Research on different compound combinations of Realgar-Indigo naturalis formula to reverse acute promyelocytic leukemia arsenic resistance by regulating autophagy through mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, the Chinese patent drug Realgar-Indigo naturalis Formula (RIF) is utilized for the therapy of acute promyelocytic leukemia (APL). Comprising four traditional Chinese herb-Realgar, Indigo naturalis, Salvia miltiorrhiza, and Pseudostellaria heterophylla-it notably includes tetra-arsenic tetra-sulfide, indirubin, tanshinone IIa, and total saponins of Radix Pseudostellariae as its primary active components. Due to its arsenic content, RIF distinctly contributes to the therapy for APL. However, the challenge of arsenic resistance in APL patients complicates the clinical use of arsenic agents. Interestingly, RIF demonstrates a high remission rate in APL patients, suggesting that its efficacy is not significantly compromised by arsenic resistance. Yet, the current state of research on RIF's ability to reverse arsenic resistance remains unclear. AIM OF THE STUDY: To investigate the mechanism of different combinations of the compound of RIF in reversing arsenic resistance in APL. MATERIALS AND METHODS: The present study utilized the arsenic-resistant HL60-PMLA216V-RARα cell line to investigate the effects of various RIF compounds, namely tetra-arsenic tetra-sulfide (A), indirubin (I), tanshinone IIa (T), and total saponins of Radix Pseudostellariae (S). The assessment of cell viability, observation of cell morphology, and evaluation of cell apoptosis were performed. Furthermore, the mitochondrial membrane potential, changes in the levels of PMLA216V-RARα, apoptosis-related factors, and the PI3K/AKT/mTOR pathway were examined, along with autophagy in all experimental groups. Meanwhile, we observed the changes about autophagy after blocking the PI3K or mTOR pathway. RESULTS: Tanshinone IIa, indirubin and total saponins of Radix Pseudostellariae could enhance the effect of tetra-arsenic tetra-sulfide down-regulating PMLA216V-RARα, and the mechanism was suggested to be related to inhibiting mTOR pathway to activate autophagy. CONCLUSIONS: We illustrated that the synergistic effect of different compound combinations of RIF can regulate autophagy through the mTOR pathway, enhance cell apoptosis, and degrade arsenic-resistant PMLA216V-RARα.

The role of Shenqi Fuzheng injection as adjuvant therapy for breast cancer: an overview of systematic reviews and meta-analyses.

BACKGROUND: Breast cancer (BC) is the most frequent malignancy in the world. Chemotherapy (CT) is a common treatment for BC but is accompanied by toxicity and side effects. Shenqi Fuzheng Injection (SFI) is an adjuvant therapy with promising results in improving efficacy and reducing toxicity in clinical studies. This overview of systematic reviews and meta-analysis (SRs/MAs) aimed to summarize the benefits and evaluate the quality of evidence supporting SFI adjuvant as CT for BC. METHODS: A systematic search for SRs/MAs of randomized controlled trials (RCTs) on SFI treatment for BC was performed by searching PubMed, Web of Science, EMbase, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases from inception to October 1, 2022. The quality of SRs/MAs was evaluated using AMSTAR-2, PRISMA 2020, ROBIS, and GRADE by two reviewers. The corrected covered area (CCA) was used to quantify the degree of duplication of the original SRs/MAs. Finally, quantitative analysis of RCTs was conducted using RevMan 5.4 software. This study was registered with PROSPERO, CRD42022377290. RESULTS: Six SRs/MAs including 61 RCTs with 5593 patients were included in this study. Studies were published between 2015 and 2019, the original RCTs ranged from 7-49, with sample sizes ranging from 336-1989. The quantitative meta-analysis found that adjuvant CT of SFI improved the clinical response rate (RR=1.37, 95% CI=1.28, 1.46; P<0.00001) and the KPS score (RR=1.66, 95% CI 1.54, 1.79, P<0.00001) of patients with BC. In terms of immune function, CD3+ (SMD=1.51, 95% CI 0.91, 2.10; P<0.00001), CD4+ (SMD=1.87, 95% CI 1.18, 2.56; P<0.00001), CD4+/CD8+ (SMD=0.86, 95% CI 0.48, 1.23; P<0.00001), and NK cell levels (SMD=0.94, 95% CI 0.63, 1.24; P<0.00001) in the adjuvant CT group SFI were better than those with CT alone. Adverse reactions following SFI adjuvant CT showed reduced incidence of leukopenia (RR=0.53, 95% CI 0.46, 0.62; P<0.00001) and gastrointestinal reactions (RR=0.48, 95% CI 0.39, 0.58; P<0.00001). However, the GRADE results showed 'very low' to 'moderate' evidence for the 42 outcomes, without high-quality evidence supporting them, limited mainly by deficiencies in the design of RCTs (42/42, 100.00%), inconsistency (19/42, 45.24%), publication bias (41/42, 97.62%), and inaccuracy (3/42, 7.14%). The unsatisfactory results of AMSTAR-2, PRISMA 2020, and ROBIS were limited to lack of registration of study protocols, explanation of inclusion basis of RCTs, description of funding sources for the included studies, incomplete search strategy and screening process, addressing heterogeneity and sensitivity, and reporting potential conflicts of interest. CONCLUSION: Adjuvant CT with SFI for BC had better benefits and a lower risk of adverse events. The methodology and quality of the evidence are generally low, highlighting a need of greater attention during study implementation. More objective and high-quality studies are needed to verify the efficacy of adjuvant CT with SFI in clinical decision-making for BC.

