao decoction by network pharmacology and experiments in vivo.

BACKGROUND: Shaoyao Gancao decoction (SGD), a classic traditional Chinese herbal formula, has been widely used to treat febrile diseases in the clinic for centuries. In recent years, a growing number of studies have found that SGD has a favorable anti-liver injury effect. PURPOSE: In this study, we want to know the potential active components of SGD treatment in liver injury. STUDY DESIGN: A novel method combining computer simulation and in vivo experiment was established for the first time and used to investigate this problem. METHODS: A network pharmacology was used to explore the active components of SGD treatment in liver injury, and preliminarily verified the results of network pharmacology through molecular docking. To further understand the active compounds of SGD in the treatment of liver injury, we compared the prototypes and metabolites of SGD in healthy rats and rats with liver injury after oral administration. In addition, a UPLC-MS/MS method was developed and successfully applied to investigate the pharmacokinetics of 9 compounds of SGD in healthy and liver injury rats. RESULTS: It showed that SGD exerted protective effects against liver injury by the active components of liquiritin and albiflorin, etc. The values of the AUC0-t, AUC0-∞, t1/2, Tmax were significantly different after oral administration of SGD in healthy and liver injury rats. This indicates that the pharmacokinetic study in the pathological state of liver injury can provide more valuable information for guiding clinical medication. CONCLUSION: In this study, the integration of network pharmacology and experiments in vivo provides a novel strategy to explore active components of TCMs to treat diseases.

Isovitexin restores sevoflurane­induced cognitive dysfunction by mediating autophagy through activation of the PGC­1α/FNDC5 signaling pathway.

Postoperative cognitive dysfunction is a severe neurological complication. How to improve the cognitive impairment caused by sevoflurane, a most common inhaled anesthetic, remains a question worthy of studying. Isovitexin (IVX) is a trihydroxyl flavonoid that is a naturally bioactive ingredient found in various medicinal plants and has antioxidant, anti­inflammatory and neuroprotective properties. The role of IVX in anesthetic­induced nerve injury is rarely reported and the mechanisms are unclear. In this study, we found that IVX improved the cognitive dysfunction induced by sevoflurane in rats. It inhibited sevoflurane­induced cell apoptosis. In addition, IVX increased sevoflurane­induced autophagy in rat brain. Mechanically, IVX activated the PGC­1α/FNDC5 pathway in rat brain, and depletion of FNDC5 could inhibit the neuroprotective function of IVX. In conclusion, our results suggested that IVX restored sevoflurane­induced cognitive dysfunction by mediating autophagy through the activation of the PGC­1α/FNDC5 pathway.

Using network pharmacology to explore the mechanism of Danggui-Shaoyao-San in the treatment of diabetic kidney disease.

Danggui-Shaoyao-San (DSS) is one of traditional Chinese medicine, which recently was found to play a protective role in diabetic kidney disease (DKD). However, the pharmacological mechanisms of DSS remain obscure. This study would explore the molecular mechanisms and bioactive ingredients of DSS in the treatment of DKD through network pharmacology. The potential target genes of DKD were obtained through OMIM database, the DigSee database and the DisGeNET database. DSS-related targets were acquired from the BATMAN-TCM database and the STITCH database. The common targets of DSS and DKD were selected for analysis in the STRING database, and the results were imported into Cytoscape to construct a protein-protein interaction network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis and Gene Ontology (GO) enrichment analysis were carried out to further explore the mechanisms of DSS in treating DKD. Molecular docking was conducted to identify the potential interactions between the compounds and the hub genes. Finally, 162 therapeutic targets of DKD and 550 target genes of DSS were obtained from our screening process. Among this, 28 common targets were considered potential therapeutic targets of DSS for treating DKD. Hub signaling pathways including HIF-1 signaling pathway, TNF signaling pathway, AMPK signaling pathway, mTOR signaling pathway, and PI3K-Akt signaling pathway may be involved in the treatment of DKD using DSS. Furthermore, TNF and PPARG, and poricoic acid C and stigmasterol were identified as hub genes and main active components in this network, respectively. In this study, DSS appears to treat DKD by multi-targets and multi-pathways such as inflammatory, oxidative stress, autophagy and fibrosis, which provided a novel perspective for further research of DSS for the treatment of DKD.