[Construction and application of virtual simulation teaching platform for in-hospital emergency nursing of craniofacial injury patients].

PURPOSE: To construct a virtual simulation teaching platform for in-hospital emergency nursing of craniofacial injury patients by virtual simulation technology, and to evaluate its application effect. METHODS: Through virtual reality, animation, human-computer interaction and other technologies, a 3D experiment scene based on high simulation virtual human was constructed to reproduce the virtual rescue scenes of craniofacial injury patients, such as emergency reception, first-aid cooperation, massive hemorrhage rescue cooperation, and tracheotomy cooperation in emergency rescue of sudden airway obstruction, and exercise modules and assessment modules were set. In the virtual simulation platform, the students used the holistic nursing theory and the PDCA cycle method to observe, evaluate and care for craniofacial injury patients. Preliminary evaluation of the platform was carried out in the training of 62 dental nurses. RESULTS: The virtual simulation platform could improve students' comprehensive first-aid ability for craniofacial injury patients. The item with the highest satisfaction rate for the virtual simulation platform was the consistency between the content of the virtual simulation platform and the theoretical course (the satisfaction rate was 91.9%), and the lowest satisfaction rate was the convenience of the virtual simulation platform operation and the page setting (the satisfaction rate was 80.6%). The evaluation module of the virtual simulation platform showed that the highest score of the comprehensive evaluation was 97, the lowest score was 56, and the average score was 80.2. CONCLUSIONS: The virtual simulation teaching platform for in-hospital first aid of craniofacial injury patients can create an immersive learning mode, provide an intuitive rescue experience to the students, and improve their comprehensive first-aid ability.

Shenqi Fuzheng Injection Combined With Chemotherapy for Gastric Cancer: An Overview of Systematic Reviews and Meta-Analyses.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor of the digestive tract. Chemotherapy (CT) is the primary treatment for GC, but it is accompanied by toxic side effects. Several systematic reviews and meta-analyses (SRs/MAs) on the combination of Shenqi Fuzheng injection (SFI) with CT for GC have been published; however, the conclusions have been inconsistent. This overview of SRs/MAs aims to assess the effectiveness and safety of SFI for GC, establishing a dependable foundation for its clinical application. METHODS: We utilized 7 databases, namely PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, to conduct our search. The retrieval period spanned from inception to August 2023. The methodological quality, bias risk, reporting quality, and evidence quality of the SRs/MAs were assessed using the evaluation tools AMSTAR-2, ROBIS, PRISMA 2020, and GRADE, respectively. Subsequently, the randomized controlled trials (RCTs) included in the SRs/MAs were quantitatively analyzed through the implementation of RevMan 5.4 software. RESULTS: Eleven SRs/MAs were included in this study, comprising 54 RCTs involving a total of 9539 patients with GC. The studies covered the period from 2012 to 2021, with the number of original RCTs per study ranging from 3 to 20 and sample sizes ranging from 159 to 1413. The methodological quality of all 11 SRs/MAs was assessed as low or very low, and the quality of evidence was determined to range from moderate to very low. The comprehensive quantitative meta-analysis revealed that the combination of SFI with CT improved the objective response rate (ORR) (RR = 1.30, 95% CI = [1.21, 1.41], P < .00001) and disease control rate (DCR) (RR = 1.13, 95% CI = [1.09, 1.18], P < .00001) in GC patients, without heterogeneity observed among the studies. In comparison with CT alone, SFI combined with CT also demonstrated improvements in the Karnofsky performance status (KPS) (RR = 1.36, 95% CI = [1.25, 1.49], P < .00001) and CD4+/CD8+ level (RR = 1.16, 95% CI = [0.87, 1.46], P < .00001) of patients. In terms of adverse reactions, the combination therapy of SFI with CT was associated with a reduced incidence of gastrointestinal reactions (RR = 0.67, 95% CI = [0.58, 0.78], P < .00001) and neurotoxicity (RR = 0.64, 95% CI = [0.50, 0.81], P = .0002). CONCLUSIONS: SFI combined with CT can enhance the clinical effectiveness and enhance the quality of life in patients with GC, while minimizing adverse reactions. Nonetheless, the evaluation of overall quality remains deficient, thus restricting the reliability and stability of the conclusions. High-quality, large-sample RCTs remain crucial for establishing dependable clinical evidence. SYSTEMATIC REVIEW REGISTRATION: INPLASY20239004.

[Electrophysiological appropriateness technique based on TCM meridian theory for postoperative pain after urethral reconstruction: A real-world study].

OBJECTIVE: To investigate the clinical efficacy of electrophysiological appropriateness technique (EAT) therapy based on the traditional Chinese medicine (TCM) meridian theory in managing postoperative pain after urethral reconstruction surgery. METHODS: Using the real-world study approach, we enrolled 61 male patients undergoing urethral reconstruction and divided them into a control group (n = 30) and an observation group (n = 31), the former receiving patient-controlled intravenous analgesia (PCIA), while the latter PCIA plus EAT at 4 pairs of acupoints (Hegu, Neiguan, Zusanli and Sanyinjiao bilaterally) and the Ashi point, with 100 mg tramadol hydrochloride given orally as remedial analgesia in both groups in case of postoperative Visual Analogue Scale (VAS) score ≥4. We compared the VAS scores at 4, 12, 24 and 48 hours postoperatively, the dose of cumulative fentanyl used at 48 hours, the number of cases needing remedial analgesia, the time to first flatus and the incidence of adverse reactions between the two groups of patients. RESULTS: The VAS scores were markedly lower in the observation than in the control group at 4, 12, 24 and 48 hours after surgery (P < 0.05), with statistically significant differences in time-dependent effect and interactive effect (P < 0.05). Significant reduction was observed in the doses of cumulative fentanyl (P < 0.05) and remedial tramadol analgesia (P < 0.05), time to first flatus (P < 0.05), and incidence of adverse reactions (P < 0.05) in the observation group in comparison with the controls. CONCLUSION: Electrophysiological therapy based on the TCM meridian theory can safely and effectively alleviate postoperative pain after urethral reconstruction, reduce opioid consumption, and decrease adverse events.

Solanum nigrum Linn.: Advances in anti-cancer activity and mechanism in digestive system tumors.

Cancer has currently become a serious public health issue in many countries worldwide, and tumors of the digestive system have attracted an increasing number of researchers' due to their numerous types, high proportion and wide area of occurrence. While tumors of the digestive system suffer from high mortality rates, leading to untimely diagnosis and a poor prognosis, making it necessary to update current treatment approaches such as surgery, radiation therapy, and chemotherapy. This highlights the importance of exploring novel therapeutic ideas and targets. Traditional Chinese medicine has a long history of clinical use due to its low toxicity and multi-factor targeting of multiple pathways. As a kind of traditional Chinese herb, S. nigrum Linn. is highly regarded for its proven antitumor activity. The aim of this study was to comprehensively recapitulate and analyze the anti-cancer effects and molecular mechanisms of treatment of gastrointestinal tumors with S. nigrum Linn. extracts and related compounds, including classical signaling pathways mediated by them as well as noncoding RNA pathways associated with tumor suppression. Components that have been found to be responsible for the anti-cancer activity of S. nigrum Linn. include solanine, solasonine, solamargine, a-L-rhhamnopyranose, uttroside B, degalactotigonin, glycoprotein, and other compounds. The underlying mechanisms of anti-cancer activity reflected in this study include apoptosis, cell cycle arrest, autophagy, anti-angiogenesis, suppression of metastasis and invasion, immune escape, and increased sensitivity to radiotherapy. S. nigrum Linn. has great potential in the treatment of tumors of the digestive system, and through further clinical trials and pharmacological mechanisms it has the potential to become a uniform and standardized anti-tumor drug.

Biochar-Assisted Catalytic Pyrolysis of Oily Sludge to Attain Harmless Disposal and Residue Utilization for Soil Reclamation.