A rare endocrine cause of ventricular tachycardia: a case series of two patients and a literature review.

Sheehan's syndrome is a type of hypopituitarism caused by massive uterine bleeding and hypovolaemic shock after or during delivery. Heart involvement has been documented sporadically among the various clinical manifestations of Sheehan's syndrome but life-threatening arrhythmias are infrequent. Here, we report on two rare cases of ventricular tachycardia caused by Sheehan's syndrome. Both female patients were diagnosed with Sheehan's syndrome 30 years previously, due to massive postpartum bleeding. Both of them terminated hormone replacement therapy recently. Both patients presented with torsade de pointes. The electrocardiogram showed prolonged QT interval. In addition to potassium supplementation and anti-arrhythmia therapy, steroids and thyroid hormone replacement therapy were employed, QT-interval prolongation and T-wave inversion were normalised, and implantable cardioverter defibrillator implantation was avoided. One of the patients was recovering well at the one-year follow up and the other patient was in a coma at the time of this report. We also review the literature for cases of Sheehan's syndrome presenting with ventricular tachycardia.

A Glimpse of Inflammation and Anti-Inflammation Therapy in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and a major cause of end-stage kidney disease (ESKD). The pathogenesis of DKD is very complex and not completely understood. Recently, accumulated evidence from in vitro and in vivo studies has demonstrated that inflammation plays an important role in the pathogenesis and the development of DKD. It has been well known that a variety of pro-inflammatory cytokines and related signaling pathways are involved in the procession of DKD. Additionally, some anti-hyperglycemic agents and mineralocorticoid receptor antagonists (MRAs) that are effective in alleviating the progression of DKD have anti-inflammatory properties, which might have beneficial effects on delaying the progression of DKD. However, there is currently a lack of systematic overviews. In this review, we focus on the novel pro-inflammatory signaling pathways in the development of DKD, including the nuclear factor kappa B (NF-κB) signaling pathway, toll-like receptors (TLRs) and myeloid differentiation primary response 88 (TLRs/MyD88) signaling pathway, adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathways, inflammasome activation, mitochondrial DNA (mtDNA) release as well as hypoxia-inducible factor-1(HIF-1) signaling pathway. We also discuss the related anti-inflammation mechanisms of metformin, finerenone, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, Dipeptidyl peptidase-4 (DPP-4) inhibitors, Glucagon-like peptide-1 (GLP-1) receptor agonist and traditional Chinese medicines (TCM).

The Non-Specific Lethal (NSL) Histone Acetyltransferase Complex Transcriptionally Regulates Yin Yang 1-Mediated Cell Proliferation in Human Cells.

The human males absent on the first (MOF)-containing non-specific lethal (NSL) histone acetyltransferase (HAT) complex acetylates histone H4 at lysine K5, K8, and K16. This complex shares several subunits with other epigenetic regulatory enzymes, which highlights the complexity of its intracellular function. However, the effect of the NSL HAT complex on the genome and target genes in human cells is still unclear. By using a CRISPR/Cas9-mediated NSL3-knockout 293T cell line and chromatin immunoprecipitation-sequencing (ChIP-Seq) approaches, we identified more than 100 genes as NSL HAT transcriptional targets, including several transcription factors, such as Yin Yang 1 (YY1) which are mainly involved in cell proliferation, biological adhesion, and metabolic processes. We found here that the ChIP-Seq peaks of MOF and NSL3 co-localized with H4K16ac, H3K4me2, and H3K4me3 at the transcriptional start site of YY1. In addition, both the mRNA and protein expression levels of YY1 were regulated by silencing or overexpressing NSL HAT. Interestingly, the expression levels of cell division cycle 6, a downstream target gene of YY1, were regulated by MOF or NSL3. In addition, the suppressed clonogenic ability of HepG2 cells caused by siNSL3 was reversed by overexpressing YY1, suggesting the involvement of YY1 in NSL HAT functioning. Additionally, de novo motif analysis of MOF and NSL3 targets indicated that the NSL HAT complex may recognize the specific DNA-binding sites in the promoter region of target genes in order to regulate their transcription.