Pyrolysis of oily sludge (OS) is a feasible technology to match the principle of reduction and recycling; however, it is difficult to confirm the feasible environmental destination and meet the corresponding requirements. Therefore, an integrated strategy of biochar-assisted catalytic pyrolysis (BCP) of OS and residue utilization for soil reclamation is investigated in this study. During the catalytic pyrolysis process, biochar as a catalyst intensifies the removal of recalcitrant petroleum hydrocarbons at the expense of liquid product yield. Concurrently, biochar as an adsorbent can inhibit the release of micromolecular gaseous pollutants (e.g. HCN, H2S, and HCl) and stabilize heavy metals. Due to the assistance of biochar, pyrolysis reactions of OS are more likely to occur and require a lower temperature to achieve the same situation. During the soil reclamation process, the obtained residue as a soil amendment can not only provide a carbon source and mineral nutrients but can also improve the abundance and diversity of microbial communities. Thus, it facilitates the plant germination and the secondary removal of petroleum hydrocarbons. The integrated strategy of BCP of OS and residue utilization for soil reclamation is a promising management strategy, which is expected to realize the coordinated and benign disposal of more than one waste.

Aucubin enhances the antitumor activity of cisplatin through the inhibition of PD-L1 expression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality in the world. However, the anticancer effects of aucubin against HCC have yet to be reported. Cisplatin often decreased CD8+ tumor-infiltrating lymphocytes in the tumor microenvironment through increasing programmed death-ligand 1 (PD-L1) expression, which seriously affected the prognostic effect of cisplatin in the treatment of patients with HCC. Therefore, it is necessary to identify a novel therapeutic avenue to increase the sensitivity of cisplatin against HCC. PURPOSE: This study aims to evaluate the anti-tumor effect of aucubin on HCC, and also to reveal the synergistic effects and mechanism of aucubin and cisplatin against HCC. STUDY DESIGN AND METHODS: An H22 xenograft mouse model was established for the in vivo experiments. Cancer cell proliferation was detected by MTT assay. RT-qPCR was performed to analyze CD274 mRNA expression in vitro. Western blotting was employed to determine the expression levels of the PD-L1, p-Akt, Akt, p-ß-catenin, and ß-catenin in vitro. Immunofluorescence was carried out to examine ß-catenin nuclear accumulation in HCC cells. Immunohistochemistry was used to detect tumoral PD-L1 and CD8α expression in xenograft mouse model. RESULTS: Aucubin inhibits tumor growth in a xenograft HCC mouse model, but did not affect HCC cell viability in vitro. Aucubin treatment significantly inhibited PD-L1 expression through inactivating Akt/ß-catenin signaling pathway in HCC cells. Overexpression of PD-L1 dramatically reversed aucubin-mediated tumoral CD8+ T cell infiltration and alleviated the antitumor activity of aucubin in xenograft mouse model. Moreover, Cisplatin could induce the expression of PD-L1 through the activation of the Akt/ß-catenin signaling pathway in HCC cells, which can be blocked by aucubin in vitro. In xenograft mouse model, cisplatin treatment induced PD-L1 expression and alleviated the infiltration of CD8+ T lymphocytes in the tumor microenvironment. Aucubin not only abrogated cisplatin-induced PD-L1 expression but also enhanced the antitumor efficacy of cisplatin in a mouse xenograft model of HCC. CONCLUSION: Aucubin exerts antitumor activity against HCC and also enhances the antitumor activity of cisplatin by suppressing the Akt/ß-catenin/PD-L1 axis.

Deoxyelephantopin Suppresses Pancreatic Cancer Progression In Vitro and In Vivo by Targeting linc00511/miR-370-5p/p21 Promoter Axis.

Objectives: Deoxyelephantopin (DET) is a kind of natural active ingredient extracted from the Chinese herbal medicine Elephantopus scaber L. Many studies have revealed the potential antitumor effect on multiple malignancies. However, the detailed mechanism of its antitumor effect in pancreatic cancer remains unclear. Recently, studies have confirmed that noncoding RNA (ncRNA) plays an important regulatory role in malignancies. This research was performed to explore the relationship between ncRNA and DET-induced tumor inhibition in pancreatic cancer. Methods: Microarray profiling was applied to identify the candidate ncRNAs associated with DET-induced tumor inhibition. Quantitative real-time PCR was used to evaluate the expression of linc00511 in pancreatic cancer cells and tissues. The influence of DET on the cell proliferation, migration, and invasion was assessed by CCK-8, colony formation, wound healing, and Transwell assays. The relationship between lncRNAs, miRNAs, and p21 promoter region was analyzed by bioinformatics and verified by luciferase reporter gene and western blotting. The effect of linc00511 on nuclear translocation of miR-370-5p was explored by cytoplasmic and nuclear RNA purification. Moreover, the effect of DET on tumor growth and metastasis, and the prophylactic effect were investigated by establishing subcutaneous and lung metastatic tumor models. Results: Microarray assay indicated linc00511 was a potential target gene. The antitumor effect of DET in pancreatic cancer depended on downregulating linc00511 expression, and linc00511 might be an oncogene in pancreatic cancer. Silencing linc00511 enhanced the antitumor function of DET; conversely, linc00511 overexpression antagonized the DET cytotoxic effect. Additionally, miR-370-5p could bind to p21 promoter to exert the RNA activation and then promote p21 expression. P21 was a downstream gene of linc00511 and associated with pancreatic cancer progression. Linc00511 regulated p21 expression by blocking miR-370-5p nuclear translocation. Conclusions: To sum up, the present finding confirmed that DET suppressed the malignant biological behavior of pancreatic cancer via linc00511/miR-370-5p/p21 promoter axis.

[Transcutaneous auricular vagus nerve stimulation promotes gastric motility by up-rgulating α7nAChR and suppressing NF-κB p65 expression in duodenum in rats with functional dyspepsia].

OBJECTIVE: To study the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on gastric sensitivity and motility in rats with functional dyspepsia (FD), so as to explore its underlying mechanism in improving FD. METHODS: A total of 48 young SD rats were randomly divided into control (n=10), model (n=9), taVNS (n=9), subdiaphragmatic vagus nerve stimulation (SDVNS, n=9) and sham SDVNS (n=7) groups. The FD model was established by gavage of 0.1% iodoa-cetamide+2% glucose, once daily for 6 days. Rats in the taVNS group received taVNS (0.5 mA) of optopoint "Heart" and "Stomach" for 30 min, once daily for 14 days, while rats in the SDVNS group received subdiaphragmatic vagus nerve stimulation through the implanted electrode, and those of the sham SDVNS group received only application of the same electrodes without electrical stimulation. Electromyogram (EMG) of the cervical trapezius muscle (reflecting gastric sensitivity) was recorded before and after intragastric expansion via an air ballon and the gastric emptying rate was calculated for assessing the gastric motility. The contents of acetylcholine (ACh), nicotinic acetylcholine receptor α7 subunit (α7nAChR), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the duodenum tissue were detected by enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor kappa B (NF-κB) p65 in the duodenum tissue was determined by Western blot. RESULTS: In comparison with the control group, the EMG change rate at intragastric pressure levels of 40, 60 and 80 mm Hg, expression of NF-κB p65 protein, and contents of IL-6, IL-1ß and TNF-α were significantly increased (P<0.05,P<0.01, P<0.001), while the gastric emptying rate, ACh and α7nAChR contents considerably decreased (P<0.05, P<0.001) in the model group. After interventions, the EMG change rate, contents of IL-6, IL-1ß and TNF-α, and expression of NF-κB p65 were notably decreased (P<0.05, P<0.01, P<0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (P<0.05, P<0.001) in both taVNS and SDVNS groups relevant to the model group. In comparison with the sham SDVNS group, the EMG change rate, contents of IL-6, IL-1ß and TNF-α, and expression of NF-κB p65 were notably decreased (P<0.01, P<0.05,P<0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (P<0.01, P<0.001) in the both SDVNS and taVNS groups. CONCLUSION: taVNS can reduce gastric sensitivity and promote gastric emptying in FD model rats, which may be closely related to its functions in up-regulating ACh and α7nAChR contents and inhibiting the activation of NF-κB p65 signaling in the duodenum.

Potent Inhibition of Human Cytochrome P450 3A4 by Biflavone Components from Ginkgo Biloba and Selaginella Tamariscina.

CYP3A4-mediated Phase I biotransformation is the rate-limiting step of elimination for many commonly used clinically agents. The modulatory effects of herbal medicines on CYP3A4 activity are one of the risk factors affecting the safe use of drug and herbal medicine. In the present study, the inhibitory effects of nearly hundred kinds of herbal medicines against CYP3A4 were evaluated based on a visual high-throughput screening method. Furthermore, biflavone components including bilobetin (7-demethylginkgetin, DGK), ginkgetin (GK), isoginkgetin (IGK), and amentoflavone (AMF) were identified as the main inhibitory components of Ginkgo biloba L. (GB) and Selaginella tamariscina (P. Beauv.) Spring (ST), which displayed very strong inhibitory effects toward CYP3A4. The inhibitory effects of these biflavones on clinical drugs that mainly undergo CYP3A4-dependent metabolism were evaluated. The IC 50 of GK toward tamoxifen, gefitinib and ticagrelor were found to be of 0.478 ± 0.003, 0.869 ± 0.001, and 1.61 ± 0.039 µM, respectively. These results suggest the potential pharmacokinetic interactions between the identified biflavones and clinical drugs undergoing CYP3A4-mediated biotransformation. The obtained information is important for guiding the rational use of herbal medicine in combination with synthetic pharmaceuticals.