Registration of intervention trials of Traditional Chinese Medicine for four neurological diseases on Chinese Clinical Trial Registry and ClinicalTrials.gov: a narrative review.

OBJECTIVE: To analyze the current status of clinical trial registration of Traditional Chinese Medicine (TCM) for the treatment of neurological diseases. METHODS: Interventional clinical trials of TCM treatment for ischemic stroke, hemorrhagic stroke, vascular cognitive impairment, tension-type headache before September 22, 2020 on the platform of Chinese Clinical Trial Registry (ChiCTR), and ClinicalTrials.gov were searched. Two researchers independently selected the literature and extracted data. RESULTS: A total of 180 interventional clinical trials were included for analysis. Out of 180 trials, 127 were from ChiCTR and 53 from ClinicalTrials.gov. The countries primary sponsoring the included trials were China (176, 97.8%), and the common categories of primary sponsors were hospital (131, 72.8%). Among the study design, the largest proportion of allocation was randomized (172, 95.6%), interventional model assignment was parallel (163, 90.6%), masking was double blind 49 (27.2%), and the sample size was ≤ 400 (144, 80.0%). The trials were most carried out at a single center (102, 56.7%). Among the included studies, 112 (62.2%) registered on ChiCTR attached the ethical approval documents. In terms of trial stages, 50 (27.7%) studies were in phase IV. The mostly used intervention was Chinese herbal medicines (99, 55%), acupuncture (68, 37.8%) was the second. By searching the registration number on China National Knowledge Infrastructure Database and PubMed, 38 (21.1%) registered trials were published, including 25 protocol studies and 14 research results with one (NCT02275949) published both the protocol and the results. CONCLUSIONS: Irregular and inadequate reporting, untimely update and publication, insufficient information on traditional medicine unique characteristics, and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological diseases. More efforts need to be made from the above aspects to standardize and improve the registration of traditional medicine trials.

MoS2/LaF3 for enhanced photothermal therapy performance of poorly-differentiated hepatoma.

Photothermal therapy (PTT) based on nanoparticle had been widely used to antitumor treatment. However, low photothermal conversion efficiency (PCE) is the main hurdle for antitumor treatment. To improve the PCE and gain ideal clinical the nanoparticle with higher photothermal conversion efficiency, we have developed a highly efficient solar absorber with MoS2/LaF3/ polydimethylsiloxane(PDMS) which can enhance the absorption of solar irradiation engergy, however, its photothermal effect irradiated by near-infrared light has not yet been investigated. The knowledge absence in photothermal effect will impede MoS2/LaF3/PDMS to be used for cancer therapy in clinic. In this study, we applied LaF3-loaded, MoS2-based photothermal conversion agents (PTAs) for improved photothermal cancer therapy. The study showed that the MoS2/LaF3 nanoflowers showed higher photothermal conversion efficiency (PCE, 42.5%) and could more effectively inhibit cancer cell proliferation compared to MoS2-based PTT agents in vitro. In vivo, the results further revealed that photothermal therapy using MoS2/LaF3 nanoflowers could significantly inhibit solid tumor growth. The study clearly demonstrated that MoS2/LaF3 could work at under low power NIR Laser in vitro and in vivo, resulting in a very impressive therapeutic effect in tumor-bearing mice. The MoS2/LaF3 nanoflowers will be prominent candidate nanoparticle for effective inhibiting tumor growth by photothermal therapy.

A Reasonable Evaluation of Chuanxiong Rhizoma Processing with Wine through Comparative Pharmacokinetic Study of Bioactive Components: Dominant Effect on Middle Cerebral Artery Occlusion Model Rats.