Auricular Vagus Nerve Stimulation Ameliorates Functional Dyspepsia with Depressive-Like Behavior and Inhibits the Hypothalamus-Pituitary-Adrenal Axis in a Rat Model.

BACKGROUND: The hypothalamus-pituitary-adrenal axis is the most important endocrine system to control irritability response. Functional dyspepsia (FD) is closely related to irritability. This study aimed to preliminarily explore the corticotropin-releasing factor (CRF) mechanism of auricular vagus nerve stimulation (aVNS) for FD model rats. METHODS: Sprague-Dawley adult male rats were randomly divided into normal group, model group, aVNS group, and sham-aVNS group. Except for the normal rats, all other rats were induced into the FD model through tail-clamping stimulation for 3 weeks. Once the rat model was developed successfully, rats in the aVNS group and sham-aVNS group were intervened with aVNS or sham-aVNS for 2 weeks. No intervention was given to rats in the normal and model groups. The effect of aVNS was assessed. The expressions of hippocampal corticotropin-releasing hormone receptor 1 (CRHR1), hypothalamus CRF, adrenocorticotropic hormone (ACTH), and corticosterone in serum were assessed. RESULTS: 1. Compared with normal rats, model-developing rats showed FD-like behavior. 2. Compared with model rats, rats in the aVNS group showed an improved general condition score and gastric motility, and increased horizontal and vertical motion scores. 3. The release of corticosterone, ACTH in serum, and CRF in the hypothalamus all increased in model rats but decreased with aVNS instead of sham-aVNS. 4. The expression of hippocampus CRHR1 was lower in model rats but higher in the aVNS group. CONCLUSION: aVNS ameliorates gastric motility and improves the mental state in the FD-like rat, probably via inhibiting the CRF pathway.

Phosphate enhanced uranium stable immobilization on biochar supported nano zero valent iron.

Uranium (U) immobilization from wastewater by zero valent iron (ZVI) was widely concerned through reduction and surface adsorption. Releasing of U due to re-oxidation of U(IV) into U(VI) limited the application of ZVI in U decontamination. In this work, a kind of biochar supported nano zero valent iron (Fe/BC(900)) was obtained by carbothermal reduction of starch mixed with ferric nitrate at 900 °C. U immobilization behavior by Fe/BC(900) in the presence of phosphate (P) was investigated. The U immobilization reaction was adjusted by controlling the sequence of U, Fe/BC(900) and P. U immobilization efficiency was enhanced to 99.9% in the presence of P. Reaction sequence of U, Fe/BC(900) and P influenced the U immobilization efficiency, which followed the order of (U-P)+Fe/BC(900)>(U- Fe/BC(900))+P>U+Fe/BC(900)>(P-Fe/BC(900))+U. P and nZVI both contributed to enhancing U immobilization through precipitation of uranyl-P and reductive co-precipitate (U(IV)) in a wide pH range. The released Fe ions could precipitate with uranyl and phosphate. Consumption of P and nZVI in the (P-Fe/BC(900))+U system limited U immobilization ability. The precipitate is highly dependent on U, P and Fe elements. U desorption in (U-P)+Fe/BC(900) system was not observed with stability.

Tanshinone IIa Induces Autophagy and Apoptosis via PI3K/Akt/mTOR Axis in Acute Promyelocytic Leukemia NB4 Cells.

Tanshinone IIa (TanIIa), an ingredient of Radix Salviae Miltiorrhizae, has an anticancer effect on various solid tumors with high efficiency and low toxicity. Nonetheless, the underlying role of TanIIa in acute promyelocytic leukemia (APL) remains unclear. Here, we revealed that TanIIa drastically inhibited NB4 cell viability with an IC50 value of 31.25 µmol/L. Using flow cytometry apoptosis assay, we identified that TanIIa dose-dependently exacerbated NB4 cell apoptosis. Mechanistically, TanIIa upregulated apoptotic factor levels, namely, cleaved-caspase 9, cleaved-caspase 3, and cleaved-PARP-1. Moreover, we noticed that TanIIa dose-dependently suppressed the PI3K/Akt/mTOR axis. This axis not only functions as an essential antiapoptotic modulator but also serves as a suppressant regulator of autophagy. Correspondingly, we detected the levels of autophagic marker, namely, LC3B, which were increased after the TanIIa treatment. Furthermore, the autophagy inhibitor Baf-A1 could effectively reverse the TanIIa-induced apoptosis, manifesting that TanIIa eliminated NB4 cells in an autophagy-dependent manner. In conclusion, tanshinone IIa exerts anti-APL effects through triggering autophagy and apoptosis in NB4 cells.

Effects of transcutaneous auricular vagus nerve stimulation on brain functional connectivity of medial prefrontal cortex in patients with primary insomnia.

As a representative of acupuncture and nonpharmaceutical therapy, auricular acupuncture has been widely for the treatment of insomnia. Transcutaneous auricular vagus nerve stimulation (taVNS) is a combination of auricular point stimulation and vagus nerve stimulation. It can not only treat primary insomnia effectively, but also is noninvasive, painless, portable and economical. The medial prefrontal cortex (mPFC) is a core region of default mode network (DMN), which is important for maintenance of sleep. However, the mechanism of taVNS in alleviating primary insomnia (PI) remains to be clarified. In this study, we found that taVNS could not only effectively reduce the score of Pittsburgh Sleep Quality Index, but also decreased functional connection (FC) between the left mPFC and bilateral dorsal anterior cingulate gyrus as well as FC between the right mPFC and the occipital cortex in patients with PI. Furthermore, the decrease in FC was positively correlated with the decline of sleep index score. Therefore, we proposed that treatment with taVNS can improve sleep quality and prolong sleep duration in patients with PI by reducing FC within DMN, FC between DMN and salience network, as well as FC between DMN and the occipital cortex. This may be one of mechanisms of taVNS in treating PI.

[Effects of transcutaneous auricular vagus nerve stimulation on autonomic nervous function in rats with functional dyspepsia].

OBJECTIVE: To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the autonomic nerve function in a rat model of functional dyspepsia (FD), so as to explore the mechanism of taVNS underlying regulation of FD. METHODS: SD rats were randomly divided into normal control group(n=8) and FD model group(n=26).The FD model was replicated with iodoacetamide gavage. The FD model rats were randomly divided into model, taVNS, sham-taVNS and Zusanli(ST36) groups, with 6 rats in each group. Rats in the taVNS group received electrical stimulation of auricular concha,while the sham-taVNS group received no electrical stimulation and rats in the ST36 group received stimulation at ST36 for 30 min once daily for 14 consecutive days. Cervical trapezius electromyography score and abdominal withdrawal reflex (AWR) score were used to evaluate gastric sensitivity. Histopathological changes of the gastric antrum tissue were observed under microscope after H.E. staining. Autonomic nerve function in rats was recorded and assessed by heart rate variability(HRV). The content of acetylcholine (Ach) and the expression of Ach receptor M3R in gastric antrum was detect by ELISA and Western blot, separately. RESULTS: Compared with the normal control group, the cervical trapezius electromyography and AWR scores of the model group increased (P<0.01, P<0.001), and there was no erosion in the gastric antral mucosa and muscle layer. The high-frequency power (HF) in HRV decreased (P<0.05), the ratio of low-frequency power/high-frequency power (LF/HF) increased (P<0.001), and the Ach content and its receptor M3R expression in gastric antrum tissue decreased (P<0.05). Following interventions, the cervical trapezius electromyography and AWR scores decreased (P<0.01,P<0.001, P<0.05), HF in HRV increased and LF/HF decreased(P<0.01，P<0.05,P<0.001), and the content of Ach in gastric antrum tissue and the expression of its receptor M3R increased (P<0.01, P<0.05) in both taVNS and ST36 groups relevant to the model group. CONCLUSION: taVNS can increase the activity of the vagus nerve and regulate the balance of the autonomic nerve function, which may be one of the mechanisms of taVNS in reducing the gastric sensitivity of rats with FD. In regulating the vagus nerve function, taVNS and acupuncture at ST36 acupoint have the similar effects.

Diversity of Endophytic Fungal Community in Leaves of Artemisia argyi Based on High-throughput Amplicon Sequencing.