According to the ancient documents and Chinese herbal medicine processing experience, Chuanxiong Rhizoma was usually processed with yellow rice wine to improve efficacy. However, the relevant mechanisms are still unclear so far. In this study, a validated ultrahigh-performance liquid chromatography tandem mass spectrometry method was used to compare the pharmacokinetics of four representative components in middle cerebral artery occlusion rats after oral administration of raw and wine-processed Chuanxiong Rhizoma. The neurobehavioral scores and 2,3,5-triphenyltetrazolium chloride staining were employed to evaluate the model. Biological samples were prepared by protein precipitation with methanol. All analytes were separated on an ACQUITY BEH C18 column through gradient elution using acetonitrile and 0.01% of formic acid as mobile phase, and the flow rate was 0.3 mL/min. The results showed that the maximum plasma concentrations, the area values under the concentration-time curves of senkyunolide A, and ferulic acid in wine-processed Chuanxiong Rhizoma were all higher than in raw Chuanxiong Rhizoma, which were completely opposite to our previous studies in normal rats. Compared with normal rats, the theory that wine processing could enhance the efficacy of Chuanxiong Rhizoma may be better reflected in model rats.

Comparative study of water-soluble polysaccharides isolated from leaves and roots of Isatis indigotica Fort.

Water-soluble polysaccharides were isolated from the leaves and roots of Isatis indigotica Fort., and their structural features were studied and compared. One neutral polysaccharide fraction (WFIP-N) and three pectin fractions (WFIP-A-A, WFIP-A-B and WFIP-A-C) were obtained from the leaves, and one neutral polysaccharide fraction (WRIP-N) and two pectin fractions (WRIP-A-A and WRIP-A-B) were obtained from the roots. WFIP-A-B (Mw = 34.6 kDa) and WRIP-A-B (Mw = 29.9 kDa) were the major pectic polysaccharides. Monosaccharide composition, FT-IR, enzymatic hydrolysis, NMR and methylation analysis indicated that both WFIP-A-B and WRIP-A-B are composed of rhamnogalacturonan I (RG-I), rhamnogalacturonan II (RG-II) and homogalacturonan (HG) domains with mass ratios of 1.5:1.0:0.4 and 0.3:1.0:1.7, respectively. WFIP-A-B and WRIP-A-B were found to be rich in RG-I and HG domains, respectively, and mainly contained type II arabinogalactan (AG-II) and α-L-1,5-arabinan side chains, but those in WRIP-A-B were more numerous and longer. Our results provide structural features and differences between these polysaccharides which will help to elucidate their functional differences.

Verbascoside enhances radiosensitivity of hepatocellular carcinoma cells through regulating miR-101-3p/Wee1 axis.

Verbascoside is a kind of phenylpropanoid glycoside derived from multiple medicinal plants, exerting anti-tumor effects in diverse human malignancies. However, the function of Verbascoside on the radiosensitivity of hepatocellular carcinoma (HCC) cells remains unknown. Human Huh7 and HepG2 cell lines were treated with Verbascosideis, and cell viability was detected with cell counting kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect miR-101-3p expression, and Western blot was used to quantify the expression of WEE1 G2 checkpoint kinase (WEE1). Then, CCK-8 and flow cytometry assays were used to detect the proliferation and apoptosis of HCC cells after Verbascoside and X-ray combined treatment, and the expressions of WEE1 and apoptosis-related proteins Bax and Bcl-2 were detected by Western blot. Verbascoside could improve the radiosensitivity of HCC cells in a dose-dependent manner. Verbascoside increased the expression of miR-101-3p but reduced WEE1 expression in HCC cells. Additionally, WEE1 was identified as a target of miR-101-3p. MiR-101-3p inhibition or WEE1 overexpression could reverse the effect of Verbascoside on the viability and apoptosis of HCC cells. Verbascoside increases the radiosensitivity of hepatocellular carcinoma cells via modulating miR-101-3p/WEE1 axis.