To investigate the community structure and diversity of endophytic fungi in the leaves of Artemisia argyi, leaf samples were collected from five A. argyi varieties grown in different cultivation areas in China, namely, Tangyin Beiai in Henan (BA), Qichun Qiai in Hubei (QA), Wanai in Nanyang in Henan (WA), Haiai in Ningbo in Zhejiang (HA), and Anguo Qiai in Anguo in Hebei (AQA), and analyzed using Illumina high-throughput sequencing technology. A total of 365,919 pairs of reads were obtained, and the number of operational taxonomic units for each sample was between 165 and 285. The alpha diversity of the QA and BA samples was higher, and a total of two phyla, eight classes, 12 orders, 15 families, and 16 genera were detected. At the genus level, significant differences were noted in the dominant genera among the samples, with three genera being shared in all the samples. The dominant genus in QA was Erythrobasidium, while that in AQA, HA, and BA was Sporobolomyces, and that in WA was Alternaria, reaching a proportion of 16.50%. These results showed that the fungal community structure and diversity in QA and BA were high. The endophytes are of great importance to the plants, especially for protection, phytohormone and other phytochemical production, and nutrition. Therefore, this study may be significant with the industrial perspective of Artemisia species.

Photocatalytic degradation of sulfamonomethoxine by mesoporous phosphorus-doped titania under simulated solar light irradiation.

Photocatalytic degradation of sulfamonomethoxine (SMM) by mesoporous phosphorus-doped TiO2 (P-TiO2) was studied under simulated solar light irradiation. The morphological structure and chemical composition of P-TiO2 were analyzed by XRD, SEM, HRTEM, BET, XPS and FTIR. Using the central composite design (CCD) of response surface methodology (RSM), the degradation of SMM was investigated with a range of antibiotic concentrations (4-8 mg L-1), catalyst dosages (400-900 mg L-1), P doping amounts (5-15 wt %) and irradiation time (90-150 min). The Ti-O-P bond formed during the calcination of TiO2, thereby generating plate-like P-TiO2, where P was uniformly distributed. Phosphorus doping can stabilize anatase TiO2, which has a larger specific surface area and a lower average particle and pore size than bare TiO2. The result obtained from the RSM model showed a significant correlation between the predicted values and the experimental results of SMM degradation (P < 0.05). Under the optimal experimental conditions (antibiotic concentration = 6 mg/L, catalyst dosage = 800 mg/L, P doping = 5 wt% and irradiation time = 90 min), the degradation rate of SMM was 99.51%, and the TOC was 50%. Toxicity showed a considerable reduction towards Vibrio-qinghaiensis sp.-Q67 after SMM photocatalytic degradation. Through free radical capture experiments, LC-MS detection and DFT calculations, the possible photocatalytic degradation mechanism of SMM using P-TiO2 as the catalyst was revealed.

Natural soluble epoxide hydrolase inhibitors from Alisma orientale and their potential mechanism with soluble epoxide hydrolase.

Inhibition of soluble epoxide hydrolase (sEH) is considered to be an effective treatment for inflammation-related diseases, and small molecules origin from natural products show promising activity against sEH. Two undescribed protostanes, 3ß-hydroxy-25-anhydro-alisol F (1) and 3ß-hydroxy-alisol G (2) were isolated from Alisma orientale and identified as new sEH inhibitors with IC50 values of 10.06 and 30.45 µM, respectively. Potential lead compound 1 was determined as an uncompetitive inhibitor against sEH, which had a Ki value of 5.13 µM. In-depth molecular docking and molecular dynamics simulations revealed that amino acid residue Ser374 plays an important role in the inhibition of 1, which also provides an idea for the development of sEH inhibitors based on protostane-type triterpenoids.

Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications.

Valerian root (Valeriana officinalis) is a popular and widely available herbal supplement used to treat sleeping disorders and insomnia. The herb's ability to ameliorate sleep dysfunction may signify an unexplored anti-tumorigenic effect due to the connection between circadian factors and tumorigenesis. Of particular interest are the structural similarities shared between valeric acid, valerian's active chemical ingredient, and certain histone deacteylase (HDAC) inhibitors, which imply that valerian may play a role in epigenetic gene regulation. In this study, we tested the hypothesis that the circadian-related herb valerian can inhibit breast cancer cell growth and explored epigenetic changes associated with valeric acid treatment. Our results showed that aqueous valerian extract reduced growth of breast cancer cells. In addition, treatment of valeric acid was associated with decreased breast cancer cell proliferation, migration, colony formation and 3D formation in vitro in a dose- and time-dependent manner, as well as reduced HDAC activity and a global DNA hypomethylation. Overall, these findings demonstrate that valeric acid can decrease the breast cancer cell proliferation possibly by mediating epigenetic modifications such as the inhibition of histone deacetylases and alterations of DNA methylation. This study highlights a potential utility of valeric acid as a novel HDAC inhibitor and a therapeutic agent in the treatment of breast cancer.